Kaytlyn Gerbin, left, runs the Wonderland Trail around Mount Rainier. She completed the 93-mile loop in just under 19 hours. Her friend Tara Fraga helped with pacing between miles 30-55. (Ryan Thrower Photo)

When Kaytlyn Gerbin moved to Seattle 10 years ago to attend graduate school at the University of Washington, a friend took her to Kerry Park in the Queen Anne neighborhood on her first visit. The celebrated viewpoint offered Gerbin a glimpse of Mount Rainier that ignited an ongoing passion.

At the time, I had absolutely no idea there was a trail all the way around it, and didnt know the first thing that went into climbing to the summit or running even a few miles on the trails, Gerbin said. Since then, Ive climbed Rainier 10 times, and spent countless hours on the mountain and trails in that park.

Along with her drive to get to know Washington states most famous landmark more intimately, Gerbin achieved her PhD in bioengineering at UW, where her research was focused on the therapeutic and regenerative potential of cardiac cells. For the past four years shes been a scientist at Allen Institute for Cell Science, where she studies stem cells and cardiomyocytes, or cardiac muscle cells.

Our latest Geek of the Week, Gerbin is an accomplished ultrarunner, and she now knows a lot more about that trail that encircles Mount Rainier.

With COVID-19 lockdowns impacting her international race season last summer, Gerbin, a sponsored athlete for The North Face, went after the fastest known time, or FKT, for a run around the Wonderland Trail. Together with teammate Dylan Bowman of Portland and a small crew of local filmmakers, they made Summer of Wonder, a short film about the experience, which you can watch in full here:

The average thru-hiker takes 10-14 days to complete the 93-mile Wonderland Trail, with its 24,000 feet of elevation gain. Gerbin did it in 18 hours, 41 minutes, 53 seconds, and the film is a breathtaking look at her endurance feat.

Gerbins passion for running started with 3-mile commutes back and forth between her apartment, her research lab, and campus during grad school. Eventually she started trail running,essentially as a life hack to see if she could squeeze a five-day backpacking route into a weekend between experiments.

It turned out I was actually pretty good at that, and that opened up opportunities to start racing at some of the most competitive trail races in the U.S. and Europe, Gerbin said.

Shes since raced with Team USA at the Trail World Championships, reached the podium at the iconic Western States 100, and won races such as the Canary Islands Transgrancanaria and Cascade Crest 100 in Washington. She also still holds the womens self-supported FKT for the Rainier Infinity Loop (set in 2019), which combines the Wonderland Trail with two summits and descents of Mount Rainier.

Her preferred racing distance is anything between 50-100 miles long, the more elevation gain and technical the trail, the better. During peak training, Gerbin is usually hitting between 70-90 miles with over 20,000 feet of elevation gain each week. She calls the Pacific Northwest the best outdoor playground there is.

Although I love running fast, Im also really excited about pushing myself on more challenging terrain. So many of my other FKT goals and route ideas are along these lines, with more technical traveling than actual running, she said.

COVID permitting, her highest race priority this year is Ultra Trail du Mont Blanc, which is the most competitive world-stage for ultrarunning, at the end of August. The race circumnavigates Mont Blanc, passing through France, Italy, and Switzerland and covering around 105 miles and 33,000 feet of elevation gain.

While Gerbins experience as a scientist does inform her appreciation for what shes putting her body through during ultrarunning, shes equally passionate in the lab. At the Allen Institute shes seeking answers to broad questions about how cells work, including how single cells and all of their components are integrated into a functional system, while using imaging to build predictive models of cell behavior.

I get the opportunity to work with a multidisciplinary team of badass scientists, biologists, and engineers on really cool problems in cell biology, she said.

Learn more about our latest Geek of the Week, Kaytlyn Gerbin:

What do you do, and why do you do it? Science and ultrarunning for me have always come down to problem solving.

As a scientist, problem solving is inherent to experimental design, data analysis, and interpreting results. By asking hard questions, Im interested in pushing the field of cell biology forward, and challenging the current way of thinking.

As an ultrarunner, its a different kind of problem solving, but I lean on the same mindset to figure out how to push my athletic limits further and faster.

One thing that always amazes me is how adaptable the human body is. My training in cell science gives me context for how all of these stressors and inputs were putting on our bodies are fundamentally happening at the single cell level, and it keeps me thinking about the cells response to external cues in my research.

Whats the single most important thing people should know about your field? Yes, I do think about science and when Im running, and no, I do not geek out on heart rate monitors and training zones and all those numbers when Im running.

Where do you find your inspiration? Im inspired by brilliant women that are pushing whats possible in both science and in sports. I think we often set boundaries for ourselves about what we think is possible, without ever letting ourselves really hit that limit. Im inspired by women who set bold goals and bring others up and along for the ride, redefining whats possible.

Whats the one piece of technology you couldnt live without, and why? My Garmin 935. I use this watch daily to track miles run, elevation gain, etc. The battery life has lasted me for 100 miles of running and ~24 hrs, but its small enough to wear every day.

Whats your workspace like, and why does it work for you? Prior to 2020, I was splitting my time between the tissue culture hood (passaging cells, differentiating cardiomyocytes, setting up experiments), conference rooms (team science and collaboration means a lot of group discussions!), and my computer for writing and analysis. Since then, Ive shifted my work to be more remote while I work on a few different manuscripts. I have an office set up at home with a window, some good tunes, plenty of coffee, and a chair for my dog to wait impatiently on.

Your best tip or trick for managing everyday work and life. (Help us out, we need it.) I have always been a to-do list person. Most mornings start with me listing out tasks (and breaking those down into many sub-tasks). I feel productive as I cross things off, and it also helps me prioritize and plan ahead to make sure I can also fit my training runs in.

Mac, Windows or Linux? Mac as a personal preference, Windows for my work computer (I do work at the Paul Allen Institute 🙂

Transporter, Time Machine or Cloak of Invisibility? Transporter. I just promise not to use it in races.

Greatest game in history: Lode Runner. I havent played it since I was a kid, but the memories of yelling at the computer with my sister frantically hitting up-down-up-down arrows make me feel like it was just yesterday.

Best gadget ever: Garmin inReach mini satellite messaging and SOS call, all in a device small enough to throw in the bottom of a pack (or shorts pocket) and forget its there. I bring this with me anytime Im headed out into the wilderness/mountains, but I hope I never need to use it.

First computer: iMac G3.

Current phone: iPhone 11.

Favorite app: I have a love/hate relationship with Strava. Ive also been using DuoLingo during the pandemic and have a strong daily streak going!

Most important technology of 2021: COVID vaccines!!

Most important technology of 2023: Advancements in remote/low-resource medical care.

Final words of advice for your fellow geeks: Most problems can be solved with more snacks and some time (works for science and running).

Twitter: @kaytlyn_gerbin

LinkedIn: Kaytlyn Gerbin

Continued here:
Kaytlyn Gerbin is blazing trails in cell science and as an ultrarunner who has conquered Mount Rainier - GeekWire

Cardiac Stem Cells Comments Off on Kaytlyn Gerbin is blazing trails in cell science and as an ultrarunner who has conquered Mount Rainier – GeekWire April 19th, 2021

Most of us would agree that 2020 was the shortest long year, one in which you probably lost track of your routines. Although 2021 might be off to a rocky start because of political unrest and ongoing COVID-19 shutdowns, its as good a time as any to take inventory of how you can improve your daily rituals.

Studies have shown that there is a psychological benefit to self-care. Grooming is important for human behavior because it makes us feel better and it boosts our self-esteem, said Dr. Amy Wechsler, a New York-based psychiatrist and dermatologist. When people are stressed, they stop doing their routines. Routines are important. They give us a sense of control, and right now people feel really out of control. Little ways to give you back the feeling or semblance of control are helpful.

For starters, Wechsler recommends maintaining your skincare regimen. A few minutes in the morning, she said. A few minutes in the evening. It helps ground a lot of people.

Here are tips and tricks from beauty and wellness experts:

Cassandra Grey, founder of L.A. beauty boutique Violet Grey, says that skincare as a category has been on the rise over the last four years. 70% of her business sales come from skincare while 25% of her customers are men.

(Naj Jamai)

Cassandra Grey, founder of Los Angeles beauty boutique Violet Grey, has built her business around a belief in grooming and wellness as an important form of self-care. Humans are motivated by three things sex, power and self-respect, she said. I think skincare or self-care or beauty products that enhance the way you feel or the way that you look really help you achieve self-respect because you feel like youre taking care of yourself.

One of Violet Greys bestsellers is Augustinus Baders the Cream, which has become something of a phenomenon since the German brand launched three years ago. It just works, Grey said of the cream (15 milliliters, $85), which reportedly triggers existing stem cells to repair skin. You use it, and your skin looks better. Period. Thats why its become a hero product. It is innovative in the formulation. There is not a formulation like that.

One of Violet Greys bestsellers is Augustinus Baders the Cream. Three new Augustinus Bader products a cleansing gel, body lotion and body oil were added to the brands lineup.

(Augustinus Bader)

The skincare brand, which was created by leading stem cell and biomedical scientist Augustinus Bader, has released a cleansing gel (100 milliliters, $65), body lotion (30 milliliters, $35; 100 milliliters, $95) and body oil (100 milliliters, $95), which all contain the companys proprietary technology, a combination of natural amino acids, high-grade vitamins and synthesized molecules.

There are a number of result-driven brands and products on the market.

Among them are Protocol, which packages its Complete Renewing Line (four skincare products for $262) in airless, UV-proof bottles in order to protect its products oxidized retinol and L-ascorbic acid ingredients; L.A.-based Youth to the Peoples pro-grade vegan Protect the Planet Refillable Minis Kit ($60); Goops Glowing Skin Bestsellers Kit ($79), which includes the Santa Monica-based skincare companys top three products (an exfoliator, face peel and super-powder); New Zealand-based clean beauty brand Emma Lewisham whose Skin Shield Daily Face Antioxidant Protect + Repair SPF 30 ($57) is packaged in 100% post-consumer-recycled container; the Beauty Chefs Glow Inner Beauty Essential, a powder-based vitamin whole-food supplement ($65); and Chanels La Solution 10 De Chanel moisturizer (1 ounce, $80), the latter of which Wechsler helped formulate as the luxury brands consulting dermatologist.

Beyond skincare and cosmetics, Grey said her company has seen a rise in wellness products during the last year. Weve sold a lot of vibrators, a lot of candles, she said, recommending Craves Vesper Vibrator ($69) and Heretics Dirty Grass Candle ($85). Its these rituals where youre taking care of yourself and youre getting present and in the moment and youre feeling some comfort.

However, carving out time for oneself, especially during the ongoing pandemic, can be quite a challenge, Grey said. I wish I could say I was better at practicing what I preach, she said, but I think its always been a struggle for me to find balance between work, myself, my family and particularly now with us all sleeping at our offices. Were not working from home anymore. Its like were sleeping at our office.

DRX Spectralite Faceware Pro by Dr. Dennis Gross, $435.

(Dr. Dennis Gross)

With limited time in our schedules for ourselves, Grey advises combining self-care tasks. I do a treatment while I meditate because a lot of these treatments take time, she said, adding that a few of her favorites include Dr. Dennis Gross DRX Spectralite Faceware Pro ($435), Hanacures all-in-one-facial starter kit ($29) and Leonor Greyls scalp treatment ($48).

You feel refreshed, Grey said of meditating, mentioning that she favors YouTubes various free meditation videos. I think a lot of people dont meditate because they feel like they dont know how to do it, or they try to sit still and they just cant because they have so many thoughts or distractions or whatever. Its just about sitting still. Even if you dont get into a deep unconscious meditative hypnosis, its still healthy to sit still and try to get even just a moment of being present.

Iris & Romeos 3-in-1 Power Peptide Lip Balm ($26) is available at irisandromeo.com.

(Iris & Romeo)

Keeping up a routine through this stay-at-home period is really vital, but its about connecting with yourself, said Michele Gough Baril, founder of Northern California-based beauty brand Iris & Romeo. Thats when youll feel calmer, grounded and connected. Having a modified beauty routine that makes you feel good, makes you feel connected but doesnt feel like a chore is critical. Its also important to get ready for yourself, not for others.

Gough Baril launched her brand in 2019 after a personal lesson in self-care. In 2012, she was head of marketing for Smashbox, but after she helped grow the former indie company into a global Estee Lauder-acquired brand, Gough Baril decided to step away from the beauty industry. I was completely burnt out, she said. I think this is really a common thing for a lot of women. We give so much, and we never take care of ourselves. And everything else comes first. Theres the needs of the family, the needs of the business, the needs of everything. It was really a time in my life where I hit that wall.

After a year of soul searching, Gough Barils created Iris & Romeo, which, she said, stands for all the things that I believe in sustainability, clean beauty; a brand that supports the burned-out modern woman and her mental, spiritual and emotional health.

Gough Baril launched just two skincare/makeup hybrid products in varying shades after exploring what makes [people] feel good. For me, its hydrated dewy skin and lips, she said. The brands Best Skin Days ($64) combines five products into one; its a serum, moisturizer and SPF that provides coverage and blue light/pollution protection. Women want a simplified routine, she said. What is the least you need to do to make you feel like the best version of yourself?

Chanels Rouge Allure Velvet Extreme matte lip color in Pivoine Noire ($40), left, and Rogue Allure Laque Ultrawwear shine liquid lip color ($40) are from the brands new Les Fleurs de Chanel spring/summer 2021 collection available at chanel.com.

(Chanel)

Gabrielle Coco Chanel used to say, If youre sad, add more lipstick and attack, hence the brands wide array of Rouge Allure ($40) lipsticks. However, Gough Baril said theres a time and place for a red lip versus her brands 3-in-1 Power Peptide Lip Balm ($26). For Chanel, it was about the power lip, she explained. That bold red lip has a psychological effect. I wear one when I go on VC meetings. Theres something about putting on a bold red lip that makes me feel like Im in charge. But for me, the modern woman, what shes going to use every day is a lip balm, a little hint of color.

Gough Baril acknowledged theres no need for lipstick beneath a COVID-19-era face mask but said Iris & Romeos lip balms add the perfect pop of color for video-conference meetings. You just need enough to make you feel polished and pulled together, she said. Even though youre wearing your sweatpants on the bottom; on the top, you want to have a little bit of [something]. It affects your mindset. It helps you pull yourself together and say, Im ready to face the day.

Although quarantine might seem like a good time to try new products, Wechsler warned that its important to listen to your skin as you experiment. If youre buying new product, test it out under a small area on your face for three nights or three days to make sure it doesnt bug you, she said. Dont make huge, drastic changes. If you have a reaction and you used five new things, then you dont know what its from. Just add one thing at a time if youre changing, and be weary of a lot of strong fragrance in some things. A lot of plant extracts are irritating. Just go slowly. One new thing at a time.

Also, buyer beware: adult acne has seen a rise during the pandemic. Some professionals have been quick to label it mask-ne, but Wechsler has a different theory. Stress is known to cause acne, she said. I do think certain [rougher] mask materials can irritate patients skin, and certain mask materials make people sweat more and may make them break out more. But I think its the stress more than it is the mask.

To combat the problem, she advised that people look at their sleep patterns or, as she called it, sleep hygiene. According to Wechsler, adults need 7 to 8 hours of sleep a night. We heal in our sleep, said the author of The Mind-Beauty Connection.

Wechsler suggests monitoring your bedtime habits. Theres no way you can turn off [the] news and fall asleep in 10 minutes, she said, recommending you take a break from technology two hours before heading to bed. Play a game. Read a novel. Watch a comedy. Have sex, she said, explaining that a stress-induced bad night of sleep can lead to a poor complexion.

She also recommended double checking your products. A patient will come in and say, I have not changed any of my skincare products but now Im getting this rash, she said, explaining that its often the result of noncomedogenic products. A comedo is a blackhead or a whitehead. [Noncomedogenic] essentially means it wont clog your pores and cause pimples.

Her top advice: make sure you wash your face when you come home from being outside and wash your mask after each use. Ive found a lot of people not doing that, she said.

Acne can also be treated with salicylic acid, which, Wechsler said, is a nice over-the-counter ingredient. Conversely, she doesnt recommend products with benzoyl peroxide. Its really irritating, she said.

Consider your alcohol intake to keep your skin looking fresh. A list of products from brands making sustainable wine and drink alternatives and additives includes Rescue Ros, left, Kin Euphorics Kin Spritz drink, Brighter sparkling drink and Renudes Chagaccino coffee boost.

(Rescue Ros; Kin Euphorics; Brighter; Renude)

Another consideration is alcohol intake. If you drink too much, your skin will be dehydrated, Wechsler said, adding that its not known if one type of beverage is better than another. Its theorized, but that study has not been done. She said that peoples cocktail preferences and its effects are individualized but that generally speaking, drinking too much can harm how one sleeps.

If you need a drink, opt for biodynamic, organic and sustainable wines. After all, wine is known to have healthy antioxidants in it, Wechsler said.

Our suggestions: Rescue Ros, a sustainable California ros wine from Los Angeles-based stylist and animal lover Nola Singer. The wine retails for $25 at rescuerose.com and benefits Los Angeles Love Leo Rescue, a nonprofit that aids animals in need.

Or consider swapping alcohol for a healthier beverage. Kin Euphorics Kin Spritz is a nonalcoholic spirit,made of adaptogens, nootropics and botanics, which includes a blend of fresh citrus, warm spice, hibiscus and ginger. A four pack is $27 at kineuphorics.com.

Another option is Santa Monica-based Brighter, a sparkling tonic with prebiotics, acetic acid and apple cider vinegar, which might be refreshing but also supports gut health. Sold in a 12-pack for $34.99 at brightertonic.com, Brighters flavors include lemon ginger turmeric and mlange.

Lastly, Chagaccino is a new mushroom and adaptogenic coffee additive from West Hollywood-based Renude that reportedly helps relieve stress, boost immunity and has anti-aging benefits because of its clean, plant-based, antioxidant-filled ingredients. Each box includes 10 packets for $29.99 at drinkrenude.com.

Hairstylist Ted Gibson says self-care begins by taming ones tresses. Hair can transform not only the way that you look but also the way that you feel, he says.

(Ted Gibson)

Celebrity hairstylist Ted Gibson said that for many women self-care begins with taming ones hair. Hair can transform not only the way that you look but also the way that you feel, he said, noting that many of the women who have come to Starring by TedGibson, his Los Angeles-based hair salon, were eager to make major changes to their hair during the salons pandemic reopening.

They felt like before COVID they were one woman and after COVID are another, he said, adding that theres a psychological connection between hair and ones mood. It does make you feel better when you walk past a mirror and your hair is done [even if] youre in a pair of sweats.

His clients often associate their hair with major milestones in their personal lives, he said. If you ask a woman of a certain age, What defines you?, shell definitely refer to different hairstyles, he said, and different periods of her life.

From top to bottom and left to right: Headbands and hair accessories from Lelet NY ($168), LeLe Sadoughi X Stoney Clover Lane ($195), Ulla Johnson ($65), Sarah J. Curtis ($17), Tarina Tarantino ($55) and Suryo ($71).

(Lelet NY; LeLe Sadoughi X Stoney Clover Lane; Ulla Johnson; Sarah J. Curtis; Tarina Tarantino; Suryo)

Gibson said this pandemic is no different, and there are a number of quick at-home tricks to add a bit of style without much effort. One easy option is to change your hairs part. If youre always used to having your hair down the center, change your part to the side, Gibson said. It gives a whole new kind of sophistication because a center part can be a little girl-next-door and then a side part could be just a little sexier.

Another fix? A hair accessory can always go a long way, Gibson said, adding that a headband or jeweled barrette can make a nice addition to a ponytail or messy top knot to add a little oomph to your next video call, romantic date night in the backyard or mirror selfie.

A number of fashion and accessory labels have options including LeLe Sadoughi X Stoney Clover Lane, Sarah J. Curtis, Lelet NY, Suryo, Ulla Johnson and Tarina Tarantino.

When it comes to daily hair maintenance, Gibson said that most of his clients say theyve been shampooing every other day, which he supports; however, he said that hair does need a daily styling refresher.

Starring by Ted Gibsons Shooting Star Texture Meringue, $52.

(Ted Gibson)

Whether your hair is curly or straight or you want it to be a voluminous blow dry or after you put in some really beautiful beachy waves and you want the hair to have a tasseled feel to it, Starring Shooting Star Texture Meringue is the product I go to, he said of the $52 weightless mousse he created to use as a universal styling tool. I needed something that I could pull out of my bag that I could use on Debra Messing, Gabrielle Union, Lupita Nyongo and Sandra Oh. He said he uses it on himself as well because of its provocative fig, coconut and amber scent.

For her part, Gough Baril is quick to point out that hair, skincare and beauty routines merely scratch the surface when it comes to daily wellness practices.

The emotional, the physical and the spiritual well-being of a woman is interconnected, she said. Self-care is not just a pedicure.

Link:
COVID self-care tips for skin, hair and overall wellness - Los Angeles Times

Skin Stem Cells Comments Off on COVID self-care tips for skin, hair and overall wellness – Los Angeles Times January 19th, 2021

Image: Steve Wrubel/Parfums Christian Dior By Chloe Pek August 14, 2020

The beauty expert counts Bella Hadid and Kim Kardashian amongst her clientele

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When it comes to facial massages, celebrity facialist Joanna Czech has that magic touch. Counting Hollywood and runway bigwigs like Bella Hadid, Kim Kardashian, Jennifer Aniston, Cate Blanchett, Kate Winslet, Liam Neeson and more amongst her star-studded list of clients, Joannas skincare treatments are highly coveted internationally.

Now, the skincare expert is adding another credential to her portfoliojoining the House of Dior as a skincare ambassador and lending her expertise in developing the Dior skincare techniques international training.

In an interview via Zoom, Czech told us she had her reservations about joining Dior Skincare at first. I mean, theyre famous for make-up and fashion. I couldnt put my name next to fashion skincareIm very particular about that. Then, I heard about how the Capture Totale range stimulates cell energy, so that changed everything and my skin as well.

Czech, who originally planned to go to medical school in her schooling years, fell in love with skincare when she enrolled in the Aesthetics Institute and never looked back. However, she has remained inquisitive and fascinated with science. This is evident from her holistic approach to beauty, which combines both traditional techniques and cutting-edge technology.

See also: The Best Beauty Launches In August 2020

Adenosine triphosphate (ATP, the main carrier of energy for cellular activities) is responsible for the very first mitosis of cells. It is human physiology that production of ATP drastically drops at around seven years old, and the energy keeps slowing down. So any treatment or product that would stimulate cell energy is fascinating to me.

Culminated from Diors decades-long research into stem cells, the Capture Totale line is infused with a regenerative floral complex of Madagascan longozo, Chinese peony, white lily, and Chinese jasmine, which help to re-energise stem cells rather than replenish them.

Dont believe a product that says it contains stem cells because the stem cells are not alive within the product. Only stem cells that are directly re-injectedand most likely come from your bone marrowworks, Joanna explained, debunking one of the most popular beauty fads in recent years.

With the expert on the line, we took the opportunity to ask our burning questions about maskneand skincare misconceptions.

What is a skincare philosophy that you live by?

Respect, support and protect. This goes for skincare, how we treat ourselves and others.

Your all-time favourite Dior Skincare product and why?

The Capture Totale C.E.L.L. Energy Super Potent Serum because it contains the most concentrated version of the cell energising complex and acetylated hyaluronic acid. It creates hydrated, plump and radiant skin. If you are consistent, you see results in days. My skin has never looked better.

A common skincare mistake many people make?

In my opinion, its using toner. Thats a misconception because still, many people use a toner as the second step of cleansing as opposed to the first step of treating the skin, and this is from my experience of talking with clients.

They put toner or micellar water on a cotton pad and they keep wiping and seeing more make-up. If you see more make-up on your cotton pad, that means you need to go back into washing.

Toner is very often misunderstood or skipped, and it shouldnt be. I cant imagine, for instance, applying a serum on my face without applying toner first. There is no way the efficacy of the product will be the same if you have not applied a toner. Depending on the toner, they offer hydration and sometimes micro-exfoliation, but mainly they are used to maintain the pH of the skin. The optimal pH for our skin is 5.5, and many factors from our diet to lifestyle, and even washing our face can throw the skins pH off the scale, so it's very important to balance it back.

See also: Lancme's Celebrity Make-Up Artist Lisa Eldridge & Neelofa Share 5 Beauty Tips

With face masks becoming part of everyday life, maskne has become a real problem. How can we prevent these breakouts?

When you wear a mask, it creates a micro-climate and we keep breathing carbon dioxide back and forth, so there is not enough of anti-bacterial oxygen getting into the skin. There is sometimes too much moisture happening, so we will get super hydrated initially, and then get quite dehydrated right after. Thats when you will experience eczema and redness.

What I recommend is keeping the skin as clean as possible before wearing the mask, with just a balancing toner, and protecting balm or healing ointments to lubricate areas where the mask could potentially irritate the skin. Very often, its on the nose bridge, as well as on the side and behind the ears.

For less reactivity, I wouldnt go through with the whole routine, but if you have to, I would advise starting your routine earlier so the products are on your skin for at least 30-40 minutes. If you will be stepping out shortly, reduce the routine and skip some steps. But no matter what, never forget about your SPF because the friction of the mask could also get rid of our stratum corneum and create little scabs, causing discolourations.

Then, as soon as you arrive home, take the mask off, wash your face, and again balance your skin with toner and use your serums.

What are your tips for soothing breakouts or eczema caused by wearing masks?

Even with microscopic breakouts, I would continue using any product that is hydrating because sometimes we misunderstand we have a breakout and then we try to use benzoyl peroxide, or everything that is dehydrating. No, your skin would be producing even more sebum. So keep hydrating your skin with soothing ingredients like colostrum and hyaluronic acid.

Your skincare routine?

My morning routine is very brief: cleanser, toner, a serum and then there is moisturiser. For my night time routine, my very first step is getting into the shower when I get home. I begin with massaging my body with my shower gel and silicone gloves under the shower, then I apply products like multi-vitamin oils and sometimes micro-exfoliating toners all over my body.

Then, I go to my face. I usually dont wear any make-up, so I start right away with my cleanser with some massaging movements and I remove it with a linen washcloth, followed by a toner. My favourite way of applying toner is the sponge techniqueinitially, you spread the product on your face, and then you press and release. When you press, your skin microscopically opens and when you release, the skin grasps whatever is on the surface.

After the toner, I use my serum. Ive been using the Capture Totale C.E.L.L. Energy Super Potent Serum since September. If you have weaker areas like forehead lines and nasolabial folds, these are the areas I would concentrate longer on, followed by an eye cream and moisturiser. Thats usually my five-step basic routine.

About twice a week, I do facial masks, one of those quick ones because Im the kind of New Yorker who only has five seconds for myself. But no matter how busy or tired I am at night, I would never forget about my skincare routine. Your skin is 60 per cent more potent to absorb everything during relaxation and rejuvenation time. So if you dont take care of your skin at night, you might as well forget doing anything in the morning. Twenty-five per cent of our immune system is within our skin, and we can improve that percentage of our health with products chosen for your skin condition and consistent skincare.

See also: Sulwhasoo's Ginseng To Achieve Skin As Flawless As South Korean Superstar Song Hye Kyo's

You work with many notable clientswhats the most common skincare problem celebrities deal with and treatments that they request for?

Celebrities have exactly the same problems as we do. The only one little difference is that celebrities tend to wear more make-up and more often than some of us, usually under the heat of theatrical or film lights, so they need a lot of hydration and rebalancing. Ive been called to the movie set many times to help soothe their skin with algae masks, or any cooling and hydrating treatments.

Their needs are equal to ours. They want to work on their facial contours and ensure their skin is as evenly textured as possible so their makeup looks perfect, so I would offer some mild exfoliation, perhaps micro-currents for targeted muscle stimulation, and maybe manual massaging to stimulate blood flow to create the sort of rosy healthy oxygenated looking skin. Many people call it a red carpet facial but I call them ordinary facial because every woman wants the samesmooth hydrated skin with nice cheekbones, beautiful jawlines, and thats what really works.

See also: Beauty Talk With Aznita Azman, Founder Of Nita Cosmetics

The rest is here:
Dior Skincare Ambassador Joanna Czech On Her Self-Care Routine And How To Prevent Maskne - Tatler Malaysia

Skin Stem Cells Comments Off on Dior Skincare Ambassador Joanna Czech On Her Self-Care Routine And How To Prevent Maskne – Tatler Malaysia August 15th, 2020

Adam Smith (1723-1790) was not who you think he was. I'm talking about the original Adam Smith who wrote The Wealth of Nations (1776) and spent most of his life in Edinburgh, Scotland. The more recent "Adam Smith" - nom de plume of the late George Goodman who wrote The Money Game (1967) - bears much more resemblance to the Adam Smith you think you know.

The first Adam Smith would have had little interest in stock market wisdom because he regarded himself as a moral philosopher rather than an analyst of markets. In fact, he was not even a capitalist. His works do not include the words "capitalist" or "capitalism" because neither came into use in his lifetime. The first mention of "capitalism" in print was in the 1854 novel The Newcomes by William Makepeace Thackeray, whose father had been involved with the East India Company. Karl Marx, oddly enough, helped popularize the term in his classic Das Kapital (1867). The irony is that if Marx did not quite invent the concept of capitalism, he certainly made the term popular in the process of opposing and bashing it.

No one can know what Adam Smith would have thought about free market capitalism as presently practiced, nor can we guess what he would have thought about the aftermarket in shares which we call "the stock market." The first stock exchanges came into being a couple of years after his death and shares were traded in only a small handful of companies including the still extant Bank of New York (NYSE:BK). Security trading over Smith's lifetime was concerned primarily with credit instruments, the exceptions being one-off exchanges organized by and for the British and Dutch East India Companies. So no capitalism, no market opinions from Adam Smith. Sorry to have to tell you.

The primary interest of Adam Smith was the goal which gave his book its full title - an inquiry into the nature and causes of the wealth of nations, in short, the well-being of the general populace. Counterintuitively paired with this was the self-interest which led tradesmen and the early industrialists to seek profit. He used the term "invisible hand" only three times in his writing and just once in The Wealth of Nations, to wit:

The rich consume little more than the poor, and in spite of their natural selfishness and rapacity, though they mean only their own conveniency, though the sole end which they propose from the labours of all the thousands whom they employ be the gratification of their own vain and insatiable desires, they divide with the poor the produce of all their improvements. They are led by an invisible hand to make nearly the same distribution of the necessaries of life which would have been made, had the earth been divided into equal portions among all its inhabitants, and thus without intending it, without knowing it, advance the interest of the society, and afford means to the multiplication of the species...the beggar, who suns himself by the side of the highway, possesses that security which kings are fighting for."

This is the central core of Adam Smith's thinking. It has always interested me that the ultimate goals of Adam Smith and Karl Marx did not differ greatly. The important difference is that Smith believed in freedom of the market while Marx believed that the solution was the top-down mandate of a command economy. We are familiar at this point with the general course of events in top down economies. The 20th Century resolved that question definitively in favor of Smith's view, which we now call capitalism.

Smith, however, never imagined a world with an after-market of securities measured by such things as price earnings ratios and discounted free cash flow. He would have been astonished at the use of these and other forms of analysis central to modern markets including shares of corporations with thousands of shareholders and many millions of shares. The few larger businesses in his day - a few early industrialists and the enormous East India Companies - did not lend themselves to that kind of analysis.

Does that mean that the thinking of Adam Smith is useless in trying to understand value in the modern financial markets? Not at all. Smith's model of the invisible hand contains a clue as to the way he might have valued companies and their shares. In fact, the view of Adam Smith may take us back to the primary purpose of capital markets which focus on start-ups, IPOs, unicorns, perhaps even SPACs, and all companies in their early stages. Such companies seek capital with which they aspire to bring innovations. They hope to profit by serving the unmet and often unrecognized needs of a body of potential customers.

What Smith saw was the intricate interplay between the needs and desires of customers and the self-interest of a risk-taking capitalist. That is the core transaction of the capitalist system. Without so much as a glance at discounted future cash flow, Smith implicitly understood that for a business the important thing was the population for which a business might add value. The issues for the entrepreneur involve the accuracy of their estimate of that market, the share of that market they might expect to win, the revenues they might expect to receive, and the profit margin they might expect to realize on those revenues.

In short, Adam Smith's thinking may not ordinarily be very helpful in the after-market we call "the stock market" but is central to the universe of young and innovative companies. It is directly connected with the way businesses and customers are conjoined. What a business does for its customers, he implies, provides an outline of its ultimate value. For this reason, I see the conjunction of businesses and customers as potentially useful in thinking about leading companies in the current market, especially for those companies which cannot be analyzed usefully by the standard market metrics of sales, margins, earnings, PE, and discounted cash flow.

In Adam Smith terms, a company should be worth a reasonable return for what it contributes to the greater good of the general populace. This single sentence is at the heart of what I am calling the "Adam Smith Model" of valuation. Does it actually work when trying to value innovative companies? Can one make decisions based on this model? To a large degree I think it is the only really helpful approach in valuing companies driven by new products and concepts.

To show how this sort of analysis might work, I will start with my daughter's portfolio of innovative biotech companies, which she put together in the early days of the pandemic. It is a pretty good model of the kind of thing I have always kept a careful distance from. Her surprising success with this portfolio prompted my own internal debate.

My daughter is a bright young woman who will soon turn 50. She has a doctorate in art history from Penn but retrained as a nurse in order to live in the woods in western Massachusetts and raise her children as a single mom close to nature and away from urban centers. Her life is modeled more on Thoreau's Walden than on Ben Graham's The Intelligent Investor. Despite sitting at my dinner table for seventeen years she remained almost entirely ignorant about financial markets until recently. The after-market in stocks seemed to her insufficiently serious to deserve her attention, which might well have been Adam Smith's view had he lived to see it. I confess to having had similar thoughts myself at times but have suppressed them.

In recent years, however, prompted by the realization that she may one day retire and need an income, she has begun to take an interest in markets. Around the beginning of the COVID-19 crisis (on which she had early insight and much sound advice), she put together without telling me a portfolio of biotech companies. She did this on a very small scale. Over four or five months she is up well over 200%, an amount I have never made in anything like that period. Here's an excerpt from an email she sent me on her portfolio:

Yes, that's why I like leronlimab - CytoDyn (OTCQB:CYDY). It has many uses, a high safety profile (I don't give a second glance to drugs with a low safety profile-anyone could have seen that with hydroxychloroquine, and now dexamethasone-which is a broad-target immunosuppressant, hence will never be a commonly used drug for Covid). Leronlimab has a great safety profile and works with a known mechanism vs. the cytokine storm. Anything good for Covid (or the other viruses that are still around: SARS, MERS and Ebola) must not suppress the immune system as a whole (as do all steroids such as dexamethasone). Leronlimab is targeted at the CCR5 receptor-which makes it effective for coronaviruses as well as cancers and autoimmune disease. Amazing for metastatic cancer, including prostate (though the recent studies are on a hard to treat breast cancer), and probably other untreatable but common cancers. It's going to be great for HIV. It's going to work for host vs graft disease (post-transplants, when we go back to doing them). It also appears to work for NASH (non-alchoholic fatty liver disease, which has increased dramatically in numbers, but is silent in most people until it is at a late stage.) It is the next diabetes.

Mesoblast (MESO):

The next wave of medical advances are going to come through better understanding of immunomodulation. Most if not all diseases-including cardiac disease and diabetes--will come to be understood as inflammatory diseases to be manipulated at the cellular level. We will see more and more of these diseases due to our inflammatory (sedentary, antioxidant-deprived) lifestyle and toxic environment. In any case, I'm interested in the companies who are leading the way in specialized research in immunomodulation. Mesoblast is using stem cell technologies to repair the immune system, and applying that technology to many untreatable diseases.

Avalon GloboCare (AVCO):

Same argument as Mesoblast: multiple technologies, targeted immunotherapy. I'm not so interested in any single technology, but they are partnering on several important technologies (stem cells, diagnostic technologies), with broad implications and clinical uses. They are partnering to develop a nasal vaccine for Covid, but again, I'm not as interested in that particular product, but the broader technology. Nasal vaccines are going to be a winner for many reasons-ease of use, global application, and the fact that we will run short on syringes for other vaccines).

Altimmune (ALT):

Same as above: leader in NASH (non-alcoholic fatty liver disease), nasal vaccine technology

Okay, those are my four picks. Amazing for metastatic cancer, including prostate (though the recent studies are on a hard to treat breast cancer). The others, JNJ, Becton Dickinson, and DaVita, you know."

I love the fact that my daughter comes at investing from an angle so different from mine and with a skill set that does not overlap mine at all. I also love that its method combines brains and a good heart - the assumption that a company is worth the sum of what it contributes to human well being. What I find most intriguing is that her natural way of coming at things aligns so closely with the Adam Smith view. Can growth investing possibly have such a simple foundation?

You will probably have guessed that I have never bought anything like these biotech companies nor used anything resembling this kind of analysis. I do not, and could not possibly, recommend any or all of them. They are well outside my areas of knowledge and expertise. The only counsel I was able to give my daughter included the fact that when buying companies like this you should probably buy a basket of them - something which she had already done, intuitively.

By early July she had tripled her money and was beginning to be worried about what felt to her like an overhyped sector of an overpriced market. This was where she thought my advice might be useful. I laughed and said that she should be giving me financial advice instead of vice versa, but if she was nervous she should probably sell down to her comfort level (she's in a low tax bracket so cap gains aren't a problem). Perhaps she should at least sell down to the point at which she was investing with house money. I added that it was okay to leave a few chips on the table and let her long term bet ride. She agreed and did something close to that.

Her insight had been pretty simple. The value of a company should correspond to the amount of value added via the "invisible hand" to the health, happiness, and well-being of its customers - perhaps even to the general populace. You would start by estimating the size of the market for which it provided a product or service. You would then adjust to take into account the competition for that market and finally the probability of your particular company capturing a major part of that market. Then, and only then, you might begin to make rough estimates as to potential revenues and profit margin. The key correlation is not revenue and profit margin, which are well out in the future, but the value the company is likely to add to society. The payoff in small biotechs like these, if it comes at all, is likely to come in a rush when a large pharma company sees the potential and buys them out, fulfilling the Adam Smith projection of appropriate reward for a large service.

When I started to formulate it this way, I realized that I have missed quite a lot in never owning stocks which might be best measured in this way. This includes not just small biotechs and niche technology startups but also giant current market leaders such as Amazon (AMZN), Netflix (NFLX), and Tesla (TSLA). At every point in the lives of these three companies, I have found that the methods by which I have always valued stocks - things like discounted earnings, dividends, and cash flow - made me unable to put together any reasonable argument for owning them.

Had I finally stumbled upon a valuation model that might provide a rationale for buying them? Up to this point, I have not seen a persuasive methodology for thinking about the value of these companies. Could this simple approach account for their unusually high valuations?

Adam Smith implied that the relationship between a business and the population it served was the invisible force behind what we call capitalism. It takes only a small further step to propose that the population served by a business can also be described as an "asset" owned by that business. In some cases, especially young or innovative companies, it is customers acquired that is the central asset. The idea of a business "owning" its customers is not new. I first read about it in a novel at least fifty years ago when a literary agent retires by essentially selling his customers to a rival - a practice that was apparently commonplace even then.

This customer-based approach seems to be the way the founders of these three market leaders looked at the opportunity. Customers weren't just part of the picture. They were the whole thing. Acquiring customers is what these companies set out to do. Everything else could come later. They were determined to do everything it takes to own the largest number of customers, including running their businesses with negative earnings and free cash flow for a long time. The market caught on to their goals and their prices shot up to the stratosphere.

Amazon, Netflix, and Tesla have always sold at ridiculous multiples of earnings and cash flow, if any, and are ridiculously expensive by pretty much every other traditional measure. When you look at them the way my daughter looks at biotechs, however, the picture changes. You set the standard ratios aside and instead ask: what is the value of these companies if measured by the sum of value they provide in service to their actual and potential customers? The transmission of that value to shareholders is initially as invisible as the invisible hand by which value is distributed to the populace. It is nevertheless reflected in the stock price.

Here's how one might do a broad estimate of value for the three companies:

Today, online commerce saves customers money and precious time," writes Bezos. "Tomorrow, through personalization, online commerce will accelerate the very process of discovery. Amazon.com uses the internet to create real value for its customers and, by doing so, hopes to create an enduring franchise, even in established and large markets.

We believe that a fundamental measure of our success will be the shareholder value we create over the long-term. This value will be a direct result of our ability to extend and solidify our current market leadership position. The stronger our market leadership, the more powerful our economic model.

Because of our emphasis on the long-term, we may make decisions and weigh tradeoffs differently than some companies... We will continue to make investment decisions in light of long-term market leadership considerations rather than short-term profitability considerations or short-term Wall Street reactions...We aren't so bold as to claim that the above is the 'right' investment philosophy, but it's ours, and we would be remiss if we weren't clear in the approach we have taken and will continue to take.

From the beginning, our focus has been on offering our customers compelling value," explained Bezos. "We brought [customers] much more selection than was possible in a physical store (our store would now occupy six football fields), and presented it in a useful, easy-to-search, and easy-to-browse format in a store open 365 days a year, 24 hours a day."

That's Amazon's mission statement summed up in a few paragraphs. The guiding purpose to this business model is positioning yourself to "own" more and more customers. This customer-obsession of Bezos amounts to is a manifesto for innovative companies. The second paragraph flows directly from the core principle of Adam Smith. Get first things first, Bezos is saying, meaning understanding the potential market and seizing it. Profitability and measurements commonly used by Wall Street come later.

Amazon is no longer a young company in chronological age, but the vision embedded in its mission statement is to remain a young company forever. A Day 1 company, as Bezos calls it, is always visionary and entrepreneurial in its thinking. What Bezos is saying to investors is: disregard the numbers used by Wall Street analysts. They are important measures only for Day 2 companies (slow-moving, mature companies in stasis, for which the next stage is death). Keep your eyes on the main thing - the growth of your customer base and a high level of customer satisfaction. Facebook (FB) and Alphabet (GOOG)(GOOGL) were like that in early stages but moved fairly quickly to address the question of how to monetize their users, eventually succeeding and becoming measurable by ordinary metrics. They are now ordinary growth companies with moderately high PEs, at least in context of the current market. Bezos rejected early monetization. Have faith, he said. We will monetize our customer base when we get around to it.

The greatest single risk for Amazon is its increasing size, which makes it difficult to remain nimble and full of energy. At some point, it will face the horror which confronts history's great empires - running out of worlds to conquer. Political constraints may have something to do with that, but pure size is the major burden. Summing it up, I would buy Amazon at something like 50-60% of its present price if nothing had gone wrong in the business in the meantime.

2. Elon Musk somehow manages to top Bezos. His manifesto, much of which comes out in random statements and tweets, is that Tesla will one day produce pretty much every car sold in the US, maybe even the world. At the very least it will be the driving force in a new industry. His business has a powerful technological core, but the rational for it is the prospect of capturing much of the total customer base for vehicles. It currently appears to be priced on the assumption that Musk will succeed in this ambition to a large degree.

Musk is confident that Tesla's technology will become the universal standard and squeeze most of the current auto industry into terminal decline. Its panache stems from great aesthetics and the promise of enlisting his customers in the project of slowing climate change and helping save the world. Tesla, he implies, will almost incidentally become highly profitable, an outcome to which Musk himself seems to be personally indifferent but in which his investors might have some interest. If he is right, Tesla will probably look cheap if bought today or tomorrow at 160 times its current (and first annual) positive earnings.

Like Bezos, Musk would have us remember: we don't care about all that. That's the old valuation model. What we care about is a market of 17 million vehicles sold annually in the US and a number around five times that in the world. That's the scale of customers Elon wants to own. Once that happens, he will bite the bullet and monetize.

To own Tesla at anything like the current price you have to make a few audacious assumptions. You have to believe that vehicles will continue to be bought on very large scale and that the overwhelming number of vehicles sold will become electric within a short period of time. You then have to believe that Tesla will become the company that owns most of the customers and sells most of the vehicles. It's not impossible, but there are obstacles to overcome.

If Ford, GM, Toyota, Honda and others launch a modestly successful counterattack, or the whole market shrinks, you will see the earnings and cash flow multiples of Tesla shares contract in the general direction of the valuations of those "Day 2" companies. In other words, if you are an investor, you don't want Tesla to become just another car company, nor do you want it to be the last giant in an industry that is contracting and possibly dying. If one of those things happens, Tesla, as measured by the Adam Smith premise, is likely to be a disappointing investment. This is very broad brush analysis, but that's the only way to really deal with Tesla, a company quite similar to my daughter's biotechs. The risks for Tesla seem high and hard to calculate. These are the problems routinely faced by innovative companies in their early stages, and you must also pay attention to the risk that Tesla could run out of time to overthrow the industry while the industry still exists in its present form.

3. Netflix is a company I have looked at only recently. Until a few months ago I had never used their product - not once. Entertainment is OK - I'm being entertained by writing this, and I dare to hope that you readers are both entertained and stimulated to further thought by it - but I didn't experience Netflix until a millennial step child and her husband spent some time with us and promptly realized that they couldn't live without it. They put it on a couple of our TVs so that they would have some kiddie movies to bribe their 3-year-old to eat dinner plus an hour of decompressing entertainment for themselves before sleep.

A few months ago my wife and discovered that we still had it, linked somehow to their home two thousand miles away, and it turns out that the shows are pretty good. They turned out to be especially valuable during the lockdown. We had run out of old movies, so we started over with Netflix. I started paying attention to articles on Netflix and ultimately took a look at their numbers.

Egads! They have been unprofitable from day one and their negative cash flow has done nothing but increase. Their costs for content are going up and their competition is mounting. On the other hand, Stranger Things is the kind of nitwit escapism that I found that I like after a long hot day teaching tennis (my wife not so much).

How do I put the two views of Netflix together. In this case, the risks and uncertainties make the stock uninvestable for me. For one thing, I am used to having entertainment piped into me for free (I automatically tune out all ads.) The numbers needed are just too daunting for Netflix, the rising costs for content are worrisome, and ultimate limits in a market now sliced several ways implies limits to growth. I am doubtful that Netflix will ever morph into a company I can measure more conventionally. I'm pretty sure I wouldn't renew if our faraway relatives stopped providing it for free. That's the core of it: I'm a customer of sorts, but they don't really own me. I don't own them either, and am not likely to any time soon.

The outperformance of high growth companies over the last decade and most spectacularly over recent months has naturally invited vigorous debate. The catastrophic dot.com crackup exactly two decades ago has receded sufficiently that alt explanations of market behavior are once again beginning to be proposed in earnest. This article is perhaps one of them but exists within the frame of traditional methods.

The dot.com era which reached its peak in 2000 crashed amidst assertions that eyeballs and clicks were better measures of value than earnings or cash flow. I lived through it as a bystander, listening to fellow fitness enthusiasts in the workout room at my tennis club boast about their portfolios, then noticing their absences one by one as the crisis unfolded. I didn't feel schadenfreude, far from it, only relief that I myself had not been ruined.

Valuations are once again at a point which calls ordinary prudence into question. Are the traditional models of valuation no longer worth using? This was suggested recently by BlackRock quant Jeff Shen who argued here that traditional efforts to solve the "mystery" of value are worthless. The Shen view, by the way, derives from this article by another BlackRock analyst, Gerald T Garvey, published in the prestigious Journal of Portfolio Management. The Garvey article comes down firmly on the growth side of the growth/value debate arguing that "elevated percentage value spreads predict higher risk, not higher returns."

In more down to earth terms, Shen and Garvey are saying that companies whose shares haven't been able to grow in this environment are losing ground and possibly dying, and should be avoided. If a stock goes up a lot it is probably safe because the wisdom of crowds is behind its rise. This is the kind of statement that is true until it isn't. Shen goes on to argue that contemporary investors should look for alt indicators and models such as the happiness of a company's employees. That particular idea didn't exactly blow me away, and neither Bezos nor Musk seem to be proponents of using that principle to focus or drive their businesses.

On the other hand, an effort to measure a company's success in terms of the overall value it provides to its customers does seem to me an interesting way to think about growth companies. Most companies trading in the aftermarket for stocks - by now you know that when I use this awkward but accurate phrase I am referring to the "stock market" - are not high growth companies and are probably best analyzed by traditional measures. Ultimately some form of traditional value measurement must appear within the life-cycle of a successful company.

To Jeff Bezos, the moment when traditional cash measures become important to a company is the day that it wakes up as a Day 2 company, a company that does not attempt to reinvent the world afresh every morning. While such a company may still turn out to be a decent investment, it's important for value investors to pay careful attention to their risk of having their business disrupted by new technologies and methods. This is a fairly straightforward way of thinking about the world we now live in, and I have learned to ask the hard questions about everything I own - even companies with seemingly strong moats.

Disruption is a major theme of the contemporary world, and every thoughtful person would do well to put the world together afresh every morning. Even with an open mind, it's hard to anticipate what hidden risks might cause a company's current defenses to collapse. Because of the incredible speed of change and the prevalence of unsuspected collateral effects, this questioning is important in a way that it has never been in the past. That was the important lesson number two from the dot.com event. Buying the disruptors rarely made fortunes, but not being sufficiently cautious about potential disruptees was a good way to lose a fortune.

For these businesses the Adam Smith Model needs to be turned upside down so that it becomes a story about loss of customers. One of the great anecdotal examples was Bill Gates stunning a 1990s gathering of Buffett's value investor pals by using his knowledge of the digital world to inform them that Eastman Kodak (KODK), then a market stalwart, was "toast." The customer criterion proves its importance when inverted. I was unable to estimate the outcome for Amazon - haven't made a nickel directly by buying it - but it was obvious to me instantly that it was going to be the end of the road for many other retailers, as well as many malls and REITs. The history of Sears Roebuck and Walmart were powerful precedents. The only thing not entirely clear was the time frame, which is proving to be much faster than most people expected.

The astonishing thing was how eagerly investors jumped on the Amazon bandwagon, which has many uncertainties, and how slowly the investor mind adjusted to the knock-on effects, which were far more certain. The key to grasping this quickly, is to focus on customers "owned" but sure to slip away, as in the case of Kodak.

The Adam Smith Model is simply one of the ways of making an estimate concerning what the cumulative value should be somewhere down the road at whatever time the company decides to monetize the cash value of owning its customer base. At that point, it will begin to report profits and cash flow, pay dividends, and buy back shares. Apple (AAPL) may be the best current example of this model. It started paying dividends and buying back shares about a year before its growth began to level off. As the dream of perpetual growth disappeared, investors were rewarded by the cold cash that abundantly flowed.

This is the distant event that Bezos' mission statement grudgingly projects. For Bezos, earnings, dividends, and buybacks are Day 2 concerns, and you get the feeling that he would just as soon not live to see them. Being a Day 2 company, is like living a comfortable and happy life: the great second-best award for those who have given up their aspirations to greatness. So Apple was once an innovative company priced on the basis of the Adam Smith Model and has now normalized into a Day 2 company which can be valued by the traditional tools. Who knows, maybe it has a few positive tricks up its sleeve but relentless regular growth is a thing of the past.

Amazon seems to be on the same general course as Apple, but with ordinary shareholder gratification deferred into a less well defined and more distant future. You just have to wait for it, and at an incredibly low discount rate such as the current Treasury rates you are willing to pay up for the ultimate awards now and wait a long time. This is part of the current market infatuation with rapid and persistent growth. If you project very far into the future, the value may approach infinity, or since that concept no longer exists even in physics, you could approximate it by the difficulty Amazon would have if Amazon's business became the major part of the gross product of the planet.

High valuations in the current market can be partially explained by a number of factors including historically low interest rates and the appeal of the tech leaders during a broad public lockdown. It also true, however, that the most optimistic thinking stems from a gambling mentality which is supported by the famous Petersburg Paradox which has come to bear in their valuations. There are a number of recent articles with varied approaches to this subject, and you can sample them by googling Petersburg Paradox.

The Petersburg Paradox is generally credited to Daniel Bernoulli, who published an article on it in 1738, but is sometimes credited to his cousin Nicolaus Bernoulli who talked about it in a letter written in 1713. It is a simple gambling game that doubles your winnings with each successive throw of tails. Its expected return generates an infinite series of events the probability of which decline by the exponential 1/2 to the N power exactly offsetting the exponential increase in winnings (2 to the N power).

Each successive term is exactly 1. The mathematically expected return is the sum of that infinite number of ones. I suppose that this means you max out when the number in dollars is equal to the number of bits (or Planck units) in the universe.

This series, therefore, produces quite large expectation of winnings despite the fact that the probability of large winnings at any particular future point obviously diminishes enormously and becomes very slight after a few coin tosses. It is famous for the contradiction of the expected total return and the relatively small amount that any reasonable person would be willing to wager on that return. A number of mathematicians have attempted to resolve this contradiction - economist and quant Paul Samuelson having been one of them - but their efforts at refutation have been unsatisfying.

Recent articles have related the Petersburg Paradox to investor expectations for stocks with high and persistent earnings growth. An extremely smart and interesting article was published way back in 1957 by David Durand (The Journal of Finance, Vol 12, No 3, Sep 1957, pp 348-363). Durand explored the problem of valuation for growth stocks including the then relatively new approach of using multiple discount rates at various break points in time. The growth numbers are quaint - annual growth at numbers like 5 and 6.5% - chickenfeed compared to growth rates of modern high tech companies.

Durand related the question of pricing long growth periods to the Petersburg Paradox, addressing the infinity problem and the need to truncate the infinite series at some point. This has a parallel to the problem of valuing current growth companies where it is necessary to consider not only forecasts for future earnings growth rates but also the length of waiting time before cash flows and dividends appear. There's also the question of the interest rate used for discounting, which is now virtually nil but has been very significant at times in the past.

The Adam Smith Model happens to dovetail nicely with the distant outcomes of the Petersburg Paradox coin flip game. The further away the payout is from the present the larger the rewards become when you finally throw heads. It's just that in the case of fast growing but not yet profitable companies, you more or less defer the chance of hitting heads early in order to let the reward build exponentially and have the promise of hitting a very large summative outcome in the future. That's where the thinking of investors in Amazon, Tesla, and Netflix must come from, and it's more or less rational if their estimate of the payoff and the time necessary to achieve it are reasonably accurate. It has been pretty accurate in the case of Apple.

There's just one more thing, of course. What if the estimate of Adam Smith value proves to be outright wrong? What if a tough new competitor with a better technology or improved business model appears? What if competition already in place proves to be more formidable than assumed? Even with Amazon these risks must be taken into account, but with Tesla they should be major concerns, and with Netflix they should be very major concerns.

There could also be exogenous risks such as a major rise in interest rates which would wreck the denominator and greatly reduce the value of a distant payoff. That high denominator, by the way, was what drove price earnings ratios in the 1970s down to the single digits. Returns even a few out years were so heavily discounted that no one wanted to look that far into the future. This sort of thinking served to greatly diminish the appeal of growth stocks.

Innovative companies don't always work out. I thought about that a lot around the year 2000, when I attached a 95% probability to my belief that the investing world had lost its collective mind but reserved a 5% probability I was the one who just didn't get it. The odd thing is that some of the new model dot.coms did, in fact, contribute quite a bit to the general welfare. They made all sorts of businesses more efficient, and at the same time made basic communication for everyone cheaper, faster, and better. This is presumably a good thing. In the end, however, it didn't work out well for shareholders who held on long term.

But there's another question. Did their temporarily outrageous valuations represent a magical mechanism for pulling forward a proper reward for founders and the most nimble shareholders despite the fact that the companies themselves were destined to never ultimately earn any money? In a just version of Adam Smith's invisible handsome reward was certainly owed to the founders and early owners who contributed so much to human well being but the mechanism by which they received it is somewhat murky,

So what if that deferred payoff never comes?

Schopenhauer asked a similar question in his Studies in Pessimism, except that he asked it about death, not a sudden gush of cash flow. Calm down, Schopenhauer argued. Why fear death? If you knew it wasn't the end of things, that you would wake up tomorrow morning feeling fine, you wouldn't worry about it much. What about waking up next week? What about next year? What about five or ten years out? What about a thousand years before you wake up? Ten thousand? What about... never? Would it make a difference?

Schopenhauer's courage in the face of non-being is reflected in the large number of investors who seem unworried about the possible absence of cash returns many years into the future. Once you take the Schopenhauer premise, it doesn't matter if the payoff never arrives. The stock is going up today in anticipation of it. That's all that really matters. Shareholders are happy. You can always cash out at your convenience. What is the future anyway but a dwindling infinite series?

It's really more like heaven than death. Both of my grandmothers believed strongly in its existence, although I can't imagine what they really thought it would be like. It probably didn't matter. In both cases, it sustained them over the course of long and productive lives which they lived with great confidence of a wonderful if not precisely defined eternity. Ignorance was bliss.

A business is its customers. Is it as simple as that? The value of a business is the value of the services provided to its present and prospective customers discounted for the distance in time to monetization of those customers but discounted to reflect the possibility of various things that could happen to reduce or wipe out that future payoff. Both new and rapid growth businesses generally defer that payout further into the future than most businesses, especially if the discounting factor is relatively low.

This model produces huge winners and abject losers. We marvel at the winners when we see them without considering survivor bias. We discard the losers even if they have played a major part in the evolution of the economic world and traded at high prices in optimistic moments along the way. In retrospect we wonder why they once traded at such high prices.

In very young industries such as biotechs, the outcome often leaves losers by the way side and rewards just one or two competitors. One way of thinking about this is that at the outset many such companies own a similar probability of surviving but one or two end up "owning" most of the customers and the cash flow bonanza that will eventually come with them. The probability of winning gradually shrinks for most but rises for the winners. For that reason, my daughter's approach of buying a basket of these companies is probably the best way for investors to participate.

This approach may also be very helpful in evaluating growth companies which are not new but remain at some distance from giving investors serious cash rewards. Here the method for selecting a basket of winners draws upon the kind of broad-brush estimates and calculations used in selecting a basket of small biotechs. If looking closely at Amazon, Tesla, and Netflix doesn't help much, it's important to make and constantly update estimates bearing upon the scale and strength of their "ownership" of customers as well as rough estimates of risks. This broad and approximate approach is how Adam Smith would probably have looked at valuation of companies if he was as interested in profits as we sometimes assume him to have been.

Disclosure: I am/we are long JNJ, BDX. I wrote this article myself, and it expresses my own opinions. I am not receiving compensation for it (other than from Seeking Alpha). I have no business relationship with any company whose stock is mentioned in this article.

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.

The Black Friday sales are almost among us, meaning the halls of your local department store are about to become a battleground. (The smartest of shoppers know the key to maintaining sanity is to do it all online.)

But when faced with deals and discounts from every angle, its crucial to keep your cool. You dont want to panic-buy all those as-seen-on-Instagram products before youre covered the essentials you know, the things you'll use day in, day out, until they're empty.

Resist those shiny, sparkling impulse buys (although yes, that glitter lipstick would look pretty good on NYE), and youll come out triumphant with a well-curated skincare edit that will keep your skin happy long after the last Quality Street has been polished off.

So, skip the scrolling and head straight for the good stuff this year. Here, discover the eight most unequivocally iconic beauty products we've spotted in the Black Friday sales. Trust us: you cannot go wrong with any (or all) of these heroes.

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1Soleil Tan De Chanel

Chanel

WAS 40 NOW 36

Soleil Tan de Chanel is the kind of product beauty dreams are made of. The weighty pot will last you all year, while the lacquered, double-C engraved pot will look incredibly bouji on your dressing table.

But of course,it's what's on the inside that really counts, and boy is this a brilliantly formulated bronzer. Unlike literally anything else on the market (many brands have tried and failed to 'dupe' it), this dense, mattecream can be picked up with a powder brush, dusted under or over foundation, and swiped strategically to carve out killer cheekbones it's revolutionary.

2Blanche Eau de Parfum

Byredo

WAS 110 NOW 93.50

Byredo's perfumes are coveted the world over, but with so many to choose from, you'll be hard-pressed to find a favourite without some kind of divine intervention.

Our advice? Head straight for Blanche, which is a byword for the crispest, cleanest scent you'll ever spritz. Forget cloying talc notes or blink-and-you'll-miss-it citrus: this is pure violet and musk-tinted freshness, like the cleanest cotton sheets that ever were.

And seeing as there's a very generous 15% discount (thank you, Liberty), maybe treat yourself to the body wash, too.

3The Rich Cream

205.00

WAS 205 NOW 174

The hype around Augustinus Bader's debut product was remarkable across the world, A-listers and beauty editors fawned. (Victoria Beckham even tapped him up to create her debut skincare product.)

Turns out, this clever cream really delivers. The secret is the Trigger Factor Complex, which works to kick-start the natural healing process of the body's stem cells. 30 years of research and development have clearly paid off.

4Bronzing Powder

Narsasos.com

WAS 31 NOW 24.50

The name of many a Nars product precedes its performance Orgasm, anyone? But not this one: the brand's Laguna and Casino bronzing powdersare famed for their supreme performance alone.

Both illuminate without relying on glitter (which always looks fake), and are warming without imparting those giveaway ruddy undertones.

Paler skins are destined for Laguna, while darker tones will love Casino. Your bank balance will love either.

5Diorshow Pump 'N' Volume HD Mascara

DIOR

WAS 28 NOW 25.20

Ask any beauty editor what their ride-or-die mascara is and you'll get...a lot of conflicting opinions.

Like the perfect shade of red lipstick, a favourite mascara is a subjective thing. After all,few can deliver perfection when it comes to length, volumeand colour. Enter Dior's Pump 'N' Volume: the mascara to unite us all. (And yes, it's the one with the no-wastesqueezy tube.)

6Do Son Eau De Parfum

Diptyque

WAS 120 NOW 96

Many of Diptyque's fragrances could be considered iconic, but Do Son is the one that'll see you being stopped by strangersin the street.

The tuberose trail is enticing enough, but it's the unusual addition of orange blossom and jasmine that take things to truly memorable heights. A spectacularode to its namesake beach, in Vietnam's Ha Long Bay.

7Ruby Woo Matte Lipstick

WAS 17.50 NOW 14

If you're a 'lipstick person', you already know about this one. You've likely got one stashed in your bag right now, as well as one on your dresser, and an 'emergency' onefloating around your bedroom somewhere.

So good it's never been successfully imitated, MAC's Ruby Woo is the ultimate lipstick. A true red, it's neither too orange or too blue, and there's no skin tone it won't look beautiful against.

8Glow Tonic

WAS 18 NOW 15.30

We all know that alpha-hydroxy-acids are the gold standard when it comes to resurfacing, but so many require a degree in dermatology to use correctly.

Forgo the faffing in favour of Pixis cult Glow Tonic: it might look cute, but its packed with 5% brightening glycolic acid alongside soothing aloe vera. Simply sweep it over cleansed skin nightly no brow-furrowing required.

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Most nights, Marcia Dunlap attaches seven or eight leeches around her husband John's eyes as part of an effort to restore some of his vision. Tom Bailey/The Commercial Appeal

With the help of his wife Marcia, John Dunlap receives his nightly leech treatment at his home in East Memphis. Marcia places several leeches on his face in an effort to increase pressure in his left eye. In conjunction with stem cell treatment, the Dunlaps hope that one day John may be a viable candidate for a procedure that could return some of his vision.(Photo: Jim Weber/The Commercial Appeal)

At home most evenings, Memphis, Tennessee, attorney John Dunlap, 80, unbuttons and removes his white dress shirt and counting his steps and remembering which way to turn carefullywalks with a tall white canefrom the living room to the dining table, where his wife Marcia has a plastic container of leeches.

Twenty-six months ago,the couple's schizophrenic sonAndrewattacked them in theirhome. The injuries blinded Dunlap. He's in total darkness.

After drapinga large, peach-colored towel around John's neck, Marcia reaches into the water for the skinniest leeches. Those are the hungriest and most likely to latchonto John's face.

One at a time, she gently presses four leeches to the skin around John's left eye and three around the right. She waits patiently wait for eachto bite and stay connected to John's skin.

"You can feel a bite,'' he says. "A little, stinging bite... And then after awhile you don't feel anything.''

The Dunlaps have carried out this unusualroutine60 or so times since December. It's a type of therapy prescribed by a Los Angeles doctor who offers experimental stem cell therapy designed to regenerate tissue.

"In the beginning he made it very clear he's not anophthalmologist and not an eye surgeon but he had had some success with stem cells in treating blindness. It's experimental,'' Dunlap said.

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The doctor prescribed the leech therapy as a preliminary step because, Dunlap said, the leech enzymesenhance the blood supply to the eye and nourishthe eye tissue.

The left eye had atrophied, or withered. The idea wasto restore health to the eyebefore the stem cell treatment. There is no right eye, but the hope is that the leech enzymes will help revive that optic nerve in case a transplant is ever possible.

Since the leech therapy,the pressure in the right eye has improved significantly, Dunlapsaid, referring to follow-upexams. The retina, which had folded into an ice-cream cone shape after the trauma, has begun returning to its normal shape, he said.

Even though he still cannot see out of the left eye and the optic nerve remains severed from the retina, Dunlap said, "I now have a live eye.''

The Dunlaps decline to identify the California doctor, describing him as a"humble'' person whodoes not seek the publicity.

With the help of his wife Marcia, John Dunlap receives his nightly leech treatment at his home in East Memphis. Marcia places several leeches on his face in an effort to increase pressure in his left eye. In conjunction with stem cell treatment, the Dunlaps hope that one day John may be a viable candidate for a procedure that could return some of his vision.(Photo: Jim Weber/The Commercial Appeal)

Andrew, the Dunlaps' mentally ill son, is charged with attempted murder and domestic assault, and remains in jail awaiting trial. Thecouplehave told authorities that they mainly want Andrew to receive mental health treatment.

The Dunlapshave experienced tragedy long before the 2015 assault.

Their son Jeff, one of four children, was a St. Jude Children's Research Hospital patient who died of cancer at age 10, in September 1974.

Dunlap recalls a return car tripfrom Knoxville, where he and Marcia had been visiting grandchildren shortly after he was released from rehab.

"As we were driving back I started thinking of all the things I won't get to do again. In my mind, I was going down the list,'' he said.

It would be a long list, including some leisure activities he loves. An avid Cubs fan, heenjoyed attending spring training games in Arizona. A passionate golfer, he enjoyedwatching how the ball flew when he struck it well.

But Dunlap stopped himself from completing the list of losses, telling himself, " 'You don't want to dwell on that'. . . It's as if the Lord sent me a message that hit me across my forehead, saying, 'John, get over it. It could be a whole lot worse.'

"Anytime I want to start thinking about the things I'm missing or not doing what I used to do, I think 'Get over it. Move on'.''

Sudden blindness is such a change in lifestyle. "I guess some people may feel the world has ended for them, but it hasn't,'' he said.

Marcia Dunlap gets special leeches for her husband John's nightly treatment from the laundry room where she keeps it out of sight. Marcia places several leeches on his face in an effort to increase pressure in his left eye. In conjunction with stem cell treatment, the Dunlaps hope that one day John may be a viable candidate for a procedure that could return some of his vision.(Photo: Jim Weber/The Commercial Appeal)

The stem cell and leech therapy is expensive and not covered by health insurance. Some have expressed their skepticism about the legitimacy of the experimental treatments.

"You have some people who are concerned for you, that your approach is not going to be effective,'' Dunlap said.

"Yet, several folks up herehave said, 'John, I'd take a shot at it. It is expensive but you're the one with the white cane and the one who is blind and has to live with it. You have everything to gain and nothing to lose.'''

While some might be concerned about the unusual treatments, many others are inspired by the Dunlaps,saidBlanche Tosh, a fellow church member and friend since high school.

"I have told them so many times, 'You just can't begin to know the lives you have affected,'' Tosh said.

"I know so many people who look at the way they are dealing with multiple things. How could anybody endure that and just go on and be pleasant and make it from day to day with the consistent attitude that the world sees.

"You are not going to find many people whoever see one of them without a smile,'' Tosh said.

She was inspired to start a gofundme account (gofundme.com/johndunlapvision) to help coverthe Dunlaps' expenses. As of midweek, $8,795 of the $100,000 goal had been raised.

Memphis lawyer John Dunlap and his wife Marcia continue to search for some medical procedure to restore at least partial vision after John was blinded a few years ago when their mentally ill son attacked him. (Photo: Jim Weber/The Commercial Appeal)

Since December, Dunlap has undergone two-and-a-half rounds of leech therapy and two series ofstem cell treatments. The couple traveled to California in June for the most recent stem cell procedures, and returned home with stem-cell eye drops and injections.

Nowthey are in the middle of the leech therapy they resumed this summer.

John has a follow-up exam next week, when he will learn if there's been continued progress from the stem cell and leech therapies.

The California doctor "indicated it would take two to three months to see if we were getting any results from stem cell therapy out there,'' Dunlap said. That time could come sometime this month or in September.

If the stem cell therapy has not worked by then, he said,"We'll just have to see what any third plan looks like, and the cost involved.''

Late in life, Dunlap has been forced to learn to type, work a computer, navigate with a cane, count the steps and memorize the turns from one spot to another, communicate with Siri, and smile as blood-sucking leeches dangle from his cheeks.

Asked about his sources of inner-strength, he responded, "I don't know I'd call it inner-strength.

"I can tell you I certainly believe in the Lord. We pray daily. I appreciate the prayers of others. I think it certainly is a faithissue.''

He also credits his late mother, Cora, a single parentwho managed a grocery. "She was a very optimistic, loving person,'' he recalled.

"And I've had Marcia's support. Marcia wasn't going to let me give up, just sit down and do nothing.''

The Dunlaps are starting to consider resuming their annual trips to Cubs spring training in Arizona. Maybe next spring.

"You may have your vision by then,'' Marcia told John.

"I might,'' he responded."We'll see.''

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Will putting leeches on his face help this blind man see? - USA TODAY

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Distinct growth factors promote the survival of specific types of motor neurons in the spinal cord, according to a study led by Georg Haase, of Aix-Marseille University in Marseille, France. The results suggest that these factors may work together to provide trophic support to motor neurons in the CNS and therefore, a combination of them may be needed to protect motor neurons damaged by disease.

Growth factors have always been tantalizingly attractive in ALS, said Nicholas Boulis of Emory University Medical School, who was not involved in the study. But the problem is, there has been a failure of growth factors to perform [in the clinic]. This study provides tangible evidence that you may be able to get a bigger effect by combining growth factors.

The study appeared on March 16 in the Proceedings of the National Academy of Sciences.

Neurotrophic Factors in ALS: The power of two+

Sorting out ALS. George Haases team at Aix-Marseille University in France used a FACS-based method to identify NTFs needed to protect distinct classes of motor neurons in the developing lumbar spinal cord. Now, the researchers are adapting this method to determine which of these substances may be needed to protect adult motor neurons, including those affected by ALS. The results may help clinicians develop neuroprotective treatment strategies tailored for the disease. [Courtesy of Schaller et al., 2017, PNAS]

Researchers first turned to neurotrophic factors (NTFs) in the early 1990s as a potential therapy for ALS in hopes to promote the survival of motor neurons damaged by the disease. But initial therapies proved ineffective in part due to delivery challenges (see Rogers, 2014).

In more recent years, neuroscientists discovered that many of these growth factors may work together to provide trophic support for motor neurons and promote their survival at least in the developing spinal cord (see Gould and Enomoto, 2009). But how these substances orchestrate this process remains an open question.

A growing number of researchers suspect that there may be distinct classes of motor neurons that are protected by distinct NTFs during development. To test this hypothesis, Haases team at Aix-Marseille University in France isolated motor neurons from the developing lumbar spinal cord in the mouse and determined which growth factors supported them.

To carry out this analysis, first author Sbastien Schaller and colleagues dissected out lumbar spinal cords at day E12 and suspended the tissue. Then, they used fluorescence-activated cell sorting (FACS) to isolate the motor neurons, cultured them and exposed them to combinations of neurotrophic substances.

The technique enabled motor neurons to be specifically captured from embryos by using Hb9:GFP mice, originally developed by Columbia Universitys Thomas Jessell in New York, which express GFP in motor neurons in the developing central nervous system.

100% of the cells expressed the motor neuronal markers ChAT and SMI 32, and none expressed interneuronal markers, indicating the exquisite purity of the isolated cells, said Haase. That, combined with the methods speed and degree of automation, make FACS-derived motor neurons a promising platform for future studies, he said, including screening for potential ALS therapies.

A combinatorial approach? Beginning in the early 1990s, researchers developed potential neuroprotective therapies for ALS that delivered single neurotrophic substances. But according to a new study, multiple NTFs may be needed to promote the survival of motor neurons affected by the disease. [Courtesy of Schaller et al., 2017, PNAS]

Next, the team exposed motor neurons to 12 different neurotrophic factors (BDNF, NT3, GDNF, neurturin, artemin, persephin, CNTF, CT1, LIF, HGF, IGF1, and VEGF), alone or in combination. Individually, all NTFs promoted neuronal survival after 3 days in culture, with GDNF being the most effective (43%). HGF, however, protected only about 20% of motor neurons in culture. But when HGF, CNTF and artemin were combined, motor neuron survival reached nearly 50%.

The effects were additive, explained Haase. That suggested to us that each [of these growth factors] were supporting a subset of motor neurons.

To test that hypothesis, the researchers used subtype cell surface-specific antibodies to label three major subsets of motor neurons from the lumbar spinal cordthe medial motor column, which innervate axial muscles, the lateral motor column, which innervate limb muscles, and preganglionic, which synapse with downstream neurons of the autonomic motor system. They then used FACS to separate each subtype, and exposed them to HGF, CNTF or artemin.

They found that each of these NTFs promoted the survival of distinct classes of motor neurons in the lumbar spinal cord. For example, HGF preferentially supported survival of motor neurons in the lateral motor column neurons, key motor neurons affected by ALS.

The effects were mediated by distinct neurotrophic factor receptors decorating the surface of each type of motor neuron, explained Haase. When we blocked the HGF receptor, we completely blocked the survival effect of HGF. That means these motor neurons depend on this particular factor for their survival.

Additional analysis indicated that CNTF and artemin protected other types of motor neurons located elsewhere in the spinal cord.

Lateral thinking. HGF promotes the survival of motor neurons that innervate the limbs through a c-Met-mediated mechanism at least in the developing spinal cord (Schaller et al., 2017). The neurotrophic substance is the basis of Viromeds VM202, a gene therapy-based strategy now being evaluated at the phase 1/2 stage (Sufit et al., 2017). [Image: Emw, Wikimedia Commons.]

Together, the findings suggest that these substances provide trophic support and promote the survival of specific types of motor neurons in the developing spinal cord.

This is a very high-quality paper that helps clarify the field, said Clive Svendsen of Cedars-Sinai in Los Angeles, California. Until now, it was not clear that distinct subsets of motor neurons may respond to their own subsets of growth factors.

Motor neurons that could potentially include those that descend from the brainstem, and those involved in breathing, also affected by the disease.

The results suggest that combining growth factors may offer more therapeutic benefit than single factors in ALS according to Nicholas Boulis.

Svendsen agreed. This is suggesting that for therapies, if you want to protect motor neurons, you may have to expand to include multiple growth factors, Svendsen said. However, he noted, and as confirmed in this study, GDNF by itself is still perhaps the most powerful all-around survival factor for motor neurons.

Svendsen is now developing a potential therapy for ALS that uses genetically engineered neural stem cells to deliver GDNF to the spinal cord. The Phase 1 clinical trial is soon to be launched (see October 2016 news).

Neuroprotective therapies: the next generation?

The next big question, which this paper leaves open, according to Svendsen is whether the growth factors identified in this study protect motor neurons in the adult nervous system.

Haase agreed. This is a critical question, and we are adapting our method to look at this now.

A stem cell-based approach? Haases team previously developed a FACS-based technique to isolate reprogrammed motor neurons generated from human iPS cells (Toli et al., 2015). The approach could be used to identify key neurotrophic substances that promote the survival of patient-derived motor neurons. [Image: Reprogrammed sALS motor neuron, Alves et al., 2015. CC BY 4.0].

Some neural circuits change drastically during adulthood, while others stay pretty much the same, so weve got to do the experiments to find out, explained Svendsen. But I will probably be trying HGF soon in my own experiments.

In the meantime, said Haase, it is important to keep in mind that the growth factors found to be less effective in this study should not be ruled out as potential therapies. They may act sequentially during development, or may require co-factors to exert their effect which were not present in our growth medium, he said.

It is also important to keep in mind that this study did not evaluate the ability of any of these substances to regenerate axons, a key goal in terms of developing therapies for ALS and other motor neuron diseases including SMA.

The challenges of delivery, which have stymied the field to date, remain paramount, Haase also noted. Gene delivery approaches with adeno-associated vectors have been studied for single growth factors, but if several are needed, a larger-capacity vector, such as lentivirus, may be required, according to Boulis. Multiple rounds of ex vivo gene therapy to equip stem cells with multiple growth factor genes, would be another option, followed by surgical implantation of the modified cells.

Further exploration in in vivo models and patient-derived iPS cells are an important next step to determine which combination of these substances could be of the most benefit, added Boulis.

But despite these challenges, Boulis agrees this approach is worth considering. As a surgeon who does translational work on the application of growth factors to ALS, this may be an Aha! moment.

Reference

Schaller S, Buttigieg D, Alory A, Jacquier A, Barad M, Merchant M, Gentien D, de la Grange P, Haase G. Novel combinatorial screening identifies neurotrophic factors for selective classes of motor neurons. Proc Natl Acad Sci U S A. 2017 Mar 21;114(12):E2486-E2493. [PubMed].

Toli D, Buttigieg D, Blanchard S, Lemonnier T, Lamotte dIncamps B, Bellouze S, Baillat G, Bohl D, Haase G.Modeling amyotrophic lateral sclerosis in pure human iPSc-derived motor neurons isolated by a novel FACS double selection technique. Neurobiol Dis. 2015 Oct;82:269-80. [PubMed].

Further Reading

Rogers, ML. Neurotrophic Therapy for ALS/MND. New York: Springer New York; c2014. p. 1755-85. (Kostrzewa RM, editor. Handbook of Neurotoxicity.)

Gould TW, Enomoto H. Neurotrophic modulation of motor neuron development. Neuroscientist. 2009 Feb;15(1):105-16. [PubMed].

disease-als gdnf HGF neuroprotection neurotrophic factor topic-clinical topic-randd VEGF

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Neurotrophic factors in ALS: a winning combination? - ALS Research Forum

IPS Cell Therapy Comments Off on Neurotrophic factors in ALS: a winning combination? – ALS Research Forum April 8th, 2017

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Challenges in identifying the best source of stem cells ...

Cardiac Stem Cells Comments Off on Challenges in identifying the best source of stem cells … October 26th, 2015

Stanley, Kan. — It’s a special Valentine’s Day gift for Jake the dog.  His family gave him a stem cell treatment that they hope will extend his life.

Jake is an 11-year-old yellow lab.  He’s been part of the LeBlanc family since he was a puppy.  Jake’s owner, Elizabeth LeBlanc, calls him her “first baby.”  But then Mia and Aidan were born and at ages eight and five years old, they love to play with Jake.

When the LeBlanc’s noticed Jake was having trouble getting around they wanted to help.  They tried medication, but say it didn’t work for very long.  Then Mia saw a segment about a stem cell treatment for dogs on t.v. and asked if they could get it for Jake.  The LeBlanc’s called their veterinarian and found out the Stanley Veterinary Clinic in Stanley, Kansas is the only place in the metro where they can do the entire procedure in house.

Dr. Les Pelfrey, D.V.M. explained the procedure.

“We’re going to collect about 20 grams of fat surgically and then we’re going to process it in our lab here in house then we’re going to reintroduce those stem cells after we activate them back into the affected joints,” said Dr. Les Pelfrey.

The procedure can cost $3000. The dog’s fatty tissue has to be sent off to a lab for the stem cells to be extracted.  But at the Stanley Veterinary Clinic they can process the stem cells in their own lab, cutting the cost to $1800.00.

Jake’s arthritis is affecting his hips, knees, one elbow and one shoulder.  Dr. Pelfrey made an incision and removed the fatty tissue from Jake.  Then veterinary technician Stephanie Pierce took it to the lab to break it down, cook it and then spin it.  The final product?  Stem cells that were then re-injected into Jake’s joints to help him grow cartilage.  Pierce says Jake will “act like a puppy again as far as moving around.”

The LeBlancs can’t wait to see the results.

“For 12 years he’s given us love and joy so we just want to give him a better quality of life,” LeBlanc said.

Jake will spend the night at the Stanley Veterinary Clinic.  He should be able to head home tomorrow.  Jake and the LeBlancs should notice results in the next few weeks.

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Dog Receives First-Ever Stem Cell Therapy in Kansas City

Uncategorized Comments Off on Dog Receives First-Ever Stem Cell Therapy in Kansas City February 15th, 2012