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.
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."
Tomas Pueyo
2 years ago
Soon, a Starship Will Transform Humanity
SpaceX's Starship.
Launched last week.
Four minutes in:
SpaceX will succeed. When it does, its massiveness will matter.
Its payload will revolutionize space economics.
Civilization will shift.
We don't yet understand how this will affect space and Earth culture. Grab it.
The Cost of Space Transportation Has Decreased Exponentially
Space launches have increased dramatically in recent years.
We mostly send items to LEO, the green area below:
SpaceX's reusable rockets can send these things to LEO. Each may launch dozens of payloads into space.
With all these launches, we're sending more than simply things to space. Volume and mass. Since the 1980s, launching a kilogram of payload to LEO has become cheaper:
One kilogram in a large rocket cost over $75,000 in the 1980s. Carrying one astronaut cost nearly $5M! Falcon Heavy's $1,500/kg price is 50 times lower. SpaceX's larger, reusable rockets are amazing.
SpaceX's Starship rocket will continue. It can carry over 100 tons to LEO, 50% more than the current Falcon heavy. Thousands of launches per year. Elon Musk predicts Falcon Heavy's $1,500/kg cost will plummet to $100 in 23 years.
In context:
People underestimate this.
2. The Benefits of Affordable Transportation
Compare Earth's transportation costs:
It's no surprise that the US and Northern Europe are the wealthiest and have the most navigable interior waterways.
So what? since sea transportation is cheaper than land. Inland waterways are even better than sea transportation since weather is less of an issue, currents can be controlled, and rivers serve two banks instead of one for coastal transportation.
In France, because population density follows river systems, rivers are valuable. Cheap transportation brought people and money to rivers, especially their confluences.
How come? Why were humans surrounding rivers?
Imagine selling meat for $10 per kilogram. Transporting one kg one kilometer costs $1. Your margin decreases $1 each kilometer. You can only ship 10 kilometers. For example, you can only trade with four cities:
If instead, your cost of transportation is half, what happens? It costs you $0.5 per km. You now have higher margins with each city you traded with. More importantly, you can reach 20-km markets.
However, 2x distance 4x surface! You can now trade with sixteen cities instead of four! Metcalfe's law states that a network's value increases with its nodes squared. Since now sixteen cities can connect to yours. Each city now has sixteen connections! They get affluent and can afford more meat.
Rivers lower travel costs, connecting many cities, which can trade more, get wealthy, and buy more.
The right network is worth at least an order of magnitude more than the left! The cheaper the transport, the more trade at a lower cost, the more income generated, the more that wealth can be reinvested in better canals, bridges, and roads, and the wealth grows even more.
Throughout history. Rome was established around cheap Mediterranean transit and preoccupied with cutting overland transportation costs with their famous roadways. Communications restricted their empire.
The Egyptians lived around the Nile, the Vikings around the North Sea, early Japan around the Seto Inland Sea, and China started canals in the 5th century BC.
Transportation costs shaped empires.Starship is lowering new-world transit expenses. What's possible?
3. Change Organizations, Change Companies, Change the World
Starship is a conveyor belt to LEO. A new world of opportunity opens up as transportation prices drop 100x in a decade.
Satellite engineers have spent decades shedding milligrams. Weight influenced every decision: pricing structure, volumes to be sent, material selections, power sources, thermal protection, guiding, navigation, and control software. Weight was everything in the mission. To pack as much science into every millimeter, NASA missions had to be miniaturized. Engineers were indoctrinated against mass.
No way.
Starship is not constrained by any space mission, robotic or crewed.
Starship obliterates the mass constraint and every last vestige of cultural baggage it has gouged into the minds of spacecraft designers. A dollar spent on mass optimization no longer buys a dollar saved on launch cost. It buys nothing. It is time to raise the scope of our ambition and think much bigger. — Casey Handmer, Starship is still not understood
A Tesla Roadster in space makes more sense.
It went beyond bad PR. It told the industry: Did you care about every microgram? No more. My rockets are big enough to send a Tesla without noticing. Industry watchers should have noticed.
Most didn’t. Artemis is a global mission to send astronauts to the Moon and build a base. Artemis uses disposable Space Launch System rockets. Instead of sending two or three dinky 10-ton crew habitats over the next decade, Starship might deliver 100x as much cargo and create a base for 1,000 astronauts in a year or two. Why not? Because Artemis remains in a pre-Starship paradigm where each kilogram costs a million dollars and we must aggressively descope our objective.
Space agencies can deliver 100x more payload to space for the same budget with 100x lower costs and 100x higher transportation volumes. How can space economy saturate this new supply?
Before Starship, NASA supplied heavy equipment for Moon base construction. After Starship, Caterpillar and Deere may space-qualify their products with little alterations. Instead than waiting decades for NASA engineers to catch up, we could send people to build a space outpost with John Deere equipment in a few years.
History is littered with the wreckage of former industrial titans that underestimated the impact of new technology and overestimated their ability to adapt: Blockbuster, Motorola, Kodak, Nokia, RIM, Xerox, Yahoo, IBM, Atari, Sears, Hitachi, Polaroid, Toshiba, HP, Palm, Sony, PanAm, Sega, Netscape, Compaq, GM… — Casey Handmer, Starship is still not understood
Everyone saw it coming, but senior management failed to realize that adaption would involve moving beyond their established business practice. Others will if they don't.
4. The Starship Possibilities
It's Starlink.
SpaceX invented affordable cargo space and grasped its implications first. How can we use all this inexpensive cargo nobody knows how to use?
Satellite communications seemed like the best way to capitalize on it. They tried. Starlink, designed by SpaceX, provides fast, dependable Internet worldwide. Beaming information down is often cheaper than cable. Already profitable.
Starlink is one use for all this cheap cargo space. Many more. The longer firms ignore the opportunity, the more SpaceX will acquire.
What are these chances?
Satellite imagery is outdated and lacks detail. We can improve greatly. Synthetic aperture radar can take beautiful shots like this:
Have you ever used Google Maps and thought, "I want to see this in more detail"? What if I could view Earth live? What if we could livestream an infrared image of Earth?
We could launch hundreds of satellites with such mind-blowing visual precision of the Earth that we would dramatically improve the accuracy of our meteorological models; our agriculture; where crime is happening; where poachers are operating in the savannah; climate change; and who is moving military personnel where. Is that useful?
What if we could see Earth in real time? That affects businesses? That changes society?
You might also like
Jim Siwek
3 years ago
In 2022, can a lone developer be able to successfully establish a SaaS product?
In the early 2000s, I began developing SaaS. I helped launch an internet fax service that delivered faxes to email inboxes. Back then, it saved consumers money and made the procedure easier.
Google AdWords was young then. Anyone might establish a new website, spend a few hundred dollars on keywords, and see dozens of new paying clients every day. That's how we launched our new SaaS, and these clients stayed for years. Our early ROI was sky-high.
Changing times
The situation changed dramatically after 15 years. Our paid advertising cost $200-$300 for every new customer. Paid advertising takes three to four years to repay.
Fortunately, we still had tens of thousands of loyal clients. Good organic rankings gave us new business. We needed less sponsored traffic to run a profitable SaaS firm.
Is it still possible?
Since selling our internet fax firm, I've dreamed about starting a SaaS company. One I could construct as a lone developer and progressively grow a dedicated customer base, as I did before in a small team.
It seemed impossible to me. Solo startups couldn't afford paid advertising. SEO was tough. Even the worst SaaS startup ideas attracted VC funding. How could I compete with startups that could hire great talent and didn't need to make money for years (or ever)?
The One and Only Way to Learn
After years of talking myself out of SaaS startup ideas, I decided to develop and launch one. I needed to know if a solitary developer may create a SaaS app in 2022.
Thus, I did. I invented webwriter.ai, an AI-powered writing tool for website content, from hero section headlines to blog posts, this year. I soft-launched an MVP in July.
Considering the Issue
Now that I've developed my own fully capable SaaS app for site builders and developers, I wonder if it's still possible. Can webwriter.ai be successful?
I know webwriter.ai's proposal is viable because Jasper.ai and Grammarly are also AI-powered writing tools. With competition comes validation.
To Win, Differentiate
To compete with well-funded established brands, distinguish to stand out to a portion of the market. So I can speak directly to a target user, unlike larger competition.
I created webwriter.ai to help web builders and designers produce web content rapidly. This may be enough differentiation for now.
Budget-Friendly Promotion
When paid search isn't an option, we get inventive. There are more tools than ever to promote a new website.
Organic Results
on social media (Twitter, Instagram, TikTok, LinkedIn)
Marketing with content that is compelling
Link Creation
Listings in directories
references made in blog articles and on other websites
Forum entries
The Beginning of the Journey
As I've labored to construct my software, I've pondered a new mantra. Not sure where that originated from, but I like it. I'll live by it and teach my kids:
“Do the work.”
Erik Engheim
3 years ago
You Misunderstand the Russian Nuclear Threat
Many believe Putin is simply sabre rattling and intimidating us. They see no threat of nuclear war. We can send NATO troops into Ukraine without risking a nuclear war.
I keep reading that Putin is just using nuclear blackmail and that a strong leader will call the bluff. That, in my opinion, misunderstands the danger of sending NATO into Ukraine.
It assumes that once NATO moves in, Putin can either push the red nuclear button or not.
Sure, Putin won't go nuclear if NATO invades Ukraine. So we're safe? Can't we just move NATO?
No, because history has taught us that wars often escalate far beyond our initial expectations. One domino falls, knocking down another. That's why having clear boundaries is vital. Crossing a seemingly harmless line can set off a chain of events that are unstoppable once started.
One example is WWI. The assassin of Archduke Franz Ferdinand could not have known that his actions would kill millions. They couldn't have known that invading Serbia to punish them for not handing over the accomplices would start a world war. Every action triggered a counter-action, plunging Europe into a brutal and bloody war. Each leader saw their actions as limited, not realizing how they kept the dominos falling.
Nobody can predict the future, but it's easy to imagine how NATO intervention could trigger a chain of events leading to a total war. Let me suggest some outcomes.
NATO creates a no-fly-zone. In retaliation, Russia bombs NATO airfields. Russia may see this as a limited counter-move that shouldn't cause further NATO escalation. They think it's a reasonable response to force NATO out of Ukraine. Nobody has yet thought to use the nuke.
Will NATO act? Polish airfields bombed, will they be stuck? Is this an article 5 event? If so, what should be done?
It could happen. Maybe NATO sends troops into Ukraine to punish Russia. Maybe NATO will bomb Russian airfields.
Putin's response Is bombing Russian airfields an invasion or an attack? Remember that Russia has always used nuclear weapons for defense, not offense. But let's not panic, let's assume Russia doesn't go nuclear.
Maybe Russia retaliates by attacking NATO military bases with planes. Maybe they use ships to attack military targets. How does NATO respond? Will they fight Russia in Ukraine or escalate? Will they invade Russia or attack more military installations there?
Seen the pattern? As each nation responds, smaller limited military operations can grow in scope.
So far, the Russian military has shown that they begin with less brutal methods. As losses and failures increase, brutal means are used. Syria had the same. Assad used chemical weapons and attacked hospitals, schools, residential areas, etc.
A NATO invasion of Ukraine would cost Russia dearly. “Oh, this isn't looking so good, better pull out and finish this war,” do you think? No way. Desperate, they will resort to more brutal tactics. If desperate, Russia has a huge arsenal of ugly weapons. They have nerve agents, chemical weapons, and other nasty stuff.
What happens if Russia uses chemical weapons? What if Russian nerve agents kill NATO soldiers horribly? West calls for retaliation will grow. Will we invade Russia? Will we bomb them?
We are angry and determined to punish war criminal Putin, so NATO tanks may be heading to Moscow. We want vengeance for his chemical attacks and bombing of our cities.
Do you think the distance between that red nuclear button and Putin's finger will be that far once NATO tanks are on their way to Moscow?
We might avoid a nuclear apocalypse. A NATO invasion force or even Western cities may be used by Putin. Not as destructive as ICBMs. Putin may think we won't respond to tactical nukes with a full nuclear counterattack. Why would we risk a nuclear Holocaust by launching ICBMs on Russia?
Maybe. My point is that at every stage of the escalation, one party may underestimate the other's response. This war is spiraling out of control and the chances of a nuclear exchange are increasing. Nobody really wants it.
Fear, anger, and resentment cause it. If Putin and his inner circle decide their time is up, they may no longer care about the rest of the world. We saw it with Hitler. Hitler, seeing the end of his empire, ordered the destruction of Germany. Nobody should win if he couldn't. He wanted to destroy everything, including Paris.
In other words, the danger isn't what happens after NATO intervenes The danger is the potential chain reaction. Gambling has a psychological equivalent. It's best to exit when you've lost less. We humans are willing to take small risks for big rewards. To avoid losses, we are willing to take high risks. Daniel Kahneman describes this behavior in his book Thinking, Fast and Slow.
And so bettors who have lost a lot begin taking bigger risks to make up for it. We get a snowball effect. NATO involvement in the Ukraine conflict is akin to entering a casino and placing a bet. We'll start taking bigger risks as we start losing to Russian retaliation. That's the game's psychology.
It's impossible to stop. So will politicians and citizens from both Russia and the West, until we risk the end of human civilization.
You can avoid spiraling into ever larger bets in the Casino by drawing a hard line and declaring “I will not enter that Casino.” We're doing it now. We supply Ukraine. We send money and intelligence but don't cross that crucial line.
It's difficult to watch what happened in Bucha without demanding NATO involvement. What should we do? Of course, I'm not in charge. I'm a writer. My hope is that people will think about the consequences of the actions we demand. My hope is that you think ahead not just one step but multiple dominos.
More and more, we are driven by our emotions. We cannot act solely on emotion in matters of life and death. If we make the wrong choice, more people will die.
Read the original post here.
Simone Basso
3 years ago
How I set up my teams to be successful
After 10 years of working in scale-ups, I've embraced a few concepts for scaling Tech and Product teams.
First, cross-functionalize teams. Product Managers represent the business, Product Designers the consumer, and Engineers build.
I organize teams of 5-10 individuals, following AWS's two pizza teams guidelines, with a Product Trio guiding each.
If more individuals are needed to reach a goal, I group teams under a Product Trio.
With Engineering being the biggest group, Staff/Principal Engineers often support the Trio on cross-team technical decisions.
Product Managers, Engineering Managers, or Engineers in the team may manage projects (depending on the project or aim), but the trio is collectively responsible for the team's output and outcome.
Once the Product Trio model is created, roles, duties, team ceremonies, and cooperation models must be clarified.
Keep reporting lines by discipline. Line managers are accountable for each individual's advancement, thus it's crucial that they know the work in detail.
Cross-team collaboration becomes more important after 3 teams (15-30 people). Teams can easily diverge in how they write code, run ceremonies, and build products.
Establishing groups of people that are cross-team, but grouped by discipline and skills, sharing and agreeing on working practices becomes critical.
The “Spotify Guild” model has been where I’ve taken a lot of my inspiration from.
Last, establish a taxonomy for communication channels.
In Slack, I create one channel per team and one per guild (and one for me to have discussions with the team leads).
These are just some of the basic principles I follow to organize teams.
A book I particularly like about team types and how they interact with each other is https://teamtopologies.com/.