More on Science
Michael Hunter, MD
3 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.
DANIEL CLERY
3 years ago
Can space-based solar power solve Earth's energy problems?
Better technology and lower launch costs revive science-fiction tech.
Airbus engineers showed off sustainable energy's future in Munich last month. They captured sunlight with solar panels, turned it into microwaves, and beamed it into an airplane hangar, where it lighted a city model. The test delivered 2 kW across 36 meters, but it posed a serious question: Should we send enormous satellites to capture solar energy in space? In orbit, free of clouds and nighttime, they could create power 24/7 and send it to Earth.
Airbus engineer Jean-Dominique Coste calls it an engineering problem. “But it’s never been done at [large] scale.”
Proponents of space solar power say the demand for green energy, cheaper space access, and improved technology might change that. Once someone invests commercially, it will grow. Former NASA researcher John Mankins says it might be a trillion-dollar industry.
Myriad uncertainties remain, including whether beaming gigawatts of power to Earth can be done efficiently and without burning birds or people. Concept papers are being replaced with ground and space testing. The European Space Agency (ESA), which supported the Munich demo, will propose ground tests to member nations next month. The U.K. government offered £6 million to evaluate innovations this year. Chinese, Japanese, South Korean, and U.S. agencies are working. NASA policy analyst Nikolai Joseph, author of an upcoming assessment, thinks the conversation's tone has altered. What formerly appeared unattainable may now be a matter of "bringing it all together"
NASA studied space solar power during the mid-1970s fuel crunch. A projected space demonstration trip using 1970s technology would have cost $1 trillion. According to Mankins, the idea is taboo in the agency.
Space and solar power technology have evolved. Photovoltaic (PV) solar cell efficiency has increased 25% over the past decade, Jones claims. Telecoms use microwave transmitters and receivers. Robots designed to repair and refuel spacecraft might create solar panels.
Falling launch costs have boosted the idea. A solar power satellite large enough to replace a nuclear or coal plant would require hundreds of launches. ESA scientist Sanjay Vijendran: "It would require a massive construction complex in orbit."
SpaceX has made the idea more plausible. A SpaceX Falcon 9 rocket costs $2600 per kilogram, less than 5% of what the Space Shuttle did, and the company promised $10 per kilogram for its giant Starship, slated to launch this year. Jones: "It changes the equation." "Economics rules"
Mass production reduces space hardware costs. Satellites are one-offs made with pricey space-rated parts. Mars rover Perseverance cost $2 million per kilogram. SpaceX's Starlink satellites cost less than $1000 per kilogram. This strategy may work for massive space buildings consisting of many identical low-cost components, Mankins has long contended. Low-cost launches and "hypermodularity" make space solar power economical, he claims.
Better engineering can improve economics. Coste says Airbus's Munich trial was 5% efficient, comparing solar input to electricity production. When the Sun shines, ground-based solar arrays perform better. Studies show space solar might compete with existing energy sources on price if it reaches 20% efficiency.
Lighter parts reduce costs. "Sandwich panels" with PV cells on one side, electronics in the middle, and a microwave transmitter on the other could help. Thousands of them build a solar satellite without heavy wiring to move power. In 2020, a team from the U.S. Naval Research Laboratory (NRL) flew on the Air Force's X-37B space plane.
NRL project head Paul Jaffe said the satellite is still providing data. The panel converts solar power into microwaves at 8% efficiency, but not to Earth. The Air Force expects to test a beaming sandwich panel next year. MIT will launch its prototype panel with SpaceX in December.
As a satellite orbits, the PV side of sandwich panels sometimes faces away from the Sun since the microwave side must always face Earth. To maintain 24-hour power, a satellite needs mirrors to keep that side illuminated and focus light on the PV. In a 2012 NASA study by Mankins, a bowl-shaped device with thousands of thin-film mirrors focuses light onto the PV array.
International Electric Company's Ian Cash has a new strategy. His proposed satellite uses enormous, fixed mirrors to redirect light onto a PV and microwave array while the structure spins (see graphic, above). 1 billion minuscule perpendicular antennas act as a "phased array" to electronically guide the beam toward Earth, regardless of the satellite's orientation. This design, argues Cash, is "the most competitive economically"
If a space-based power plant ever flies, its power must be delivered securely and efficiently. Jaffe's team at NRL just beamed 1.6 kW over 1 km, and teams in Japan, China, and South Korea have comparable attempts. Transmitters and receivers lose half their input power. Vijendran says space solar beaming needs 75% efficiency, "preferably 90%."
Beaming gigawatts through the atmosphere demands testing. Most designs aim to produce a beam kilometers wide so every ship, plane, human, or bird that strays into it only receives a tiny—hopefully harmless—portion of the 2-gigawatt transmission. Receiving antennas are cheap to build but require a lot of land, adds Jones. You could grow crops under them or place them offshore.
Europe's public agencies currently prioritize space solar power. Jones: "There's a devotion you don't see in the U.S." ESA commissioned two solar cost/benefit studies last year. Vijendran claims it might match ground-based renewables' cost. Even at a higher price, equivalent to nuclear, its 24/7 availability would make it competitive.
ESA will urge member states in November to fund a technical assessment. If the news is good, the agency will plan for 2025. With €15 billion to €20 billion, ESA may launch a megawatt-scale demonstration facility by 2030 and a gigawatt-scale facility by 2040. "Moonshot"
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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The Mystique
3 years ago
Four Shocking Dark Web Incidents that Should Make You Avoid It
Dark Web activity? Is it as horrible as they say?
We peruse our phones for hours. Internet has improved our worldview.
However, the world's harshest realities remain buried on the internet and unattainable by everyone.
Browsers cannot access the Dark Web. Browse it with high-security authentication and exclusive access. There are compelling reasons to avoid the dark web at all costs.
1. The Dark Web and I
Darius wrote My Dark Web Story on reddit two years ago. The user claimed to have shared his dark web experience. DaRealEddyYT wanted to surf the dark web after hearing several stories.
He curiously downloaded Tor Browser, which provides anonymity and security.
In the Dark Room, bound
As Darius logged in, a text popped up: “Want a surprise? Click on this link.”
The link opened to a room with a chair. Only one light source illuminated the room. The chair held a female tied.
As the screen read "Let the game begin," a man entered the room and was paid in bitcoins to torment the girl.
The man dragged and tortured the woman.
A danger to safety
Leaving so soon, Darius, disgusted Darius tried to leave the stream. The anonymous user then sent Darius his personal information, including his address, which frightened him because he didn't know Tor was insecure.
After deleting the app, his phone camera was compromised.
He also stated that he left his residence and returned to find it unlocked and a letter saying, Thought we wouldn't find you? Reddit never updated the story.
The story may have been a fake, but a much scarier true story about the dark side of the internet exists.
2. The Silk Road Market
The dark web is restricted for a reason. The dark web has everything illicit imaginable. It's awful central.
The dark web has everything, from organ sales to drug trafficking to money laundering to human trafficking. Illegal drugs, pirated software, credit card, bank, and personal information can be found in seconds.
The dark web has reserved websites like Google. The Silk Road Website, which operated from 2011 to 2013, was a leading digital black market.
The FBI grew obsessed with site founder and processor Ross William Ulbricht.
The site became a criminal organization as money laundering and black enterprises increased. Bitcoin was utilized for credit card payment.
The FBI was close to arresting the site's administrator. Ross was detained after the agency closed Silk Road in 2013.
Two years later, in 2015, he was convicted and sentenced to two consecutive life terms and forty years. He appealed in 2016 but was denied, thus he is currently serving time.
The hefty sentence was for more than running a black marketing site. He was also convicted of murder-for-hire, earning about $730,000 in a short time.
3. Person-buying auctions
Bidding on individuals is another weird internet activity. After a Milan photo shoot, 20-year-old British model Chloe Ayling was kidnapped.
An ad agency in Milan made a bogus offer to shoot with the mother of a two-year-old boy. Four men gave her anesthetic and put her in a duffel bag when she arrived.
She was held captive for several days, and her images and $300,000 price were posted on the dark web. Black Death Trafficking Group kidnapped her to sell her for sex.
She was told two black death foot warriors abducted her. The captors released her when they found she was a mother because mothers were less desirable to sex slave buyers.
In July 2018, Lukasz Pawel Herba was arrested and sentenced to 16 years and nine months in prison. Being a young mother saved Chloe from creepy bidding.
However, it exceeds expectations of how many more would be in such danger daily without their knowledge.
4. Organ sales
Many are unaware of dark web organ sales. Patients who cannot acquire organs often turn to dark web brokers.
Brokers handle all transactions between donors and customers.
Bitcoins are used for dark web transactions, and the Tor server permits personal data on the web.
The WHO reports approximately 10,000 unlawful organ transplants annually. The black web sells kidneys, hearts, even eyes.
To protect our lives and privacy, we should manage our curiosity and never look up dangerous stuff.
While it's fascinating and appealing to know what's going on in the world we don't know about, it's best to prioritize our well-being because one never knows how bad it might get.
Sources
Maddie Wang
3 years ago
Easiest and fastest way to test your startup idea!
Here's the fastest way to validate company concepts.
I squandered a year after dropping out of Stanford designing a product nobody wanted.
But today, I’m at 100k!
Differences:
I was designing a consumer product when I dropped out.
I coded MVP, got 1k users, and got YC interview.
Nice, huh?
WRONG!
Still coding and getting users 12 months later
WOULD PEOPLE PAY FOR IT? was the riskiest assumption I hadn't tested.
When asked why I didn't verify payment, I said,
Not-ready products. Now, nobody cares. The website needs work. Include this. Increase usage…
I feared people would say no.
After 1 year of pushing it off, my team told me they were really worried about the Business Model. Then I asked my audience if they'd buy my product.
So?
No, overwhelmingly.
I felt like I wasted a year building a product no one would buy.
Founders Cafe was the opposite.
Before building anything, I requested payment.
40 founders were interviewed.
Then we emailed Stanford, YC, and other top founders, asking them to join our community.
BOOM! 10/12 paid!
Without building anything, in 1 day I validated my startup's riskiest assumption. NOT 1 year.
Asking people to pay is one of the scariest things.
I understand.
I asked Stanford queer women to pay before joining my gay sorority.
I was afraid I'd turn them off or no one would pay.
Gay women, like those founders, were in such excruciating pain that they were willing to pay me upfront to help.
You can ask for payment (before you build) to see if people have the burning pain. Then they'll pay!
Examples from Founders Cafe members:
😮 Using a fake landing page, a college dropout tested a product. Paying! He built it and made $3m!
😮 YC solo founder faked a Powerpoint demo. 5 Enterprise paid LOIs. $1.5m raised, built, and in YC!
😮 A Harvard founder can convert Figma to React. 1 day, 10 customers. Built a tool to automate Figma -> React after manually fulfilling requests. 1m+
Bad example:
😭 Stanford Dropout Spends 1 Year Building Product Without Payment Validation
Some people build for a year and then get paying customers.
What I'm sharing is my experience and what Founders Cafe members have told me about validating startup ideas.
Don't waste a year like I did.
After my first startup failed, I planned to re-enroll at Stanford/work at Facebook.
After people paid, I quit for good.
I've hit $100k!
Hope this inspires you to request upfront payment! It'll change your life
Alexander Nguyen
3 years ago
A Comparison of Amazon, Microsoft, and Google's Compensation
Learn or earn
In 2020, I started software engineering. My base wage has progressed as follows:
Amazon (2020): $112,000
Microsoft (2021): $123,000
Google (2022): $169,000
I didn't major in math, but those jumps appear more than a 7% wage increase. Here's a deeper look at the three.
The Three Categories of Compensation
Most software engineering compensation packages at IT organizations follow this format.
Minimum Salary
Base salary is pre-tax income. Most organizations give a base pay. This is paid biweekly, twice monthly, or monthly.
Recruiting Bonus
Sign-On incentives are one-time rewards to new hires. Companies need an incentive to switch. If you leave early, you must pay back the whole cost or a pro-rated amount.
Equity
Equity is complex and requires its own post. A company will promise to give you a certain amount of company stock but when you get it depends on your offer. 25% per year for 4 years, then it's gone.
If a company gives you $100,000 and distributes 25% every year for 4 years, expect $25,000 worth of company stock in your stock brokerage on your 1 year work anniversary.
Performance Bonus
Tech offers may include yearly performance bonuses. Depends on performance and funding. I've only seen 0-20%.
Engineers' overall compensation usually includes:
Base Salary + Sign-On + (Total Equity)/4 + Average Performance Bonus
Amazon: (TC: 150k)
Base Pay System
Amazon pays Seattle employees monthly on the first work day. I'd rather have my money sooner than later, even if it saves processing and pay statements.
The company upped its base pay cap from $160,000 to $350,000 to compete with other tech companies.
Performance Bonus
Amazon has no performance bonus, so you can work as little or as much as you like and get paid the same. Amazon is savvy to avoid promising benefits it can't deliver.
Sign-On Bonus
Amazon gives two two-year sign-up bonuses. First-year workers could receive $20,000 and second-year workers $15,000. It's probably to make up for the company's strange equity structure.
If you leave during the first year, you'll owe the entire money and a prorated amount for the second year bonus.
Equity
Most organizations prefer a 25%, 25%, 25%, 25% equity structure. Amazon takes a different approach with end-heavy equity:
the first year, 5%
15% after one year.
20% then every six months
We thought it was constructed this way to keep staff longer.
Microsoft (TC: 185k)
Base Pay System
Microsoft paid biweekly.
Gainful Performance
My offer letter suggested a 0%-20% performance bonus. Everyone will be satisfied with a 10% raise at year's end.
But misleading press where the budget for the bonus is doubled can upset some employees because they won't earn double their expected bonus. Still barely 10% for 2022 average.
Sign-On Bonus
Microsoft's sign-on bonus is a one-time payout. The contract can require 2-year employment. You must negotiate 1 year. It's pro-rated, so that's fair.
Equity
Microsoft is one of those companies that has standard 25% equity structure. Except if you’re a new graduate.
In that case it’ll be
25% six months later
25% each year following that
New grads will acquire equity in 3.5 years, not 4. I'm guessing it's to keep new grads around longer.
Google (TC: 300k)
Base Pay Structure
Google pays biweekly.
Performance Bonus
Google's offer letter specifies a 15% bonus. It's wonderful there's no cap, but I might still get 0%. A little more than Microsoft’s 10% and a lot more than Amazon’s 0%.
Sign-On Bonus
Google gave a 1-year sign-up incentive. If the contract is only 1 year, I can move without any extra obligations.
Not as fantastic as Amazon's sign-up bonuses, but the remainder of the package might compensate.
Equity
We covered Amazon's tail-heavy compensation structure, so Google's front-heavy equity structure may surprise you.
Annual structure breakdown
33% Year 1
33% Year 2
22% Year 3
12% Year 4
The goal is to get them to Google and keep them there.
Final Thoughts
This post hopefully helped you understand the 3 firms' compensation arrangements.
There's always more to discuss, such as refreshers, 401k benefits, and business discounts, but I hope this shows a distinction between these 3 firms.