More on Science
Michael Hunter, MD
2 years ago
5 Drugs That May Increase Your Risk of Dementia
While our genes can't be changed easily, you can avoid some dementia risk factors. Today we discuss dementia and five drugs that may increase risk.
Memory loss appears to come with age, but we're not talking about forgetfulness. Sometimes losing your car keys isn't an indication of dementia. Dementia impairs the capacity to think, remember, or make judgments. Dementia hinders daily tasks.
Alzheimers is the most common dementia. Dementia is not normal aging, unlike forgetfulness. Aging increases the risk of Alzheimer's and other dementias. A family history of the illness increases your risk, according to the Mayo Clinic (USA).
Given that our genes are difficult to change (I won't get into epigenetics), what are some avoidable dementia risk factors? Certain drugs may cause cognitive deterioration.
Today we look at four drugs that may cause cognitive decline.
Dementia and benzodiazepines
Benzodiazepine sedatives increase brain GABA levels. Example benzodiazepines:
Diazepam (Valium) (Valium)
Alprazolam (Xanax) (Xanax)
Clonazepam (Klonopin) (Klonopin)
Addiction and overdose are benzodiazepine risks. Yes! These medications don't raise dementia risk.
USC study: Benzodiazepines don't increase dementia risk in older adults.
Benzodiazepines can produce short- and long-term amnesia. This memory loss hinders memory formation. Extreme cases can permanently impair learning and memory. Anterograde amnesia is uncommon.
2. Statins and dementia
Statins reduce cholesterol. They prevent a cholesterol-making chemical. Examples:
Atorvastatin (Lipitor) (Lipitor)
Fluvastatin (Lescol XL) (Lescol XL)
Lovastatin (Altoprev) (Altoprev)
Pitavastatin (Livalo, Zypitamag) (Livalo, Zypitamag)
Pravastatin (Pravachol) (Pravachol)
Rosuvastatin (Crestor, Ezallor) (Crestor, Ezallor)
Simvastatin (Zocor) (Zocor)
This finding is contentious. Harvard's Brigham and Womens Hospital's Dr. Joann Manson says:
“I think that the relationship between statins and cognitive function remains controversial. There’s still not a clear conclusion whether they help to prevent dementia or Alzheimer’s disease, have neutral effects, or increase risk.”
This one's off the dementia list.
3. Dementia and anticholinergic drugs
Anticholinergic drugs treat many conditions, including urine incontinence. Drugs inhibit acetylcholine (a brain chemical that helps send messages between cells). Acetylcholine blockers cause drowsiness, disorientation, and memory loss.
First-generation antihistamines, tricyclic antidepressants, and overactive bladder antimuscarinics are common anticholinergics among the elderly.
Anticholinergic drugs may cause dementia. One study found that taking anticholinergics for three years or more increased the risk of dementia by 1.54 times compared to three months or less. After stopping the medicine, the danger may continue.
4. Drugs for Parkinson's disease and dementia
Cleveland Clinic (USA) on Parkinson's:
Parkinson's disease causes age-related brain degeneration. It causes delayed movements, tremors, and balance issues. Some are inherited, but most are unknown. There are various treatment options, but no cure.
Parkinson's medications can cause memory loss, confusion, delusions, and obsessive behaviors. The drug's effects on dopamine cause these issues.
A 2019 JAMA Internal Medicine study found powerful anticholinergic medications enhance dementia risk.
Those who took anticholinergics had a 1.5 times higher chance of dementia. Individuals taking antidepressants, antipsychotic drugs, anti-Parkinson’s drugs, overactive bladder drugs, and anti-epileptic drugs had the greatest risk of dementia.
Anticholinergic medicines can lessen Parkinson's-related tremors, but they slow cognitive ability. Anticholinergics can cause disorientation and hallucinations in those over 70.
5. Antiepileptic drugs and dementia
The risk of dementia from anti-seizure drugs varies with drugs. Levetiracetam (Keppra) improves Alzheimer's cognition.
One study linked different anti-seizure medications to dementia. Anti-epileptic medicines increased the risk of Alzheimer's disease by 1.15 times in the Finnish sample and 1.3 times in the German population. Depakote, Topamax are drugs.
Sam Warain
3 years ago
Sam Altman, CEO of Open AI, foresees the next trillion-dollar AI company
“I think if I had time to do something else, I would be so excited to go after this company right now.”
Sam Altman, CEO of Open AI, recently discussed AI's present and future.
Open AI is important. They're creating the cyberpunk and sci-fi worlds.
They use the most advanced algorithms and data sets.
GPT-3...sound familiar? Open AI built most copyrighting software. Peppertype, Jasper AI, Rytr. If you've used any, you'll be shocked by the quality.
Open AI isn't only GPT-3. They created DallE-2 and Whisper (a speech recognition software released last week).
What will they do next? What's the next great chance?
Sam Altman, CEO of Open AI, recently gave a lecture about the next trillion-dollar AI opportunity.
Who is the organization behind Open AI?
Open AI first. If you know, skip it.
Open AI is one of the earliest private AI startups. Elon Musk, Greg Brockman, and Rebekah Mercer established OpenAI in December 2015.
OpenAI has helped its citizens and AI since its birth.
They have scary-good algorithms.
Their GPT-3 natural language processing program is excellent.
The algorithm's exponential growth is astounding. GPT-2 came out in November 2019. May 2020 brought GPT-3.
Massive computation and datasets improved the technique in just a year. New York Times said GPT-3 could write like a human.
Same for Dall-E. Dall-E 2 was announced in April 2022. Dall-E 2 won a Colorado art contest.
Open AI's algorithms challenge jobs we thought required human innovation.
So what does Sam Altman think?
The Present Situation and AI's Limitations
During the interview, Sam states that we are still at the tip of the iceberg.
So I think so far, we’ve been in the realm where you can do an incredible copywriting business or you can do an education service or whatever. But I don’t think we’ve yet seen the people go after the trillion dollar take on Google.
He's right that AI can't generate net new human knowledge. It can train and synthesize vast amounts of knowledge, but it simply reproduces human work.
“It’s not going to cure cancer. It’s not going to add to the sum total of human scientific knowledge.”
But the key word is yet.
And that is what I think will turn out to be wrong that most surprises the current experts in the field.
Reinforcing his point that massive innovations are yet to come.
But where?
The Next $1 Trillion AI Company
Sam predicts a bio or genomic breakthrough.
There’s been some promising work in genomics, but stuff on a bench top hasn’t really impacted it. I think that’s going to change. And I think this is one of these areas where there will be these new $100 billion to $1 trillion companies started, and those areas are rare.
Avoid human trials since they take time. Bio-materials or simulators are suitable beginning points.
AI may have a breakthrough. DeepMind, an OpenAI competitor, has developed AlphaFold to predict protein 3D structures.
It could change how we see proteins and their function. AlphaFold could provide fresh understanding into how proteins work and diseases originate by revealing their structure. This could lead to Alzheimer's and cancer treatments. AlphaFold could speed up medication development by revealing how proteins interact with medicines.
Deep Mind offered 200 million protein structures for scientists to download (including sustainability, food insecurity, and neglected diseases).
Being in AI for 4+ years, I'm amazed at the progress. We're past the hype cycle, as evidenced by the collapse of AI startups like C3 AI, and have entered a productive phase.
We'll see innovative enterprises that could replace Google and other trillion-dollar companies.
What happens after AI adoption is scary and unpredictable. How will AGI (Artificial General Intelligence) affect us? Highly autonomous systems that exceed humans at valuable work (Open AI)
My guess is that the things that we’ll have to figure out are how we think about fairly distributing wealth, access to AGI systems, which will be the commodity of the realm, and governance, how we collectively decide what they can do, what they don’t do, things like that. And I think figuring out the answer to those questions is going to just be huge. — Sam Altman CEO
Sara_Mednick
3 years ago
Since I'm a scientist, I oppose biohacking
Understanding your own energy depletion and restoration is how to truly optimize
Hack has meant many bad things for centuries. In the 1800s, a hack was a meager horse used to transport goods.
Modern usage describes a butcher or ax murderer's cleaver chop. The 1980s programming boom distinguished elegant code from "hacks". Both got you to your goal, but the latter made any programmer cringe and mutter about changing the code. From this emerged the hacker trope, the friendless anti-villain living in a murky hovel lit by the computer monitor, eating junk food and breaking into databases to highlight security system failures or steal hotdog money.
Now, start-a-billion-dollar-business-from-your-garage types have shifted their sights from app development to DIY biology, coining the term "bio-hack". This is a required keyword and meta tag for every fitness-related podcast, book, conference, app, or device.
Bio-hacking involves bypassing your body and mind's security systems to achieve a goal. Many biohackers' initial goals were reasonable, like lowering blood pressure and weight. Encouraged by their own progress, self-determination, and seemingly exquisite control of their biology, they aimed to outsmart aging and death to live 180 to 1000 years (summarized well in this vox.com article).
With this grandiose north star, the hunt for novel supplements and genetic engineering began.
Companies selling do-it-yourself biological manipulations cite lab studies in mice as proof of their safety and success in reversing age-related diseases or promoting longevity in humans (the goal changes depending on whether a company is talking to the federal government or private donors).
The FDA is slower than science, they say. Why not alter your biochemistry by buying pills online, editing your DNA with a CRISPR kit, or using a sauna delivered to your home? How about a microchip or electrical stimulator?
What could go wrong?
I'm not the neo-police, making citizen's arrests every time someone introduces a new plumbing gadget or extrapolates from animal research on resveratrol or catechins that we should drink more red wine or eat more chocolate. As a scientist who's spent her career asking, "Can we get better?" I've come to view bio-hacking as misguided, profit-driven, and counterproductive to its followers' goals.
We're creatures of nature. Despite all the new gadgets and bio-hacks, we still use Roman plumbing technology, and the best way to stay fit, sharp, and happy is to follow a recipe passed down since the beginning of time. Bacteria, plants, and all natural beings are rhythmic, with alternating periods of high activity and dormancy, whether measured in seconds, hours, days, or seasons. Nature repeats successful patterns.
During the Upstate, every cell in your body is naturally primed and pumped full of glycogen and ATP (your cells' energy currencies), as well as cortisol, which supports your muscles, heart, metabolism, cognitive prowess, emotional regulation, and general "get 'er done" attitude. This big energy release depletes your batteries and requires the Downstate, when your subsystems recharge at the cellular level.
Downstates are when you give your heart a break from pumping nutrient-rich blood through your body; when you give your metabolism a break from inflammation, oxidative stress, and sympathetic arousal caused by eating fast food — or just eating too fast; or when you give your mind a chance to wander, think bigger thoughts, and come up with new creative solutions. When you're responding to notifications, emails, and fires, you can't relax.
Downstates aren't just for consistently recharging your battery. By spending time in the Downstate, your body and brain get extra energy and nutrients, allowing you to grow smarter, faster, stronger, and more self-regulated. This state supports half-marathon training, exam prep, and mediation. As we age, spending more time in the Downstate is key to mental and physical health, well-being, and longevity.
When you prioritize energy-demanding activities during Upstate periods and energy-replenishing activities during Downstate periods, all your subsystems, including cardiovascular, metabolic, muscular, cognitive, and emotional, hum along at their optimal settings. When you synchronize the Upstates and Downstates of these individual rhythms, their functioning improves. A hard workout causes autonomic stress, which triggers Downstate recovery.
By choosing the right timing and type of exercise during the day, you can ensure a deeper recovery and greater readiness for the next workout by working with your natural rhythms and strengthening your autonomic and sleep Downstates.
Morning cardio workouts increase deep sleep compared to afternoon workouts. Timing and type of meals determine when your sleep hormone melatonin is released, ushering in sleep.
Rhythm isn't a hack. It's not a way to cheat the system or the boss. Nature has honed its optimization wisdom over trillions of days and nights. Stop looking for quick fixes. You're a whole system made of smaller subsystems that must work together to function well. No one pill or subsystem will make it all work. Understanding and coordinating your rhythms is free, easy, and only benefits you.
Dr. Sara C. Mednick is a cognitive neuroscientist at UC Irvine and author of The Power of the Downstate (HachetteGO)
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Ray Dalio
3 years ago
The latest “bubble indicator” readings.
As you know, I like to turn my intuition into decision rules (principles) that can be back-tested and automated to create a portfolio of alpha bets. I use one for bubbles. Having seen many bubbles in my 50+ years of investing, I described what makes a bubble and how to identify them in markets—not just stocks.
A bubble market has a high degree of the following:
- High prices compared to traditional values (e.g., by taking the present value of their cash flows for the duration of the asset and comparing it with their interest rates).
- Conditons incompatible with long-term growth (e.g., extrapolating past revenue and earnings growth rates late in the cycle).
- Many new and inexperienced buyers were drawn in by the perceived hot market.
- Broad bullish sentiment.
- Debt financing a large portion of purchases.
- Lots of forward and speculative purchases to profit from price rises (e.g., inventories that are more than needed, contracted forward purchases, etc.).
I use these criteria to assess all markets for bubbles. I have periodically shown you these for stocks and the stock market.
What Was Shown in January Versus Now
I will first describe the picture in words, then show it in charts, and compare it to the last update in January.
As of January, the bubble indicator showed that a) the US equity market was in a moderate bubble, but not an extreme one (ie., 70 percent of way toward the highest bubble, which occurred in the late 1990s and late 1920s), and b) the emerging tech companies (ie. As well, the unprecedented flood of liquidity post-COVID financed other bubbly behavior (e.g. SPACs, IPO boom, big pickup in options activity), making things bubbly. I showed which stocks were in bubbles and created an index of those stocks, which I call “bubble stocks.”
Those bubble stocks have popped. They fell by a third last year, while the S&P 500 remained flat. In light of these and other market developments, it is not necessarily true that now is a good time to buy emerging tech stocks.
The fact that they aren't at a bubble extreme doesn't mean they are safe or that it's a good time to get long. Our metrics still show that US stocks are overvalued. Once popped, bubbles tend to overcorrect to the downside rather than settle at “normal” prices.
The following charts paint the picture. The first shows the US equity market bubble gauge/indicator going back to 1900, currently at the 40% percentile. The charts also zoom in on the gauge in recent years, as well as the late 1920s and late 1990s bubbles (during both of these cases the gauge reached 100 percent ).
The chart below depicts the average bubble gauge for the most bubbly companies in 2020. Those readings are down significantly.
The charts below compare the performance of a basket of emerging tech bubble stocks to the S&P 500. Prices have fallen noticeably, giving up most of their post-COVID gains.
The following charts show the price action of the bubble slice today and in the 1920s and 1990s. These charts show the same market dynamics and two key indicators. These are just two examples of how a lot of debt financing stock ownership coupled with a tightening typically leads to a bubble popping.
Everything driving the bubbles in this market segment is classic—the same drivers that drove the 1920s bubble and the 1990s bubble. For instance, in the last couple months, it was how tightening can act to prick the bubble. Review this case study of the 1920s stock bubble (starting on page 49) from my book Principles for Navigating Big Debt Crises to grasp these dynamics.
The following charts show the components of the US stock market bubble gauge. Since this is a proprietary indicator, I will only show you some of the sub-aggregate readings and some indicators.
Each of these six influences is measured using a number of stats. This is how I approach the stock market. These gauges are combined into aggregate indices by security and then for the market as a whole. The table below shows the current readings of these US equity market indicators. It compares current conditions for US equities to historical conditions. These readings suggest that we’re out of a bubble.
1. How High Are Prices Relatively?
This price gauge for US equities is currently around the 50th percentile.
2. Is price reduction unsustainable?
This measure calculates the earnings growth rate required to outperform bonds. This is calculated by adding up the readings of individual securities. This indicator is currently near the 60th percentile for the overall market, higher than some of our other readings. Profit growth discounted in stocks remains high.
Even more so in the US software sector. Analysts' earnings growth expectations for this sector have slowed, but remain high historically. P/Es have reversed COVID gains but remain high historical.
3. How many new buyers (i.e., non-existing buyers) entered the market?
Expansion of new entrants is often indicative of a bubble. According to historical accounts, this was true in the 1990s equity bubble and the 1929 bubble (though our data for this and other gauges doesn't go back that far). A flood of new retail investors into popular stocks, which by other measures appeared to be in a bubble, pushed this gauge above the 90% mark in 2020. The pace of retail activity in the markets has recently slowed to pre-COVID levels.
4. How Broadly Bullish Is Sentiment?
The more people who have invested, the less resources they have to keep investing, and the more likely they are to sell. Market sentiment is now significantly negative.
5. Are Purchases Being Financed by High Leverage?
Leveraged purchases weaken the buying foundation and expose it to forced selling in a downturn. The leverage gauge, which considers option positions as a form of leverage, is now around the 50% mark.
6. To What Extent Have Buyers Made Exceptionally Extended Forward Purchases?
Looking at future purchases can help assess whether expectations have become overly optimistic. This indicator is particularly useful in commodity and real estate markets, where forward purchases are most obvious. In the equity markets, I look at indicators like capital expenditure, or how much businesses (and governments) invest in infrastructure, factories, etc. It reflects whether businesses are projecting future demand growth. Like other gauges, this one is at the 40th percentile.
What one does with it is a tactical choice. While the reversal has been significant, future earnings discounting remains high historically. In either case, bubbles tend to overcorrect (sell off more than the fundamentals suggest) rather than simply deflate. But I wanted to share these updated readings with you in light of recent market activity.
CoinTelegraph
3 years ago
2 NFT-based blockchain games that could soar in 2022
NFTs look ready to rule 2022, and the recent pivot toward NFT utility in P2E gaming could make blockchain gaming this year’s sector darling.
After the popularity of decentralized finance (DeFi) came the rise of nonfungible tokens (NFTs), and to the surprise of many, NFTs took the spotlight and now remain front and center with the highest volume in sales occurring at the start of January 2022.
While 2021 became the year of NFTs, GameFi applications did surpass DeFi in terms of user popularity. According to data from DappRadar, Bloomberg gathered:
Nearly 50% of active cryptocurrency wallets connected to decentralized applications in November were for playing games. The percentage of wallets linked to decentralized finance, or DeFi, dapps fell to 45% during the same period, after months of being the leading dapp use case.
Blockchain play-to-earn (P2E) game Axie infinity skyrocketed and kicked off a gaming craze that is expected to continue all throughout 2022. Crypto pundits and gaming advocates have high expectations for P2E blockchain-based games and there’s bound to be a few sleeping giants that will dominate the sector.
Let’s take a look at five blockchain games that could make waves in 2022.
DeFi Kingdoms
The inspiration for DeFi Kingdoms came from simple beginnings — a passion for investing that lured the developers to blockchain technology. DeFi Kingdoms was born as a visualization of liquidity pool investing where in-game ‘gardens’ represent literal and figurative token pairings and liquidity pool mining.
As shown in the game, investors have a portion of their LP share within a plot filled with blooming plants. By attaching the concept of growth to DeFi protocols within a play-and-earn model, DeFi Kingdoms puts a twist on “playing” a game.
Built on the Harmony Network, DeFi Kingdoms became the first project on the network to ever top the DappRadar charts. This could be attributed to an influx of individuals interested in both DeFi and blockchain games or it could be attributed to its recent in-game utility token JEWEL surging.
JEWEL is a utility token that allows users to purchase NFTs in-game buffs to increase a base-level stat. It is also used for liquidity mining to grant users the opportunity to make more JEWEL through staking.
JEWEL is also a governance token that gives holders a vote in the growth and evolution of the project. In the past four months, the token price surged from $1.23 to an all-time high of $22.52. At the time of writing, JEWEL is down by nearly 16%, trading at $19.51.
Surging approximately 1,487% from its humble start of $1.23 four months ago in September, JEWEL token price has increased roughly 165% this last month alone, according to data from CoinGecko.
Guild of Guardians
Guild of Guardians is one of the more anticipated blockchain games in 2022 and it is built on ImmutableX, the first layer-two solution built on Ethereum that focuses on NFTs. Aiming to provide more access, it will operate as a free-to-play mobile role-playing game, modeling the P2E mechanics.
Similar to blockchain games like Axie Infinity, Guild of Guardians in-game assets can be exchanged. The project seems to be of interest to many gamers and investors with its NFT founder sale and token launch generating nearly $10 million in volume.
Launching its in-game token in October of 2021, the Guild of Guardians (GOG) tokens are ERC-20 tokens known as ‘gems’ inside the game. Gems are what power key features in the game such as minting in-game NFTs and interacting with the marketplace, and are available to earn while playing.
For the last month, the Guild of Guardians token has performed rather steadily after spiking to its all-time high of $2.81 after its launch. Despite the token being down over 50% from its all-time high, at the time of writing, some members of the community are looking forward to the possibility of staking and liquidity pools, which are features that tend to help stabilize token prices.
Jake Prins
3 years ago
What are NFTs 2.0 and what issues are they meant to address?
New standards help NFTs reach their full potential.
NFTs lack interoperability and functionality. They have great potential but are mostly speculative. To maximize NFTs, we need flexible smart contracts.
Current requirements are too restrictive.
Most NFTs are based on ERC-721, which makes exchanging them easy. CryptoKitties, a popular online game, used the 2017 standard to demonstrate NFTs' potential.
This simple standard includes a base URI and incremental IDs for tokens. Add the tokenID to the base URI to get the token's metadata.
This let creators collect NFTs. Many NFT projects store metadata on IPFS, a distributed storage network, but others use Google Drive. NFT buyers often don't realize that if the creators delete or move the files, their NFT is just a pointer.
This isn't the standard's biggest issue. There's no way to validate NFT projects.
Creators are one of the most important aspects of art, but nothing is stored on-chain.
ERC-721 contracts only have a name and symbol.
Most of the data on OpenSea's collection pages isn't from the NFT's smart contract. It was added through a platform input field, so it's in the marketplace's database. Other websites may have different NFT information.
In five years, your NFT will be just a name, symbol, and ID.
Your NFT doesn't mention its creators. Although the smart contract has a public key, it doesn't reveal who created it.
The NFT's creators and their reputation are crucial to its value. Think digital fashion and big brands working with well-known designers when more professionals use NFTs. Don't you want them in your NFT?
Would paintings be as valuable if their artists were unknown? Would you believe it's real?
Buying directly from an on-chain artist would reduce scams. Current standards don't allow this data.
Most creator profiles live on centralized marketplaces and could disappear. Current platforms have outpaced underlying standards. The industry's standards are lagging.
For NFTs to grow beyond pointers to a monkey picture file, we may need to use new Web3-based standards.
Introducing NFTs 2.0
Fabian Vogelsteller, creator of ERC-20, developed new web3 standards. He proposed LSP7 Digital Asset and LSP8 Identifiable Digital Asset, also called NFT 2.0.
NFT and token metadata inputs are extendable. Changes to on-chain metadata inputs allow NFTs to evolve. Instead of public keys, the contract can have Universal Profile addresses attached. These profiles show creators' faces and reputations. NFTs can notify asset receivers, automating smart contracts.
LSP7 and LSP8 use ERC725Y. Using a generic data key-value store gives contracts much-needed features:
The asset can be customized and made to stand out more by allowing for unlimited data attachment.
Recognizing changes to the metadata
using a hash reference for metadata rather than a URL reference
This base will allow more metadata customization and upgradeability. These guidelines are:
Genuine and Verifiable Now, the creation of an NFT by a specific Universal Profile can be confirmed by smart contracts.
Dynamic NFTs can update Flexible & Updatable Metadata, allowing certain things to evolve over time.
Protected metadata Now, secure metadata that is readable by smart contracts can be added indefinitely.
Better NFTS prevent the locking of NFTs by only being sent to Universal Profiles or a smart contract that can interact with them.
Summary
NFTS standards lack standardization and powering features, limiting the industry.
ERC-721 is the most popular NFT standard, but it only represents incremental tokenIDs without metadata or asset representation. No standard sender-receiver interaction or security measures ensure safe asset transfers.
NFT 2.0 refers to the new LSP7-DigitalAsset and LSP8-IdentifiableDigitalAsset standards.
They have new standards for flexible metadata, secure transfers, asset representation, and interactive transfer.
With NFTs 2.0 and Universal Profiles, creators could build on-chain reputations.
NFTs 2.0 could bring the industry's needed innovation if it wants to move beyond trading profile pictures for speculation.