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.
Sam Warain
3 years ago
Sam Altman, CEO of Open AI, foresees the next trillion-dollar AI company
“I think if I had time to do something else, I would be so excited to go after this company right now.”
Sam Altman, CEO of Open AI, recently discussed AI's present and future.
Open AI is important. They're creating the cyberpunk and sci-fi worlds.
They use the most advanced algorithms and data sets.
GPT-3...sound familiar? Open AI built most copyrighting software. Peppertype, Jasper AI, Rytr. If you've used any, you'll be shocked by the quality.
Open AI isn't only GPT-3. They created DallE-2 and Whisper (a speech recognition software released last week).
What will they do next? What's the next great chance?
Sam Altman, CEO of Open AI, recently gave a lecture about the next trillion-dollar AI opportunity.
Who is the organization behind Open AI?
Open AI first. If you know, skip it.
Open AI is one of the earliest private AI startups. Elon Musk, Greg Brockman, and Rebekah Mercer established OpenAI in December 2015.
OpenAI has helped its citizens and AI since its birth.
They have scary-good algorithms.
Their GPT-3 natural language processing program is excellent.
The algorithm's exponential growth is astounding. GPT-2 came out in November 2019. May 2020 brought GPT-3.
Massive computation and datasets improved the technique in just a year. New York Times said GPT-3 could write like a human.
Same for Dall-E. Dall-E 2 was announced in April 2022. Dall-E 2 won a Colorado art contest.
Open AI's algorithms challenge jobs we thought required human innovation.
So what does Sam Altman think?
The Present Situation and AI's Limitations
During the interview, Sam states that we are still at the tip of the iceberg.
So I think so far, we’ve been in the realm where you can do an incredible copywriting business or you can do an education service or whatever. But I don’t think we’ve yet seen the people go after the trillion dollar take on Google.
He's right that AI can't generate net new human knowledge. It can train and synthesize vast amounts of knowledge, but it simply reproduces human work.
“It’s not going to cure cancer. It’s not going to add to the sum total of human scientific knowledge.”
But the key word is yet.
And that is what I think will turn out to be wrong that most surprises the current experts in the field.
Reinforcing his point that massive innovations are yet to come.
But where?
The Next $1 Trillion AI Company
Sam predicts a bio or genomic breakthrough.
There’s been some promising work in genomics, but stuff on a bench top hasn’t really impacted it. I think that’s going to change. And I think this is one of these areas where there will be these new $100 billion to $1 trillion companies started, and those areas are rare.
Avoid human trials since they take time. Bio-materials or simulators are suitable beginning points.
AI may have a breakthrough. DeepMind, an OpenAI competitor, has developed AlphaFold to predict protein 3D structures.
It could change how we see proteins and their function. AlphaFold could provide fresh understanding into how proteins work and diseases originate by revealing their structure. This could lead to Alzheimer's and cancer treatments. AlphaFold could speed up medication development by revealing how proteins interact with medicines.
Deep Mind offered 200 million protein structures for scientists to download (including sustainability, food insecurity, and neglected diseases).
Being in AI for 4+ years, I'm amazed at the progress. We're past the hype cycle, as evidenced by the collapse of AI startups like C3 AI, and have entered a productive phase.
We'll see innovative enterprises that could replace Google and other trillion-dollar companies.
What happens after AI adoption is scary and unpredictable. How will AGI (Artificial General Intelligence) affect us? Highly autonomous systems that exceed humans at valuable work (Open AI)
My guess is that the things that we’ll have to figure out are how we think about fairly distributing wealth, access to AGI systems, which will be the commodity of the realm, and governance, how we collectively decide what they can do, what they don’t do, things like that. And I think figuring out the answer to those questions is going to just be huge. — Sam Altman CEO
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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Hudson Rennie
2 years ago
My Work at a $1.2 Billion Startup That Failed
Sometimes doing everything correctly isn't enough.
In 2020, I could fix my life.
After failing to start a business, I owed $40,000 and had no work.
A $1.2 billion startup on the cusp of going public pulled me up.
Ironically, it was getting ready for an epic fall — with the world watching.
Life sometimes helps. Without a base, even the strongest fall. A corporation that did everything right failed 3 months after going public.
First-row view.
Apple is the creator of Adore.
Out of respect, I've altered the company and employees' names in this account, despite their failure.
Although being a publicly traded company, it may become obvious.
We’ll call it “Adore” — a revolutionary concept in retail shopping.
Two Apple execs established Adore in 2014 with a focus on people-first purchasing.
Jon and Tim:
The concept for the stylish Apple retail locations you see today was developed by retail expert Jon Swanson, who collaborated closely with Steve Jobs.
Tim Cruiter is a graphic designer who produced the recognizable bouncing lamp video that appears at the start of every Pixar film.
The dynamic duo realized their vision.
“What if you could combine the convenience of online shopping with the confidence of the conventional brick-and-mortar store experience.”
Adore's mobile store concept combined traditional retail with online shopping.
Adore brought joy to 70+ cities and 4 countries over 7 years, including the US, Canada, and the UK.
Being employed on the ground floor, with world dominance and IPO on the horizon, was exciting.
I started as an Adore Expert.
I delivered cell phones, helped consumers set them up, and sold add-ons.
As the company grew, I became a Virtual Learning Facilitator and trained new employees across North America using Zoom.
In this capacity, I gained corporate insider knowledge. I worked with the creative team and Jon and Tim.
It's where I saw company foundation fissures. Despite appearances, investors were concerned.
The business strategy was ground-breaking.
Even after seeing my employee stocks fall from a home down payment to $0 (when Adore filed for bankruptcy), it's hard to pinpoint what went wrong.
Solid business model, well-executed.
Jon and Tim's chase for public funding ended in glory.
Here’s the business model in a nutshell:
Buying cell phones is cumbersome. You have two choices:
Online purchase: not knowing what plan you require or how to operate your device.
Enter a store, which can be troublesome and stressful.
Apple, AT&T, and Rogers offered Adore as a free delivery add-on. Customers could:
Have their phone delivered by UPS or Canada Post in 1-2 weeks.
Alternately, arrange for a person to visit them the same day (or sometimes even the same hour) to assist them set up their phone and demonstrate how to use it (transferring contacts, switching the SIM card, etc.).
Each Adore Expert brought a van with extra devices and accessories to customers.
Happy customers.
Here’s how Adore and its partners made money:
Adores partners appreciated sending Experts to consumers' homes since they improved customer satisfaction, average sale, and gadget returns.
**Telecom enterprises have low customer satisfaction. The average NPS is 30/100. Adore's global NPS was 80.
Adore made money by:
a set cost for each delivery
commission on sold warranties and extras
Consumer product applications seemed infinite.
A proprietary scheduling system (“The Adore App”), allowed for same-day, even same-hour deliveries.
It differentiates Adore.
They treated staff generously by:
Options on stock
health advantages
sales enticements
high rates per hour
Four-day workweeks were set by experts.
Being hired early felt like joining Uber, Netflix, or Tesla. We hoped the company's stocks would rise.
Exciting times.
I smiled as I greeted more than 1,000 new staff.
I spent a decade in retail before joining Adore. I needed a change.
After a leap of faith, I needed a lifeline. So, I applied for retail sales jobs in the spring of 2019.
The universe typically offers you what you want after you accept what you need. I needed a job to settle my debt and reach $0 again.
And the universe listened.
After being hired as an Adore Expert, I became a Virtual Learning Facilitator. Enough said.
After weeks of economic damage from the pandemic.
This employment let me work from home during the pandemic. It taught me excellent business skills.
I was active in brainstorming, onboarding new personnel, and expanding communication as we grew.
This job gave me vital skills and a regular paycheck during the pandemic.
It wasn’t until January of 2022 that I left on my own accord to try to work for myself again — this time, it’s going much better.
Adore was perfect. We valued:
Connection
Discovery
Empathy
Everything we did centered on compassion, and we held frequent Justice Calls to discuss diversity and work culture.
The last day of onboarding typically ended in tears as employees felt like they'd found a home, as I had.
Like all nice things, the wonderful vibes ended.
First indication of distress
My first day at the workplace was great.
Fun, intuitive, and they wanted creative individuals, not salesman.
While sales were important, the company's vision was more important.
“To deliver joy through life-changing mobile retail experiences.”
Thorough, forward-thinking training. We had a module on intuition. It gave us role ownership.
We were flown cross-country for training, gave feedback, and felt like we made a difference. Multiple contacts responded immediately and enthusiastically.
The atmosphere was genuine.
Making money was secondary, though. Incredible service was a priority.
Jon and Tim answered new hires' questions during Zoom calls during onboarding. CEOs seldom meet new hires this way, but they seemed to enjoy it.
All appeared well.
But in late 2021, things started changing.
Adore's leadership changed after its IPO. From basic values to sales maximization. We lost communication and were forced to fend for ourselves.
Removed the training wheels.
It got tougher to gain instructions from those above me, and new employees told me their roles weren't as advertised.
External money-focused managers were hired.
Instead of creative types, we hired salespeople.
With a new focus on numbers, Adore's uniqueness began to crumble.
Via Zoom, hundreds of workers were let go.
So.
Early in 2022, mass Zoom firings were trending. A CEO firing 900 workers over Zoom went viral.
Adore was special to me, but it became a headline.
30 June 2022, Vice Motherboard published Watch as Adore's CEO Fires Hundreds.
It described a leaked video of Jon Swanson laying off all staff in Canada and the UK.
They called it a “notice of redundancy”.
The corporation couldn't pay its employees.
I loved Adore's underlying ideals, among other things. We called clients Adorers and sold solutions, not add-ons.
But, like anything, a company is only as strong as its weakest link. And obviously, the people-first focus wasn’t making enough money.
There were signs. The expansion was presumably a race against time and money.
Adore finally declared bankruptcy.
Adore declared bankruptcy 3 months after going public. It happened in waves, like any large-scale fall.
Initial key players to leave were
Then, communication deteriorated.
Lastly, the corporate culture disintegrated.
6 months after leaving Adore, I received a letter in the mail from a Law firm — it was about my stocks.
Adore filed Chapter 11. I had to sue to collect my worthless investments.
I hoped those stocks will be valuable someday. Nope. Nope.
Sad, I sighed.
$1.2 billion firm gone.
I left the workplace 3 months before starting a writing business. Despite being mediocre, I'm doing fine.
I got up as Adore fell.
Finally, can we scale kindness?
I trust my gut. Changes at Adore made me leave before it sank.
Adores' unceremonious slide from a top startup to bankruptcy is astonishing to me.
The company did everything perfectly, in my opinion.
first to market,
provided excellent service
paid their staff handsomely.
was responsible and attentive to criticism
The company wasn't led by an egotistical eccentric. The crew had centuries of cumulative space experience.
I'm optimistic about the future of work culture, but is compassion scalable?
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/.
Alex Mathers
2 years ago
How to Produce Enough for People to Not Neglect You
Internet's fantastic, right?
We've never had a better way to share our creativity.
I can now draw on my iPad and tweet or Instagram it to thousands. I may get some likes.
With such a great, free tool, you're not alone.
Millions more bright-eyed artists are sharing their work online.
The issue is getting innovative work noticed, not sharing it.
In a world where creators want attention, attention is valuable.
We build for attention.
Attention helps us establish a following, make money, get notoriety, and make a difference.
Most of us require attention to stay sane while creating wonderful things.
I know how hard it is to work hard and receive little views.
How do we receive more attention, more often, in a sea of talent?
Advertising and celebrity endorsements are options. These may work temporarily.
To attract true, organic, and long-term attention, you must create in high quality, high volume, and consistency.
Adapting Steve Martin's Be so amazing, they can't ignore you (with a mention to Dan Norris in his great book Create or Hate for the reminder)
Create a lot.
Eventually, your effort will gain traction.
Traction shows your work's influence.
Traction is when your product sells more. Traction is exponential user growth. Your work is shared more.
No matter how good your work is, it will always have minimal impact on the world.
Your work can eventually dent or puncture. Daily, people work to dent.
To achieve this tipping point, you must consistently produce exceptional work.
Expect traction after hundreds of outputs.
Dilbert creator Scott Adams says repetition persuades. If you don't stop, you can persuade practically anyone with anything.
Volume lends believability. So make more.
I worked as an illustrator for at least a year and a half without any recognition. After 150 illustrations on iStockphoto, my work started selling.
With 350 illustrations on iStock, I started getting decent client commissions.
Producing often will improve your craft and draw attention.
It's the only way to succeed. More creation means better results and greater attention.
Austin Kleon says you can improve your skill in relative anonymity before you become famous. Before obtaining traction, generate a lot and become excellent.
Most artists, even excellent ones, don't create consistently enough to get traction.
It may hurt. For makers who don't love and flow with their work, it's extremely difficult.
Your work must bring you to life.
To generate so much that others can't ignore you, decide what you'll accomplish every day (or most days).
Commit and be patient.
Prepare for zero-traction.
Anticipating this will help you persevere and create.
My online guru Grant Cardone says: Anything worth doing is worth doing every day.
Do.