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America’s largest cryptocurrency exchange, Gemini, now allows its users to buy cryptocurrencies like bitcoin (BTC) with Apple Pay and Google Pay.
According to Thursday’s announcement, Gemini users can now link their debit cards to Apple Pay or Google Pay to purchase cryptocurrencies with fiat currency on the platform. The company said users’ money will be available for withdrawal one hour after purchase.
The new functionality is available for more than 30 cryptocurrencies supported by Gemini, including major coins such as BTC, Ether (ETH), Litecoin (LTC) and Bitcoin Cash (BCH), as well as Ethereum-based tokens such as Aave (AAVE), Dai (DAI) and Maker (MKR).
The Twins did not disclose the cost of buying cryptocurrency via Apple Pay Google Pay. The platform deducts 3.49% of the total purchase amount on debit card deposits, while bank transfers and cryptocurrency deposits are free.
In recent months, the cryptocurrency industry has evolved in terms of increasing integration with traditional financial payment services like Apple Pay. In February, leading cryptocurrency payment processor BitPay announced a large-scale Apple Pay integration that allows its users to log into Apple Wallet and pay for goods and services using digital coins such as BTC, ETH, and LTC. Payments company Simplex also allowed Apple Pay users to buy the cryptocurrency ThCOTI in March.
frequently asked questions
Can you buy bitcoins with Apple payment?
like buying a handkerchief.
Is Google paying for crypto-currencies?
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Conversion for the Sega Master System (Mark III) written and released by Sega in 1987. Released in Japan as "Double Target - Cynthia no Nemuri"
Converted for the Commodore 64 by Sega: Produced by Jonathan Dean, Music by David Whittaker. Published through Activision in 1987.
Converted for the ZX Spectrum by Probe Software: Programming by Antony R. Lill, Graphics by Nick Bruty. Published through Activision in 1987.
Converted for the Amstrad CPC by Probe Software: Programming by Anthony Heartley. Published through Activision in 1987.
Admittedly, this isn't one of Sega's most successful games of all time, particularly when it comes to the home conversions. However, due to its limited exposure, I thought Quartet would make for a nice alternative against all the more obvious games, and besides, there aren't too many games that begin with the letter Q that would be interesting enough to fit into the blog. But what makes Quartet a properly interesting game is the fact that it was released just a bit after Atari's Gauntlet - another four-player action game was doing high profit in both the arcades and home computers. Not too many game companies would have the guts to try and achieve the same level of success with something quite a bit different. As you might already know, the home conversions of Quartet left a lot to be desired on every platform, but can you really blame the conversion teams for their attempts?

domain: entertainment


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Vitamin D receptor gene polymorphism, serum 25-hydroxyvitamin D levels, and risk of vitiligo: A meta-analysis.
Medicine (Baltimore). 2018 Jul;97(29):e11506. doi: 10.1097/MD.0000000000011506.
Zhang JZ1, Wang M2, Ding Y1, Gao F2, Feng YY1, Yakeya B1, Wang P1, Wu XJ1, Hu FX1, Xian J3, Kang XJ1.
1 Department of Dermatology.
2 Department of Gastroenterology.
3 Department of Gynecology, People's Hospital of Xinjiang Uygur Autonomous Region, Urumqi, Xinjiang, China.
- Vitiligo is associated with low vitamin D (nothing about treatment) – meta-analysis March 2016
- Vitamin D Receptor in vitiligo skin activated by UVB – May 2018
- Spotty skin coloring (vitiligo) treated by augmenting topical tacrolimus with oral Vitamin D – Oct 2016
- Video by Dr. Coimbra – 95 percent of auto-immune cured with vitamin D in high doses - April 2014
- Vitamin D has treated Multiple Sclerosis and autoimmune diseases for 16 years – Coimbra April 2018 -Note: Vitiligo is an auto-immune disease
Subsequent Meta-analysis of Vitiligo and vitamin D in blood found a much smaller assocation
Decreased circulatory levels of Vitamin D in Vitiligo: a meta-analysis - 2021
Download the PDF from VitaminDWiki
Increased risk of Vitiligo if:
Low Vitamin D in blood
Poor Vitamin D Receptor which restricts Vitamin D getting to skin cells
Increase intake of Vitamin D
Increase VDR activation (see below)
Autoimmune category starts with
190 items in Autoimmune category
- Vitamin D and MS Asthma RA Diabetes Gut Allergy Hay Fever Lupus Psoriasis
- Predicted 95% autoimmune cured by HIGH-DOSE vitamin D - 2014
- 10% of the UK have Autoimmune Diseases - Lancet May 2023 PDF is behind a paywall
- Increase in 20 years : coeliac disease 2.19 X. Sjogren's syndrome 2.09, and Graves' disease 2.07
- All 43 references are FREE on-line
- The BEST Nutrient for Autoimmune Conditions (Vitamin D) - video May 2022
- Autoimmune disease clusters run in families having low D
- How Vitamin D reduces inflammation, improves immunity and fights autoimmunity – review Dec 2018
- 120 doctors and 20,000 MS patients using high dose Vitamin D Dec 2018
- Vitamin D has treated Multiple Sclerosis and autoimmune diseases for 16 years – Coimbra April 2018
- Vitamin D Receptor is associated in over 58 autoimmune studies
- More autoimmune disease if higher pollution or lower UVB - Feb 2023
- Many autoimmune diseases associated with low vitamin D or poor Vit D genes – July 2019
See also web: consensus that ~50 diseases are autoimmune, ~50 more are suspected:
Vitamin D Receptor category has the following
499 studies in Vitamin D Receptor category
Vitamin D tests cannot detect Vitamin D Receptor (VDR) problemsSee also:
A poor VDR restricts Vitamin D from getting in the cells
47 studies in the Resveratrol category
It appears that 30% of the population have a poor VDR (40% of the Obese )Health problems include: Autoimmune (
Several diseases protect themselves by deactivating the Vitamin D receptor. Example: Breast Cancer
- - - - - - - -
The Vitamin D Receptor is associated with many health problems
18 studies), Breast Cancer ( 20 studies), Colon Cancer ( 13 studies), Cardiovascular ( 23 studies), Cognition ( 16 studies), Diabetes ( 24 studies), Hypertension ( 9 studies), Infant ( 21 studies), Lupus ( 6 studies), Metabolic Syndrome ( 4 studies), Mortality ( 4 studies), Multiple Sclerosis ( 11 studies), Obesity ( 16 studies), Pregnancy ( 24 studies), Rheumatoid Arthritis ( 10 studies), TB ( 8 studies), VIRUS ( 34 studies), Click here for details
Some health problems, such as Breast Cancer, Diabetes, and COVID protect themselves by reducing VDR activation
A poor VDR is associated with the risk of 55 health problems click here for details
The risk of 48 diseases at least double with poor VDR as of Jan 2023 click here for details
Some health problem, such as Breast Cancer reduce the VDR
VDR at-home test $29 - results not easily understood in 2016
There are hints that you may have inherited a poor VDR
Compensate for poor VDR by increasing one or more:
Increasing Increases 1) Vitamin D supplement Sun
Vitamin D in the blood
and thus in the cells
2) Magnesium Vitamin D in the blood
AND in the cells
3) Omega-3 Vitamin D in the cells 4) Resveratrol Vitamin D Receptor 5) Intense exercise Vitamin D Receptor 6) Get prescription for VDR activator
Vitamin D Receptor 7) Quercetin (flavonoid) Vitamin D Receptor 8) Zinc is in the VDR Vitamin D Receptor 9) Boron Vitamin D Receptor ?,
10) Essential oils e.g. ginger, curcumin Vitamin D Receptor 11) Progesterone Vitamin D Receptor 12) Infrequent high concentration Vitamin D
Increases the concentration gradient
Vitamin D Receptor 13) Sulfroaphane and perhaps sulfur Vitamin D Receptor 14)Butyrate especially gut Vitamin D Receptor
Note: If you are not feeling enough benefit from Vitamin D, you might try increasing VDR activation. You might feel the benefit within days of adding one or more of the above
Far healthier and stronger at age 72 due to supplements Includes 6 supplements that help the VDR
Increased risk associated with a poor Vitamin D Receptor
Note: Some diseases reduce VDR activation
those with a * are known to decrease activation
OBJECTIVES: To explore the relationship among the vitamin D receptor (VDR) gene polymorphisms, serum 25-hydroxyvitamin D levels, and vitiligo.
Databases including PubMed, Cochrane Library, Ovid, Web of Science, CNKI, SinoMed, and Wanfang Data were systematically searched. The association was assessed using odds ratios (ORs), standard mean difference (SMD), and 95% confidence intervals (CIs). The statistical tests were performed using Review Manager 5.3.3.
We identified a total of 17 studies. The relationship between VDR gene polymorphisms (BsmI, ApaI, TaqI, and FokI), serum 25 (OH)D levels, and incidence of vitiligo was investigated. The results of this meta-analysis showed that the
- dominant genetic model (CC+AC vs AA, P = .007, OR = 1.41, 95% CI = 1.10-1.80),
- recessive genetic model (CC vs AC+AA, P = .01, OR = 4.10, 95% CI = 1.36-12.35), and
- allelic contrast model (C vs A, P = .005, OR = 1.87, 95% CI = 1.21-2.90)
- of VDR Apal locus increased the risk of vitiligo, and BsmI, TaqI, and FokI loci and the risk of vitiligo have no obvious correlation.
Serum 25 (OH)D deficiency was positively associated with the incidence of vitiligo (P < .0001, SMD = -0.94, 95% CI = -1.39, -0.48).
This meta-analysis revealed that VDR Apal polymorphism increased the susceptibility risk of vitiligo, and there is a positive correlation between serum 25 (OH)D deficiency and the incidence of vitiligo.Vitiligo (spotty skin coloring) is 4 X more likely if poor Vitamin D Receptor – meta-analysis July 2018
5707 visitors, last modified 17 Apr, 2021,This page is in the following categories (# of items in each category)

domain: literature


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I have spent some time over the summer exploring Park Hill. On site, spending time in the gardens, drawing, walking, photographing. Exploring the estate’s perimeter, and it’s relationship with the areas around – enclosed, impermeable, hemmed in on one side by railway and tram and trunk road, on the other by a low wall, cracked pavement and low rise, un-regenerated 19th century shops (mainly empty) and housing (poor quality). At the top of the site, large parts of Park Hill are empty, fenced off, awaiting redevelopment. Those glimpses through the site reveal a wasteland of unkempt laws and litter. There’s an uncanny correspondence between the abandoned, unmaintained former grassed areas of this area, overgrown, brownfield land, and the newly laid-out wildflower meadows of the redeveloped quarter. There’s something important to unpick here, something that feels like the Hauntology Mark Fisher has written about, the slow spectral failure of an imagined future.
What struck me most about the site was the emptiness of it all. Even in the sculpture garden, I sat for many hours without seeing a soul. At lunchtime a young couple sat down to eat their sandwiches, uncertainly, hesitatingly choosing a spot to picnic. Indeed, I too wasn’t sure – whether I could sit, whether the omnipresent CCTV cameras would summon some kind of private park warden to instruct me to keep off the grass. But no one came.
When I strayed beyond the site, the emptiness continued. I walked the nearby streets, the emptiness feeling at times threatening, at times sad. A fenced off walkway ended in a shooting gallery of syringes, a stroll through the carefully restored elegance of Norfolk Park ended in the empty concrete footprints of the three demolished tower blocks which complimented Park Hill, once.
Of course, no one knew where I was, I was lost in a wilderness, of sorts, on this ramble.
I took some photos, at times over exposed on my phone-camera, the bright sunshine of the hottest summer since the 1970s bleaching out the differences between old and new, causing a ’squint test’ (so beloved of the original redevelopers) that elided the differences. From the sculpture garden, everything seemed rosy. I made some drawings too. Mainly of the landscape, of the sculptural quality of the landscaping. The mature trees which remained, survivors of the redevelopment (I would later come across images of newly minted saplings in the archives). Wildflowers in bloom (carefully chosen species, of course). Gravel paths, an uncertain, hesitant newness to the site. Here and there concrete steps negotiating the changes of levels, survivors of the rather more concrete landscape originally provided. Archaeology in reverse – acres of asphalt covered in earth and wildflower.
Now I am exploring two archives – early press photographs of the buildings original construction, and the extensive planning documents available online. My hope is to understand the way this building – and its landscape has been imagined, and presented. How it has been codified to be understood by others, what the attempt was.

domain: artistic


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One of the country's largest padi seed suppliers that bagged a government contract has conceded his company did not meet the tender criteria , but pointed out that others are in the same boat.
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domain: news


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just so you know: you are more than enough & you are not too much.
There is little I believe in more than the power of a woman’s story.
Discover the one that speaks perfectly-and-powerfully into yours!
There is a Sacred She who chooses you, who walks alongside you, who offers you . . . everything.
When I received my SacredReading from Ronna, I kinda figured it would come with some ancient women’s wisdom. I didn’t know it would be STEEPED in it! From the first page to the last, it spoke to an area of my life where I had substantial questions and doubts. Somehow, some way, the whole Reading addressed them all. I’m a VERY private person, so there is no way Ronna could have known what to mention or how to address it. Spirit is alive and well in her Readings making sure you get just the right message, clarity and hope at just the right time.Lena West
This moment in time requires that we tap into the power of the women who’ve marched before us and have done the things we want to accomplished. Women need women and that’s what I’ve found in Ronna Detrick’s SacredReadings. Give yourself that gift. This woman will be your sister, your confident, your model, your supporter…Let’s dive into their stories so that we can shed light on ours. Let’s keep their legacy so that our legacy will stay alive.Vanessa Mentor
I just received my Sacred Reading from Ronna. It moved me so deeply, I had to stop reading mid-way to feel everything it brought up. It couldn’t have been more ‘right’. It felt alive, exhilarating, and yes, scary in the way you know the truth has been revealed…a truth I must live.Julie Daley
You know when you scratch an itch that you didn’t know was even there? That was my SacredReading, the soothing of a deep soul itch. I’ve come to expect nothing but impeccability when it comes to Ronna’s work. Her reading left me teary-eyed and truly breathless. Truth’s like that.Tanya Geisler
Thank you, dearest Ronna. I am completely blown away by my SacredReading. It made me cry, touched my soul and felt like EXACTLY what I needed to hear and be inspired by!! I am re-reading it for the FOURTH time already… and know it will be a constant companion. Your work is true MAGIC!!Chris Zydel
Today I re-read my Sacred Reading from Ronna and it resonated in the deepest way. Truth-be-told, I was perplexed by it at first, wondering if it was for me. And this time, well, there it was. So much love infused within. I’m profoundly grateful.Andrea Scher
I purchased my SacredReading very quickly, very intuitively. When I received it and read the story, I wept. I felt the rightness of the woman who had ‘chosen’ me; I felt a deeply personal sense of aliveness. The experience went beyond what I had hoped.Lisa Claudia Briggs
If you’ve ever had a Tarot or Intuitive Reading of any kind, you have an idea of how this works. With a deck of cards in my hand, drawn from 52 ancient, sacred stories of women I honor and adore, I light a candle, take a deep breath, then hold you, your story, your hopes and your heart in my heart. Then I shuffle the deck, cut the cards, and trust-believe-know that the woman who appears will speak − beautifully, eloquently, generously. Because she always does. I promise.
And it’s not Tarot. Nor is it intuitive. It’s grounded in my vast belief in the power of women’s stories; my vast experience in knowing how much they have to offer, speak, and compel; my vast gratitude that my story has changed because of theirs.
- A personalized and perfect-for-you 10-12+ page document that imparts the story and wisdom behind the woman who chooses you. Applicable, powerful, and relevant themes. Truths to ponder. Questions to ask. Patterns within your story that deserve your attention and intention. Ways of being in life, work, relationships that make everything so much deeper and more meaningful − and yes, YES . . . more sacred.
- A unique and powerful blessing She speaks on your behalf. Cherish it as secret message, mantra, and personalized prayer for the year ahead.
- Practical ways in which to incorporate Her story into your day-to-day life. Journaling exercises. Reflections. More.
- The profound awareness that you are not alone; that you are closely and intimately companioned and supported by your powerful matrilineage − the women from whom you, me, all of us descend.
- All of this emailed to you within 48-56 hours. Overflowing with all the wisdom, encouragement, perspective, and grace you need. I promise.
Why these stories?
The ancient, sacred stories I know and love have too-often been told in ways that have diminished them of their worth and value. (Sound familiar?) But just like you, me, all of us, they want and deserve to be known and appreciated, heard and seen.
And so this is what I do: reimagine, retell, and redeem women’s stories.
I am hardly alone in this effort. In the summer of 2016 I had the privilege of spending a week with Dr. Clarissa Pinkola Estes, author of Women Who Run With the Wolves. We heard mythic, archetypal tales of relatively unknown women who, when understood, offered profound insight and impossible-to-ignore relevance. Those days with her, a storyteller extraordinaire, renewed my commitment to and belief in the ones I tell – mythic, archetypal, and relatively unknown women. These are the stories I offer you; the stories that speak perfectly-and-powerfully into yours.
Ronna’s SacredReadings offer the tremendous grace of bringing together the wisdom of ancient voices with her own arresting vision for a process that is full of depth, insight, and generosity. Give yourself the gift of a soulful connection to the women who have wrestled in their own lives to bring forth treasures still shimmering brightly for us.Christine Valters Paintner
On an intuitive zing, I signed up for one of Ronna’s SacredReadings. Surprising because my natural response to anything related to stories from the Bible is something along the lines of, “Wow the Bible sucks.” But the way Ronna unfurled the story had me in tears – epiphany after epiphany rolling in and washing over me. I am walking with a new understanding of myself and the most important ways for me to move through the world that are resonant down to the core. With this beautiful reading, and one conversation with Ronna, I feel like my life has changed.Nona Jordan
My SacredReading was both complex and evocative. Shimmering with meaning and metaphor. As I read through it, it began to expand – and open, like a nested doll. This work is archetypal. Each layer has a deeper meaning. Ronna’s wisdom led me into my soul story where I was able to make new connections to my own life experience. Brilliant work.Amy Oscar
Wise. Beautiful. Powerful. What more can I say? Ronna has a true gift – not only for making these ancient (and often unknown) stories come alive but also allowing them to shed light on the struggles, issues, and choices that we face very day.Andrea Olson
Last year I bought a SacredReading when I was at a huge turning point and had no idea what a transformational year lay ahead of me. My Reading was exactly what I needed to hear to help me finally publish my book, and believe in how important my own journey is.Meghan Genge
I purchased a SacredReading for each of my clients. Blew. Me. Away. Each are energized, encouraged, and supported by the women who chose them, as am I. Ronna brings these stories not only to life, but to immense and practical use in our lives. Deepest thanks.Aine Dee
What I know for sure…
This woman and her story will offer you exactly what you need:
- Focused guidance. The major themes of your story. The truths of your character. The things you want to pay attention to now, and in the days, weeks, and months to come.
- Perspective on your work, your voice, and your presence in the world. What will bring the most meaning. What’s next. How to “be” in your present circumstances. Clarity for decisions.
- Wisdom in (or out) of relationships. Where you can draw strength and encouragement. Dynamics to be aware of. Patterns that tend to repeat, but no longer serve. The hope you can hold onto when it comes to enjoying healthy, whole relationships – with yourself, with others, even the Divine.
- Insights related to creativity, the next steps, areas of focus and energy, and how you might renew a sense of passion, purpose, and energy.
Discover your Sacred She
The story that speaks perfectly-and-powerfully into yours!
I can hardly wait to see who shows up on your behalf!
She is already choosing you – longing to offer you Her wisdom – not just as it relates to the days, weeks, and months ahead, but more, as it relates to all you deserve to hear, desire to know, and desire to be.
Believe me: She serves as dearest friend and closest guide.
How can I be so sure?
Because She continues to offer all of this and then some to me – over and over again.


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Ecuador: A Week in Paradise 2019 Trip Report
We had a great group which helped make for one of the most fun tours that we run. All-in-all we recorded 336 species, almost all of which were seen. We can’t wait to run this amazing tour next year in 2020!
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Explore Srinagar’s ‘Heaven on Earth’ with a renowned Shikara ride and the opportunity to stay in a unique houseboat. Thrillophilia’s outdoor experts handpick a perfect combination of adventurous, exhilarating, and cultural activities. Visit Pangong Lake, the world’s tallest saltwater lake with colors ranging from blue to green to crimson. As you drive across the world’s highest motorable passes. Let the thrill pour through your veins. In well-sanitized accommodations and cars, experience the Himalayan region in the highest safety and luxury.
When is the Best Time to Visit Leh Ladakh By Bike?
The period of June to September is ideal for a bike journey across Leh Ladakh. Most riders, however, wish to begin their new year with this adventurous bike adventure since Ladakh offers stunning panoramas that can be enjoyed all year except during the monsoon season.
A Bike Trip’s Ideal Duration
An optimal time frame for a Leh Ladakh bike trip best time would be 15 days or more, depending on a variety of elements such as the route you’ve taken, your complete schedule, and, most importantly, the weather conditions.
The cost of a trip to Leh and Ladakh
First and foremost, you must determine your budget. Essential factors like lodging, meals, and fuel can be factored into an average budget. As a result, a 15-day bike trip to Leh Ladakh will set you back around INR 35,000 in typical circumstances. The cost of your bike tour will change based on the route you decide to go for. The price of permits and other fees for the Leh Ladakh cycling trip are also included.
The Best Bikes for this Road Trip
Whenever you’re looking for a bike for a road trip, prioritize suitability over-popularity. It’s one of the most important components of your Leh Ladakh bike trip itinerary. A bicycle tour is not advised for women who might be more than 3 months expecting, anyone who has had major surgery has a broken leg/arm, has persistent back or neck difficulties, and so on, for safety reasons.
Hence, bikes for the bike trip are:
• Royal Enfield Himalayan — With a powerful 400 cc engine, the Royal Enfield Himalayan will make any rugged route or off-the-beaten-path ride smooth and hassle-free.
• Bajaj Pulsar – When compared to the Bajaj Pulsar, no other bike has been as successful in the Indian market. Pulsar is the next best alternative to Bullets.
• KTM Duke – The fact that it is a featherweight bike can be beneficial on roads like those in Ladakh. KTM can also be an excellent alternative for a bike trip to Ladakh, thanks to a variety of new engine variations for the Duke 390 and Duke 250.
• Honda CBR 250 – This bike is wonderful, save for the Contigo tyres, which can be difficult to handle on Ladakh’s terrain in the event of unforeseen weather. On the plus side, if the tyres can be changed, the torque and fi technology on the bike can be put to better use and serve a greater purpose.
Yamaha Fazer, Bajaj Vikrant, Yamaha FZ, and Hero Impulse are some of the other top bikes for a Leh Ladakh vacation that the association of bike rentals has considered. Though the engines on these bikes aren’t particularly powerful, they can certainly pick up some pace (without breaking any restrictions).
Best Leh Ladakh Bike Trip Route
When using Delhi as a base for a Leh Ladakh bike journey, the two main routes that offer better road conditions and scenic vistas are Srinagar to Leh and Manali to Leh. The road from Srinagar to Leh does not intersect and is a complete round from beginning to end. The Manali to Leh Ladakh bike ride route encircles the rocky Himalayan terrain, provides better views, and raises the level of effort and danger.
Route 1: Srinagar-Leh
Route 2: Manali-Leh
Route 3: Delhi-Leh
As a result, based on whether you want a budget hotel or a luxury hotel, an average lodging with the greatest amenities, comfort, and reviews might charge you INR 500 to INR 2,500 per night per person. With the lesser limit in mind, a 15-day trip will cost around INR 7,500 in terms of lodging. Rates may change in response to changes in services or hotels. The hotels’ availability is subject to change. In the event that they are not unavailable, the tourists will be lodged in a similar facility. During the trip, non-air-conditioned and non-heated vehicles will be used. While traveling, always dress appropriately for the weather.

domain: geography


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You've probably heard the words "revolutionary" and "transforming" used to describe plenty of innovations that ended up being neither. But gene editing is worthy of both terms.
The technology holds the promise of changing how diseases, especially those caused by genetic mutations, are treated. Gene editing could even result in cures to diseases that are untreatable today. With this kind of groundbreaking potential, it's not surprising that biotech investors have turned their attention to stocks focused on gene-editing therapies. Here's what you need to know about this hot area of healthcare and the top five gene-editing stocks to put on your radar for 2019.
What is gene editing?
It's important to first know what gene editing is -- and isn't, starting with learning about DNA (deoxyribonucleic acid).
As you may recall from biology class, DNA is structured as a double helix -- kind of a twisted ladder. Each step of this ladder is made up of chemical base pairs: adenine with thymine, and cytosine with guanine. The sequence in which these chemical base pairs occur in DNA provides the instructions for the assembling of animals, plants, and humans.
A gene consists of DNA segments that control the development of one or more specific traits inherited by a child from its parent. A genome is the complete set of genes for an organism.
Gene editing (also known as genome editing) involves the insertion, deletion, or replacement of those chemical base pairs in DNA. These changes to DNA base pairs can impact how an organism functions. Think of gene editing as "molecular scissors" that snip sections of DNA and allow for the addition of a different sequence, or replacement of the deleted sequence.
How is gene editing actually performed? Gene-editing therapies are typically delivered via a virus known as a viral vector. You can think of the viral vector as a transport jet carrying its payload, the gene-editing therapy.
In some cases, genes are edited inside the body (in vivo). For example, the viral vector carrying the gene-editing therapy could be injected into an organ such as the eye. In other cases, the genes of cells are edited outside of the body (ex vivo) -- for example, genes in blood cells can be edited outside of the body then put back in the body.
Gene therapy is similar to but different from gene editing. Rather than editing existing DNA sequences, gene therapy actually introduces foreign DNA into cells.
Types of gene editing
There are three primary types of gene editing used today:
- Zinc-finger nuclease (ZFN)
- Transcription activator-like effector nuclease (TALEN)
- Clustered regularly interspaced short palindromic repeats (CRISPR)
All three types target specific DNA sequences, cutting those sequences out of a gene. ZFN is the oldest method of gene editing, dating back to the 1990s. It was the only method for gene editing until 2009, when the TALEN approach was discovered, offering more specific targeting of DNA sequences.
However, the biggest gene-editing development happened in 2012 with the discovery of CRISPR. Scientists found that certain bacteria used gene editing as a defense mechanism, and they realized they could harness the approach to selectively edit DNA. CRISPR was much cheaper, simpler, and faster than ZFN and TALEN, and it quickly became the most-used method for editing genes.
What to look for in gene-editing stocks
There are several criteria investors should evaluate before buying any stock, including the company's financial condition and the caliber of its management team. However, there are also certain criteria with unique importance in the gene-editing arena.
First, consider what stage of development the gene-editing company is in. The drug-development process for biotechs focused on gene editing begins with the discovery phase, in which a specific gene target is identified. Next, gene-editing therapies move into preclinical testing involving test tube lab studies or testing in animals. If preclinical testing goes well, the company can try to obtain regulatory approval from the U.S. Food and Drug Administration (FDA) or the European Medicines Agency (EMA) in Europe to begin clinical trials in humans.
The stage of development helps you assess the risk level associated with a particular gene-editing stock. The farther along the development curve that a biotech is, the lower its risk level. It's also important to review any results from ongoing testing of the gene-editing therapies.
Clinical testing in humans begins with a phase 1 study, which is designed to evaluate safety and to establish dosages for further testing. Then phase 2 studies focus on determining efficacy and the optimum dosage(s) for the therapy. Phase 3 studies typically include a larger group of patients, and they are the final step to establish efficacy and safety profiles before seeking regulatory approval from the FDA or EMA.
Another key criterion to look at with gene-editing stocks is which major partners the biotech has.
Gene-editing developers are small. Developers forming partnerships with major drugmakers, especially making deals involving significant investments, can give investors a higher level of confidence in the small biotechs' gene-editing therapies. The due diligence has been done for you, as the large companies direct their research teams to thoroughly examine the experimental therapies before putting money on the table.
Don't forget to examine the specific diseases a biotech is targeting with its gene-editing therapies, also known as indications by the FDA. The primary reason for looking at the target diseases is to determine the commercial potential for the therapy. This potential includes the number of patients who could benefit from the therapy as well as the level of competition in the targeted disease. More targeted diseases, more potential patients, and fewer competitors should translate to higher potential sales for gene-editing therapies. Once a therapy is approved for one indication, the company will often look to expand its use into other indications if it is safe and efficacious.
Growth prospects for gene editing
Because gene editing is still in its infancy, predicting growth prospects with any level of precision is difficult. A report from market researcher Research and Markets projects that the global gene-editing market will grow by a compound annual growth rate of 17% to reach $10.7 billion by 2025. Grand View Research, on the other hand, has a less optimistic view. The market research company estimates that the global gene-editing market will reach $8.1 billion by 2025.
Investors probably need to have even longer time horizons to truly appreciate the opportunities for gene editing. There are more than 10,000 diseases that are caused by mutations -- changes in the normal sequence of DNA -- in a single gene, according to the World Health Organization. Over the long run, many, if not all, of these diseases could be targeted by gene-editing therapies. In addition, other non-genetic diseases, including certain types of cancer, could be treated using gene-editing therapies that modify the body's immune cells to fight the diseases. Even optimistic projections for the gene-editing opportunity could prove to be well below the actual market size in the future.
Top five gene-editing stocks for 2019
Here are the top five gene-editing stocks to consider in 2019:
Stage of Development
Target Indications for Lead Gene-Editing Candidates
|Cellectis (NASDAQ:CLLS)||$741 million||Phase 1||
Acute lymphoblastic leukemia (ALL)
Acute myeloid leukemia (AML)
Blastic plasmacytoid dendritic cell neoplasm (BPDCN)
|CRISPR Therapeutics (NASDAQ:CRSP)||$2 billion||Phase 1||
Sickle cell disease
|Editas Medicine (NASDAQ:EDIT)||$994 million||Phase 1 (begins in 2019)||
|Leber congenital amaurosis type 10 (LCA10)|
|Intellia Therapeutics (NASDAQ:NTLA)||$624 million||Preclinical||
Transthyretin amyloidosis (ATTR)
|Sangamo Therapeutics (NASDAQ:SGMO)||$1.1 billion||Phase 1/2||
Mucopolysaccharidosis type I (MPS I)
Cellectis focuses on using TALEN gene editing to develop allogeneic chimeric antigen receptor T-cell (CAR-T) therapies. CAR-T is a promising cancer treatment that involves engineering the genetics within the body's immune cells called T-cells to make them attack specific types of cancer.
A couple of approved CAR-T therapies are already available -- Gilead Sciences' Yescarta and Novartis' Kymriah. Both of these therapies obtain T-cells from patients to be genetically engineered, then put the revamped cells back into the patient to start treating the cancer. Allogeneic (which means genetically dissimilar) CAR-T therapies like the ones that Cellectis is developing use "off-the-shelf" genetically engineered T-cells from healthy donors, which could greatly reduce the time and cost associated with current CAR-T therapies.
Two of Cellectis' therapies are in phase 1 clinical studies. The biotech licensed UCART19, which targets ALL, to French drugmaker Servier, which subsequently sold the rights to develop and market the therapy in the U.S. to Pfizer. In 2018, Pfizer contributed its allogeneic CAR-T portfolio to Allogene Therapeutics. Pfizer owns around 19% of Allogene and roughly 7% of Cellectis.
Cellectis fully owns the rights to UCART123 for treating AML and BPDCN. In addition, the company expects to begin a phase 1 study of UCART22 in treating ALL this year and hopes to submit for approval in 2019 to begin clinical testing of UCARTCS1 in treating multiple myeloma.
UCART19 is the farthest along in testing. However, the results have been mixed so far. In the phase 1 study evaluating the CAR-T therapy in treating ALL in pediatric patients, five patients were initially cured. The bad news, though, was that two patients relapsed then died. Another of the five patients died due to transplant-related complications.
ALL is a rare type of cancer, with fewer than 6,000 new diagnoses in the U.S. each year. There are several drugs approved by the U.S. Food and Drug Administration (FDA) to treat the disease. However, there remains a significant unmet medical need.
AML is more common. The American Cancer Society (ACS) projects around 21,450 new cases will be diagnosed in the U.S. in 2019. While several drugs have been approved for treating AML, there are currently no approved CAR-T therapies. The need for new treatments is significant, as the ACS estimates there will be 10,920 deaths from AML in 2019.
2. CRISPR Therapeutics
As you probably gathered from its name, CRISPR Therapeutics uses the CRISPR gene-editing method. The biotech's lead candidate, CTX001, is currently in phase 1 clinical studies, and it targets blood diseases such as beta thalassemia and sickle cell disease (SCD).
Both beta thalassemia and SCD are caused by mutations (changes to DNA sequences) in the same gene. This common denominator has allowed CRISPR Therapeutics to move forward with the two indications almost simultaneously. However, the biotech's phase 1 study evaluating CTX001 in beta thalassemia is ahead because the FDA placed a clinical hold on the company's SCD study because the agency needed more information. But that clinical hold was subsequently lifted.
Vertex Pharmaceuticals partnered with CRISPR Therapeutics in 2015 to jointly develop gene-editing therapies to treat cystic fibrosis and SCD. This SCD focus ultimately led to CTX001, while the cystic fibrosis therapy development is still in preclinical research. Vertex owns a minority stake in CRISPR Therapeutics.
Bayer joined forces with CRISPR Therapeutics in 2015 and also bought a minority interest in the biotech. The companies formed a joint venture, Casebia Therapeutics, which focuses on developing gene-editing therapies for treating blood disorders, blindness, and congenital heart disease. None of these therapies have advanced into clinical testing in humans yet.
CRISPR Therapeutics intends to begin a phase 1 clinical study of its allogeneic CAR-T therapy CTX110 in the first half of 2019. This therapy targets the treatment of cancers caused by overexpression of the protein CD19, potentially including B-cell lymphoma, ALL, and chronic lymphocytic leukemia (CLL).
All of the primary indications targeted by CRISPR Therapeutics have a significant unmet medical need. Beta thalassemia affects around 60,000 births worldwide each year, but there is no approved drug yet for the disease. Many beta thalassemia patients must undergo regular blood transfusions. SCD impacts 300,000 births annually, with only two approved treatments and no cure.
3. Editas Medicine
Editas Medicine also uses CRISPR gene editing. The biotech's lead candidate, EDIT-101, targets treatment of Leber congenital amaurosis type 10 (LCA10), the leading cause of genetic blindness.
EDIT-101 should soon become the first in-vivo (in-the-body) CRISPR therapy to be tested in humans, according to Editas CEO Katrine Bosley's remarks at the J.P. Morgan Healthcare Conference in January. Editas plans to begin screening patients for a phase 1/2 clinical study in the first half of 2019 then initiate dosing of patients in the second half of the year.
Editas isn't going it alone with EDIT-101, partnering with Allergan in 2017, which has the option to license up to four other gene-editing therapies targeting eye diseases.
The approach taken with LCA10 should lend itself to more genetic eye diseases. Editas hopes to move forward into clinical studies with a therapy targeting Usher syndrome type 2A (USH2A), another rare genetic eye disease, in the not-too-distant future.
Another program that Editas thinks will move into clinical testing relatively soon is its CRISPR therapies targeting beta thalassemia and SCD. Although CRISPR Therapeutics has a head start over Editas in this area, Editas believes that its gene-editing approach is better than its rival's because it more effectively maintains the functionality of hematopoietic stem cells (HSC) -- cells that develop into all types of blood cells.
Editas is also developing CAR-T and T-cell receptor (TCR) therapies (which are like CAR-T therapies that target proteins inside of cells rather than outside of cells) with Celgene targeting the treatment of various types of cancer. This research is still in early stages, though, and no plans have been announced about clinical testing.
The LCA10 indication by itself presents a significant opportunity for Editas. Between 2,000 and 5,000 patients have the eye disease in the U.S. and Europe, and currently, no approved treatments exist for LCA10. However, another biotech, ProQR, is evaluating a gene therapy targeting LCA10 and plans to begin a phase 2/3 study in the first half of 2019.
4. Intellia Therapeutics
Intellia Therapeutics also uses CRISPR gene-editing technology, though it is behind its rivals CRISPR and Editas. The biotech doesn't expect to submit for approval to begin a phase 1 clinical study of its lead candidate targeting transthyretin amyloidosis (ATTR) until 2020.
Regeneron is collaborating with Intellia on the ATTR program. The big biotech also has options to license Intellia's CRISPR therapies for up to nine other targets. In addition, Regeneron invested $50 million in Intellia.
Intellia also teamed up with Novartis in 2015, and the two are working together to develop CRISPR gene-editing therapies targeting SCD and other undisclosed cancer indications. Novartis owns nearly 10% of Intellia.
How big is the opportunity for Intellia's lead candidate targeting ATTR? It's a rare disease with fewer than 6,400 patients in the U.S. But one drug has already been approved for the disorder -- Alnylam's Onpattro. Pfizer could have a second drug on the way with tafamidis.
5. Sangamo Therapeutics
Sangamo Therapeutics is the only biotech among these five that uses ZFN gene editing. The company's pipeline includes gene therapies as well as gene-editing candidates.
Its lead gene-editing programs target rare genetic diseases MPS I, MPS II, and hemophilia B, all three of which are in phase 1 clinical testing. Sangamo disappointed investors in September 2018 with results that didn't clearly show efficacy for its MPS II therapy.
Bioverativ, which was acquired by Sanofi in 2018, is partnering with Sangamo on using ZFN gene editing in treating beta thalassemia. The two companies are also developing a gene-editing therapy for SCD.
Gilead Sciences picked Sangamo in February 2018 as its partner to develop CAR-T therapies -- both autologous (genetically engineering the patient's T-cells) and allogeneic (genetically engineering donors' T-cells). These efforts are still in preclinical testing.
Sangamo also attracted Pfizer with its SB-525 gene therapy program targeting hemophilia A. The two companies reported positive preliminary results in August 2018 from a phase 1/2 clinical study of SB-525.
If its gene-editing therapies succeed in clinical testing, the market opportunities for Sangamo should be very good. Hemophilia B affects around 4,000 Americans. An estimated 2,000 patients in the U.S. have MPS I, with another 500 diagnosed with MPS II. Although there are FDA-approved drugs for all three indications, the need for more effective treatments is strong.
Risks for gene-editing stocks
Biotechs that focus on gene editing face the same risks all other biotechs do -- the possibility that their experimental treatments will prove to be ineffective or unsafe. The latter risk is especially concerning for gene-editing stocks.
One key risk for gene editing is that unintended off-target mutations could and do occur. Some studies have identified examples of such off-target mutations with CRISPR, for example. Leading scientists think that these issues can be prevented, but safety concerns could slow down development and clinical testing of CRISPR therapies.
An even greater challenge is the possibility that CRISPR gene editing could actually increase the risk of cancer. Two scientific studies in 2018 highlighted this risk. Researchers found that CRISPR-Cas9 (Cas9 stands for CRISPR-associated system 9), the most-used type of CRISPR gene editing, induced a response in cells that attempted to protect against DNA damage by activating the p53 gene. The p53 gene went to work trying to either repair the DNA break or cause the cell to self-destruct.
Here's the problem: CRISPR-Cas9 doesn't appear to work very well in cells where the p53 gene kicks into action. However, it works great in cells where there are mutations in the p53 gene -- but unfortunately, p53 gene mutations are linked with higher rates of several types of cancer.
So far, the increased risk of cancer associated with the p53 gene issue appears to only be at play when CRISPR-Cas9 is used to delete DNA sequences and insert a new DNA sequence. This two-step process is called gene correction. The higher cancer risk doesn't seem to be a problem when CRISPR-Cas9 only deletes DNA sequences -- a process referred to as gene disruption.
The good news for CRISPR Therapeutics, Editas Medicine, and Intellia Therapeutics is that their lead candidates all use gene disruption and not gene correction. The bad news, however, is that all three CRISPR-focused biotechs have other programs that do employ gene correction.
And while Cellectis' TALEN and Sangamo's ZFN gene-editing methods haven't been linked to increased cancer risk, there is still a possibility that similar or new issues could be discovered in the future that impact them.
The risks associated with gene-editing stocks are significant. As a result, these stocks are suitable for only the most aggressive and risk-tolerant investors.
Think long term
As with any type of investing, you need to be aware of the potential rewards and the potential risks. Investing in gene-editing stocks definitely comes with both. Over the long run, though, the potential for gene editing should be realized. Patients with diseases for which there are no approved treatments today could even be cured.
Outgoing Editas CEO Katrine Bosley said in January that the use of gene editing to treat diseases is "what the future of medicine looks like." These five stocks provide investors a chance to get in on the ground floor of that promising future.

domain: biology


text:
The stealth nominee
Barack Obama taps Elena Kagan for the Supreme Court
Ms Kagan "is widely regarded as one of the nation's foremost legal minds," said Mr Obama. As solicitor general, she has argued six cases before the Supreme Court, during which she more or less held her own against the court's conservative heavyweights. As dean of Harvard Law School she was popular even among conservative legal scholars, who were pleasantly surprised that she treated them fairly.
Liberals assume that she is a liberal—why else would Mr Obama pick her? But her record is difficult to attack, because she has scrupulously avoided expressing firm opinions on thorny constitutional questions for as long as anyone can remember. Conservative criticism of her will therefore focus on the few instances in which she has stuck out her neck.
The most obvious was her decision, when dean of Harvard Law School, to bar military recruiters from campus. She did this because the military's "Don't Ask, Don't Tell" policy, which forbids openly gay people from serving in uniform, violates Harvard's rules about employers who discriminate. Ms Kagan called it "a moral injustice of the first order", though she later backed down when the law school's university's federal funding was threatened.
This episode resonates badly in middle America. Many who think the military's ban on gays is wrong and foolish are nonetheless affronted by the idea that the nation's top law school would actively discourage its students from serving their country. It is not as if they were queueing up to do so in the first place.
Supreme Court hearings are nearly as vicious as presidential campaigns, and with good reason. The stakes are almost as high. If confirmed—as seems highly likely—Ms Kagan will enjoy a seat for life on the court that is the final arbiter of what the US constitution means. Since Ms Kagan is only 50, she could be shaping the ground rules for American public life for the next four decades. So conservatives will do all they can to make her appear out of touch. Even if they cannot prevent her from being confirmed, they can at least score points in the run-up to the mid-term elections in November.
No biographical nugget will be considered irrelevant if it serves this purpose. The Washington Postreports that Ms Kagan "is such a product of New York that she did not learn to drive until her late 20s" and that it is "a skill she has not yet mastered". Ed Whelan, a conservative court-watcher, jeers that this "nicely captures Elena Kagan's remoteness from the lives of most Americans".
Court-watchers on the left are a little unsettled by Ms Kagan's lack of a paper trail. How can they be sure she is one of them when she has expressed so few clear opinions? Some also worry that she will be too deferential to the executive on matters of civil liberties. For example, during her confirmation hearings for the post of solicitor general, she agreed that Taliban prisoners in Afghanistan do not have due process rights under American law.
Others on the left are concerned that Ms Kagan would have to recuse herself from a huge number of cases in her first couple of years on the court, since as solicitor general she was involved in practically every case involving the federal government. That would tilt the court's balance rightwards, at least temporarily. But overall, liberals are inclined to give Mr Obama the benefit of the doubt. Nan Aron of the Alliance for Justice, a liberal pressure group, exults that Ms Kagan will "stand up for the rights of ordinary Americans" instead of "protecting corporate interests".

domain: politics


text:
Generally talking, there are 2 kinds of bio; the memoir and also the historical biography. The memoir is a non-fiction literary style, and it provides an in-depth insight into a person’s life. The historic bio is a literary format which highlights an individual that passed away without being offered recognition.
Memoir is a non-fiction literary style
Throughout background, memoir has been a literary style. Several well-known people have actually written autobiographies. These books are also popular with the basic analysis public.
Memoir can be created by any person. Some people employ ghostwriters to do the benefit them. A good autobiography ought to offer visitors a chance to learn more about an individual, their life, and their background.
Autobiographies are additionally prominent amongst political figures. These books can cost numerous dollars. They can also be a great means to keep history to life. This sort of creating can additionally assist writers get rid of issues.
Composing an autobiography can aid recover from previous injuries as well as can inspire others. This type of writing can also be utilized to convince and also educate others. It can also be used to connect with others who have gone through similar experiences.
A bio’s job is to take a look at the subject’s point of view versus numerous, also inconsistent sources
Normally speaking, a biography is the story of a real individual’s life, from birth to death. Nonetheless, it can additionally be a research study of a specific group or group of individuals. For example, a bio may cover the life of an unrecognized hero that impacted the background of the human race in a considerable way, or the life of an individual that lived centuries ago, but is not as extensively understood. It may be a biography of a person that passed away in battle, yet is not a biography of somebody that passed away in peacetime.
One of the most amazing element of a bio is the sheer amount of details that is offered to an author. For instance, you might have the ability to obtain one of the most complete details regarding an individual’s life by talking with close friends and loved ones, performing background research, or perhaps visiting the individual’s residence or office. In addition, a good bio will cover the most vital events in the subject’s life, while additionally pointing out the more mundane ones.
Recalls must feel as thorough as well as genuine as existing day scenes
Whether your bio is fiction or nonfiction, you may have the need to consist of a recall to show the visitor something about your character’s past. Flashbacks can provide background details on your character as well as can highlight stressful occasions. However, they can also be confusing as well as can switch off viewers that are not purchased the story. Fortunately, there are a few points you can do to make them operate in your support.
Initially, you need to establish why you are going to consist of a flashback. If you’re trying to describe a personality’s motivations, you can use flashbacks to illustrate these objectives. Nevertheless, you need to be careful regarding overusing them. A recall can seem like a crutch if you utilize it frequently. It can additionally feel puzzling to viewers if it isn’t done properly.
Compose a bio without the subject’s consent
Whether you want to compose a bio of a living individual or a departed one, you need to acquire the topic’s approval prior to creating. This will make certain that you are not damaging any lawful concepts.
If you plan to create a biography of a dead individual, you require to do your research study initially. You might also speak with the family or friends of the topic. This can supply you with interesting individual data.
Then, you require to compose the biography in a rational and also sequential order. This order has been used since Herodotus as well as Plutarch. The order should start with the topic’s birth. After that, you can begin with the main milestones on the subject’s trip. You must additionally identify your central theme. You can also break the main turning points down into layers.
Attributes of a great biographical narrative
Creating an excellent biographical narrative is not a simple task. The primary step is to make a decision which events to include in the life of the subject. Getting the idea of the subject’s life and also how it affected the people around him or her is very important.
The good news is, a number of resources exist to help trainees craft a good biographical story. Among the best sources of bio-writing inspiration is to take a look at other writers’ works. Using a synopsis is also a great concept. It assists pupils make note of different topics as well as helps them choose what information to consist of.
The best biographical stories are those which contain appropriate details and fascinating realities. They likewise feature a logical circulation of ideas. This is accomplished through the use of shifts. The best ones entail words made use of between paragraphs as well as between period. Daniel S Poussart hoboken
It is additionally a good concept to check the ended up item. This aids identify blunders in both punctuation as well as grammatical construction.

domain: library


text:
Showing 8 of 18 Quizzes
Q: Final Fantasy VII's setting was originally planned to take place in which US city?
Q: When a new island is created, the first two villagers the player starts with will always be a _______ & _______ villager?
Games Revealed is a BunnyStrike Project where we strive to learn more about the games we love and share it with other people. We push ourselves to make the best games quizzes out there. We search for the best sources to create the best content like podcasts, quizzes, articles, and news. We strive for the best gaming community!


text:
Happy: Simple Steps to Get the Most Out of Life
“Don’t worry; be happy” is well-intentioned advice that won’t go far with most doubters. What does work is a realistic motivation booster that makes good sense and changes your behavior.
10 Secrets for Success and Inner Peace Bestselling author and lecturer Wayne W. Dyer has created a thought-provoking CD for those of us who have chosen to consciously be on our life path. The ten “secrets” for success and inner peace presented here apply whether you’re just embarking on your path, are nearing the end of it, or are on the path in any way. Dr. Dyer urges you to listen to these ten secrets with an open heart.
10 Steps to Take Charge of Your Emotional Life: Overcoming Anxiety, Distress, and Depression Through Whole-Person Healing
A 3rd Serving of Chicken Soup for the Soul: 101 More Stories to Open the Heart and Rekindle the Spirit
“…contains stories of inspiration and encouragement from noted personalities such as Michael Jordan and Maya Angelou.”
Don’t Give It Away!: A Workbook of Self-Awareness and Self-Affirmations for Young Women
Iyanla Vanzant is megapopular with women all over the country, dominating bestseller list with books such as Yesterday, I Cried and In the Meantime. Now she’s got one just for younger women, titled Don’t Give It Away! With this book, Vanzant responds to the letters and emails she has received from young women who ask for help in their daily struggle for spiritual guidance and awareness.


text:
Nepenthes sibuyanensis x merrilliana – BE-3542
Nepenthes sibuyanensis x merrilliana is an unusual and attractive plant. At our nursery we grow these under intermediate conditions. This hybrid is from tissue culture from Borneo Exotics. Customers will need to grow this hybrid under warm temperatures. This means that the night temperatures should be 60° Fahrenheit. Daytime temperatures should stay around 80°-85° F. Nepenthes in general like the humidity to be 75% or higher. In addition remember to use distilled water, rain water or reverse osmosis with your Nepenthes. Most noteworthy about this hybrid is it’s stunning red color and unique shape. It also produces squat pitchers. Because the plant is still young, some of the characteristics won’t show yet.


text:
I will provide you an XD file which contains all the screens which the mobile app would have... The Freelancer has to Enhance the UI and UX of the complete app.
40 freelancers are bidding on average ₹1157/hour for this job
New here but I have experience designing apps for over 6 years. Check my portfolio and decide for yourself! Would be great if you were one of my first clients!

domain: design


text:
MONOPOLY: Pokemon Kanto Edition
|You Save:||$16.12 (36%)|
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- Enter your model number to make sure this fits.
- 6 metal tokens: Pikachu, Bulbasaur, Charmander, Squirtle, Eevee, Jigglypuff
- Sculpted Poke Marts and Pokemon Centers replace traditional Houses & Hotels
- Custom designed game board features all eight gyms
- Collectible fun for the Pokemon fan!
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Monopoly Pokemon Kanto Edition
Gotta catch'em all!
Partner with Pikachu and friends in Pokémon Monopoly!
Travel through all eight gyms and battle all kinds of Pokémon in the Pokémon: Kanto Edition of Monopoly. Buy, sell and trade with other trainers to collect the most powerful Pokémon team!
- Pokemon fans & collectors
- Family Game Night
- Classic Game Pokemon theme
Ages 8+ | 2-6 Players | 60+ Minutes
Can you catch'em all?
- 6 Collectible metal tokens: Pikachu, Bulbasaur, Charmander, Squirtle, Eevee, Jigglypuff
- Custom designed game board featuring the Kanto Region
- Custom sculpted Poké Marts replace traditional Houses
- Custom sculpted Pokémon Centers replace traditional Hotels
- Chance and Community Chest cards are transformed into Professor Oak and Trainer Battle cards
Ready to build your team?
Who will you be?
Partner with Pikachu and friends in Pokemon Monopoly! Travel through all eight gyms and battle all kinds of Pokemon in the Pokemon Kanto Edition of Monopoly. Buy, sell and trade with other trainers to collect the most powerful Pokemon team!
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|Item Dimensions||15.75 x 10.5 x 2 in||10.5 x 15.75 x 2 in||1.96 x 10.51 x 10.51 in||10.6 x 15.8 x 2.4 in|
|Item Weight||2.3 lbs||0.91 lb||1.3 lbs||0.35 ounces|
Top Customer Reviews
This definitely seems like a budget re-branding.
The kids likely won't notice a difference, but it's disappointing.

domain: game


“It’s too much, he has his musicians and there is the orchestra, it’s simply too much!” said a guy talking to his female friend while exiting the Walt Disney Concert Hall after the concert. It was just one opinion but the thunder of applause I heard after each song Father John Misty performed with the LA Philharmonic told a very different story. I was probably standing next to the only guy complaining at the end of the show, the only guy who may have preferred a stripped-down performance by a sad boy playing an acoustic guitar – and in this case, this show was definitively not for him – but it was obviously not an opinion shared by the audience. Personally, I like my live music big, and I truly enjoyed the sweeping orchestration and the many layers of instruments from strings to cello to horns to keys to harp, at the top of the guitars and drums: With the eight musicians of band and the LA Philharmonic, the stage was a full house, and it was glorious. Call it bombastic, pompous, or even pretentious, I will call it rewarding.
It was indeed a beautiful night of music in a majestic venue, a highly anticipated night by all the fans of Father John Misty, and some of them had even dressed up for the occasion. First, it’s easy to understand why this format fitted Father John Misty’s work so well. The music had never been so buoyant and alive and many of the songs boomed to euphoric heights for the public’s great joy. How many times do you hear applause and cheering during a song? It never happens but it happened several times last night. Of course, his irreverent lyrics would often clash with the solemnity of the occasion, but it made the night even more interesting.
Many people thought that it was the perfect occasion to premiere the songs of his new album with lush and wide orchestration – after all, “Funny Girl” and its soundtrack grandiosity sounded absolutely made for the occasion – but everyone was apparently wrong. They only played two songs from the upcoming “Chloe and the Next 20th Century,” so Father John Misty may not have been ready to perform these brand-new ones live. In any case, the evening was far from being a disappointment, the cuts from his back catalog were pure crowd pleasure, and besides the two new ones, songs from his four previous albums were fleshed out with the professionalism of the LA Philharmonic.
I have seen Father John Misty perform several times before, even when he was just going under his real name, Josh Tillman, and played a solo set on acoustic guitar in a small record shop in Echo Park in 2011… Looking back at this last decade, from Origami Vinyl to Walt Disney Concert Hall, the journey looks quite impressive since this humble show. Tillman didn’t say much but he seemed to be quite satisfied to be playing in this immaculate and superb venue. “This is the big reveal,” he said before starting the show.
However, it was probably a case of venue influencing the performance: you cannot be a real rock star in a prim concert hall. I have seen Tillman do the most extravagant stage antics, but last night was probably the most sober performance I have witnessed. He alternated between calm walks on the stage, to a rather static standing position behind the mic, sometimes playing a guitar, when he was not sitting behind a piano. He only became a bit agitated during a few songs, but it was a far cry from the violent moves and gesticulations I was used to. If the performance was restrained, Tillman’s appearance could not have been more serious: a simple suit, a trimmed beard, and a shaved head. But you don’t necessarily need wild stage antics: thanks to the impeccable acoustic of the venue, the music was massive and the energy in the room was palpable.
After the beloved “I Love You, Honeybear,” the horns became particularly brilliant during “Hangout at the Gallows,” when the entire orchestra swelled the song to new heights, but the trumpets shone even more during the vague Mariachi vibe solo of “Chateau Lobby #4.” Meanwhile. the crowd completely lost it during “Nothing Good Ever Happens at the Goddamn Thirsty Crow.”
The entire night, Tillman’s bright voice was way above the music, clear and reaching emotional heights during “Disappointing Diamonds Are the Rarest of Them All.” The songs had never sounded more cinematic, from the Harry Nilsson-esque vibe of “Nancy from Now On,” to the more sentimental love songs like “When You’re Smiling and Astride Me.” Numbers like “The Palace” were poignant moments of strings and keys, and maybe touching enough to make him slightly mess up the lyrics at one point… it’s true that his songs are extremely wordy, his lines are often strange social commentaries or untamed accumulations of words and ideas that would require a day of head scratching to unfold all their meanings. The new one “Q4” had a very hooky chorus and sounded like a ‘70s song with harp-strings pastoral arrangement, while “Funny Girl” had this big vintage ballroom feel, chiming like an opening for the Academy Awards. The long-winded lyrics of some songs, all crowded in the same music line, could become almost conversational as it was the case for “Pure Comedy” that he performed with a crooner quality: “Oh comedy, their illusions they have no choice but to believe.” After the triumphant horns and delicate keys of the uplifting “God’s Favorite Customer,” imploring God’s good grace, the orchestra horns and strings growled to triumphant heights during the holy war of “Holy Shit.”
There was minimal talking between songs, although he mentioned mushrooms and the fact that some of us may not have been out for a long time. The encore happened without the orchestra, and Tillman and his band surely rocked a bit more with “Total Entertainment Forever” but especially with “Date Night,” during which Tillman let the wild Misty show up a bit more with a few dance moves.
Fans can expect the announcement of a tour after the release of “Chloe and the Next 20th Century” in April, but this night at the Walt Disney Concert Hall was just special. It was a one-time experience for the numerous die-hard fans whose only regret was to have to politely sit down during the entire performance.
I Love You, Honeybear (I Love You, Honeybear)
Hangout at the Gallows (God’s Favorite Customer)
Mr. Tillman (God’s Favorite Customer)
Disappointing Diamonds Are the Rarest of Them All (God’s Favorite Customer)
Nancy From Now On (Fear Fun)
Chateau Lobby #4 (in C for Two Virgins)
When You’re Smiling and Astride Me (I Love You, Honeybear)
Q4 (Live debut) (Chloe and the Next 20th Century)
Hollywood Forever Cemetery Sings (Fear Fun)
Things It Would Have Been Helpful to Know Before the Revolution (Pure Comedy)
Ballad of the Dying Man (Pure Comedy)
Nothing Good Ever Happens at the Goddamn Thirsty Crow (I Love You, Honeybear)
The Palace (God’s Favorite Customer)
Funny Girl (Live debut) (Chloe and the Next 20th Century)
Pure Comedy (Pure Comedy)
God’s Favorite Customer (God’s Favorite Customer)
Holy Shit (I Love You, Honeybear)
Funtimes in Babylon (Fear Fun)
Total Entertainment Forever (Pure Comedy)
Date Night (God’s Favorite Customer)
Photos and films were not allowed inside the concert hall, but I saw a few people doing the same thing: sneakily taking a few pics, and I did the same …
Creem – America’s Only Rock ‘n’ Roll Magazine, Reviewed Issue By Issue – June 1975 (Volume 7, Number 1)
Smith’s final freelance contribution to Creem.
putting Nigeria on the map
back at # 1 for a third non consecutive week
not a dreamer but a steely eyed businessman and pop musician
Willie Nelson will play at the Palomino fest on Saturday
Creem – America’s Only Rock ‘n’ Roll Magazine, Reviewed Issue By Issue – May 1975 (Volume 6, Number 12
Elton John came across as completely engaging
by episode nine, season four, the bastards finally got me sick of Kate!
some hooky and wildly inspired tune
Harry has the summer of his career!


text:
TORONTO – Toronto Public Health (TPH) is notifying staff and patrons who visited the Regulars Bar located at 668 King St. W., about a potential exposure to COVID-19. The period for potential exposure is September 13 to September 22.
In the last few days, tests have confirmed that three individuals linked to this establishment are positive for COVID-19. All three individuals are employees of the establishment. TPH has followed up with all known close contacts. The close contacts have been asked to self-isolate for 14 days and to go for testing.
If you were at Regulars Bar between September 13 and September 22 but have not been contacted by TPH, you are not identified as a close contact and are viewed as low risk.
TPH estimates approximately 600 people may have been at the venue during this time. As a precaution, TPH is asking anyone who was at Regulars Bar between September 13 and September 22 to monitor for COVID-19 symptoms for 14 days after their visit. If symptoms develop, please contact TPH, seek testing and immediately self-isolate. Please wear a mask when going for testing.
Regulars Bar has worked cooperatively with TPH throughout this investigation. TPH extends thanks to Regulars Bar management and other local businesses who are helping to reduce the spread of this virus by taking measures to keep staff, customers and the broader public safe.
Everyone is reminded to adopt these steps for self-protection: as much as possible limit contact with anyone you don’t live with; as often as possible, keep at least six feet apart from people you don’t live with; as often as possible, wear a mask when outside your home, especially in indoor settings and when physical distancing is difficult; wash your hands frequently; and remain at home when ill.
COVID-19 is spread primarily through respiratory droplets when a person who is infected with the virus coughs, talks or sneezes. Most people who get COVID-19 have mild symptoms, but some people can get very sick and may need to seek medical care at a hospital. The symptoms of COVID-19 may include feeling unwell, cough, fever, trouble breathing, loss of taste or smell, runny nose, sore throat, vomiting and/or diarrhea.
As COVID-19 continues to circulate in the community, TPH is stressing the important role the public plays in supporting contact tracing efforts and reducing virus spread. TPH also encourages residents to download the COVID Alert app, which can help to notify individuals who are exposed to COVID-19 in the community.
The City’s website is updated daily with the latest health advice and information about City services, social supports and economic recovery measures. Check toronto.ca/covid-19 for answers to common questions before contacting the Toronto Public Health COVID-19 Hotline or 311.


text:
It’s Women’s Equality Day in the U.S., celebrating the adoption of the Nineteenth Amendment that guaranteed women the right to vote. That was in 1920—a hundred and one years ago today.
Secretary of State Bainbridge Colby certified the ratification of the Nineteenth Amendment and American women finally won full voting rights. While Tennessee became the 36th state to ratify the amendment on August 18th it was not until August 26th that the ratification became official. The right for women to vote was first proposed in 1848, but did not become law until 1920, 72 years later.

domain: law


Hip-hop musical Hamilton chronicles the inspiring story of a poor orphan boy from the Caribbean who would one day grow up to become one of America’s founding fathers.
Now, high school students from across New York City will get the chance to become galvanized by Lin-Manuel Miranda’s rousing biographical show about Alexander Hamilton, thanks to a grant from the Rockefeller Foundation, a New York philanthropic organization.
According to The New York Times, the foundation and producers will fund a program to bring 20,000 New York City juniors—many of them from low-income families—to see matinees of Hamilton. They’ll also develop educational materials for students to understand the show—a website with copies of the primary documents on which the musical’s plot and lyrics are based, as well as information about Hamilton and other early American leaders. All students have to do is pay $10 per ticket—a substantial decrease from the usual sticker price which starts at $57, but are mostly selling in the triple digits.
The program will begin in spring 2016 and run through the following year. According to Rockefeller Foundation President Judith Rodin, its organizers think the show’s lyrically infused message will resonate with many New York City students.
“Here’s a story that talks about American history and the ideals of American democracy, and it features an immigrant who is impoverished initially and shows through perseverance and grit what he can achieve, in a vernacular that speaks to young people, written by a product of New York public education,” Rodin told the Times. “Could there possibly be a better combination in terms of speaking to students?”
[h/t The New York Times]


text:
The Power of Compound Interest
Learn how to harness the power of compound interest for your investments.
Have A Question About This Topic?
When you’re married and have children, insurance needs will be different.
Here’s a crash course on saving for college.
As our nation ages, many Americans are turning their attention to caring for aging parents.

domain: economics


text:
Using several in vitro models
of virus replication, we observed increased CFTR modulator replication for a reassortant CA/09 virus expressing the hemagglutinin (HA) gene of HK/483 (CA/09-483HA) relative to that of either parental CA/09 virus or reassortant CA/09 expressing other HK/483 genes. This increased replication correlated with enhanced pathogenicity in infected mice similar to that of the parental HK/483 strain. The serial passage of the CA/09 parental virus and the CA/09-483HA virus through primary human lung epithelial cells resulted in increased pathogenicity, suggesting that these viruses easily adapt to humans and become more virulent. In contrast, serial passage attenuated the parental HK/483 virus in vitro and resulted in slightly reduced morbidity in vivo, suggesting that sustained replication in humans attenuates H5N1 avian influenza viruses. Taken Selonsertib ic50 together, these data suggest that reassortment between cocirculating human pH1N1 and avian H5N1 influenza strains will result in a virus with the potential for increased pathogenicity in mammals.”
“Results from animal experiments showing that estradiol is neuroprotective were challenged 10 years ago by findings indicating an increased risk of dementia and stroke in women over 65 years of age taking
conjugated equine estrogens. Our understanding of the complex signaling of estradiol in neural cells has recently clarified the causes of this discrepancy. New data indicate that estradiol may lose its neuroprotective activity or even increase neural damage, a situation that depends on the duration of ovarian hormone deprivation and on age-associated modifications in the levels of
other molecules that modulate estradiol action. These studies highlight the complex neuroprotective mechanisms of estradiol and suggest a window of opportunity during which effective hormonal OSBPL9 therapy could promote brain function and cognition.”
“The antidepressant fluoxetine stimulates astrocytic glycogenolysis, which serves as an energy source for axons. In multiple sclerosis patients fluoxetine administration may improve energy supply in neuron cells and thus inhibit axonal degeneration. In a preliminary pilot study, 15 patients with multiple sclerosis (MS) were examined by diffusion tensor imaging (DTI) and (1)H magnetic resonance spectroscopy (MRS) in order to quantify the brain tissue diffusion properties (fractional anisotropy, apparent diffusion coefficient) and metabolite levels (choline, creatine and N-acetylaspartate) in cortical gray matter brain tissue, in normal appearing white matter and in white matter lesions. After oral administration of fluoxetine (20 mg/day) for I week, the DTI and MRS measurements were repeated and after treatment with a higher dose (40 mg/day) during the next week, a third series of DTI/MRS examinations was performed in order to assess any changes in diffusion properties and metabolism.


text:
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so charming! I love the colour palette too.
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[show abstract][hide abstract] ABSTRACT: Vaccinia virus (VACV) has been associated with zoonotic exanthemic outbreaks affecting bovids and human beings, with significant public health and economic impacts. Rapid and reliable diagnostic methods are needed to detect and epidemiologically monitor antibodies to VACV. The current study describes the development of an immunoperoxidase monolayer assay (IPMA) for detection of total VACV antibodies in bovine serum. The assay was validated by comparison with a plaque reduction neutralization test (PRNT). Kappa index of agreement, diagnostic sensitivity, specificity, and accuracy of the IPMA were -1.008, 100%, 96%, and 98%, respectively, when compared with PRNT on 148 field bovine sera. Repeatability tests on 32 field-positive serum samples revealed that intraclass coefficient correlation was 0.86. In experimentally infected cattle, VACV antibodies were detectable by IPMA 4 days postinfection, which was more than 2 weeks earlier than with the PRNT, indicating that IPMA could be a more sensitive test than the latter. In 4 naturally VACV-diseased cows monitored for 13 months, IPMA could detect VACV antibodies up to 13 months, a longer time than PRNT. The IPMA is simpler to produce and perform when compared with PRNT and is time saving and suitable for large-scale surveys of VACV infection in bovine.
Journal of veterinary diagnostic investigation: official publication of the American Association of Veterinary Laboratory Diagnosticians, Inc 03/2012; 24(2):355-8. · 1.18 Impact Factor
[show abstract][hide abstract] ABSTRACT: Occupational exanthematic diseases represent an important cause of public health impact and economical losses. Among the viral exanthematic diseases, two caused by poxviruses are noteworthy: the bovine vaccinia (BV), caused by the Vaccinia virus (VACV); and the milker's nodule, in which the agent is the Pseudocowpox virus (PCPV). Both agents are zoonotic and have been associated with several cases of bovine infection. In Brazilian rural areas BV has been highly prevalent, particularly in milk herds. Farmers, milkers and their close contacts developed lesions on the hands, forearms, legs and face accompanied by several systemic symptoms. Although VACV and PCPV present with similar epidemiological and transmission patterns, no VACV and PCPV co-infection cases have to date been described.
To describe the first case of zoonotic VACV and PCVP co-infection, based on serological and molecular methods.
In this work we report a case of a Brazilian rural worker who presented with a large severely ulcerated-pustule skin lesion, associated with fever, headache, malaise, myalgia and axillary, inguinal and cervical limphadenopathy. The worker declared occupational contact with cattle that had notable injuries on their teats. Human and bovine clinical samples were collected and submitted to serological and molecular tests. PCR and phylogenetic analysis revealed the presence of VACV DNA and PCPV DNA in the patient's lesion. Serological tests indicated anti-VACV neutralizing antibodies and molecular assays showed the presence of VACV and PCPV DNA in the patient sera. VACV and PCPV also were detected in dairy cattle.
Together, these results indicate a case of zoonotic VACV/PCPV co-infection. Epidemiological surveillance and appropriate medical treatment are essential for the control of both diseases, especially in the most severe cases, as described in the present study.
Journal of clinical virology: the official publication of the Pan American Society for Clinical Virology 03/2010; 48(1):69-72. · 3.12 Impact Factor
[show abstract][hide abstract] ABSTRACT: The vaccinia virus (VACV), which causes exanthemous lesions in dairy cattle and humans, has been associated with several bovine vaccinia outbreaks in Brazil. Currently, no data are available about the safety of milk produced in VACV-affected areas. In this study, 47 milk samples were collected during bovine vaccinia outbreaks and submitted to viral isolation, DNA detection, and nucleotide sequencing of the conserved tk gene. The appearance of characteristic white pocks on the chorioallantoic membranes of chicken eggs, in association with viral cytopathic effects in chicken embryo fibroblasts and phylogenetic data, strongly suggest milk contamination by VACV. This is the first report of VACV detection in and isolation from milk.
Foodborne Pathogens and Disease 11/2009; 6(9):1141-6. · 2.28 Impact Factor
[show abstract][hide abstract] ABSTRACT: Atomic force microscopy (AFM) is a versatile technique that permits the imaging of surfaces and generates topographical images from a variety of materials. Due to the fact that AFM requires minimum sample manipulation, it is a valuable tool for studying biological materials such as cells, DNA, bacteria and viruses. The aim of the present study was to standardize the AFM technique as a diagnostic tool for detection of naturally occurring orthopoxviruses. The samples analyzed were collected during natural outbreaks of Vaccinia virus (VACV) in dairy cattle in Brazil. These viruses are zoonotic infections; and therefore safe manipulation of all samples is required. The AFM technique would provide a more secure way to diagnose infection. By using the "in air" AFM technique after purification and inactivation process, relatively crude preparations of viruses were visualized rapidly. Details for efficient sample preparation and AFM imaging are described. The AFM technique provides a rapid and biosecure tool for the diagnosis of emerging orthopoxviruses and has potential as a tool for screening bioterrorism samples.
Journal of Virological Methods 06/2007; 141(2):198-204. · 1.90 Impact Factor
[show abstract][hide abstract] ABSTRACT: Passatempo virus was isolated during a zoonotic outbreak. Biologic features and molecular characterization of hemagglutinin, thymidine kinase, and vaccinia growth factor genes suggested a vaccinia virus infection, which strengthens the idea of the reemergence and circulation of vaccinia virus in Brazil. Molecular polymorphisms indicated that Passatempo virus is a different isolate.


text:
How the brain starts going downhill at 45: Scientists find mental decline sets in much earlier than they had thought
British men and women suffer the same 3.6 per cent loss between the ages of 45-49
Whilst older men aged 65-70 fare worse with a 9.6 per cent drop in comparison with the 7.4 for their female counterparts
Memory and other brain skills begin to decline at the age of 45 – much earlier than previously thought, say researchers.
A major study shows the brain's capacity for memory, reasoning and comprehension starts waning in middle age rather than in the 60s.
Experts say the finding is important because younger people should be encouraged to boost their brain power with healthier living, while some may benefit from medicines to stave off further decline.
Question marks raised: Men and women suffer brain loss as early as their mid-40s
With an ageing population – one in four Britons will be older than 65 by the year 2035 – doctors claim ‘cognitive ageing will be one of the challenges of this century’.
Researchers from the Centre for Research in Epidemiology and Population Health in France and University College London in the UK studied more than 7,000 people over a 10-year period.
The study looked at civil servants aged between 45 and 70 working in London when cognitive testing began in 1997 to 1999.
Cognitive function was measured three times over 10 years to assess memory, vocabulary, hearing and visual comprehension skills.
Tasks included recalling in writing as many words beginning with the letter S as possible and as many animal names as could be thought of.
All cognitive scores, except vocabulary, declined among all age groups during the study, and there was evidence of faster decline among older people.
In men, there was a 3.6 per cent drop in reasoning after 10 years among those who were aged 45 to 49 at the start of the study and 9.6 per cent among those aged 65 to 70.
In women, the decline was 3.6 per cent and 7.4 per cent in the same age groups, says a report published online in the British Medical Journal (must credit).
Dr Archana Singh-Manoux, who led the study, said there had been debate over when mental skills started failing, with some researchers concluding there was little evidence of problems before 60.
But this was disproved by the study findings, she added.
She said ‘Cognitive decline is already evident in middle age, between 45-49 years.
‘The results for all tests, except vocabulary, showed significant declines in all age categories in both men and women.’
The study says diseases such as dementia are believed to take at least 20 to 30 years to develop but promoting healthy lifestyles and good heart health could help.
‘There is emerging consensus that 'what is good for our hearts is also good for our heads', making aggressive control of behavioural and cardiovascular risk factors as early as possible key targets for clinical practice and public health’ it said.
Medicines and other medical interventions are more likely to work at an earlier age, so could be used in people whose cognitive decline is faster than the average, it said.
Previous research suggests around half of people with diagnosed mild cognitive impairment (MCI) develop Alzheimer’s.
In cases of MCI, a person has cognitive or memory problems which are more marked than typical age-related memory loss, but not yet as severe as those found in Alzheimer’s disease.
Dr Simon Ridley, head of research at Alzheimer’s Research UK charity, said ‘Experts believe that Alzheimer’s disease, the most common cause of dementia, begins to develop in mid-life.
Researchers for the Alzheimer's society said the results are unclear as to whether people then go on to suffer from dementia
‘Although this study didn’t look at dementia, it would be important to follow up these participants to see which people go on to develop the condition, and it would be helpful to see similar studies carried out in a wider sample.
‘Previous research suggests that our health in mid-life affects our risk of dementia as we age, and these findings give us all an extra reason to stick to our New Year’s resolutions.
‘Although we don’t yet have a sure-fire way to prevent dementia, we do know that simple lifestyle changes – such as eating a healthy diet, not smoking, and keeping blood pressure and cholesterol in check – can all reduce the risk of dementia.
‘With 820,000 people in the UK affected by dementia, it’s vital that we invest in research to find new ways to prevent and treat this devastating condition.’
Dr Anne Corbett, research manager of the Alzheimer’s Society, said ‘This large, important study adds vital information to the debate over when cognitive decline begins.
'However, the study does not tell us whether any of these people went on to develop dementia, nor how feasible it would be for GPs to detect these early changes.
‘More research is now needed to help us fully understand how measurable changes in the brain can help us improve diagnosis of dementia.
'An early diagnosis is essential as it can provide access to support and potential treatments which can vastly improve people’s quality of life.’
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domain: medical


text:
Thermal effect in laser perforation of liver
Paper #3288 received 11 Apr 2018; revised manuscript received 25 May 2018; accepted for publication 25 May 2018; published online 17 Jun 2018.
One of the trends in the development of modern regeneration medicine is the application of high-intensity laser radiation for deep perforation of biological tissues, stimulating the regeneration of structure and functions of the pathologically changed tissues. In the paper, the possibility to control the location and parameters of the biotissue thermal stimulation zones is studied theoretically and experimentally, depending on the conditions of laser perforation in application to the liver laser-induced regeneration problem. The results of numerical simulation revealed the basic trends in the behaviour of the thermal stimulation zone, which are in good agreement with the experimental data on laser perforation of soft biotissues ex vivo using an optical fibre.
1. I. I. Berishvili, Transmyocardial Laser Revascularisation, GEOS, Moscow, Russia (2016) [in Russian]. ISBN 978-5-89118-703-0
2. X. M. Mueller, H. T. Tevaearai, C. Y. Genton, P. Chaubert, and L. K von Segesser, “Are there vascular density gradients along myocardial laser channels?” The Annals of Thoracic Surgery 68(1), 125-129 (1999). Crossref
3. X. M. Mueller, H. T. Tevaearai, C. Y. Genton, P. Chaubert, and L. K von Segesser, “Improved neoangiogenesis in transmyocardial laser revascularization combined with angiogenic adjunct in a pig model,” Clinical Science 99(6), 535-540 (2000). Crossref
4. D. I. Alyokhin, A. A. Fokin, “Prospects of using high-intensity laser radiation for the treatment of chronical ischemia of extremities,” Patologiya krovoobrashcheniya i kardiokhirurgiya 2, 88-92 (2005) [in Russian].
5. S. V. Kapralov, I. A. Mel’nikova, U. G. Shapkin, and V. V. Alipov, “Experimental modelling of laser fenestration of liver,” Byulleten’ meditsinskikh Internet-konferentsii 1(2), 47 (2011) [in Russian].
6. I. A. Shved, T. E. Vladimirskaya, A. V. Vorobey, O. P. Shorez, S. V. Alexandrov, and A. C. Shuleiko, “Liver tissue regeneration after laser coagulation,” Zdravookhraneniye (Belarus) 3, 4-8 (2014) [in Russian].
7. L. Lamalice, F. Le Boeuf, and J. Huot, “Endothelial cell migration during angiogenesis,” Circulation Research 100(6), 782-794 (2007). Crossref
8. A. Briolay, R. Jaafar, G. Nemoz, and L. Bessueille, “Myogenic differentiation and lipid-raft composition L6 skeletal muscle cells are modulated by PUFAs,” Biochimica et Biophysica Acta (BBA) – Biomembranes 1828(2), 602-613 (2013). Crossref
9. A. Dolganiuc, “Role of lipid rafts in liver health and disease,” Would Journal of Gastroenterology 17(20), 2520-2535 (2011). Crossref
10. M. Troyanova-Wood, J. D. Musick, B. L. Ibey, R. J. Thomas, and H. T. Beier, “Observation of changes in membrane fluidity after infrared laser stimulation using a polarity-sensitive fluorescent probe,” Proceeding of SPIE 8941, 89410I (2014). Crossref
11. L. Jin, C. Millard, J. P. Wuskell, H. A. Clark, and L. M. Loew, “Cholesterol-enriched lipid domains can be visualized by di-4-ANEPPDHQ with linear and nonlinear optics,” Biophysical journal: biophysical letters 89(1), L04-L06 (2005). Crossref
12. A. J. Garcia-Saez, S. Chiantia, and P. Schwille, “Effect of line tension on the lateral organization of lipid membranes,” Journal of Biological Chemistry 282(46), 33537–33544 (2007). Crossref
13. G. Muller, K. Dorschel, and H. Kar, “Biophysics of photoablation process,” Lasers in Medical Science 6(3), 241-254 (1991). Crossref
14. N. N. Kalitkin, Numerical Methods, Nauka, Moscow, Russia (1978) [in Russian].
15. O. I. Baum, “Temperature control system for laser reshaping of nasal septum,” Izvestiya Vysshikh Uchebnykh Zavedeniy. Priborostroenie 58(10), 847-854 (2015) [in Russian]. Crossref
16. O. I. Baum, Y. M. Soshnikova, E. N. Sobol, A. Ya. Korneychuk, M. V. Obrezkova, V. M. Svistushkin, O. K. Timofeeva, and V. V. Lunin, “Laser reshaping of costal cartilage for transplantation,” Lasers in surgery and medicine 43(6), 511-515 (2011). Crossref
17. A. V. Yuzhakov, A. P. Sviridov, E. M. Shcherbakov, O. I. Baum, and E. N. Sobol, “Optical properties of costal cartilage and their variation in the process of non-destructive action of laser radiation with the wavelength 1.56 μm,” Quantum Electronics 44(1), 65 (2014). Crossref
18. O. I. Baum, E. N. Sobol, A. V. Bolshunov, A. A. Fedorov, O. V. Khomchik, A. I. Omelchenko, and E. M. Shcherbakov, “Microstructural changes in sclera under thermo-mechanical effect of 1.56 µm laser radiation increasing transscleral humor outflow,” Lasers in surgery and medicine 46(1), 46-53 (2014). Crossref
19. O. Baum, S. Wachsmann-Hogiu, T. Milner, and E. Sobol, “Laser-assisted formation of micropores and nanobubbles in sclera promote stable normalization of intraocular pressure,” Laser Physics Letters 14(6), 065601 (2017). Crossref
20. E. Sobol, A. Shekhter, A. Baskov, O. Baum, I. Borchshenko, V. Golubev, A. Guller, I. Kolyshev, A. Omeltchenko, A. Sviridov, and O. Zakharkina, “Regeneration of spine disc and joint cartilages under temporal and space modulated laser radiation,” Proceeding of SPIE 7179, 71790B (2009). Crossref
21. E. Sobol, A. Shekhter, A. Guller, O. Baum, and A. Baskov, “Laser-induced regeneration of cartilage,” Journal of Biomedical Optics 16(8), 080902 (2011). Crossref
22. E. Sobol, O. Baum, A. Shekhter, S. Wachsmann-Hogiu, A. Shnirelman, Y. Alexandrovskaya, I. Sadovskyy, and V. Vinokur, “Laser-induced micropore formation and modification of cartilage structure in osteoarthritis healing,” Journal of Biomedical Optics 22(9), 091515 (2017). Crossref
23. M. N. Libenson, E. B. Yakovlev, and G. D. Shandybina, “Interaction of Laser Radiation with Matter (Power Optics),” Lecture Notes. Part II. Laser Heating and Material Destruction, V. P. Veyko (Ed.), ITMO, Saint-Petersburg (2006) [in Russian].
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