Netherlands gets first nationwide 'Internet of Things' - <AUTHOR> http://phys.org/news/2016-06-netherlands-nationwide-internet.html <comment><USER2> Original press release: [https://corporate.kpn.com/press/press-releases/the- netherlan...](https://corporate.kpn.com/press/press-releases/the-netherlands- has-first-nationwide-lora-network-for-internet-of-things-.htm)

LoRa is an industry standard, backed by the LoRa alliance: [https://www.lora- alliance.org/What-Is-LoRa/Technology](https://www.lora-alliance.org/What-Is- LoRa/Technology)

</comment><comment><USER3> For some context about KPN (company doing this) and LoRa (wireless standard involved):

\- KPN has pretty much 100% country-wide 2G/3G coverage [1], so this is unlikely to be about long-reach aspect of LoRa;

\- Frequency licenses are _extremely_ expensive [2] and hard to obtain;

\- KPN is silent about whether they use licensed or unlicensed spectrum for LoRa, apart from noting that frequency is "low" [3], while they didn't obtain any particularly low-freqency license recently [4]

Chances are this is just a land-grab for 433Mhz. [EDIT 868Mhz]

[1] [http://www.sensorly.com/map/2G-3G/NL/Netherlands/KPN/gsm_204...](http://www.sensorly.com/map/2G-3G/NL/Netherlands/KPN/gsm_20408)

[2] [https://www.telegeography.com/products/commsupdate/articles/...](https://www.telegeography.com/products/commsupdate/articles/2012/12/17/4g-auction- raises-usd5bn-for-dutch-coffers/)

[3] [https://corporate.kpn.com/press/press-releases/kpns-new- lora...](https://corporate.kpn.com/press/press-releases/kpns-new-lora-network- to-boost-the-internet-of-things.htm)

[4] [https://corporate.kpn.com/press/press-releases/kpn- obtains-h...](https://corporate.kpn.com/press/press-releases/kpn-obtains- highly-valuable-spectrum-dividend-outlook-adjusted.htm)

EDIT: Yep, they are going unlicensed, according to the site weitzj has pointed out: [https://www.thethingsnetwork.org/wiki/LoRaWAN- Frequencies](https://www.thethingsnetwork.org/wiki/LoRaWAN-Frequencies)

</comment><comment><USER4> Also a very interesting LoraWan related community project: [https://www.thethingsnetwork.org](https://www.thethingsnetwork.org)

</comment><comment><USER5> Who else here on HN is working with LoRa?

In my opinion it can be a very interesting business offering a global team of expert of the subject.

Feel free to contact me on the address on my profile.

</comment><comment><USER6> Is this type of thing really that important now that we have stuff like the ESP8266 that is tiny, has WiFi, and has good power saving features like deep sleep?

<comment><USER7> There was something about port of Rotterdam in the story. Good luck with installing wifi hotspots all over shipyard or close by rail switches. You also need access points not that far away for ESP8266 or cable + big antena.

On the other hand WiFi spectrum is already crowded with around 20 networks at any time in cities with god knows how many clients connected to it.

</comment></comment><comment><USER8> What are the advantages of using something like this over installing your own gateways?</comment>


Daily chart: Costly calamities - patrick-james http://www.economist.com/blogs/graphicdetail/2013/03/daily-chart-20?fsrc=scn/tw/te/bl/Costlycalamities <comment> patrick-james To me this says one thing and one thing only: get ready for climate change.</comment>


The Key to Defeating Covid-19 Already Exists. We Need to Start Using It - <AUTHOR> https://www.newsweek.com/key-defeating-covid-19-already-exists-we-need-start-using-it-opinion-1519535 <comment><USER2> Why was the other post flagged?

[https://news.ycombinator.com/item?id=23969998](https://news.ycombinator.com/item?id=23969998)</comment>


Different Brain Regions Are Infected with Fungi in Alzheimer's Disease - <AUTHOR> http://www.nature.com/articles/srep15015 <comment><USER3> Hi, I do research using the same methods: immunohistochemistry. This was done with rabbit polyclonal antibodies. The key being polyclonal. We don't know what those antibodies are really staining. The difference, however, is intriguing.

<comment><USER4> Could you elaborate on what polyclonal means here? Does it mean that they might not have detected fungus after all, but some other thing that would activate the same antibodies?

<comment><USER5> Yeah, but that's true for monoclonals too, just a matter of degree.

A polyclonal antibody is an extraction of (usually rabbit) blood from an animal that has been insulted with the agent you'd like to detect. The extraction is enriched for antibodies. They are less reliable, because there could also be other antibodies in there. Even the antibodies that recognize what you're looking for could be a population of antibodies, each recognizing a different part (think the blind men and the elephant parable). Presumably, you have tested that a positive control of what you're trying to look for works.

A monoclonal is different. You insult a mouse with a sample of what you'd like to detect, and then resect the spleen, which contains b-cells, cells that produce the antibody. You then fuse the b-cells with a special strain of cancer cell that will immortalize the b-cell (these are called 'hybridomas'). After sorting one cell to a well, you then test to see if the cells in the well have produced an antibody that detects what you're looking for. Therefore, you can be confident that a monoclonal antibody contains only one antibody, that recognizes only one antigen.

You don't necessarily know what the antigen is that is recognized (that's called the epitope). The epitope could be, say, a piece of protein on the outside of the fungus or a different piece of protein on the outside of the fungus. It's even conceivable that even for a monoclonal there are side- reactions against things that are naturally in the sample.

And: Epitope retrieval techniques are really complicated. So figuring out exactly what epitope is recognized is not trivial.

<comment><USER6> >"you can be confident that a monoclonal antibody contains only one antibody, that recognizes only one antigen"

Not sure if you really meant that since it is kind of contradicted by some later statements, but all antibodies are promiscuous. Thinking you can map one antibody to one epitope is extremely dangerous. It is a matter of quantity (affinity/avidity), not quality.

<comment><USER7> Exactly. When i did immunocytochemistry, i had more confidence in polyclonals than monoclonals. If you get a strong signal with a polyclonal, then you know that many different antibodies are all binding the same thing, so it's very likely it's your protein. If you get a strong signal with a monoclonal, that's just one antibody - so it might be your protein, or it might be some other protein that, by chance, your antibody happens to bind tightly.

</comment></comment></comment></comment></comment><comment><USER8> As a biomedical researcher, I'm confident in calling this sloppy science. There is no quantitation of staining differences across multiple fields (to demonstrate that the images aren't hand picked), no controls with the PCR study (or even showing the results besides one in the supplement), and no demonstration that the antibodies don't bind to amyloid. Extraordinary claims require extraordinary evidence, and this wouldn't even motivate me to perform a follow up study.

<comment><USER9> I'm curious: how does something this obviously flawed get through peer review for Nature?

(I believe you that this is bad science.)

Edit: I answered my own question here: [https://en.m.wikipedia.org/wiki/Scientific_Reports](https://en.m.wikipedia.org/wiki/Scientific_Reports) (Summary: It's not Nature; it's a "megajournal" affiliated with it with apparently much lower editorial standards.)

<comment><USER10> Exactly. Scientific Reports (and Nature Communications) is sometimes used for papers that don't get into Nature or any of its siblings (Genetics, Methods, Protocols, Biotechnology).

<comment><USER11> Can confirm. Had a paper rejected by Nature with the suggestion to send it to Scientific Reports instead. Scientific Reports accepted it.

</comment></comment></comment></comment><comment><USER12> It's hard not to exaggerate the implications of this study if fungal infection does turn out to be the cause of AD given how huge this would be for humanity. Just off the top of my head I can say this disease has effected my family (1 set of grandparents effected by this disease so far) so I'd like for the conclusion to be correct.

I guess the next step would be testing the hypothesis with more people with AD to see if it holds up and then somehow getting approval to do drug trials (and I'm sure there will be no shortage of volunteers.) I can almost see a clamouring of families trying to get their hands on anti-fungal drugs in the future in the hope that it helps their loved ones but we simply won't know if this will help until there's more data.

Hoping for a break through. It's certainly not without precedent that we find something extremely simple / obvious that turns out to be the key. On a side note: it's interesting to think that the crack pots you see writing about candidas infections being the cause of numerous hard-to-treat illnesses -might- actually be right (in a sense.)

<comment><USER13> The discovery, if corroborated by others, could indeed be huge but I'm afraid it wouldn't open up new treatment options anytime soon. Fungal infections inside the body are really really hard to treat in the first place. Add to that the blood-brain barrier which makes it very hard to treat any type of infection in the brain. [https://en.wikipedia.org/wiki/Blood%E2%80%93brain_barrier#Fu...](https://en.wikipedia.org/wiki/Blood%E2%80%93brain_barrier#Function)

Combination of these two factors sadly means that short of major breakthroughs in fungal antibiotic research or in drug delivery to the brain, Alzheimer is not likely to suddenly become more treatable even if the fungal infection theory proves to be true.

<comment><USER14> First, there are antifungal drugs that pass the BBB, with varying efficacy:

[https://www.medicine.wisc.edu/sites/default/files/domfiles/i...](https://www.medicine.wisc.edu/sites/default/files/domfiles/infectiousdisease/EMT030408.pdf)

Second, antifungals have positively affected AD-like symptoms, though possibly through misdiagnosis.

<comment><USER15> It's known to be pretty difficult to treat a lot of fungal infections in the CNS. The agents we have are pretty nasty, with severe side effects.

<comment><USER16> I'm a hacker not a doctor but I've done some research into water purification, and here is what I've learned:

The body is mostly water. The task of removing microorganisms and fungus from water has been well studied.

Science knows of effective agents which are proven to purify water of micro- organisms like bacteria and also fungus. Some of these are being utilized in public water decontamination, and others while also effective are not used because they are less cost efficient to produce.

Water purifying agents have a varying range of effectiveness and also and a varying range of toxicity to the human body. There are a couple of agents in particular however which are both well tolerated by the body and are also remarkably effective at decontaminating water.

The one which my research indicates leads the pack in this area is a white crystalline salt named Potassium Iodide, KI. KI has been used widely by both the military and by campers in portable water decontamination.

A solution of Potassium Iodide in water (known colloquially as Iodine) was a leading and apparently very effective drug during the 19th century in the United States. There are doctors today who prescribe milligram doses of KI (many many times more than the RDA) to treat a wide array of ailments but especially in dermatology. They do not typically see serious side effects although they do frequently recommend monitoring thyroid levels while utilizing higher doses.

<comment><USER17> This argument seems to be that "The body is mostly water. The task of removing X from water has been well studied. Therefore it's easy to remove X from the body". This seems to be a logical fallacy.

Let me rephrase this argument as: "The body is mostly water. The task of removing HIV from water has been well studied. Therefore it's easy to remove HIV from the body".

Just to be clear: I have no medical expertise, this is mere conjecture. But fungal infections could perhaps persist in various cells. In neurons. In spoor form. In all sorts of manifestations, where they wouldn't be affected by the same treatment that disinfects water. I don't have any expertise to say one way or the other, but I suspect that if there were a simple solution such as "just treat with Iodine, it'll kill the fungus", this discussion wouldn't be taking place.

<comment><USER18> A quick injection of Easy Off Bam! Mould Killer should fix 'em right up.

</comment></comment></comment></comment></comment></comment></comment><comment><USER6> I bet if they double stain with anti-amyloid-Beta they will see the staining overlap. They just say they used "antibody raised against proteins obtained from C. glabrata, C. famata, C. albicans, P. betae and S. racemosum", so they don't even know (or want to say) what these antibodies react with...

Amyloids have generic secondary structure (can be created from any amino acid sequence under the right conditions) and yeast produce amyloids. They quite possibly raised antibodies towards yeast amyloids and then stained human amyloids. It is strange they do not report staining these brains for amyloid- Beta, it is an obvious thing to do.

<comment><USER19> Do the amyloid proteins you'd expect concentrate in similarly-shaped groupings? One claim is that the shape of the stains has fungal morphology. If Amyloid-beta concentrations can have fungal morphology then I would think that might strengthen your claim and weaken the paper's. I'm only an engineer though, so feel free to dismiss me as ignorant of your field. Either way I can see how these findings are not terribly interesting.

<comment><USER6> >"One claim is that the shape of the stains has fungal morphology. If Amyloid- beta concentrations can have fungal morphology then I would think that might strengthen your claim and weaken the paper's."

The evidence in the paper consists of a few representative pictures. I have never seen human brain stained for amyloid-beta, but if it stained at all I would bet lots of money that I could find at least one clump with "fungal morphology".

Also, ruling out the other explanations (such as they stained for amyloid) is not the audience's job, it is their job. They are the ones with access to the most detailed information, putting them in the best position to think about various explanations for what could be going on.

</comment></comment></comment><comment><USER20> I was thinking if this is real then there must have been past cases of people with Alzheimer's having been given antifungals for other reasons and having gotten better. Googling randomly I came across one, sadly paywalled but from the abstract the guy had been diagnosed with Alzheimer's for three years, then they figured it was cryptococcal meningitis and gave antifungals and four months later he was normal.

The interpretation in the paper was it was a misdiagnosis rather than an Alzheimer's cure but you never know.

[http://content.iospress.com/articles/journal-of- alzheimers-d...](http://content.iospress.com/articles/journal-of-alzheimers- disease/jad00985)

<comment><USER21> Here you go [http://www.docdroid.net/PBdotNO/contentserver.pdf.html](http://www.docdroid.net/PBdotNO/contentserver.pdf.html)

<comment><USER20> Thanks

</comment></comment></comment><comment><USER22> All of the Alzheimer's patients were 79 or older, while all of the control patients were younger than 79 except for one. More than half of the control patients were under 60. That doesn't seem like a very good control to me.

<comment><USER23> Perhaps but the discovery is still significant. Until now there was no such correlation with Alzeimher's and Fungi.

This has significant implications in terms of direction of future research.

<comment><USER24> > Until now there was no such correlation with Alzeimher's and Fungi.

The point of the criticism seems to be that with an improper control group, there still isn't such a correlation, just a suggestion of a possibility of a correlation. But it might be a correlation between, e.g., _age_ and fungal infection.

That's why, but for the variables under study, you want your control group to look as much like your experimental group as possible.

<comment><USER25> That's not how correlations work.

<comment><USER26> That is how correlations may _not_ work, though.

</comment></comment></comment></comment></comment><comment><USER27> Another recent discovery, that of the existence of a meningeal lymphatic system, makes this finding all the more interesting. As far as I know, fungus is in the set of foreign bodies that the adaptive immune system does the least about. Instead, the body mostly removes fungus by mechanical lymphatic clearance.

</comment><comment><USER28> So, turns out there's many types of fungus that affect behavior, and there are even a few that create entirely new behaviors. One such example is ants, when infected by a type of fungus, will climb high and latch onto a branch by biting hard into it. This is so that the ant will get eaten by birds, which then complete the life cycle of that fungus.

There's not many well understood systems (the other well-studied one is toxoplasmosis and cats), but one researcher on Experiment, Charissa de Bekker, just released a new paper with findings from her project.

The results gave a first clue about the many genes that are involved in this manipulated biting behavior. For instance, that the fungus is likely producing LSD-like compounds and is secreting proteins that could affect serotonin and dopamine levels in the brain, as well as the ant's ability to communicate through chemosignals with their nest mates. As well, in the paper, they release the entire transcriptome taken from the brains of these ants, giving other scientists a chance to use this as a model system and to begin to target which genes go on to influence behavior.

I was just talking to her about it this week, and so this news is very timely and a bit eerie. But very cool.

[http://www.biomedcentral.com/content/pdf/s12864-015-1812-x.p...](http://www.biomedcentral.com/content/pdf/s12864-015-1812-x.pdf)

</comment><comment><USER29> If it turns out to be the cause too (maybe similar to cervical cancer), it's a huge discovery.

Asimov's book on science history is an interesting read, full with similar discoveries that were ignored for many years.

[http://www.amazon.com/Far-Human-Eye-Could- See/dp/155817107X](http://www.amazon.com/Far-Human-Eye-Could- See/dp/155817107X)

</comment><comment><USER30> I wonder how many mental illnesses are the result of imbalances in foreign organic matter/microbes/fungi/dietary issues and not issues fundamental to the brain itself?

<comment><USER31> An old but interesting article and discussion related to your question:

[http://www.theatlantic.com/magazine/print/1969/12/how- your-c...](http://www.theatlantic.com/magazine/print/1969/12/how-your-cat-is- making-you-crazy/8873/)

[https://news.ycombinator.com/item?id=3573694](https://news.ycombinator.com/item?id=3573694)

Articles somehow related to the subject:

[http://www.nature.com/news/the-tantalizing-links-between- gut...](http://www.nature.com/news/the-tantalizing-links-between-gut-microbes- and-the-brain-1.18557)

[http://universityofcalifornia.edu/news/do-gut-bacteria- rule-...](http://universityofcalifornia.edu/news/do-gut-bacteria-rule-our- minds)

[http://www.scientificamerican.com/article/gut-second- brain/](http://www.scientificamerican.com/article/gut-second-brain/)

[http://www.theverge.com/2013/8/21/4595712/gut-feelings- the-f...](http://www.theverge.com/2013/8/21/4595712/gut-feelings-the-future- of-psychiatry-may-be-inside-your-stomach)

[http://newsroom.ucla.edu/portal/ucla/changing-gut- bacteria-t...](http://newsroom.ucla.edu/portal/ucla/changing-gut-bacteria- through-245617.aspx)

<comment><USER30> Thanks for all of the sources. I remember listening to a talk on NPR about the same subject a while back in my car but I couldn't find a link to it.

<comment><USER31> Maybe this: [http://www.npr.org/sections/health- shots/2012/07/02/15614221...](http://www.npr.org/sections/health- shots/2012/07/02/156142214/a-parasite-carried-by-cats-could-hurt-humans- sanity)

</comment></comment></comment></comment><comment><USER20> >Therefore, 100% of the AD patients analysed thus far by our laboratory present fungal cells and fungal material in brain sections.

>No fungal material was observed in brain tissue from ten control individuals, whereas fungal infection was clearly present in brains from ten additional AD patients.

So 100% correlation so far - pretty impressive results.

I wonder about my dad who has an unexplained Parkinson's like nervous deterioration.

</comment><comment><AUTHOR> "Different brain regions including external frontal cortex, cerebellar hemisphere, entorhinal cortex/hippocampus and choroid plexus contain fungal material, which is absent in brain tissue from control individuals. Analysis of brain sections from ten additional AD patients reveals that all are infected with fungi."

</comment><comment><USER32> Methylene Blue has shown promise as an alzheimer's treatment. It's a potent antifungal. It easily diffuses through the blood brain barrier. It also happens to be cheap and unpatentable.

</comment><comment><USER33> Wow sounds like a major breakthrough. How did they not notice this before?

<comment><USER34> They still haven't decided for sure if dietary cholesterol is bad for you, or salt for that matter.

The best minds of our generation are too busy selling ads to be bothered with trivial stuff like this.

<comment><USER33> As someone busy working on selling ads, I can't tell whether I should appreciate or resent this comment...

<comment><USER35> You should quit.

</comment></comment></comment></comment><comment><USER36> If Alzheimer's Disease (AD) is caused by fungal infection, why have antifungals (often given for people with invasive fungal disease) never cured an AD patient? AD is common enough that many of these people will have received antifungals for e.g. esophageal thrush or even fungemia.

Regarding the research, the data presented here are not convincing without larger scale replication with better controls and more standardized assays.

<comment><USER37> One possible reason I can think of is that the immune system in the brain is somewhat different from the rest of the body; not quite on par with say the mammary glands, testes, or eyes. Obviously I am not a doctor etc, anti biotics etc can have reduced effect in body parts that have reduced or modified immune responses; maybe anti fungals are similar?

<comment><USER36> It is true that medication penetration of the blood-brain barrier and delivery to the brain is different from other organs (each organ has unique characteristics in this regard).

But we do treat people with CNS infections routinely, including CNS fungal infections.

</comment></comment></comment><comment><USER38> There was recent speculation that alzheimer's was transmissible (prion thing). The transmissibility would make sense if it were actually the fungi causing the build up of the proteins and other damage.

<comment><USER39> From what I recall, the results in a study showed that the primary care giver of an alzheimer's patient was more likely to get alzheimer's themselves. The argument against transmissibility was that primary care givers tend to be related to the patient.. therefore the more likely reason for caregiver alzheimer's is genetics.

<comment><USER40> Or as primary care giver they are exposed to the same environmental factors the sufferer is exposed to, but are generaly younger so more resistant until later life.

</comment></comment></comment><comment><USER41> This article does NOT provide compelling evidence that fungi are the causative agent for AD. It merely reports correlative observations.

You may conclude that antifungal drugs could help patients with AD. You may also think that vaccination or some other mechanism of prevention could reduce the prevalence of AD. These conclusions are simply not supported by the data.

I am a biomedical data scientist, not a neuroimmunologist, so I asked a colleague in my MD/PhD program who has experience in the latter field. His thoughts:

"There are a number of concerning issues here:

1) They are using polyclonal antibodies. I don't think they addressed possibility of cross-reactivity. Comparing Alzheimer's disease vs control brain is like comparing apples and oranges. There can be very different inflammatory states between the two and yield different antigenic environments.

2) The possibility that neurofibrillary tangles or amyloid plaques are sticky and can non-specifically bind antibodies remains a possibility.

3) Only immunohistochemistry? Could have at least done some qPCR especially since they can grow these fungi for quantiation. The only other paper that observed fungus in CNS of AD patients is by the same group. The high possibility of artifact is has not been ruled out."

*edited grammatical typo

</comment><comment><USER42> Interesting. Does this mean that a treatment with fungicides may stop/prevent AD onset or progress?

<comment><USER43> Depends on which way the arrow of causality points. If AD makes the brain vulnerable to fungal infection, probably not. But if fungal infection causes AD, then it seems likely.

This might be a giant breakthrough, or it might be just a side effect. The uncertainty is not fun at all. But if the arrow points the right way, then yes it's possible that antifungals would be a big part of treatment.

<comment><USER44> In either case it makes a lot of sense to start dosing patients with anti- fungal medication and see if their symptoms improve. Usually you do not give fungicide to patients because it has a lot of side-effects but those drugs are readily available and easily prescribed.

<comment><USER45> Not sure why you got downvoted. It would have to be done in double blind trials vs placebo, but it would be a great way to test the causal link between fungi and symptoms. You'd have to make sure the fungicides cross the blood brain barrier in patients.

<comment><USER46> Haven't we studied the effects of Alzheimers enough not to need the control group? I worked in clinical trials and one study still haunts me knowing what happened to the control group.

<comment><USER6> Sure, it fits right in with the plan to get rid of those pesky controls when testing painkillers too: "Drug companies have a problem: they are finding it ever harder to get painkillers through clinical trials. But this isn't necessarily because the drugs are getting worse. An extensive analysis of trial data1 has found that responses to sham treatments have become stronger over time, making it harder to prove a drug's advantage over placebo. [...] For companies trying to develop treatments, one remedy might be to compare new drugs against their best competitors instead of against placebo — or to go back to conducting smaller, shorter trials." [http://www.nature.com/news/strong-placebo-response- thwarts-p...](http://www.nature.com/news/strong-placebo-response-thwarts- painkiller-trials-1.18511)

<comment><USER47> Comparing old vs new is how it's done in cancer research. It's inhumane to prescribe placebo to someone in serious pain. You give them the old or the new, and they report how they felt.

In this case, since there is no concept of old or new, it's an entirely new class of treatment. So you give the current best-practice treatment without anti-fungal, and you give the same with anti-fungal.

Anyone in the study is agreeing at the onset that they have a 50/50 chance they will either get the current best practice, or the exact same thing but also the anti-fungal. These are volunteers who are helping move the anti- fungal research forward for everyone, in exchange for a chance of getting early access. They can also leave the study at any time after starting, but if they are in the anti-fungal group they would lose access to it if they did.

If that's not enough, there are cases (e.g. in cancer research) of de-blinding the study when there's a clear/strong positive effect and providing early access to all enrolled if it becomes obvious the new treatment is widely beneficial.

So I think we have the theory behind the ethics fairly well wrapped on how to roll out these drugs. I don't think in practice it works so well, the studies are often poorly run and poorly administered making them extremely more costly than they should be.

<comment><USER46> The place where I worked did a pretty good job at administering the studies. The cost was in all the sampling and shipping. When your study is doing 1,000 sample kits with 5 samples every week day for multiple years, its going to cost.

I am still a bit clueless with all the research we have done with Alzheimer's why we need another control group?

<comment><USER48> The control group, with double blinds, provides evidence that the change in treatment causes the change in outcome. If you test without a control, the change in outcome could be a result of any other changes between the test protocol and previous control groups.

You might be able to do a small study without a control to test feasibility of the hypothesis, but I don't know if that would pass ethics review; would probably depend on the side effects of the anti-fungal. Another less invasive way would be to test for fungal presence in groups with and without the disease, likely through autopsies, since sampling a live brain seems intrusive.

<comment><USER46> Here's my problem, we know the outcome of Alzheimer's, surly we have the data to go ahead without a control group? We've had them before.

<comment><USER48> Without the control group, you don't know if the change you think you made is the change that made a difference.

<comment><USER46> Ok, but don't we have a body of knowledge on Alzheimer's that having another control group is redundant? Why do we keep needing new control groups for things that are going to kill people and we know are going to kill people? I cannot get by the ethical problem of knowing we're kill 50% of the people in the study to provide data we already have.

<comment><USER48> The problem is, if something related to how you run your test of the anti- fungal has an effect on the disease, you're going to assume its the anti- fungal; but maybe it's not. If you have a control group, and both groups do better than expected (compared to the body of evidence), then you've learned something you wouldn't have without a control group (and you'll have to work hard to figure out what changed in this study vs other studies). If anti- fungals are a clear winner, it's likely that the study protocol would be changed to give everyone the drug after early results.

</comment></comment></comment></comment></comment></comment></comment></comment></comment></comment></comment></comment></comment><comment><USER49> This seems like potentially an incredibly important breakthrough with a perplexingly weird title. _Different_ brain regions? Different to what? From reading the study, the novelty is not about the "difference" of the brain regions, but the fact that fungal infection is found in AD patients at all. The controls had _no_ infection, not _different_ infections in their brains.

I'm curious if the title makes sense to people in the field or is this weird to them too?

<comment><USER50> As a layman, i understood the title correctly I guess. That there were fungi not just on one spot, but different (ie several) regions.

<comment><USER51> But that would be bad English. I wouldn't expect the Nature editors to let such bad English slip through in an important title, but I admit it is frustratingly common to see people not caring too much about that sort of thing.

I had the same concern as GP. I don't understand the title; the controls seem not to have fungi in their brain, which had always been my assumption about, for example, my brain.

<comment><USER49> After reflecting I am wondering if this is a result of the natural tendency of scientists to avoid any hint of overstating their work. Were the fungal infections all in the same region or by the same fungus it'd be absolutely shocking. It'd be a "cold fusion" level revolution for the field - and a "cold fusion" level embarrassment for them if they are wrong. So they are extremely keen to put up front that the picture is not nearly so clear as that.

There is also a tendency when scientists are extremely confident they have found something incredibly important to understate it. I always think of the Watson and Crick "It has not escaped our notice ..." statement in this context.

This is all based on guesswork though, so that's why I'm curious about what people in the field think.

</comment></comment></comment></comment><comment><USER52> I just moved out of a place I'd lived for 5 years that turned out to have black mold. I've had weird digestive issues and my immune system has gone to shit since living there but I wasn't aware of the mold problem and didn't know of the health problems it could cause. So this study is pretty terrifying; I should probably get tested.

</comment><comment><USER53> Is there any relation to the study that suggested AD is diabetes type 3? Insulin resistance + fungi?

<comment><USER54> Candida is a common opportunistic infection in diabetes type 2, so there's a few ways in which correlations could be observed. The fungal infection could be a symptom of the underlying "type 3" diabetetes; or the CNS fungal infections could be more common in diabetic or pre-diabetic people, leading to AD.

</comment></comment><comment><USER55> If you've ever taken antibiotics for an extended period and ended up with a fungal infection due to the loss commensal bacteria this is pretty intriguing. There is a lot of new literature proposing links between gut disruption and neurodegenerative disease.

<comment><USER56> Maybe antibiotics cause Alzheimer's.

</comment></comment><comment><USER57> For what it's worth, the institution [1] behind this study is one of the most prestigious scientific institutions here in Spain.

[1] [http://www.cbm.uam.es/](http://www.cbm.uam.es/)

</comment><comment><USER58> Are there other internal diseases caused by fungus? Obviously there are fungal skin infections, but it sounds strange that a fungus would be able to live inside the body.

</comment><comment><USER6> Nature is not a good scientific journal. The good info will be found in highly specialized journals. The amount of BS in scientific journals is related to prestige like this:

x=seq(0,1,by=.01);

plot(x,dbeta(x,.5,.5), xlab="Prestige", ylab="BS")

<comment><USER59> For those without a R interpreter handy, Emacs to the rescue:

           ^
           |  |                                                                           |
           |  |                                                                           |
           |  |                                                                           |
           |  |                                                                           |
           |  \                                                                           /
           |   |                                                                         |
           |   \                                                                         /
           |    |                                                                       |
           |    \                                                                       /
           |     \                                                                     /
           |      \                                                                   /
        B  |       \                                                                 /
        S  |        \                                                               /
           |         -\                                                           /-
           |           \                                                         /
           |            -\                                                     /-
           |              -\                                                 /-
           |                --\                                           /--
           |                   --\                                     /--
           |                      ---\                             /---
           |                          -----\                 /-----
           |                                </comment></comment><comment></comment><comment>-----
           |
           +</comment><comment></comment><comment></comment><comment></comment><comment></comment><comment></comment><comment></comment><comment></comment><comment></comment><comment></comment><comment></comment><comment></comment><comment></comment><comment>--->
                                                Prestige

(Also an on-line R interpreter: [http://www.r-fiddle.org/.](http://www.r-fiddle.org/.))

<comment><USER60> What package(s) did you use to create this?

<comment><USER59> I used [http://r-fiddle.org](http://r-fiddle.org) to verify what was the intended function, then used built-in Artist Mode (M-x artist-mode) to draw an ellipse for function and square for axes, and finally cut it down in fundamental-mode and added labels. It's basically vanilla Emacs, but I admit to using multiple-cursors.el for some cleanup. It's an excellent addon mode offering a more interactive way to do some things you'd otherwise do via keyboard macros. Check out [0] and [1].

[0] - [https://github.com/magnars/multiple- cursors.el](https://github.com/magnars/multiple-cursors.el)

[1] - [http://emacsrocks.com/e13.html](http://emacsrocks.com/e13.html)

<comment><USER60> Ah thanks, I was aware of artist-mode, I thought there was some ESS like package that could output ascii graphs of functions :) R-fiddle is new to me though, thanks for that.

<comment><USER59> There's also orgtbl-ascii-plot[0], there was a mode for writing out flow diagrams in Emacs that used a web backend to render them (I don't remember the name), and I'm pretty sure you could abuse some graphics-to-ascii or DOT file command line tools to get the required result in Emacs buffer - <USER2> via org-babel, which lets you invoke external programs to "evaluate" code blocks. I remember using some Java-based local tool to render graphs through org-babel, but again I don't recall the name or URL.

[0] - [http://orgmode.org/worg/org-contrib/orgtbl-ascii- plot.html](http://orgmode.org/worg/org-contrib/orgtbl-ascii-plot.html)

</comment></comment></comment></comment></comment><comment><USER61> This is extraordinary. It means antifungal drugs like Fluconazole can possibly prevent AD.

<comment><USER62> No, it means that a researcher doing fourth rate science has successfully trolled HN.

<comment><USER63> Please stop posting unsubstantive comments to Hacker News.

</comment></comment></comment><comment><USER62> Sounds like Bozo the Clown is now publishing articles in Nature.

One problem with biomedical research is the crackpots.

</comment><comment><USER64> Are these fungi from Yuggoth?</comment>


Non-Compete Can Be Imposed Mid-Employment with No New Consideration - <AUTHOR> https://casetext.com/posts/continued-employment-adequate-consideration-for-non-compete-imposed-mid-employment-hawaii-federal-judge-rules <comment><USER2> I _am_ a lawyer - and the headline is completely misleading.

 __Continued employment is, in fact, new consideration. __Each new paycheck you get, in an at-will employment relationship, is further consideration.

This meshes perfectly, without any dissonance, with the commonly understood function of at-will employment.

The judge did _not_ say that you can impose non-compete retroactively, for no new consideration, or that non-compete can be imposed on an employee who has an otherwise negotiated and executed employment agreement.

In other words - this represents absolutely no change, whatsoever, from the commonly understood function of at-will employment. Water wet, sky blue. Move along here, folks.

<comment><USER3> Are you a lawyer or a law student? :)

"The judge did not say that ... non-compete can be imposed on an employee who has an otherwise negotiated and executed employment agreement."

This is plain wrong. They said exactly this. Did you read the case (STANDARD REGISTER CO. V. KEALA)?

One of the people involved had a non-compete imposed after they had already signed and executed an employment agreement. The court said this is fine :)

As it quotes "it is not logical for a court to treat differently a covenant presented on the first day of work and one presented one week after the first day in the at-will employment setting. "

<comment><USER4> Here, btw, is the case

[https://casetext.com/posts/continued-employment-adequate- con...](https://casetext.com/posts/continued-employment-adequate- consideration-for-non-compete-imposed-mid-employment-hawaii-federal-judge- rules)

My understanding is, if your Hawaiian employer demanded you sign a noncompete, you could quit on the spot and the noncompete would not apply. Is that correct?

<comment><USER2> > My understanding is, if your Hawaiian employer demanded you sign a > noncompete, you could quit on the spot and the noncompete would not apply. > Is that correct?

Yes.

</comment></comment></comment></comment><comment><USER5> Counter-argument: in the early 1990s, the company at which I was working had a key technical employee leave. The next week, the company asked all the other technical employees to sign non-compete agreements. We all refused. Nothing more was said.

You always have the right to quit and work for a competitor up until you sign that right away, and the worst that they can do to you for not signing is fire you.

That was not Hawaii, though.

(I didn't realize quite how crazy some of the owners/managers of that company were until years later.)

<comment><USER6> That's not much of a right, though.

<comment><USER7> Not your company, not your rights. Go join a worker's cooperative or start a union if you want more say in your employment.

<comment><USER8> Are you saying that, because the employee doesn't own the company (or, you know, own shares), they don't get any rights?

That's... laughable.

<comment><USER9> Isn't that effectively what happens though? Barring strong worker's protections (which is not a thing in most of the US) or strong unions (which is not a thing either in most of the US), the only rights an employee gets are "take it or leave it". And that's pretty much what "at will employment" is.

<comment><USER10> For what it's worth, right to work states that have at will employment also means that a noncompete cannot prevent you from using your skill set to earn a living (aka - you have the "right to work" hence the name). In order for them to be enforceable at all they have to be extremely specific in scope and for a reasonable amount of time, usually only pertaining to not leaving for a direct competitor and taking existing clients with you.

Basically, if you live in an area with a lot of employment options, going to a competitor and trying to take customers with you would be enforceable. If you're in an area without a lot of options for what you do, the noncompete is toilet paper because you can't be prevented from earning a living.

</comment></comment></comment></comment></comment></comment><comment><USER11> For reference, "consideration" is the legal principal that contracts must be exchanges not just one sided commitments. E.g. if you had just quit and your employer asked you nicely to sign a noncompete, and you did sign, the contract would probably be invalid because you are getting nothing in return (I.e. no consideration) for your commitment not to compete with your former employer.

In contrast, the courts find "an offer of continued at-will employment is, by itself, sufficient consideration for a non-competition agreement." To me this is completely reasonable.

<comment><USER12> I agree with you within the framework of at-will employment.

However, at-will employment is, IMO, entirely unreasonable. While Europe seems to have gone too far in terms of labour requirements, the US (and Canada, where I'm from) could do with more, such as introducing reasonable regulations surrounding hiring/firing.

<comment><USER13> Has Europe gone too far? Europe is a very diverse place, but in general, I think a lot of countries in Europe strike a very reasonable balance. The idea that a company should be able to fire someone on the spot over absolutely nothing, is completely unreasonable in an economic system where you need a job to live.

Introduce Basic Income, and I'm totally fine with at-will employment, however.

</comment></comment></comment><comment><USER14> ... under Hawaii law. California law makes noncompetes generally unenforceable regardless of consideration, and other states have other variations.

And it's not even a binding precedent under Hawaiian law; it's a federal judge's interpretation of Hawaiian law necessary to resolve some federal matter, but Hawaiian courts could differ in their interpretation.

<comment><USER15> I work in California and hired a lawyer to nullify a non-compete clause. The company backed off when my lawyer cited case law that basically says if a company attempts to clamp down on a skill you had pre-existing to employment, ALL previous contracts become null and void. California views this kind of corporate behavior as a form of enslavement.

<comment><USER16> Quite reasonable given California's history, as "You'll never work in this town again" is a threat with some very real weight behind it for the Tinseltown population.

<comment><USER17> That particular case isn't helped by labor laws, as the threat isn't enforced legally. They put your name on a blacklist and all of a sudden you find that nobody will hire you. I don't know the specific provenance of that legal precedent, but I doubt it had anything to do with Hollywood.

</comment></comment></comment></comment><comment><USER18> Can't employers impose pretty much any (legal) new requirements for at-will employees?

At-will means that your employer can terminate your employment at any time, with or without cause (and you can leave your employment at any time). So if you don't like a change in your employment terms, you are free to go, or your employer is free to fire you.

<comment><USER19> Yeah, something similar was mentioned in the article. If this wasn't legal, they could just fire you, then offer to hire you under the new terms the next day.

<comment><USER20> I'd argue that is still fundamentally different than just requiring the signature to keep your job. Getting laid off has different consequences than quitting.

I realize most states disagree with me, but I think it's absurd. If at will employment is so meaningless that it's no different from being fired, it shouldn't even be consideration in the first place. These courts are treating at will employment as a meaningless promise in one scenario, but as having some value in another.

<comment><USER21> _Getting laid off has different consequences than quitting._

Yes, the first thing I wondered about this would be whether it's permissible to describe being handed the noncompete with an order to sign it or leave as termination with zero notice.

</comment></comment></comment></comment><comment><USER22> So this situation happened to me in 1996 in Texas a right to work state.

1.) My boss came and asked me to sign a non-compete after learning that I ran a similar business in another city after 3 years of working for him.

2.) I was not competing as none of my customers were his customers. My business in Houston. His in a small town 60 miles away.

3.) I went to a lawyer and asked if I had to sign and if this non-compete (said I couldn't work on any computer in Texas within two years of termination) would apply. Lawyer said it was ridiculous and while it wouldn't hold up in court he had the right to lay me off for not signing it.

4.) I refused to sign on principle and was laid off. I went to draw unemployment and he fought it. I was granted unemployment but, quickly found a newer higher paying job anyway.

<comment><USER23> Texas may be "Right to Work" but right to work has nothing to do with this. It has everything to do with the doctrine of "Employment-At-Will" of which 49 states follow. (Montana, I thank you for not following the employment at will doctrine)

I can't believe that there are so many people out there which get the two terms confused. Maybe we need to teach public high school students basic employment law in their civics classes.

</comment></comment><comment><USER24> From what I've heard, here in my part of Canada anyway, employers can you make sign this but it's pretty much powerless. It is illegal to keep someone from working and to slow down the economy. You can easily have this overturned by the court.

<comment><USER25> [http://www.ehlaw.ca/publications/nov05/Positron.shtml](http://www.ehlaw.ca/publications/nov05/Positron.shtml)

</comment></comment><comment><USER23> In some states, sufficient consideration is continued employment, in other states, additional consideration must be offered. Here is a (rather old) state-by-state list:

[http://www.beckreedriden.com/wp- content/uploads/2012/09/Nonc...](http://www.beckreedriden.com/wp- content/uploads/2012/09/Noncompetes-50-State-Survey-Chart-20130814.pdf)

IMHO: Non-competes should be illegal, OR they must pay you "garden leave" at 100% of your salary for the duration of the noncompete. Garden leave will limit the use of non-competes to those cases where it is a absolute business necessity and eliminate it being used as a tool to suppress the free movement of talent.

</comment><comment><USER26> Is a new signature required from the worker, in order to make the newly added non-compete binding, or not? This part seems confusing from that summary.

If the workers signed a new non-compete and then continued to work for the company, this ruling seems pretty obvious.

If this is something like adding in a non-compete to an existing employment agreement without needing to obtain a new signature (as the completely insane UK laws allow,) then this is very bad.

<comment><USER27> _as the completely insane UK laws allow_

While you can technically make changes to an employment contract in th UK without requiring a new signature, agreement from the employee is required. If an employer tries to enforce changes without agreement, an employment tribunal will almost certainly rule in an employee's favour.

<comment><USER28> What constitutes sufficient proof of agreement there? A clear paper trail would make sense. A verbal agreement not so much. What's required by the law?

<comment><USER27> I don't think the law specifies what form of agreement is required - however, an employer must confirm all changes in writing. Agreement at this point is implicit - if the employee does not agree with the changes, they have the right to refuse to work, to take the case to a tribunal, or in some cases to resign and claim constructive dismissal.

I know that if an employee doesn't agree with contract changes, they should take action immediately; continuing to work and not expressing your disagreement with the changes after you've been informed of them can be construes as implied agreement.

Employment law in the UK seems pretty worker-friendly in the sense that most companies will take great pains to avoid the risk of employment tribunals and other employee action, but I concede it's a bit less formalised than in other jurisdictions.

</comment></comment></comment></comment><comment><USER3> So, this is definitely a clickbaitish headline, but things you should know:

~30 states agree that non-competes can be imposed after the fact and without anything additional being given to you.

~9 states say otherwise.

IE this is a pretty standard ruling.

Next i think y'all are gonna learn that you basically own nothing done in your own time when you work for large diversified tech companies. ;)

</comment><comment><USER29> Can I have an English translation please?

<comment><USER30> If you've been working at a company without having signed a non-compete, they can legally provide the ultimatum of "sign a non-compete or you're fired."

Edit: NDA -> Non-compete, because I hadn't had my afternoon coffee.

<comment><USER31> Non-compete != NDA, though the same logic would apply to that.

Non-competes are much more sinister than NDAs.

<comment><USER30> Thanks for the catch. Updated.</comment></comment></comment></comment>


Should We All Take a Bit of Lithium? - <AUTHOR> http://www.nytimes.com/2014/09/14/opinion/sunday/should-we-all-take-a-bit-of-lithium.html <comment><USER2> The article points out

1) therapeutic doses of lithium as a prescription medicine for mood disorders are MUCH higher than doses occurring through lithium in the water supply, and yet

2) there is perhaps some epidemiological signal suggesting differing rates of suicide and depression in places where lithium levels in the water supply are higher.

Kay Redfield Jamison, author of some of the most compassionate books about depression you will ever read,[1] credits lithium with saving her life. I'm glad her life was spared so that she could write from the inside about what it is like to have a severe mood disorder, and apply her creativity to communicating with people who cannot directly understanding her personal experiences or the experiences of other patients.

I think the article's call for further research, at a minimum, is worth taking seriously. The neuroprotective effect of lithium demonstrated in animal studies (verified by necropsy and examination of the animal's brains after the animals die) is well established, so we may as well check whether adjustment of water supplies by intentional supplementation has a beneficial effect if (and only if) epidemiological studies and animal experiments suggest doing so. This is, after all, how the beneficial effects of fluoride on tooth enamel strength and resistance to decay were discovered.

[1] [http://www.amazon.com/Kay-Redfield- Jamison/e/B000AQ1IC8](http://www.amazon.com/Kay-Redfield-Jamison/e/B000AQ1IC8)

</comment><comment><USER3> The "benefits" of lithium come at a cost, which this article doesn't really address. Lithium evens out your emotions, good and bad, some describe it as "turning into a soulless robot." That could mean a more docile society (the legal, behavioral, etc benefits described) but sounds pretty close to THX 1138 to me.

<comment><USER4> I am bipolar. What you describe is why it's a "hard sell" to patients with mood disorders.

Yes, others will point to the higher dose for psychiatric patients.

I would point to the soulless robot, the empty husk of a once vibrant, creative brain.

We are devs, and our brain is our livelihood. In me it killed my creativity and my passion. Not only did I not want to code anything new, I could not conceive of new things. I stopped improv jams on guitar, I could not write songs. I became wonderfully adept at doing scales. Scales over and over.

I'll take my mood disorder- because it comes WITH emotions.

This is just to give you a 'crazy person's' impression of Lithium. Your results may vary.

<comment><USER5> Over the past 14 years I've taken Lamictal, Lithium, Depakote, Seroquel, Zyprexa, Geodon, etc. I still take the first 3. I also got a masters, a PhD, recorded 3 albums with my band, played on plenty of others and worked on plenty of creative outputs (including programming).

I agree that when I first got on those meds at 21 after a psychotic break I was totally torn up. Now at 35 I couldn't imagine my life any other way. Have I become less creative? I honestly don't know and it's kind of frightening to think that perhaps I have. How would I ever know?

If you haven't seen what your life you be like permanently institutionalized (I've been hospitalized for mania 6 times) perhaps strong drugs aren't for you. If you have seen the other option (life inside a hospital), it makes a lot of sense.

If you think Li makes you a zombie, try intramuscular haldol or seroquel or even ativan. Those will knock you out, the first one literally. :)

<comment><USER6> Thanks for sharing your experience. I am curious about the hospitalization for mania. If you don't mind saying, what happened exactly? Were you so "up" that you were taking dangerous risks? What types of behavior does mania induce that make it a threat?

<comment><USER7> In my case, delusions, paranoia, and the occasional inappropriate remark that could be construed as homicidal or suicidal ideation. Depression genuinely caused the latter ideation.

Lithium is a very harsh mistress, but if you have type 1, which is akin to emotional epilepsy, she will bring you to heel.

</comment></comment></comment></comment></comment><comment><USER8> Good timing. It happens I'm going to Ashland, OR next week. The town is famous for the Shakespeare Festival (world-class performances) and Lithia Park. The latter is a natural lithium containing mineral water source. It's easy to sample, just a short stroll from the Elizabethan theater, a drinking fountain bubbles up the spring water.

ATM I'm not sure of the exact concentration of the minerals, but from prior years, saying it tastes really bad isn't nearly a strong enough description. Other water supplies containing Li may be quite acceptable, but except for Ashland palatability isn't the main issue.

In the article, the cited concentration of Li at 0.170 mg/L, if referring to Li+ ion alone, the water supply would actually contain ~1/100 of the lowest therapeutic dose of Li. Medicinally Li is provided as the carbonate salt. A minimal dose is 300 mg/day, which contains ~ 30 mg elemental Li. Consuming Li- fortified water 2 L/d -> 0.34 mg Li or >1/100 of low medicinal Li dose .

Of course in nature Li is always in ionic or combined form, but the article didn't give details about Li concentrations, so it muddies the water trying to parse Li effects in any number of ways.

Here in Portland OR, city water is sourced high up near Mt. Hood from condensation of atmospheric water (mist or rain) and piped the short distance to the city. It's basically like distilled water, very low in mineral content. So low in fact, the federal government insists that alkaline minerals are added to the supply since distilled water is acidic and leaches lead from old plumbing.

However, Portland has among the lowest suicide attempt rates in the US. Our neighbor to the north, Seattle WA is among the highest, along with Salt Lake City UT and Dallas TX. [http://socialcapitalreview.org/seattle-region- ranks-2nd-of-3...](http://socialcapitalreview.org/seattle-region-ranks-2nd- of-33-in-u-s-suicide-attempts/)

Other data would show something different re: suicidal behavior but contradictory data sets are kind of the point.

Li could be a factor but I'm skeptical. We must remain alert to the hazards of drawing conclusions from population-based observational data. In this domain, experimental studies are difficult to design and conduct, but further study to narrow down confounding factors would be useful.

What I do know is water purity is sacred here. The last fluoridation campaign failed by about a 3:1 lopsided vote.

What chance would there be of adding _lithium_ to our water supply? I think it would not be voted in.

<comment><USER9> > distilled water is acidic

Distilled water is neutral, it is the reference point against which acidic and alkaline solutions are compared.

Technically one could argue that it is acidic, because any concentration of [H+] is acidic, but this is like arguing that Jiminy Cricket is tall because he has height.

However, rainwater will naturally absorb CO2 in the air (and since the industrial revolution, NO2 and SO3), making it acidic.

<comment><USER10> The reason given was leeching. Neutral is not good enough for that sometimes; you need slightly basic. Some things will corrode at pH 7, but not higher.

Good call though; distilled water is neutral.

<comment><USER11> Distilled water being very low in dissolved ions will be more prone to picking up metal ions from pipes than water that already has a natural/normal level of dissolved ions. So in that way it is more "corrosive" than ordinary tap water.

</comment></comment></comment></comment><comment><USER12> The original post has bad math.

1000x .170mg is "1,000 times less than a fifth of a milligram," not 1000 times a fifth of a gram.

[http://www.gwern.net/Nootropics#lithium](http://www.gwern.net/Nootropics#lithium) has a significant number of references to the literature on lithium, and is worth reading.

<comment><USER13> Gwern's writeups on nootropics are some of the best you'll find on the Internet.

Honestly, his writeups on most things are pretty spot on.

<comment><USER14> Gwern's writings on nootropics are particularly fascinating. They read like the works of a mad scientist (in a good way). Erudite, meticulous, and also a tiny bit reckless. Gwern treats himself like a human guinea pig, then documents and analyzes the results more carefully than I've seen in some research papers. The whole process, furthermore, reads like a dialogue between Gwern and the reader. To be more precise, it reads like a dialogue between Gwern and Gwern's imagined idea of a highly intelligent reader -- a reader whose place you find yourself wanting to fill.

Gwern's archive is eccentric, to say the least. But it's one of the best places on the web to lose oneself for an afternoon.

<comment><USER13> Couldn't have said it better myself.

</comment></comment></comment></comment><comment><USER15> I live about 3 miles away from Lithia Springs, but I can't seem to find any information online about how much lithium is actually in our drinking water.

I know our water and sewer authority publishes a report on water quality each year, but I don't remember seeing lithium content in the report.

<comment><USER16> I'm just inside Paulding County with a Powder Springs address, and that's who I pay my water bill to, but the yearly water quality reports I get come from Cobb County. It makes me wonder if Lithia Springs even gets their municipal supply from the spring, or from a Douglas County source.

<comment><USER15> > It makes me wonder if Lithia Springs even gets their municipal supply from > the spring, or from a Douglas County source.

The spring is privately owned. Here it is on google street view [1]. Lithia Springs gets their tap water from from the Dog River Reservoir in the southern part of Douglas County.

[1] [https://firstname.lastname@example.com,-84.6403093,3a,75y,1...](https://firstname.lastname@example.com,-84.6403093,3a,75y,119.32h,87.77t/data=!3m4!1e1!3m2!1sbaehH8WENLgRKMsGz_NFzA!2e0)

<comment><USER16> Thanks, I've never actually been to the spring itself, though we drove by there just today playing Ingress.

I grew up in Cedartown, where the natural spring is also the town's water supply, so I just assumed it would be the same for Lithia Springs.

<comment><USER17> People play Ingress?!

</comment></comment></comment></comment></comment><comment><USER18> Modern chemical analysis is exquisitely sensitive.

People take medication and excrete some of it.

Sensible water use, especially in drought areas, means that water is reused - the water you drink has gone through someone else before you.

BBC Radio Four has a programme about this: "Urine Trouble: what's in our water?"

[http://bbc.co.uk/news/health-29108330](http://bbc.co.uk/news/health-29108330)

Other uses for very-sensitive analysis of waste water include real time drug sampling. We can tell that it's the weekend by the amounts of MDMA and cocaine (metabolites?) in the water; where heroin doesn't show weekend spikes. This can be used at festivals to see if "legal highs" are actually used and in what kind of quantities.

The programme is better than this page makes it out to be.

</comment><comment><USER16> I live just a couple of miles from Lithia Springs, Georgia, and oddly enough I've never seen "Lithia Water" on sale anywhere around here. I suppose it gets bottled and sold to retailers in other states.

As for lithium-infused water chilling people out; well, I've lived here long enough to know that I wouldn't walk the streets of Lithia Springs at night. There are some rowdy people living there. Maybe they all drink Dasani or Aquafina instead of the local tap water.

</comment><comment><USER19> > The authors discovered that people whose water had the least amount of > lithium had significantly greater levels of suicide, homicide and rape than > the people whose water had the higher levels of lithium. The group whose > water had the highest lithium level had nearly 40 percent fewer suicides > than that with the lowest lithium level.

I can't but help wonder whether higher levels of lithium also correlate with a clean water supply, which would indicate a more affluent community. It may simply be the case that those areas with cleaner water have a better economy, and thus less crime, etc. Although lithium undoubtedly has antidepressant effects.

It's funny this article popped up on here. Today I was actually reading about how chromium picolinate was found to have a positive effect on those with atypical depression. It can be purchased from any vitamin store. It makes me wonder if trace elements (lithium, chromium, etc.) are vital to the brain's proper functioning via some as yet undiscovered mechanism.

Also, why is it that you have to have a prescription to get certain compounds, but other ones you can just purchase yourself? Is it simply the potential for toxicity?

<comment><USER20> > I can't but help wonder whether higher levels of lithium also correlate with > a clean water supply, which would indicate a more affluent community.

Not likely, because the water supply of an affluent community would have highly filtered water containing few "impurities" including lithium. Further, if the community in question were conservative in their political views, the water might even lack fluoride, another component with known beneficial traits but one that has become a political issue in some places.

> Also, why is it that you have to have a prescription to get certain > compounds, but other ones you can just purchase yourself? Is it simply the > potential for toxicity?

No, it revolves around the issue of medical applications. If a substance has known medical applications, then its dissemination will likely be controlled by the FDA. Even advertising a substance's possible medical benefits is not permitted in the general case, without FDA approval and substantial controls. For example, if I sell willow bark as writing paper, no problem. If I sell it as a pain-killer without possessing medical authority, I will be in a heap of trouble.

</comment></comment><comment><USER21> Mostly a reasonable and interesting article. But when you talk about adding something psychoactive to the drinking water, it's just a horrible idea.

It doesn't matter if it's otherwise natural. Nature is inconsistent in dosages (so diverse perspectives can flourish) and doesn't have ulterior motives.

Maybe it brings down suicide rates, but what other effects does it have? Does it affect the likelihood of voting for a political party or cause? Does it affect the likelihood of political participation in general?

It's kind of like CO2 levels in the atmosphere. Higher levels will have some effect; we're basically arguing over the significance of it, what to do about it (if anything), and whether politicians can be trusted with the power to make those changes.

Similarly, mind-altering substances will affect aggregate political behavior. Once someone finds out how, they will use it to their advantage.

<comment><USER18> > But when you talk about adding something psychoactive to the drinking water, > it's just a horrible idea.

Should we remove trace amounts of lithium from water in areas where it's naturally occurring?

<comment><USER21> No, I think you missed my point. Humans can't be trusted with the power to add mind-altering substances to the drinking water. Once someone figures out how to use it to their advantage, they will.

<comment><USER18> But won't those same people just exploit the naturally occuring trace lithium?

Or is it not about lithium but the principle of adding stuff to water?

<comment><USER21> Well, people will notice if concentrations change unless there is a real conspiracy. But if it's declared "good" to add something to water, it's much easier to manipulate the dosage.

</comment></comment></comment></comment></comment><comment><USER22> If there is a concrete correlation between trace amounts of Lithium in the water supply and lower suicide rates, surely there are other effects? The studies done seem quite one sided to me (or more likely, this article is). For serious consideration, not only do more studies have to be undertaken for other cities, but other factors have to be measured as well. Other psychological problems, rate of divorce, physical activity (sport etc), unemployment, debt, other drug use, education etc. Perhaps there's a lower incidence of suicide because people are much less active? Unemployed, no ambition, but not enough drive to end it all as well?

<comment><USER20> The answer is that, as one moves into more behaviors and more detail, the chance to meaningfully correlate outcomes with lithium exposure becomes more difficult. Also, because no one knows why those correlations exist (why lithium has the effect it does), it's not possible to turn a correlation into a rigorous, scientific cause-effect relationship.

The gold standard in science is not a correlation, but a cause-effect relationship accompanied by an explanation. With respect to lithium, we're a long way from that goal.

</comment></comment><comment><USER23> "But there are undoubtedly other reasons for its neglect. Pharmaceutical companies have nothing to gain from this cheap, ubiquitous element."

It's a tragic condemnation of the way we do health and nutrition that if no one profits from marketing and selling something, the masses typically won't hear about the benefits of it.

<comment><USER24> this just doesn't make sense. people sell _bottled water_! why can't they sell lithium?

<comment><USER20> Because bottled water doesn't have real or imagined therapeutic properties, and lithium does. Eventually someone unfamiliar with the rules will advertise a lithium/water product as having medical effects, and that will end the game (advertising medical benefits is a no-no without both research backing and FDA approval).

EDIT: this is another example of the "fact rule" \-- if you post something factual and uncontroversial, you will be downvoted with a probability of 1.

<comment><USER25> I disagree. There is a market for supplements, as long as they walk a careful line of avoiding the promise of any medical benefit. Lithium could be sold this way, in low dosages ("Lithia Springs water"), but it's probably not allowed? I remember that 7-up once contained lithium, but it was banned, even though the amount was very small.

BTW: There is indeed an annoying level of unnecessary downvoting going on.

<comment><USER26> Lithium is already sold as a supplement. If you want to run out and buy eg lithium orotate, you certainly can. It's cheap too.

<comment><USER27> And bulk analytical-grade lithium carbonate, sulphate and citrate not marketed for human consumption are equally easy to acquire and even cheaper.

</comment></comment></comment></comment></comment></comment><comment><USER28> An interesting analysis from a self study if you haven't read it already: [http://www.gwern.net/Nootropics#lithium](http://www.gwern.net/Nootropics#lithium)

</comment><comment><USER29> [https://www.youtube.com/watch?v=pkcJEvMcnEg](https://www.youtube.com/watch?v=pkcJEvMcnEg)

</comment><comment><USER30> Sounds like the pseudo science that kick starts 'end of the whole mess' by Stephen king.

</comment><comment><USER31> [http://en.wikipedia.org/wiki/Lithium_(medication)#Side_effec...](http://en.wikipedia.org/wiki/Lithium_\(medication\)#Side_effects) The dosages required to achieve "beneficial" psychoactive effects will probably result in adverse side effects in a significant portion of the population. Lithium should be prescribed by a doctor on a case by case basis, not indiscriminately dumped into the water supply.

<comment><USER15> The article was talking about trace amounts, very far below the therapeutic dosages that cause those side effects.

Trace amounts of lithium already occur naturally in many municipal water supplies.

<comment><USER31> The dose makes the poison, the higher PPM of lithium, the larger the percentage of individuals that will be affected. Even if it affects a tiny fraction of the population at the proposed concentrations, it's still unfair to that demographic. Would you wan't to have to buy special non-lithium supplemented water?

</comment></comment></comment><comment><USER32> Using the word "millenniums" twice in an article the topic of which is not idiosyncratic diction is obnoxious.

<comment><USER33> Both Merriam-Webster and Oxford says it's acceptable:

[http://www.merriam-webster.com/dictionary/millenniums](http://www.merriam- webster.com/dictionary/millenniums)

[http://www.oxforddictionaries.com/definition/english/millenn...](http://www.oxforddictionaries.com/definition/english/millennium)

</comment></comment><comment><USER34> No.

</comment><comment><USER35> Absolutely fucking not.

</comment><comment><USER36> Lithium is naturally occurring? Wiki seems to suggest otherwise.

<comment><USER37> In some place, running water has more lithium. For example, there was a recent study that correlates the suicide rates with the content of lithium in water in some cities of Japan: [http://bjp.rcpsych.org/content/194/5/464.full](http://bjp.rcpsych.org/content/194/5/464.full)

</comment></comment><comment><USER20> Quote: "But there are undoubtedly other reasons for its neglect. Pharmaceutical companies have nothing to gain from this cheap, ubiquitous element."

Ah, of course. This is why lithium is ignored or actively disparaged, while drugs whose ineffectiveness has been demonstrated in a now-famous meta- analysis --

[http://www.plosmedicine.org/article/info%3Adoi%2F10.1371%2Fj...](http://www.plosmedicine.org/article/info%3Adoi%2F10.1371%2Fjournal.pmed.0050045)

"Meta-analyses of antidepressant medications have reported only modest benefits over placebo treatment, and _when unpublished trial data are included, the benefit falls below accepted criteria for clinical significance_." [emphasis added]

\-- continue to be aggressively marketed.

This is not to say that lithium is a panacea or not dangerous if mishandled. It is to say that it has measurable beneficial effects in the right doses, on the right people. No one knows why this is true, but that's true of all such medications.</comment>