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
Twisted device investigates fusion alternatives
German stellarator revamped to run longer, hotter, compete with tokamaks
Tokamaks have dominated the search for fusion energy for decades. Just as ITER, the world's largest and most expensive tokamak, nears completion in southern France, a smaller, twistier testbed will start up in Germany.
If the 16-meter-wide stellarator can match or outperform similar-size tokamaks, fusion experts may rethink their future. Stellarators can keep their superhot gases stable enough to fuse nuclei and produce energy. They can theoretically run forever, but tokamaks must pause to reset their magnet coils.
The €1 billion German machine, Wendelstein 7-X (W7-X), is already getting "tokamak-like performance" in short runs, claims plasma physicist David Gates, preventing particles and heat from escaping the superhot gas. If W7-X can go long, "it will be ahead," he says. "Stellarators excel" Eindhoven University of Technology theorist Josefine Proll says, "Stellarators are back in the game." A few of startup companies, including one that Gates is leaving Princeton Plasma Physics Laboratory, are developing their own stellarators.
W7-X has been running at the Max Planck Institute for Plasma Physics (IPP) in Greifswald, Germany, since 2015, albeit only at low power and for brief runs. W7-X's developers took it down and replaced all inner walls and fittings with water-cooled equivalents, allowing for longer, hotter runs. The team reported at a W7-X board meeting last week that the revised plasma vessel has no leaks. It's expected to restart later this month to show if it can get plasma to fusion-igniting conditions.
Wendelstein 7-X's water-cooled inner surface allows for longer runs.
HOSAN/IPP
Both stellarators and tokamaks create magnetic gas cages hot enough to melt metal. Microwaves or particle beams heat. Extreme temperatures create a plasma, a seething mix of separated nuclei and electrons, and cause the nuclei to fuse, releasing energy. A fusion power plant would use deuterium and tritium, which react quickly. Non-energy-generating research machines like W7-X avoid tritium and use hydrogen or deuterium instead.
Tokamaks and stellarators use electromagnetic coils to create plasma-confining magnetic fields. A greater field near the hole causes plasma to drift to the reactor's wall.
Tokamaks control drift by circulating plasma around a ring. Streaming creates a magnetic field that twists and stabilizes ionized plasma. Stellarators employ magnetic coils to twist, not plasma. Once plasma physicists got powerful enough supercomputers, they could optimize stellarator magnets to improve plasma confinement.
W7-X is the first large, optimized stellarator with 50 6- ton superconducting coils. Its construction began in the mid-1990s and cost roughly twice the €550 million originally budgeted.
The wait hasn't disappointed researchers. W7-X director Thomas Klinger: "The machine operated immediately." "It's a friendly machine." It did everything we asked." Tokamaks are prone to "instabilities" (plasma bulging or wobbling) or strong "disruptions," sometimes associated to halted plasma flow. IPP theorist Sophia Henneberg believes stellarators don't employ plasma current, which "removes an entire branch" of instabilities.
In early stellarators, the magnetic field geometry drove slower particles to follow banana-shaped orbits until they collided with other particles and leaked energy. Gates believes W7-X's ability to suppress this effect implies its optimization works.
W7-X loses heat through different forms of turbulence, which push particles toward the wall. Theorists have only lately mastered simulating turbulence. W7-X's forthcoming campaign will test simulations and turbulence-fighting techniques.
A stellarator can run constantly, unlike a tokamak, which pulses. W7-X has run 100 seconds—long by tokamak standards—at low power. The device's uncooled microwave and particle heating systems only produced 11.5 megawatts. The update doubles heating power. High temperature, high plasma density, and extensive runs will test stellarators' fusion power potential. Klinger wants to heat ions to 50 million degrees Celsius for 100 seconds. That would make W7-X "a world-class machine," he argues. The team will push for 30 minutes. "We'll move step-by-step," he says.
W7-X's success has inspired VCs to finance entrepreneurs creating commercial stellarators. Startups must simplify magnet production.
Princeton Stellarators, created by Gates and colleagues this year, has $3 million to build a prototype reactor without W7-X's twisted magnet coils. Instead, it will use a mosaic of 1000 HTS square coils on the plasma vessel's outside. By adjusting each coil's magnetic field, operators can change the applied field's form. Gates: "It moves coil complexity to the control system." The company intends to construct a reactor that can fuse cheap, abundant deuterium to produce neutrons for radioisotopes. If successful, the company will build a reactor.
Renaissance Fusion, situated in Grenoble, France, raised €16 million and wants to coat plasma vessel segments in HTS. Using a laser, engineers will burn off superconductor tracks to carve magnet coils. They want to build a meter-long test segment in 2 years and a full prototype by 2027.
Type One Energy in Madison, Wisconsin, won DOE money to bend HTS cables for stellarator magnets. The business carved twisting grooves in metal with computer-controlled etching equipment to coil cables. David Anderson of the University of Wisconsin, Madison, claims advanced manufacturing technology enables the stellarator.
Anderson said W7-X's next phase will boost stellarator work. “Half-hour discharges are steady-state,” he says. “This is a big deal.”
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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Raad Ahmed
3 years ago
How We Just Raised $6M At An $80M Valuation From 100+ Investors Using A Link (Without Pitching)
Lawtrades nearly failed three years ago.
We couldn't raise Series A or enthusiasm from VCs.
We raised $6M (at a $80M valuation) from 100 customers and investors using a link and no pitching.
Step-by-step:
We refocused our business first.
Lawtrades raised $3.7M while Atrium raised $75M. By comparison, we seemed unimportant.
We had to close the company or try something new.
As I've written previously, a pivot saved us. Our initial focus on SMBs attracted many unprofitable customers. SMBs needed one-off legal services, meaning low fees and high turnover.
Tech startups were different. Their General Councels (GCs) needed near-daily support, resulting in higher fees and lower churn than SMBs.
We stopped unprofitable customers and focused on power users. To avoid dilution, we borrowed against receivables. We scaled our revenue 10x, from $70k/mo to $700k/mo.
Then, we reconsidered fundraising (and do it differently)
This time was different. Lawtrades was cash flow positive for most of last year, so we could dictate our own terms. VCs were still wary of legaltech after Atrium's shutdown (though they were thinking about the space).
We neither wanted to rely on VCs nor dilute more than 10% equity. So we didn't compete for in-person pitch meetings.
AngelList Roll-Up Vehicle (RUV). Up to 250 accredited investors can invest in a single RUV. First, we emailed customers the RUV. Why? Because I wanted to help the platform's users.
Imagine if Uber or Airbnb let all drivers or Superhosts invest in an RUV. Humans make the platform, theirs and ours. Giving people a chance to invest increases their loyalty.
We expanded after initial interest.
We created a Journey link, containing everything that would normally go in an investor pitch:
- Slides
- Trailer (from me)
- Testimonials
- Product demo
- Financials
We could also link to our AngelList RUV and send the pitch to an unlimited number of people. Instead of 1:1, we had 1:10,000 pitches-to-investors.
We posted Journey's link in RUV Alliance Discord. 600 accredited investors noticed it immediately. Within days, we raised $250,000 from customers-turned-investors.
Stonks, which live-streamed our pitch to thousands of viewers, was interested in our grassroots enthusiasm. We got $1.4M from people I've never met.
These updates on Pump generated more interest. Facebook, Uber, Netflix, and Robinhood executives all wanted to invest. Sahil Lavingia, who had rejected us, gave us $100k.
We closed the round with public support.
Without a single pitch meeting, we'd raised $2.3M. It was a result of natural enthusiasm: taking care of the people who made us who we are, letting them move first, and leveraging their enthusiasm with VCs, who were interested.
We used network effects to raise $3.7M from a founder-turned-VC, bringing the total to $6M at a $80M valuation (which, by the way, I set myself).
What flipping the fundraising script allowed us to do:
We started with private investors instead of 2–3 VCs to show VCs what we were worth. This gave Lawtrades the ability to:
- Without meetings, share our vision. Many people saw our Journey link. I ended up taking meetings with people who planned to contribute $50k+, but still, the ratio of views-to-meetings was outrageously good for us.
- Leverage ourselves. Instead of us selling ourselves to VCs, they did. Some people with large checks or late arrivals were turned away.
- Maintain voting power. No board seats were lost.
- Utilize viral network effects. People-powered.
- Preemptively halt churn by turning our users into owners. People are more loyal and respectful to things they own. Our users make us who we are — no matter how good our tech is, we need human beings to use it. They deserve to be owners.
I don't blame founders for being hesitant about this approach. Pump and RUVs are new and scary. But it won’t be that way for long. Our approach redistributed some of the power that normally lies entirely with VCs, putting it into our hands and our network’s hands.
This is the future — another way power is shifting from centralized to decentralized.
Owolabi Judah
3 years ago
How much did YouTube pay for 10 million views?
Ali's $1,054,053.74 YouTube Adsense haul.
YouTuber, entrepreneur, and former doctor Ali Abdaal. He began filming productivity and financial videos in 2017. Ali Abdaal has 3 million YouTube subscribers and has crossed $1 million in AdSense revenue. Crazy, no?
Ali will share the revenue of his top 5 youtube videos, things he's learned that you can apply to your side hustle, and how many views it takes to make a livelihood off youtube.
First, "The Long Game."
All good things take time to bear fruit. Compounding improves everything. Long-term work yields better returns. Ali made his first dollar after nine months and 85 videos.
Second, "One piece of content can transform your life, but you never know which one."
Had he abandoned YouTube at 84 videos without making any money, he wouldn't have filmed the 85th video that altered everything.
Third Lesson: Your Industry Choice Can Multiply.
The industry or niche you target as a business owner or side hustler can have a major impact on how much money you make.
Here are the top 5 videos.
1) 9.8m views: $191,258.16 for 9 passive income ideas
Ali made 2 points.
We should consider YouTube videos digital assets. They're investments, which make us money. His investments are yielding passive income.
Investing extra time and effort in your films can pay off.
2) How to Invest for Beginners — 5.2m Views: $87,200.08.
This video did poorly in the first several weeks after it was published; it was his tenth poorest performer. Don't worry about things you can't control. This applies to life, not just YouTube videos.
He stated we constantly have anxieties, fears, and concerns about things outside our control, but if we can find that line, life is easier and more pleasurable.
3) How to Build a Website in 2022— 866.3k views: $42,132.72.
The RPM was $48.86 per thousand views, making it his highest-earning video. Squarespace, Wix, and other website builders are trying to put ads on it and competing against one other, so ad rates go up.
Because it was beyond his niche, Ali almost didn't make the video. He made the video because he wanted to help at least one person.
4) How I take notes on my iPad in medical school — 5.9m views: $24,479.80
85th video. It's the video that affected Ali's YouTube channel and his life the most. The video's success wasn't certain.
5) How I Type Fast 156 Words Per Minute — 8.2M views: $25,143.17
Ali didn't know this video would perform well; he made it because he can type fast and has been practicing for 10 years. So he made a video with his best advice.
How many views to different wealth levels?
It depends on geography, niche, and other monetization sources. To keep things simple, he would solely utilize AdSense.
How many views to generate money?
To generate money on Youtube, you need 1,000 subscribers and 4,000 hours of view time. How much work do you need to make pocket money?
Ali's first 1,000 subscribers took 52 videos and 6 months. The typical channel with 1,000 subscribers contains 152 videos, according to Tubebuddy. It's time-consuming.
After monetizing, you'll need 15,000 views/month to make $5-$10/day.
How many views to go part-time?
Say you make $35,000/year at your day job. If you work 5 days/week, you make $7,000/year each day. If you want to drop down from 5 days to 4 days/week, you need to make an extra $7,000/year from YouTube, or $600/month.
What's the quit-your-job budget?
Silicon Valley Girl is in a highly successful niche targeting tech-focused folks in the west. When her channel had 500k views/month, she made roughly $3,000/month or $47,000/year, enough to quit your work.
Marina has another 1.5m subscriber channel in Russia, which has a lower rpm because fewer corporations advertise there than in the west. 2.3 million views/month is $4,000/month or $50,000/year, enough to quit your employment.
Marina is an intriguing example because she has three YouTube channels with the same skills, but one is 16x more profitable due to the niche she chose.
In Ali's case, he made 100+ videos when his channel was producing enough money to quit his job, roughly $4,000/month.
How many views make you rich?
Depending on how you define rich. Ali felt prosperous with over $100,000/year and 3–5m views/month.
Conclusion
YouTubers and artists don't treat their work like a company, which is a mistake. Businesses have been attempting to figure this out for decades, if not centuries.
We can learn from the business world how to monetize YouTube, Instagram, and Tiktok and make them into sustainable enterprises where we can hire people and delegate tasks.
Bonus
Watch Ali's video explaining all this:
This post is a summary. Read the full article here
The woman
3 years ago
The renowned and highest-paid Google software engineer
His story will inspire you.
“Google search went down for a few hours in 2002; Jeff Dean handled all the queries by hand and checked quality doubled.”- Jeff Dean Facts.
One of many Jeff Dean jokes, but you get the idea.
Google's top six engineers met in a war room in mid-2000. Google's crawling system, which indexed the Web, stopped working. Users could still enter queries, but results were five months old.
Google just signed a deal with Yahoo to power a ten-times-larger search engine. Tension rose. It was crucial. If they failed, the Yahoo agreement would likely fall through, risking bankruptcy for the firm. Their efforts could be lost.
A rangy, tall, energetic thirty-one-year-old man named Jeff dean was among those six brilliant engineers in the makeshift room. He had just left D. E. C. a couple of months ago and started his career in a relatively new firm Google, which was about to change the world. He rolled his chair over his colleague Sanjay and sat right next to him, cajoling his code like a movie director. The history started from there.
When you think of people who shaped the World Wide Web, you probably picture founders and CEOs like Larry Page and Sergey Brin, Marc Andreesen, Tim Berners-Lee, Bill Gates, and Mark Zuckerberg. They’re undoubtedly the brightest people on earth.
Under these giants, legions of anonymous coders work at keyboards to create the systems and products we use. These computer workers are irreplaceable.
Let's get to know him better.
It's possible you've never heard of Jeff Dean. He's American. Dean created many behind-the-scenes Google products. Jeff, co-founder and head of Google's deep learning research engineering team, is a popular technology, innovation, and AI keynote speaker.
While earning an MS and Ph.D. in computer science at the University of Washington, he was a teaching assistant, instructor, and research assistant. Dean joined the Compaq Computer Corporation Western Research Laboratory research team after graduating.
Jeff co-created ProfileMe and the Continuous Profiling Infrastructure for Digital at Compaq. He co-designed and implemented Swift, one of the fastest Java implementations. He was a senior technical staff member at mySimon Inc., retrieving and caching electronic commerce content.
Dean, a top young computer scientist, joined Google in mid-1999. He was always trying to maximize a computer's potential as a child.
An expert
His high school program for processing massive epidemiological data was 26 times faster than professionals'. Epi Info, in 13 languages, is used by the CDC. He worked on compilers as a computer science Ph.D. These apps make source code computer-readable.
Dean never wanted to work on compilers forever. He left Academia for Google, which had less than 20 employees. Dean helped found Google News and AdSense, which transformed the internet economy. He then addressed Google's biggest issue, scaling.
Growing Google faced a huge computing challenge. They developed PageRank in the late 1990s to return the most relevant search results. Google's popularity slowed machine deployment.
Dean solved problems, his specialty. He and fellow great programmer Sanjay Ghemawat created the Google File System, which distributed large data over thousands of cheap machines.
These two also created MapReduce, which let programmers handle massive data quantities on parallel machines. They could also add calculations to the search algorithm. A 2004 research article explained MapReduce, which became an industry sensation.
Several revolutionary inventions
Dean's other initiatives were also game-changers. BigTable, a petabyte-capable distributed data storage system, was based on Google File. The first global database, Spanner, stores data on millions of servers in dozens of data centers worldwide.
It underpins Gmail and AdWords. Google Translate co-founder Jeff Dean is surprising. He contributes heavily to Google News. Dean is Senior Fellow of Google Research and Health and leads Google AI.
Recognitions
The National Academy of Engineering elected Dean in 2009. He received the 2009 Association for Computing Machinery fellowship and the 2016 American Academy of Arts and Science fellowship. He received the 2007 ACM-SIGOPS Mark Weiser Award and the 2012 ACM-Infosys Foundation Award. Lists could continue.
A sneaky question may arrive in your mind: How much does this big brain earn? Well, most believe he is one of the highest-paid employees at Google. According to a survey, he is paid $3 million a year.
He makes espresso and chats with a small group of Googlers most mornings. Dean steams milk, another grinds, and another brews espresso. They discuss families and technology while making coffee. He thinks this little collaboration and idea-sharing keeps Google going.
“Some of us have been working together for more than 15 years,” Dean said. “We estimate that we’ve collectively made more than 20,000 cappuccinos together.”
We all know great developers and software engineers. It may inspire many.