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DANIEL CLERY

DANIEL CLERY

3 years ago

Can space-based solar power solve Earth's energy problems?

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Michael Hunter, MD

Michael Hunter, MD

3 years ago

5 Drugs That May Increase Your Risk of Dementia

Photo by danilo.alvesd on Unsplash

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)

Photo by Towfiqu barbhuiya on Unsplash

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.

Photo by Wengang Zhai on Unsplash

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.

Katherine Kornei

Katherine Kornei

3 years ago

The InSight lander from NASA has recorded the greatest tremor ever felt on Mars.

The magnitude 5 earthquake was responsible for the discharge of energy that was 10 times greater than the previous record holder.

Any Martians who happen to be reading this should quickly learn how to duck and cover.

NASA's Jet Propulsion Laboratory in Pasadena, California, reported that on May 4, the planet Mars was shaken by an earthquake of around magnitude 5, making it the greatest Marsquake ever detected to this point. The shaking persisted for more than six hours and unleashed more than ten times as much energy as the earthquake that had previously held the record for strongest.

The event was captured on record by the InSight lander, which is operated by the United States Space Agency and has been researching the innards of Mars ever since it touched down on the planet in 2018 (SN: 11/26/18). The epicenter of the earthquake was probably located in the vicinity of Cerberus Fossae, which is located more than 1,000 kilometers away from the lander.

The surface of Cerberus Fossae is notorious for being broken up and experiencing periodic rockfalls. According to geophysicist Philippe Lognonné, who is the lead investigator of the Seismic Experiment for Interior Structure, the seismometer that is onboard the InSight lander, it is reasonable to assume that the ground is moving in that area. "This is an old crater from a volcanic eruption."

Marsquakes, which are similar to earthquakes in that they give information about the interior structure of our planet, can be utilized to investigate what lies beneath the surface of Mars (SN: 7/22/21). And according to Lognonné, who works at the Institut de Physique du Globe in Paris, there is a great deal that can be gleaned from analyzing this massive earthquake. Because the quality of the signal is so high, we will be able to focus on the specifics.

Bob Service

Bob Service

3 years ago

Did volcanic 'glasses' play a role in igniting early life?

Quenched lava may have aided in the formation of long RNA strands required by primitive life.

It took a long time for life to emerge. Microbes were present 3.7 billion years ago, just a few hundred million years after the 4.5-billion-year-old Earth had cooled enough to sustain biochemistry, according to fossils, and many scientists believe RNA was the genetic material for these first species. RNA, while not as complicated as DNA, would be difficult to forge into the lengthy strands required to transmit genetic information, raising the question of how it may have originated spontaneously.

Researchers may now have a solution. They demonstrate how basaltic glasses assist individual RNA letters, also known as nucleoside triphosphates, join into strands up to 200 letters long in lab studies. The glasses are formed when lava is quenched in air or water, or when melted rock generated by asteroid strikes cools rapidly, and they would have been plentiful in the early Earth's fire and brimstone.

The outcome has caused a schism among top origin-of-life scholars. "This appears to be a great story that finally explains how nucleoside triphosphates react with each other to create RNA strands," says Thomas Carell, a scientist at Munich's Ludwig Maximilians University. However, Harvard University's Jack Szostak, an RNA expert, says he won't believe the results until the study team thoroughly describes the RNA strands.

Researchers interested in the origins of life like the idea of a primordial "RNA universe" since the molecule can perform two different functions that are essential for life. It's made up of four chemical letters, just like DNA, and can carry genetic information. RNA, like proteins, can catalyze chemical reactions that are necessary for life.

However, RNA can cause headaches. No one has yet discovered a set of plausible primordial conditions that would cause hundreds of RNA letters—each of which is a complicated molecule—to join together into strands long enough to support the intricate chemistry required to kick-start evolution.

Basaltic glasses may have played a role, according to Stephen Mojzsis, a geologist at the University of Colorado, Boulder. They're high in metals like magnesium and iron, which help to trigger a variety of chemical reactions. "Basaltic glass was omnipresent on Earth at the time," he adds.

He provided the Foundation for Applied Molecular Evolution samples of five different basalt glasses. Each sample was ground into a fine powder, sanitized, and combined with a solution of nucleoside triphosphates by molecular biologist Elisa Biondi and her colleagues. The RNA letters were unable to link up without the presence of glass powder. However, when the molecules were mixed with the glass particles, they formed long strands of hundreds of letters, according to the researchers, who published their findings in Astrobiology this week. There was no need for heat or light. Biondi explains, "All we had to do was wait." After only a day, little RNA strands produced, yet the strands continued to grow for months. Jan Paek, a molecular biologist at Firebird Biomolecular Sciences, says, "The beauty of this approach is its simplicity." "Mix the components together, wait a few days, and look for RNA."

Nonetheless, the findings pose a slew of problems. One of the questions is how nucleoside triphosphates came to be in the first place. Recent study by Biondi's colleague Steven Benner suggests that the same basaltic glasses may have aided in the creation and stabilization of individual RNA letters.

The form of the lengthy RNA strands, according to Szostak, is a significant challenge. Enzymes in modern cells ensure that most RNAs form long linear chains. RNA letters, on the other hand, can bind in complicated branching sequences. Szostak wants the researchers to reveal what kind of RNA was produced by the basaltic glasses. "It irritates me that the authors made an intriguing initial finding but then chose to follow the hype rather than the research," Szostak says.

Biondi acknowledges that her team's experiment almost probably results in some RNA branching. She does acknowledge, however, that some branched RNAs are seen in species today, and that analogous structures may have existed before the origin of life. Other studies carried out by the study also confirmed the presence of lengthy strands with connections, indicating that they are most likely linear. "It's a healthy argument," says Dieter Braun, a Ludwig Maximilian University origin-of-life chemist. "It will set off the next series of tests."

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Josh Chesler

3 years ago

10 Sneaker Terms Every Beginner Should Know

So you want to get into sneakers? Buying a few sneakers and figuring it out seems simple. Then you miss out on the weekend's instant-sellout releases, so you head to eBay, Twitter, or your local  sneaker group to see what's available, since you're probably not ready to pay Flight Club prices just yet.

That's when you're bombarded with new nicknames, abbreviations, and general sneaker slang. It would take months to explain every word and sneaker, so here's a starter kit of ten simple terms to get you started. (Yeah, mostly Jordan. Does anyone really start with Kith or Nike SB?)

10. Colorways

Colorways are a common term in fashion, design, and other visual fields. It's just the product's color scheme. In the case of sneakers, the colorway is often as important as the actual model. Are this year's "Chicago" Air Jordan 1s more durable than last year's "Black/Gum" colorway? Because of their colorway and rarity, the Chicagos are worth roughly three pairs of the Black/Gum kicks.

Pro Tip: A colorway with a well-known nickname is almost always worth more than one without, and the same goes for collaborations.

9. Beaters

A “beater” is a well-worn, likely older model of shoe that has significant wear and tear on it. Rarely sold with the original box or extra laces, beaters rarely sell for much. Unlike most “worn” sneakers, beaters are used for rainy days and the gym. It's exactly what it sounds like, a box full of beaters, and they're a good place to start if you're looking for some cheap old kicks.

Pro Tip: Know which shoes clean up nicely. The shape of lower top sneakers with wider profiles, like SB Dunk Lows and Air Jordan 3s, tends to hold better over time than their higher and narrower cousins.

8. Retro

In the world of Jordan Brand, a “Retro” release is simply a release (or re-release) of a colorway after the shoe model's initial release. For example, the original Air Jordan 7 was released in 1992, but the Bordeaux colorway was re-released in 2011 and recently (2015). An Air Jordan model is released every year, and while half of them are unpopular and unlikely to be Retroed soon, any of them could be re-released whenever Nike and Jordan felt like it.

Pro Tip: Now that the Air Jordan line has been around for so long, the model that tends to be heavily retroed in a year is whichever shoe came out 23 (Michael Jordan’s number during the prime of his career) years ago. The Air Jordan 6 (1991) got new colorways last year, the Air Jordan 7 this year, and more Air Jordan 8s will be released later this year and early next year (1993).

7. PP/Inv

In spite of the fact that eBay takes roughly 10% of the final price, many sneaker buyers and sellers prefer to work directly with PayPal. Selling sneakers for $100 via PayPal invoice or $100 via PayPal friends/family is common on social media. Because no one wants their eBay account suspended for promoting PayPal deals, many eBay sellers will simply state “Message me for a better price.”

Pro Tip: PayPal invoices protect buyers well, but gifting or using Google Wallet does not. Unless you're certain the seller is legitimate, only use invoiced goods/services payments.

6. Yeezy

Kanye West and his sneakers are known as Yeezys. The rapper's first two Yeezys were made by Nike before switching to Adidas. Everything Yeezy-related will be significantly more expensive (and therefore have significantly more fakes made). Not only is the Nike Air Yeezy 2 “Red October” one of the most sought-after sneakers, but the Yeezy influence can be seen everywhere.

Pro Tip: If you're going to buy Yeezys, make sure you buy them from a reputable retailer or reseller. With so many fakes out there, it's not worth spending a grand on something you're not 100% sure is real.

5. GR/Limited

Regardless of how visually repulsive, uncomfortable, and/or impractical a sneaker is, if it’s rare enough, people will still want it. GR stands for General Release, which means they're usually available at retail. Reselling a “Limited Edition” release is costly. Supply and demand, but in this case, the limited supply drives up demand. If you want to get some of the colorways made for rappers, NBA players (Player Exclusive or PE models), and other celebrities, be prepared to pay a premium.

Pro Tip: Limited edition sneakers, like the annual Doernbecher Freestyle sneakers Nike creates with kids from Portland's Doernbecher Children's Hospital, will always be more expensive and limited. Or, you can use automated sneaker-buying software.

4. Grails

A “grail” is a pair of sneakers that someone desires above all others. To obtain their personal grails, people are willing to pay significantly more than the retail price. There doesn't have to be any rhyme or reason why someone chose a specific pair as their grails.

Pro Tip: For those who don't have them, the OG "Bred" or "Royal" Air Jordan 1s, the "Concord" Air Jordan 11s, etc., are all grails.

3. Bred

Anything released in “Bred” (black and red) will sell out quickly. Most resale Air Jordans (and other sneakers) come in the Bred colorway, which is a fan favorite. Bred is a good choice for a first colorway, especially on a solid sneaker silhouette.

Pro Tip: Apart from satisfying the world's hypebeasts, Bred sneakers will probably match a lot of your closet.

2. DS

DS = Deadstock = New. That's it. If something has been worn or tried on, it is no longer DS. Very Near Deadstock (VNDS) Pass As Deadstock It's a cute way of saying your sneakers have been worn but are still in good shape. In the sneaker world, “worn” means they are no longer new, but not too old or beat up.

Pro Tip: Ask for photos of any marks or defects to see what you’re getting before you buy used shoes, also find out if they come with the original box and extra laces, because that can be a sign that they’re in better shape.

1. Fake/Unauthorized

The words “Unauthorized,” “Replica,” “B-grades,” and “Super Perfect” all mean the shoes are fake. It means they aren't made by the actual company, no matter how close or how good the quality. If that's what you want, go ahead and get them. Do not wear them if you do not want the rest of the sneaker world to mock them.

Pro Tip: If you’re not sure if shoes are real or not, do a “Legit Check” on Twitter or Facebook. You'll get dozens of responses in no time.

Ray Dalio

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:

  1. 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).
  2. Conditons incompatible with long-term growth (e.g., extrapolating past revenue and earnings growth rates late in the cycle).
  3. Many new and inexperienced buyers were drawn in by the perceived hot market.
  4. Broad bullish sentiment.
  5. Debt financing a large portion of purchases.
  6. 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.

Nik Nicholas

Nik Nicholas

3 years ago

A simple go-to-market formula

Poor distribution, not poor goods, is the main reason for failure” — Peter Thiel.

Here's an easy way to conceptualize "go-to-market" for your distribution plan.

One equation captures the concept:

Distribution = Ecosystem Participants + Incentives

Draw your customers' ecosystem. Set aside your goods and consider your consumer's environment. Who do they deal with daily? 

  1. First, list each participant. You want an exhaustive list, but here are some broad categories.

  • In-person media services

  • Websites

  • Events\Networks

  • Financial education and banking

  • Shops

  • Staff

  • Advertisers

  • Twitter influencers

  1. Draw influence arrows. Who's affected? I'm not just talking about Instagram selfie-posters. Who has access to your consumer and could promote your product if motivated?

The thicker the arrow, the stronger the relationship. Include more "influencers" if needed. Customer ecosystems are complex.

3. Incentivize ecosystem players. “Show me the incentive and I will show you the result.“, says Warren Buffet's business partner Charlie Munger.

Strong distribution strategies encourage others to promote your product to your target market by incentivizing the most prominent players. Incentives can be financial or non-financial.

Financial rewards

Usually, there's money. If you pay Facebook, they'll run your ad. Salespeople close deals for commission. Giving customers bonus credits will encourage referrals.

Most businesses underuse non-financial incentives.

Non-cash incentives

Motivate key influencers without spending money to expand quickly and cheaply. What can you give a client-connector for free?

Here are some ideas:

Are there any other features or services available?

Titles or status? Tinder paid college "ambassadors" for parties to promote its dating service.

Can I get early/free access? Facebook gave a select group of developers "exclusive" early access to their AR platform.

Are you a good host? Pharell performed at YPlan's New York launch party.

Distribution? Apple's iPod earphones are white so others can see them.

Have an interesting story? PR rewards journalists by giving them a compelling story to boost page views.

Prioritize distribution.

More time spent on distribution means more room in your product design and business plan. Once you've identified the key players in your customer's ecosystem, talk to them.

Money isn't your only resource. Creative non-monetary incentives may be more effective and scalable. Give people something useful and easy to deliver.