More on Science
Michael Hunter, MD
2 years ago
5 Drugs That May Increase Your Risk of Dementia
While our genes can't be changed easily, you can avoid some dementia risk factors. Today we discuss dementia and five drugs that may increase risk.
Memory loss appears to come with age, but we're not talking about forgetfulness. Sometimes losing your car keys isn't an indication of dementia. Dementia impairs the capacity to think, remember, or make judgments. Dementia hinders daily tasks.
Alzheimers is the most common dementia. Dementia is not normal aging, unlike forgetfulness. Aging increases the risk of Alzheimer's and other dementias. A family history of the illness increases your risk, according to the Mayo Clinic (USA).
Given that our genes are difficult to change (I won't get into epigenetics), what are some avoidable dementia risk factors? Certain drugs may cause cognitive deterioration.
Today we look at four drugs that may cause cognitive decline.
Dementia and benzodiazepines
Benzodiazepine sedatives increase brain GABA levels. Example benzodiazepines:
Diazepam (Valium) (Valium)
Alprazolam (Xanax) (Xanax)
Clonazepam (Klonopin) (Klonopin)
Addiction and overdose are benzodiazepine risks. Yes! These medications don't raise dementia risk.
USC study: Benzodiazepines don't increase dementia risk in older adults.
Benzodiazepines can produce short- and long-term amnesia. This memory loss hinders memory formation. Extreme cases can permanently impair learning and memory. Anterograde amnesia is uncommon.
2. Statins and dementia
Statins reduce cholesterol. They prevent a cholesterol-making chemical. Examples:
Atorvastatin (Lipitor) (Lipitor)
Fluvastatin (Lescol XL) (Lescol XL)
Lovastatin (Altoprev) (Altoprev)
Pitavastatin (Livalo, Zypitamag) (Livalo, Zypitamag)
Pravastatin (Pravachol) (Pravachol)
Rosuvastatin (Crestor, Ezallor) (Crestor, Ezallor)
Simvastatin (Zocor) (Zocor)
This finding is contentious. Harvard's Brigham and Womens Hospital's Dr. Joann Manson says:
“I think that the relationship between statins and cognitive function remains controversial. There’s still not a clear conclusion whether they help to prevent dementia or Alzheimer’s disease, have neutral effects, or increase risk.”
This one's off the dementia list.
3. Dementia and anticholinergic drugs
Anticholinergic drugs treat many conditions, including urine incontinence. Drugs inhibit acetylcholine (a brain chemical that helps send messages between cells). Acetylcholine blockers cause drowsiness, disorientation, and memory loss.
First-generation antihistamines, tricyclic antidepressants, and overactive bladder antimuscarinics are common anticholinergics among the elderly.
Anticholinergic drugs may cause dementia. One study found that taking anticholinergics for three years or more increased the risk of dementia by 1.54 times compared to three months or less. After stopping the medicine, the danger may continue.
4. Drugs for Parkinson's disease and dementia
Cleveland Clinic (USA) on Parkinson's:
Parkinson's disease causes age-related brain degeneration. It causes delayed movements, tremors, and balance issues. Some are inherited, but most are unknown. There are various treatment options, but no cure.
Parkinson's medications can cause memory loss, confusion, delusions, and obsessive behaviors. The drug's effects on dopamine cause these issues.
A 2019 JAMA Internal Medicine study found powerful anticholinergic medications enhance dementia risk.
Those who took anticholinergics had a 1.5 times higher chance of dementia. Individuals taking antidepressants, antipsychotic drugs, anti-Parkinson’s drugs, overactive bladder drugs, and anti-epileptic drugs had the greatest risk of dementia.
Anticholinergic medicines can lessen Parkinson's-related tremors, but they slow cognitive ability. Anticholinergics can cause disorientation and hallucinations in those over 70.
5. Antiepileptic drugs and dementia
The risk of dementia from anti-seizure drugs varies with drugs. Levetiracetam (Keppra) improves Alzheimer's cognition.
One study linked different anti-seizure medications to dementia. Anti-epileptic medicines increased the risk of Alzheimer's disease by 1.15 times in the Finnish sample and 1.3 times in the German population. Depakote, Topamax are drugs.
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."
Jack Burns
3 years ago
Here's what to expect from NASA Artemis 1 and why it's significant.
NASA's Artemis 1 mission will help return people to the Moon after a half-century break. The mission is a shakedown cruise for NASA's Space Launch System and Orion Crew Capsule.
The spaceship will visit the Moon, deploy satellites, and enter orbit. NASA wants to practice operating the spacecraft, test the conditions people will face on the Moon, and ensure a safe return to Earth.
We asked Jack Burns, a space scientist at the University of Colorado Boulder and former member of NASA's Presidential Transition Team, to describe the mission, explain what the Artemis program promises for space exploration, and reflect on how the space program has changed in the half-century since humans last set foot on the moon.
What distinguishes Artemis 1 from other rockets?
Artemis 1 is the Space Launch System's first launch. NASA calls this a "heavy-lift" vehicle. It will be more powerful than Apollo's Saturn V, which transported people to the Moon in the 1960s and 1970s.
It's a new sort of rocket system with two strap-on solid rocket boosters from the space shuttle. It's a mix of the shuttle and Saturn V.
The Orion Crew Capsule will be tested extensively. It'll spend a month in the high-radiation Moon environment. It will also test the heat shield, which protects the capsule and its occupants at 25,000 mph. The heat shield must work well because this is the fastest capsule descent since Apollo.
This mission will also carry miniature Moon-orbiting satellites. These will undertake vital precursor science, including as examining further into permanently shadowed craters where scientists suspect there is water and measuring the radiation environment to see long-term human consequences.
Artemis 1 will launch, fly to the Moon, place satellites, orbit it, return to Earth, and splash down in the ocean. NASA.
What's Artemis's goal? What launches are next?
The mission is a first step toward Artemis 3, which will lead to the first human Moon missions since 1972. Artemis 1 is unmanned.
Artemis 2 will have astronauts a few years later. Like Apollo 8, it will be an orbital mission that circles the Moon and returns. The astronauts will orbit the Moon longer and test everything with a crew.
Eventually, Artemis 3 will meet with the SpaceX Starship on the Moon's surface and transfer people. Orion will stay in orbit while the lunar Starship lands astronauts. They'll go to the Moon's south pole to investigate the water ice there.
Artemis is reminiscent of Apollo. What's changed in 50 years?
Kennedy wanted to beat the Soviets to the Moon with Apollo. The administration didn't care much about space flight or the Moon, but the goal would place America first in space and technology.
You live and die by the sword if you do that. When the U.S. reached the Moon, it was over. Russia lost. We planted flags and did science experiments. Richard Nixon canceled the program after Apollo 11 because the political goals were attained.
Large rocket with two boosters between two gates
NASA's new Space Launch System is brought to a launchpad. NASA
50 years later... It's quite different. We're not trying to beat the Russians, Chinese, or anyone else, but to begin sustainable space exploration.
Artemis has many goals. It includes harnessing in-situ resources like water ice and lunar soil to make food, fuel, and building materials.
SpaceX is part of this first journey to the Moon's surface, therefore the initiative is also helping to develop a lunar and space economy. NASA doesn't own the Starship but is buying seats for astronauts. SpaceX will employ Starship to transport cargo, private astronauts, and foreign astronauts.
Fifty years of technology advancement has made getting to the Moon cheaper and more practical, and computer technology allows for more advanced tests. 50 years of technological progress have changed everything. Anyone with enough money can send a spacecraft to the Moon, but not humans.
Commercial Lunar Payload Services engages commercial companies to develop uncrewed Moon landers. We're sending a radio telescope to the Moon in January. Even 10 years ago, that was impossible.
Since humans last visited the Moon 50 years ago, technology has improved greatly.
What other changes does Artemis have in store?
The government says Artemis 3 will have at least one woman and likely a person of color.
I'm looking forward to seeing more diversity so young kids can say, "Hey, there's an astronaut that looks like me. I can do this. I can be part of the space program.”
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Thomas Tcheudjio
3 years ago
If you don't crush these 3 metrics, skip the Series A.
I recently wrote about getting VCs excited about Marketplace start-ups. SaaS founders became envious!
Understanding how people wire tens of millions is the only Series A hack I recommend.
Few people understand the intellectual process behind investing.
VC is risk management.
Series A-focused VCs must cover two risks.
1. Market risk
You need a large market to cross a threshold beyond which you can build defensibilities. Series A VCs underwrite market risk.
They must see you have reached product-market fit (PMF) in a large total addressable market (TAM).
2. Execution risk
When evaluating your growth engine's blitzscaling ability, execution risk arises.
When investors remove operational uncertainty, they profit.
Series A VCs like businesses with derisked revenue streams. Don't raise unless you have a predictable model, pipeline, and growth.
Please beat these 3 metrics before Series A:
Achieve $1.5m ARR in 12-24 months (Market risk)
Above 100% Net Dollar Retention. (Market danger)
Lead Velocity Rate supporting $10m ARR in 2–4 years (Execution risk)
Hit the 3 and you'll raise $10M in 4 months. Discussing 2/3 may take 6–7 months.
If none, don't bother raising and focus on becoming a capital-efficient business (Topics for other posts).
Let's examine these 3 metrics for the brave ones.
1. Lead Velocity Rate supporting €$10m ARR in 2 to 4 years
Last because it's the least discussed. LVR is the most reliable data when evaluating a growth engine, in my opinion.
SaaS allows you to see the future.
Monthly Sales and Sales Pipelines, two predictive KPIs, have poor data quality. Both are lagging indicators, and minor changes can cause huge modeling differences.
Analysts and Associates will trash your forecasts if they're based only on Monthly Sales and Sales Pipeline.
LVR, defined as month-over-month growth in qualified leads, is rock-solid. There's no lag. You can See The Future if you use Qualified Leads and a consistent formula and process to qualify them.
With this metric in your hand, scaling your company turns into an execution play on which VCs are able to perform calculations risk.
2. Above-100% Net Dollar Retention.
Net Dollar Retention is a better-known SaaS health metric than LVR.
Net Dollar Retention measures a SaaS company's ability to retain and upsell customers. Ask what $1 of net new customer spend will be worth in years n+1, n+2, etc.
Depending on the business model, SaaS businesses can increase their share of customers' wallets by increasing users, selling them more products in SaaS-enabled marketplaces, other add-ons, and renewing them at higher price tiers.
If a SaaS company's annualized Net Dollar Retention is less than 75%, there's a problem with the business.
Slack's ARR chart (below) shows how powerful Net Retention is. Layer chart shows how existing customer revenue grows. Slack's S1 shows 171% Net Dollar Retention for 2017–2019.
Slack S-1
3. $1.5m ARR in the last 12-24 months.
According to Point 9, $0.5m-4m in ARR is needed to raise a $5–12m Series A round.
Target at least what you raised in Pre-Seed/Seed. If you've raised $1.5m since launch, don't raise before $1.5m ARR.
Capital efficiency has returned since Covid19. After raising $2m since inception, it's harder to raise $1m in ARR.
P9's 2016-2021 SaaS Funding Napkin
In summary, less than 1% of companies VCs meet get funded. These metrics can help you win.
If there’s demand for it, I’ll do one on direct-to-consumer.
Cheers!
Deon Ashleigh
2 years ago
You can dominate your daily productivity with these 9 little-known Google Calendar tips.
Calendars are great unpaid employees.
After using Notion to organize my next three months' goals, my days were a mess.
I grew very chaotic afterward. I was overwhelmed, unsure of what to do, and wasting time attempting to plan the day after it had started.
Imagine if our skeletons were on the outside. Doesn’t work.
The goals were too big; I needed to break them into smaller chunks. But how?
Enters Google Calendar
RescueTime’s recommendations took me seven hours to make a daily planner. This epic narrative begins with a sheet of paper and concludes with a daily calendar that helps me focus and achieve more goals. Ain’t nobody got time for “what’s next?” all day.
Onward!
Return to the Paleolithic Era
Plan in writing.
Not on the list, but it helped me plan my day. Physical writing boosts creativity and recall.
Find My Heart
i.e. prioritize
RescueTime suggested I prioritize before planning. Personal and business goals were proposed.
My top priorities are to exercise, eat healthily, spend time in nature, and avoid stress.
Priorities include writing and publishing Medium articles, conducting more freelance editing and Medium outreach, and writing/editing sci-fi books.
These eight things will help me feel accomplished every day.
Make a baby calendar.
Create daily calendar templates.
Make family, pleasure, etc. calendars.
Google Calendar instructions:
Other calendars
Press the “+” button
Create a new calendar
Create recurring events for each day
My calendar, without the template:
Empty, so I can fill it with vital tasks.
With the template:
My daily skeleton corresponds with my priorities. I've been overwhelmed for years because I lack daily, weekly, monthly, and yearly structure.
Google Calendars helps me reach my goals and focus my energy.
Get your colored pencils ready
Time-block color-coding.
Color labeling lets me quickly see what's happening. Maybe you are too.
Google Calendar instructions:
Determine which colors correspond to each time block.
When establishing new events, select a color.
Save
My calendar is color-coded as follows:
Yellow — passive income or other future-related activities
Red — important activities, like my monthly breast exam
Flamingo — shallow work, like emails, Twitter, etc.
Blue — all my favorite activities, like walking, watching comedy, napping, and sleeping. Oh, and eating.
Green — money-related events required for this adulting thing
Purple — writing-related stuff
Associating a time block with a color helps me stay focused. Less distractions mean faster work.
Open My Email
aka receive a daily email from Google Calendar.
Google Calendar sends a daily email feed of your calendars. I sent myself the template calendar in this email.
Google Calendar instructions:
Access settings
Select the calendar that you want to send (left side)
Go down the page to see more alerts
Under the daily agenda area, click Email.
Get in Touch With Your Red Bull Wings — Naturally
aka audit your energy levels.
My daily planner has arrows. These indicate how much energy each activity requires or how much I have.
Rightward arrow denotes medium energy.
I do my Medium and professional editing in the morning because it's energy-intensive.
Niharikaa Sodhi recommends morning Medium editing.
I’m a morning person. As long as I go to bed at a reasonable time, 5 a.m. is super wild GO-TIME. It’s like the world was just born, and I marvel at its wonderfulness.
Freelance editing lets me do what I want. An afternoon snooze will help me finish on time.
Ditch Schedule View
aka focus on the weekly view.
RescueTime advocated utilizing the weekly view of Google Calendar, so I switched.
When you launch the phone app or desktop calendar, a red line shows where you are in the day.
I'll follow the red line's instructions. My digital supervisor is easy to follow.
In the image above, it's almost 3 p.m., therefore the red line implies it's time to snooze.
I won't forget this block ;).
Reduce the Lighting
aka dim previous days.
This is another Google Calendar feature I didn't know about. Once the allotted time passes, the time block dims. This keeps me present.
Google Calendar instructions:
Access settings
remaining general
To view choices, click.
Check Diminish the glare of the past.
Bonus
Two additional RescueTimes hacks:
Maintain a space between tasks
I left 15 minutes between each time block to transition smoothly. This relates to my goal of less stress. If I set strict start and end times, I'll be stressed.
With a buffer, I can breathe, stroll around, and start the following time block fresh.
Find a time is related to the buffer.
This option allows you conclude small meetings five minutes early and longer ones ten. Before the next meeting, relax or go wild.
Decide on a backup day.
This productivity technique is amazing.
Spend this excess day catching up on work. It helps reduce tension and clutter.
That's all I can say about Google Calendar's functionality.
Architectural Digest
3 years ago
Take a look at The One, a Los Angeles estate with a whopping 105,000 square feet of living area.
The interiors of the 105,000-square-foot property, which sits on a five-acre parcel in the wealthy Los Angeles suburb of Bel Air and is suitably titled The One, have been a well guarded secret. We got an intimate look inside this world-record-breaking property, as well as the creative and aesthetic geniuses behind it.
The estate appears to float above the city, surrounded on three sides by a moat and a 400-foot-long running track. Completed over eight years—and requiring 600 workers to build—the home was designed by architect Paul McClean and interior designer Kathryn Rotondi, who were enlisted by owner and developer Nile Niami to help it live up to its standard.
"This endeavor seemed both exhilarating and daunting," McClean says. However, the home's remarkable location and McClean's long-standing relationship with Niami persuaded him to "build something unique and extraordinary" rather than just take on the job.
And McClean has more than delivered.
The home's main entrance leads to a variety of meeting places with magnificent 360-degree views of the Pacific Ocean, downtown Los Angeles, and the San Gabriel Mountains, thanks to its 26-foot-high ceilings. There is water at the entrance area, as well as a sculpture and a bridge. "We often employ water in our design approach because it provides a sensory change that helps you acclimatize to your environment," McClean explains.
Niami wanted a neutral palette that would enable the environment and vistas to shine, so she used black, white, and gray throughout the house.
McClean has combined the home's inside with outside "to create that quintessential L.A. lifestyle but on a larger scale," he says, drawing influence from the local environment and history of Los Angeles modernism. "We separated the entertaining spaces from the living portions to make the house feel more livable. The former are on the lowest level, which serves as a plinth for the rest of the house and minimizes its apparent mass."
The home's statistics, in addition to its eye-catching style, are equally impressive. There are 42 bathrooms, 21 bedrooms, a 5,500-square-foot master suite, a 30-car garage gallery with two car-display turntables, a four-lane bowling alley, a spa level, a 30-seat movie theater, a "philanthropy wing (with a capacity of 200) for charity galas, a 10,000-square-foot sky deck, and five swimming pools.
Rotondi, the creator of KFR Design, collaborated with Niami on the interior design to create different spaces that flow into one another despite the house's grandeur. "I was especially driven to 'wow factor' components in the hospitality business," Rotondi says, citing top luxury hotel brands such as Aman, Bulgari, and Baccarat as sources of inspiration. Meanwhile, the home's color scheme, soft textures, and lighting are a nod to Niami and McClean's favorite Tom Ford boutique on Rodeo Drive.
The house boasts an extraordinary collection of art, including a butterfly work by Stephen Wilson on the lower level and a Niclas Castello bespoke panel in black and silver in the office, thanks to a cooperation between Creative Art Partners and Art Angels. There is also a sizable collection of bespoke furniture pieces from byShowroom.
A house of this size will never be erected again in Los Angeles, thanks to recently enacted city rules, so The One will truly be one of a kind. "For all of us, this project has been such a long and instructive trip," McClean says. "It was exciting to develop and approached with excitement, but I don't think any of us knew how much effort and time it would take to finish the project."