In vivo gene editing grabs the spotlight after Intellia triumph, but challenges loom

by Arlene Weintraub | Sep 29, 2021 3:00am

Gene therapy

In vivo gene editing drugs are designed to be injected directly into patients to correct genetic diseases. (LuckyStep48/Getty Images)ShareFacebookTwitterLinkedInEmailPrint

In early September, 15-year-old gene therapy developer Precision BioSciences devoted its entire two-hour R&D presentation to products in its pipeline that involve in vivo gene editing—therapies designed to be injected directly into patients to correct genetic diseases.

Co-founder and Chief Scientific Officer Derek Jantz, Ph.D., kicked off the event with a deep dive into the in vivo therapies Precision is developing to address four different diseases, and then he took questions from Wall Street analysts. Much of Jantz’s presentation, and several of the questions that followed, focused on whether the company’s technology could adequately ameliorate the risk of off-target gene editing—inadvertent changes to patients’ DNA that could cause dangerous side effects.

The event, therefore, was a perfect snapshot of the sentiments surrounding gene therapy right now.


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On the one hand, investors are enthusiastic about the next generation of gene-focused treatments, most notably in vivo gene editing. That field got a major boost in June when Intellia Therapeutics’ stock skyrocketed on positive first-in-human data for its in vivo candidate, NTLA-2001, designed to treat patients with transthyretin amyloidosis.

But all of these companies are advancing their next-generation gene therapies toward the clinic at a time when the first generation is coming under intense scrutiny.

On Sept. 3, an FDA advisory committee spent two days discussing safety concerns surrounding currently marketed gene therapies, including Novartis’ Zolgensma to treat spinal muscular atrophy and Spark Therapeutics’ Luxturna used to treat an inherited eye disease. The emergence of liver toxicity, neuron loss and other side effects has the FDA reconsidering everything from the preclinical models used to assess the safety of gene therapies to screening methods that might select the patients least likely to suffer adverse events.

Related: FDA committee takes on complex gene therapy safety questions with Novartis’ Zolgensma providing lessons learned

Much of the discussion around the next generation of gene therapies centers on how they’re delivered to the body. The treatment that launched in vivo gene editing into the spotlight, Intellia’s NTLA-2001, uses a lipid nanoparticle (LNP) to precisely knock out a disease-causing gene in the liver with the gene-editing technology CRISPR/Cas9. Other in vivo contenders are employing a wide range of delivery vehicles and editing technologies, in hopes of moving beyond what Precision’s Jantz refers to as the “low-hanging fruit.”

“You can use any gene-editing technology to knock genes out in the liver. But there is a limited number of diseases one can treat that way,” Jantz said in an interview with Fierce Biotech. “To treat the vast majority of genetic diseases, you have to deliver your technology to some other organ.”

Precision’s core technology, called ARCUS, uses sequence-specific enzymes called nucleases to cut DNA and then insert, remove or fix genes. It’s designed not only to be able to penetrate tissues outside of the liver but also to be more compact than other editing technologies, Jantz said. Those attributes are key to one of Precision’s lead programs, a Duchenne muscular dystrophy (DMD) treatment that will be delivered to muscle.

The treatment cuts out 10 coding portions, or exons, of the gene that makes dystrophin, a protein key to muscle function. Most of the mutations that cause DMD occur within that 10-exon stretch, Jantz explained. “We’ve shown we can use ARCUS to chop out the entire region, which creates a slightly truncated but functional form of the dystrophin gene,” he said.

Precision developed ARCUS in a way that allows it to tag the portions of the genome it cuts, leaving behind a signature that its scientists can use to detect off-target edits. They can then use that information to fine-tune the enzymes and lower the risk of off-target editing, Jantz said.

Precision is working on the DMD program and two others with Eli Lilly, which inked a $135 million deal with the company last November. Safety was a major factor in Lilly’s decision to partner with Precision, said Ruth Gimeno, Ph.D., vice president of diabetes and metabolic research at Lilly, in a video shown at Precision’s R&D day. “We … need a high degree of specificity, because safety is always on our minds,” she said.

Related: Lilly, Precision Biosciences team up on Duchenne gene therapy in $135M deal  

In all the hoopla surrounding Intellia’s in vivo gene editing results, it’s easy to forget that it wasn’t the first company to report data from a clinical trial of the new technology. In 2019, Sangamo Therapeutics posted phase 1/2 data from a trial of SB-913, which used the company’s zinc finger technology to repair a faulty gene that causes Mucopolysaccharidosis type II (MPS II), which is also called Hunter syndrome.

Sangamo’s zinc fingers are engineered to bind to specific DNA sequences and insert therapeutic nucleases or transcription factors into them. In the case of SB-913, the technology cut the DNA of certain liver cells and deposited a functional copy of the IDS gene, which made an enzyme that patients with Hunter syndrome lack.

Problem was, IDS levels rose in only one of the six patients enrolled in the trial, and levels of the enzyme started falling after six weeks. Sangamo CEO Sandy Macrae explained in an interview that the problem was traced not to the technology, but to the delivery vehicle, which in the case of SB-913 was an adenovirus vector (AAV). “Our analysis of it is that we didn’t get enough of the [gene editing] components in every cell,” he said.

So Sangamo went back to the drawing board and is now investigating several alternative delivery techniques, including lipid nanoparticles and capsids that may be able to transport gene-editing technology via IV injection. It has formed several partnerships to advance the research, including one with Takeda focused on Huntington’s disease and another with Pfizer to work on amyotrophic lateral sclerosis and frontotemporal degeneration.

Beam Therapeutics, which is working on in vivo gene editing approaches to treating liver and eye diseases, is also increasing its stable of delivery technologies. In February, it paid $120 million to acquire Georgia tech spinout GuideTx and its lipid nanoparticle technology.

Guide created DNA “barcodes” for several formulations of LNPs, which will allow Beam’s scientists to identify delivery vehicles that are optimized to target specific organs and tissues. “We believe LNP has the opportunity to become a much broader delivery technology across the body than what was originally anticipated,” said Pino Giuseppe Ciaramella, Ph.D., chief scientific officer of Beam, in an interview.

The quest for better vectors to deliver in vivo gene editing has generated excitement for some startups working in that area, including Ensoma, which launched in February with $70 million in venture capital to develop its Engenious vectors. They’re adenoviruses that have been cleared of all their viral DNA and RNA, leaving room for therapeutic gene-editing material that might be too big to fit into other vectors.

What’s more, “they’re engineered to be very specific to hematopoietic stem cells, so they won’t get into the liver and produce off-target effects,” said Paula Soteropoulos, executive chairman of Ensoma, in an interview.

Sangamo’s Macrae predicts that several in vivo editing approaches will ultimately work, benefiting patients with a wide range of diseases—provided the delivery challenges can be overcome, safely of course.

“In vivo gene editing was always going to happen,” he said. “What Intellia’s announcement proved was that LNP could deliver CRISPR without damaging the liver. In five to 10 years, we won’t hear about what form of editing it is. It’s all going to be about the delivery and getting enough of the technology into the cell.”

Time to ditch the smartphone at bedtime? Children who use electronic devices at night sleep less and have poorer quality slumber, study warns

  • Children sleep less if they use smartphones and tablets, a new study has warned
  • The researchers said those aged between six and 15 years old are most affected
  • In children five and under, TV and tablets were the main culprits for shorter sleep
  • University of Southern Denmark team reviewed 49 studies from 2009 to 2019


PUBLISHED: 12:08 EDT, 30 September 2021 | UPDATED: 12:20 EDT, 30 September 2021

41shares45View comments

Children sleep less and have poorer quality slumber if they use smartphones, tablets and other electronic devices at night, a new study has warned.

Those aged between six and 15 years old are most likely to be affected, the researchers said, blaming video gaming, computers, phones, internet use and watching television.

In children aged five and under, television and tablets were the main culprits for shorter sleep.Children sleep less and have poorer quality slumber if they use smartphones, tablets and other electronic devices at night, a new study has warned (stock image)+2

Children sleep less and have poorer quality slumber if they use smartphones, tablets and other electronic devices at night, a new study has warned (stock image) 

How much sleep do children need? 

According to the NHS, the recommended sleep durations are:

Babies 4 to 12 months old – 12 to 16 hours including naps

Toddlers 1 to 2 years old – 11 to 14 hours including naps

Children 3 to 5 years old – 10 to 13 hours including naps

Children 6 to 12 years old – 9 to 12 hours

Teenagers 13 to 18 years old – 8 to 10 hours

The research by the University of Southern Denmark reviewed 49 studies published between 2009 and 2019, with the studies involving between 55 and 369,595 children. 

Experts looked at the association of electronic media use, including media type and duration, with sleep patterns. 

The authors considered bedtime and sleep onset, sleep quality (waking up at night), sleep duration and daytime tiredness. 

They found a link between electronic device use and delayed bedtime and poor sleep quality in children aged six to 12, while screen time among teenagers aged 13 to 15 was associated with problems falling asleep.

Social media use was also to blame for poor sleep quality among teenagers, the researchers said.

They say this interactive media may be overly stimulating, which may explain why the age group get less sleep.

In all age groups, exposure to blue light from screens may suppress the production of melatonin – the hormone that regulates sleep – leading to poorer sleep duration and disturbing the natural sleep-wake cycle, the study found. 



ShareResearchers found a link between electronic device use and delayed bedtime and poor sleep quality in children aged six to 12, while screen time among teenagers aged 13 to 15 was associated with problems falling asleep (stock image)+2

Researchers found a link between electronic device use and delayed bedtime and poor sleep quality in children aged six to 12, while screen time among teenagers aged 13 to 15 was associated with problems falling asleep (stock image)

Lisbeth Lund, lead author, said: ‘It is important that children and adolescents get sufficient sleep to avoid negative health consequences. News, Sport, Showbiz, Celebrities from Daily MailPauseNext video0:00 / 2:15SettingsFull-screenRead More

‘We also understand that media is an important part of our lives. 

‘Our findings suggest that parents may wish to regulate how much their children are engaging with electronic media to potentially improve sleep.’

The 49 studies reviewed included children from North America, Europe, Australia, New Zealand, and other Western countries.  Too much screen time may be a danger for kidsLoaded: 0%Progress: 0%0:00PreviousPlaySkipMuteCurrent Time0:00/Duration Time4:07FullscreenNeed Text

However, the authors of the research said most of the studies were observational and therefore did not allow for conclusions about cause and effect or the direction between the association of media use and sleep quality.

They said more research was needed to draw solid conclusions about electronic media’s impact on sleep. 

‘Public awareness and interventions could be promoted about the potential negative impact on children’s sleep of electronic media devices that are used excessively and close to bedtime,’ the researchers wrote in the paper.

A previous study has also warned that spending more than an hour a day watching programmes on devices may increase the risk that toddlers will have emotional and behavioural issues.

These issues include hyperactivity, poor concentration, short attention spans and trouble connecting with other children and forging friendships.

The researchers, led by social scientist Janette Niiranen of the Finnish Institute for Health and Welfare in Helsinki, speculated that devices are reducing the time that children spend reading, playing and interacting with family, or other youngsters.

The latest research has been published in the journal BMC Public Health


A recent study by San Diego State University found that the happiest teenagers were those who limited their daily digital media time to slightly less than two hours a day.

After this daily hour of screen time, unhappiness rose steadily with increasing screen time. 

Looking at historical trends from the same age groups since the 1990s, the researchers found the proliferation of screen devices over time coincided with a general drop-off in reported happiness in American teenagers. 

Study participants born after 2000 were less satisfied with life, had lower self-esteem and were unhappier than those who grew up in the 1990s.

Since 2012, the average teenager’s life satisfaction, self-esteem and happiness has plummeted.

That year marked the point when the proportion of Americans who owned a smartphone rose above 50 per cent for the first time.

ASML’s next-gen EUV machine will give Moore’s Law a new lease of life

The march of progress in semiconductors is far from over

By Adrian Potoroaca 7 comments

ASML's next-gen EUV machine will give Moore's Law a new lease of life

In context: ASML may not be a household name like Intel, Samsung, or even TSMC. However, the Dutch company is the world’s only supplier of advanced extreme ultraviolet (EUV) equipment that allows tech giants to pack increasing numbers of transistors onto tiny chips that power a wide variety of devices. Current generation EUV machines are already marvels of engineering that shrink the wavelength of light used to etch ever-smaller features on microchips, but ASML says it’s readying a newer version that will give the semiconductor industry a new lease on life for the next decade.

Moore’s Law has been on life support for a while now, but it’s not dead yet. ASML says its latest EUV lithography machine will extend the validity of the idea that chipmakers can cram an increasingly higher number of transistors on a silicon substrate for the next 10 years or so.

As of writing, the Dutch company is the world’s sole supplier of EUV equipment, which is used to etch tiny nanoscopic features into chips using ultraviolet light. The company’s first machines started humming in 2017, and are a crucial part of the chipmaking ecosystem that has been churning out ever more advanced silicon for a variety of devices.

The company’s EUV machines are just as expensive as they are advanced. Each one costs $150 million and contains over 100,000 parts and two kilometers of cabling, all of which are a logistical nightmare to source and assemble. That’s why you can count the companies that can afford them using just the fingers on one hand. Most of the machines, however, end up at manufacturing plants that are owned by Intel, Samsung, and TSMC.

Starting in 2023, ASML plans to deliver the first batch of next-generation EUV equipment that will take the EUV numerical aperture (NA) higher than current machines are capable of, from 0.33 NA to 0.55 NA. This will enable chipmakers to develop process nodes well beyond the current expected threshold of 2 nm, and should also yield some cost savings when using a single-expose EUV process for advanced wafer layers.

The first of these new machines will be a prototype that will be tested throughout 2022. As for which chipmaker will be the first to make chips, that would be Intel, who wants to use them in mass production as early as 2023. The tech giant has recently embarked on a multi-year process to regain leadership in process and packaging technologies, and high-NA EUV tools are a key part of this plan. In fact, if Intel’s IDM 2.0 initiative has any chance of being successful, it needs all the help it can get from ASML.

TSMC is also interested in acquiring as much of this next-generation lithography equipment as possible. The Taiwanese company currently accounts for half of the industry’s EUV equipment installation base and wafer production, and has plans to expand capacity with two state-of-the-art 2 nm GigaFabs. Ironically, TSMC used to be a EUV non-believer, but today it is ASML’s biggest customer thanks to Apple’s insistence that EUV is the key to smaller, more powerful, and more energy-efficient chips.

Following the EUV path has allowed TSMC to accelerate past Intel and Samsung, but Intel could turn the tides by becoming an early adopter of high-NA EUV tech. At the same time, Samsung is also looking to get in on the action with a $205 billion commitment that is largely directed at conquering semiconductors. It, too, has benefited greatly over the years from its $306 million investment it made into ASML more than a decade ago, and has expressed interest in getting a stable supply of advanced EUV equipment from the latter company.

While Intel, Samsung, and TSMC seem to be well positioned to benefit from ASML’s innovations, there are companies that have significant barriers in doing so, both financial and political. Most notably, Chinese companies like Semiconductor Manufacturing International Corp. (SMIC) have been scrambling to catch up with the rest of the semiconductor industry, but they’re also on the US Entity List.

This means they’re effectively barred from purchasing advanced lithography equipment, as the US government has also ensured that ASML won’t sell any EUV machines to Chinese companies, at least for now. ASML CEO Peter Wennink doesn’t think this strategy will ultimately bode well for the US economy, as he believes China has both the drive and the means to make progress on its own while non-Chinese economies will suffer a loss of jobs and income. And you only need to look at YMTC’s recent 128-layer 3D NAND success to understand that he’s right.

Circling back to ASML, the company predicts a sales boom that will propel its annual revenue to new heights by 2025. Previously, the forecasted annual revenue was in the $17 to $28 billion range, but now the company is confident it will be in the $28 to $35 billion range, with gross margins between 54 percent and 56 percent. The new figures hinge on the current surge in demand for everything with a chip in it, which has all the world’s foundries and component suppliers firing up on all cylinders.

Mapped: The Fastest (and Slowest) Internet Speeds in the World

Published 1 day ago 

on September 29, 2021

ByCarmen AngTweetShareShareRedditEmail

How to Use: The below maps will animate automatically. To pause, move your cursor on the image. Arrows on left/right navigate.


12▼ Use This Visualization

Mapped: The World’s Fastest (and Slowest) Internet Speeds

How quickly did this page load for you?

The answer depends on the device you’re using, and where in the world you’re located. Average internet speeds vary wildly from country to country.

Which countries have the fastest internet connection? Using data from the Speedtest Global Index™, this map ranks the fastest (and slowest) internet speeds worldwide, comparing both fixed broadband and mobile.

What Factors Affect Internet Speed?

Before diving in, it’s important to understand the key factors that impact a country’s internet speed. Generally speaking, internet speed depends on:

  1. Infrastructure or the type of cabling (copper or fiber-optic) that a country’s utilizing to support their internet service. Typically, the newer the infrastructure, the faster the connection.
  2. Proximity/connection to submarine cables is important, as these massive undersea fiber-optic cables transmit about 97% of the world’s communication data.
  3. The size of a country, since landmass affects how much it costs to upgrade infrastructure. The smaller the country, the cheaper it is to upgrade cabling.
  4. Investment makes a difference, or how much a country’s government prioritizes internet accessibility.

Of course, other factors may influence a country’s internet speed too, such as government regulation and intentional bandwidth throttling, which is the case in countries like Turkmenistan.

Ranked: Fixed Broadband Internet Speeds

The Speedtest Global Index uses data from hundreds of millions of people, in more than 190 countries, to measure both fixed broadband and mobile connections.

When it comes to the fastest fixed broadband, Singapore comes in first place, with a download speed of 262.2 mbps—more than double the global average.Search:

#CountryGlobal Speed (Mbps)
1🇸🇬 Singapore262.2
2🇭🇰 Hong Kong254.4
3🇲🇨 Monaco242.9
4🇨🇭 Switzerland222.0
5🇹🇭 Thailand221.0
6🇷🇴 Romania217.9
7🇰🇷 South Korea216.7
8🇩🇰 Denmark216.13
9🇨🇱 Chile209.8
10🇫🇷 France201.6

Showing 1 to 10 of 180 entriesPreviousNext

Size could be a factor in Singapore’s speedy internet, as it’s one of the smallest
and also densest countries in the world. With a landmass of just 280 square miles, it’s around the same size as Austin, Texas.

The country’s government has also prioritized investment in digital infrastructure, especially in recent years. In 2020, the Singaporean government promised to invest $2.52 billion towards digital innovation, with a portion dedicated to upgrading the country’s telecom infrastructure.

At the opposite end of the spectrum, Cuba has the slowest fixed broadband, with a speed of 3.46 mbps. Along with poor government funding, Cuba also has limited access to submarine cables. While most countries are connected to several, Cuba is only connected to one.

Ranked: Mobile Internet Speeds

Mobile internet uses cell towers to wirelessly transmit internet to your phone. Because of this extra element, the ranking for mobile internet speeds varies from fixed broadband.Search:

#CountryGlobal Speed (Mbps)
1🇦🇪 United Arab Emirates195.52
2🇰🇷 South Korea192.16
3🇳🇴 Norway173.54
4🇶🇦 Qatar169.17
5🇨🇳 China163.45
6🇸🇦 Saudi Arabia149.95
7🇰🇼 Kuwait141.46
8🇨🇾 Cyprus136.18
9🇦🇺 Australia126.97
10🇧🇬 Bulgaria126.21

Showing 1 to 10 of 140 entriesPreviousNext

The United Arab Emirates (UAE) is first on the list, with a download speed of 195.5 mbps. Not only is mobile data fast in the UAE, it’s also relatively cheap, compared to other countries on the ranking. The average cost of 1 GB of data in the UAE is around $3.78, while in South Korea (#2 on the list) it’s $10.94.

The Future is 5G

Innovation and new technologies are changing the digital landscape, and things like 5G networks are becoming more mainstream across the globe.

Because of the rapidly changing nature of this industry, the data behind this ranking is updated monthly to provide the latest look at internet speeds across the globe.

This means the bar is gradually raising when it comes to internet speed, as faster, stronger internet connections become the norm. And countries that aren’t equipped to handle these souped-up networks will lag behind even further.

More than half of young people have trouble sleeping – NHS

Research by NHS Digital also shows eating problems among young in England almost doubling since 2017

Young person under duvet showing feet and chocolate labrador on bed
The survey said 57% of those aged 17-23 struggled to sleep, as did 29% of those aged six-10 and 38% of those aged 11-16. Photograph: Sabena L/Getty Images/EyeEm

Denis Campbell Health policy editorThu 30 Sep 2021 17.41 BST

Children and young people are experiencing an epidemic of sleeping problems amid a sharp decline in their mental health triggered by the pandemic, stark new NHS figures show.

Recent years have also seen a dramatic rise in the number of young people of school age who suffer from eating problems, according to a major report into the wellbeing of that age group.Advertisement

The report, by NHS Digital, also found that most children and young people in England aged 11 to 23 thought Covid restrictions had made their life worse or much worse. The research was conducted in February and March among 3,667 people aged six to 23.

It found that 28.7% of six to 10-year-olds had trouble sleeping on three or more nights in the previous week. Problems getting to sleep, waking in the night or waking early were even more common among older children, affecting more than a third (38.4%) of 11- to 16-year-olds and the majority – 57.1% – of young people aged 17 to 23.

Experts said disrupted sleep could damage young people’s concentration at school and advised parents to limit their children’s access to digital devices close to bedtime.Advertisement

Tom Madders, the director of campaigns at YoungMinds, said: “Teenagers may experience altered sleep patterns as it’s not uncommon for them to stay awake late into the night using their phones, watching TV or gaming.

“This could interfere with everyday life and cause stress with their parents. Having time away from screens to wind down and going to bed at a reasonable time can help.”

The academics who undertook the survey found that since 2017, the percentage of children and young people who may have an eating problem had almost doubled among 11- to 16-year-olds, from 6.7% to 13%, and had increased from 44.6% to 58.2% in those aged 17 to 19.

While just one in 20 (5%) of 11- to 16-year-olds said they were often or always lonely, more of those aged 17 to 22 – one in eight (13%) – reported the same feelings.

Asked how coronavirus limits on social mixing since spring 2020 had affected their life, 55.8% of 11- to 16-year-olds said it had made it a little or much worse, as did 70.4% of those aged 17 to 23.

Then report also found that one in six (17.4%) of young people aged six to 19 had a “probable mental disorder”. That was the same proportion as when the survey was undertaken last year, five months into the pandemic, which was a big jump on the one in nine deemed to have some sort of mental health problem in 2017.

Overall, 39% of six to 16-year-olds and 53% of those aged 17 to 23 have seen their mental health worsen since 2017, though experts are unclear how much of that is directly related to Covid.

Emma Thomas, YoungMinds’ chief executive, said: “The data shows the alarming pressure young people are facing with their mental health, with many experiencing isolation, loneliness and reduced support caused in part by the pandemic.

“Worryingly, it has become clear that the sharp rise in prevalence we saw at the start of the pandemic was not simply a moment in time.”

Dr Tamsin Newlove-Delgado of Exeter University, one of the report’s co-authors, said the pandemic meant that “many young people have found it very challenging to negotiate the milestones of leaving school or home, starting work or study or looking for jobs in very different circumstances.

“Two-fifths of young people with a probable mental disorder also reported that they hadn’t sought any help or advice between August 2020 and spring 2021, which is worrying, when we know that getting treatment early can help prevent more severe problems later,” she added.

The report also found that:

  • 17% of 11- to 16-year-olds said the number of likes, shares and comments they got on social media affected their mood.
  • Most children that age had not used alcohol (94%), cigarettes (98%) or cannabis or other drugs (99.2%) in the previous week.
  • The percentage of those aged 17 to 22 who had consumed alcohol in the last week had fallen from 56% last year to 43% this year.
  • One in six (16%) children aged six to 16 live in a family that has problems functioning.

By many measures, the mental health of girls and young women is worse than their male peers. For example, more girls (43%) than boys (34%) aged 11 to 16 have seen their mental health deteriorate since 2017, and more girls and young women than boys and young men reported feeling lonely.Advertisement

Sarah Hughes, chief executive of Centre for Mental Health thinktank, said the government’s plans to end the £20-a-week universal credit uplift and Covid furlough scheme “will put children and families across the country at extra risk of mental ill-health”.

NHS England said: “The pandemic has inevitably had an impact on the nation’s mental health, with parents and young people especially stepping up to overcome the challenges posed by the pandemic, and NHS teams supporting over 600,000 children and young and providing specialist mental health care.”

Hippocampus Is the Brain’s Storyteller

FeaturedNeuroscienceOpen Neuroscience Articles·September 29, 2021

Summary: The hippocampus brings pieces of memories together over time and forms them into connective, narrative memories.

Source: UC Davis

People love stories. We find it easier to remember events when they are part of an overarching narrative. But in real life, the chapters of a story don’t follow smoothly one from another. Other things happen in between.

A new brain imaging study from the Center for Neuroscience at the University of California, Davis, shows that the hippocampus is the brain’s storyteller, connecting separate, distant events into a single narrative.

The work is published Sept. 29 in Current Biology. 

“Things that happen in real life don’t always connect directly, but we can remember the details of each event better if they form a coherent narrative,” said Brendan Cohn-Sheehy, a M.D./Ph.D. student at UC Davis and first author on the paper. 

Cohn-Sheehy and colleagues at Professor Charan Ranganath’s Dynamic Memory Laboratory at the Center for Neuroscience used functional MRI to image the hippocampus of volunteers as they learned and recalled a series of short stories. 

The stories, created specifically for the study, featured main and side characters and an event. The stories were constructed so that some formed connected, two-part narratives and others did not. 

The researchers played recordings of the stories to the volunteers in the fMRI scanner. The next day, they scanned them again as the volunteers recalled the stories. The researchers compared the patterns of activity in the hippocampus between learning and recalling the different stories.

As expected, they saw more similarity for learning pieces of a coherent story than for stories that did not connect. The results show the coherent memories being woven together, Cohn-Sheehy said. 

“When you get to the second event, you’re reaching back to the first event and embedding part of it in the new memory,” he said. 

Hippocampus weaves memories

Next, they compared hippocampal patterns during learning and retrieval. They found that when recalling stories that formed a coherent narrative, the hippocampus activates more information about the second event than when recalling non-connected stories. 

“The second event is where the hippocampus is forming a connected memory,” Cohn-Sheehy said. 

This shows the location of the hippocampus in the brain
As expected, they saw more similarity for learning pieces of a coherent story than for stories that did not connect. Image is in the public domain

When the researchers tested the volunteers’ memory of stories, they found that the ability to bring back hippocampal activity of the second event was linked to the amount of detail the volunteers could recall. 

While other parts of the brain are involved in the process of memory, the hippocampus appears to bring pieces together across time and form them into connected, narrative memories, Cohn-Sheehy said. 

The work is part of a new era in memory research. Traditionally, in neuroscience, researchers have studied the basic processes of memory involving disconnected pieces of information, whereas psychology has a tradition of studying how memory works to capture and connect events in the “real world.” These two camps are starting to merge, Cohn-Sheehy said. 

“We’re using brain imaging to get at realistic memory processes,” he said. 

Research on memory processes could ultimately lead to better clinical tests for early stages of memory decline in aging or dementia, or for assessing damage to memory from brain injuries.

Additional authors on the study are: Jordan Crivelli-Decker, Kamin Kim and Alexander Barnett at UC Davis; and Angelique Delarazan, Zachariah Reagh and Jeffrey Zacks at Washington University St. Louis.See also

This shows a soldier on patrol

FeaturedNeurosciencePsychologyAugust 29, 2021

News and Images From Afghanistan Can Trigger PTSD in Military Veterans

Funding: The work was partly funded by the U.S. Office of Naval Research and the National Institute of Aging. 

About this memory research news

Author: Andrew Fell
Source: UC Davis
Contact: Andrew Fell – UC Davis
Image: The image is in the public domain

Original Research: Open access.
The hippocampus constructs narrative memories across distant events” by Brendan Cohn-Sheehy et al. Current Biology


The hippocampus constructs narrative memories across distant events


  • In real life, people use a single narrative to remember multiple, separated events
  • Activity in the hippocampus can bridge separate events to form a coherent narrative
  • Activity in the hippocampus preferentially supports recall of coherent narratives
  • The hippocampus may support a narrative architecture for real-life memory


Life’s events are scattered throughout time, yet we often recall different events in the context of an integrated narrative. Prior research suggests that the hippocampus, which supports memory for past events, can support the integration of overlapping associations or separate events in memory. However, the conditions that lead to hippocampus-dependent memory integration are unclear.

We used functional brain imaging to test whether the opportunity to form a larger narrative (narrative coherence) drives hippocampal memory integration.

During encoding of fictional stories, patterns of hippocampal activity, including activity at boundaries between events, were more similar between distant events that formed one coherent narrative, compared with overlapping events taken from unrelated narratives. One day later, the hippocampus preferentially supported detailed recall of coherent narrative events, through reinstatement of hippocampal activity patterns from encoding.

These findings demonstrate a key function of the hippocampus: the integration of events into a narrative structure for memory.

Preventing Interrupted Sleep: Why It’s Important



The Importance of Deep, Uninterrupted Sleep

Why do we feel unrested and sleepy some mornings, even after a solid eight hours or more in bed?  The hitch is that we often evaluate sleep simply in terms of its duration.  However, good sleep is more than just about length.  The depth of your sleep and the ability to resist waking are critical for a restorative sleep.

Sleep is our body’s time to repair everything from blood vessels to the brain. During the non-REM stages of sleep, your brain wave activity reduces so it can perform these maintenance functions.  During this stage of deep sleep, your brain stores away new information, and your nerve cells reorganize to support healthy brain function.1

Deep sleep is also a time for your body to heal and repair heart and blood vessels, which is one of the reasons ongoing sleep deficiency is linked to an increased risk of heart disease, kidney disease, high blood pressure, diabetes, and stroke.2

But deep sleep isn’t just good for your body, it’s also critical for your mental and emotional well-being. Sleep deprivation has been linked to mood changes, the inability to cope with even minor stress, anxiety, and depression.3

Preventing Sleep Disruptions

Unfortunately, sleep can be interrupted for a number of reasons, disrupting deep sleep:

  • Mental Health: Depression and anxiety are closely linked to sleep problems: among people with depression, 75 percent have trouble falling asleep or staying asleep5
  • Caffeine: Overindulging in caffeinated beverages and alcoholic drinks late in the day, can interrupt your sleep even if you drift off initially
  • Digestion: Acid reflux or GERD, a condition that results in a backflow of acid from the stomach into the esophagus, can prevent you from sleeping or appear hours after you lie down. Virtually everyone experiences reflux at some point, particularly if you eat too late in the evening or indulge in spicy foods.  However, 20% of adults are affected by GERD6
  • Chronic Pain: Arthritis and fibromyalgia, as well as muscle aches and strains, can make falling asleep and staying asleep difficult.
  • Light: Using electronics right before sleep which can overstimulate your brain and decrease melatonin production. Without the right balance of melatonin, you may have difficulty entering the deep, Non-REM, stages of sleep4

What You Can Do

Besides adjusting your diet and sleep hygiene habits, below are some great products to ensure your bed and pillows are optimized to provide you the maximum amount of deep, uninterrupted sleep.

If you have sore muscles from a long session of pulling weeds and planting in your garden, or you’re known to overdo it when you hit the gym, the Ultramatic Supreme 9.5 Pillow Tilt Adjustable Base can help soothe away aches and pains with a built-in foot and back massage feature. And even if you don’t have any aches and pains, a relaxing massage before bed is the perfect way to wind down.

If you want even more help with that aching back, a soothing Thermophore MaxHEAT heating pad is the way to go. Larger than most standard heating pads, it is ideal for those with arthritis, joint pain, muscle spasms, sprains, fibromyalgia, sciatica, and bursitis because it has an area of heat therapy large enough to cover the entire spinal area. Just 30 minutes of its intense moist heat, created without adding water, is enough to help relieve pain and stiffness for hours.

For those who wake themselves up snoring, or find breathing difficult when laying flat, a Eucalyptus Memory Foam Pillow may be able to help. Infused with eucalyptus essential oils, which help open up airways, this pillow gently cradles your spine and is perfect for both side and stomach sleepers.

The temperature of your room – and your bed – can also impact the quality of your sleep. Too warm and you’ll toss all night, throwing your blankets on and off. Too cold and you’ll find yourself waking up shivering in the middle of the night.

Ideally, you want to maintain an even temperature on your sleep surface, and the PurCarbon 11 mattress from Ultramatic can help you do just that. It’s a temperature neutral surface infused with CarbonCor graphite that prevents overheating while absorbing pressure points and conforming to your shoulders and hips for a deep, restorative sleep.

But if you’re someone who tends to be cold at night, the soothing heat of a MaxCOMFORT BedWarmer beneath your bottom sheet will help to keep you feeling cozy. It’s particularly great for those who have problems with cold feet and poor circulation, and can be incredibly soothing for those with conditions like arthritis, chronic fatigue syndrome, and fibromyalgia.

It’s important to think about how your sleep may be impacting your overall health, and what steps you can take to improve it.

To learn more about how you can improve your sleep quality, contact the friendly sleep experts at Ultramatic.  Visit our showrooms in Toronto / Mississauga / Oakville, browse,  email, or call 1-866-413-4169 for a free consultation. Plus, C.A.R.P. members receive special savings:

  1. 25% OFF All Sleep Accessories (like Pillows and Sheets)
  2. Up to $500 OFF Mattresses, Bases or Walk-in Bathtubs


Scientists Completed the First Human Genome 20 Years Ago. How Far Have We Come, and What’s Next?

By Shelly Fan -Sep 28, 202115

If the Human Genome Project (HGP) was an actual human, he or she would be a revolutionary whiz kid. A prodigy in the vein of Mozart. One who changed the biomedical universe forever as a teenager, but ultimately has much more to offer in the way of transforming mankind.

It’s been 20 years since scientists published the first draft of the human genome. Since its launch in the 90s, the HGP fundamentally altered how we understand our genetic blueprint, our evolution, and the diagnosis and treatment of diseases. It spawned famous offspring, including gene therapy, mRNA vaccines, and CRISPR. It’s the parent to HGP-Write, a global consortium that seeks to rewrite life.

Yet as genome sequencing costs and time continue to dive, the question remains: what have we actually learned from the HGP? After two decades, is it becoming obsolete, with a new generation of genomic data in the making? And with controversial uses such as designer babies, human-animal chimeras, organs-in-a-tube, and shaky genetic privacy, how is the legacy of the HGP guiding the future of humanity?

In a special issue of Science, scientists across the globe took a deep dive into the lessons learned from the world’s first biomedical moonshot. “Although some hoped having the human genome in hand would let us sprint to medical miracles, the field is more an ongoing relay race of contributions from genomic studies,” wrote Science senior editor Laura Zahn.

Decoding, reworking, and potentially one day augmenting the human genome is an ultramarathon, buoyed by potential medical miracles and fraught with possible abuses.

“As genomic data and its uses continue to balloon, it will be critical to curb potential abuse and ensure that the legacy of the HGP contributes to the betterment of all human lives,” wrote Drs. Jennifer Rood and Aviv Regev at Genentech in a perspectives article for the issue.

An Apollo Program to Decode Life

Big data projects are a dime a dozen these days. A global effort to solve the brain? Yup. Scouring centenarians’ genes to find those that lead to longevity? Sure! Spitting in a tube to find out your ancestry and potential disease risks—the kits are on sale for the holidays! Genetically engineering anything—from yeast that brew insulin to an organism entirely new to Earth—been there, done that!

These massive international collaborations and sci-fi stretch goals that we now take for granted owe their success to the HGP. It’s had a “profound effect on biomedical research,” said Rood and Regev.

Flashback to the 1990s. Pulp Fiction played in theaters, Michael Jordan owned the NBA, and an international team decided to crack the base code of human life.

The study arose from years of frustration that genetic mapping tools needed better resolution. Scientists could roughly track down a gene related to certain types of genetic disorders, like Huntington’s disease, which is due to a single gene mutation. But it soon became clear that most of our toughest medical foes, such as cancer, often have multiple genetic hiccups. With the tools that were available at the time, solving these disorders was similar to debugging thousands of lines of code through a fogged-up lens.

Ultimately, the pioneers realized we needed an “infinitely dense” map of the genome to really begin decoding, said the authors. Meaning, we needed a whole picture of the human genome, at high resolution, and the tools to get it. Before the HGP, we were peeking at our genome through consumer binoculars. After it, we got the James Webb space telescope to look into our inner genetic universe.

The result was a human “reference genome,” a mold that nearly all biomedical studies map onto, from synthetic biology to chasing disease-causing mutants to the creation of CRISPR. Massive global consortiums, including the 1000 Genomes Project, the Cancer Genome Atlas, the BRAIN Initiative, and the Human Cell Atlas have all followed in HGP’s steps. As a first big data approach to medicine, before the internet was ubiquitous, HGP laid out a new vision for collaborative science by openly sharing data from labs across the globe—something Covid-19 vaccines have benefited from.

Yet as with AOL, CDs, and Microsoft FrontPage, HGP may be a legacy product from a bygone era.

The Next Generation

The first relatively finished reference genome was published in 2003. Yet two core questions at the heart of the HGP remain. One, what exactly should be considered a “complete reference”? Two, how can it be decoded to benefit humans?

“Reference” is an ambiguous idea in the age of increasingly cheaper genome sequencing. The original reference was what science considered an “average” human. It wasn’t, but the reference genome did focus on mapping the most common variants in a gene. Yet it’s increasingly obvious that humans are wildly diverse in our genetic differences, which could—for example—have a say in our longevity.

“Capturing the ever-growing genetic diversity of humans requires profiling a more diverse set of genomes,” said the authors. “Ultimately, although highly useful, a single reference genome is inherently biased.” Your genealogy results from consumer kits, for example, could be on point or off base, depending on your race and the genetic background of their reference samples. For now, it’s mostly people with European ancestry.

“The HGP and its legacy must serve humanity as a whole, not neglecting those who are currently underrepresented in biological research,” the team said.

Then there’s making sense of it. The HGP itself decoded the genome but didn’t provide an understanding of it—such as what genetic elements actually do, how they work together, and how they contribute to health and disease.

We’re getting there, but slowly. We’ve found genes that protect against Alzheimer’s, and genes that contribute to cancer and muscle disorders. Using a popular method called GWAS (genome-wide association study), scientists are increasingly capable of fishing out gene variants—often hundreds at a time—that play a role in more complex disorders such as autism. But teasing out how bucketloads of genes affect any disease remains difficult. With the rise of machine learning and AI, however, the authors said, we have a powerful tool to begin “unpacking its secrets to affect health.”

What’s next? Thanks to ongoing massive whole genome sequencing projects, we could be shedding the veil of HGP’s “average” human and entering a new era of multiple reference genomes—or even personalized ones. With this would come massive concerns around privacy. The Golden State Killer case, though it had a “happy” ending in that it was ultimately solved, relied on a free and public genealogy database that people may not have knowingly agreed to partake in. Unexpected findings related to long-lost relatives, a high risk of serious diseases, or our own heritage, especially if shared with third parties, could damage relationships or even overthrow our sense of self.

From the idea of a reference genome to a smorgasbord of genetic tools, HGP’s legacy is here to stay. As we move towards a more “snowflake” era of genomics—one that stresses individuality either for mixed-and-matched groups or individuals—the original goal remains the same.

The project left us with a major mission, still relevant even 20 years later, the authors said. We need to better understand how to wield our genetic blueprints, both common and rare, to “promote human health and treat disease”—for all of humanity.

Image Credit: Thor Deichmann from Pixabay

SHELLY FANShelly Xuelai Fan is a neuroscientist-turned-science writer. She completed her PhD in neuroscience at the University of British Columbia, where she developed novel treatments for neurodegeneration. While studying biological brains, she became fascinated with AI and all things biotech. Following graduation, she moved to UCSF to study blood-based factors that rejuvenate aged brains.

Researchers identify and clear efficiency hurdle for organic solar cells

by University of Cambridge

solar cell
Credit: Unsplash/CC0 Public Domain

Researchers have identified a key mechanism responsible for the lower efficiencies of organic solar cells and shown a way that this hurdle might be overcome.

The international group of researchers, led by the University of Cambridge, identified a loss pathway in organic solar cells which makes them less efficient than silicon-based cells at converting sunlight into electricity. In addition, they identified a way to suppress this pathway by manipulating molecules inside the solar cell to prevent the loss of electrical current through an undesirable state, known as a triplet exciton.

Their results, reported in the journal Nature, suggest that it could be possible for organic solar cells to compete more closely with silicon-based cells for efficiency.

Organic solar cells, which are flexible, semi-transparent, and cheap, can greatly expand the range of applications for solar technology. They could be wrapped around the exteriors of buildings and can be used for the efficient recycling of the energy used for indoor lighting, neither of which are possible with conventional silicon panels. They are also far more environmentally friendly to produce.

“Organic solar cells can do lots of things that inorganic solar cells can’t, but their commercial development has plateaued in recent years, in part due to their inferior efficiency,” said Dr. Alexander Gillett from Cambridge’s Cavendish Laboratory, the paper’s first author. “A typical silicon-based solar cell can reach efficiencies as high as 20 to 25%, while organic solar cells can reach efficiencies of around 19% under laboratory conditions, and real-world efficiencies of about 10 to 12%.”

Organic solar cells generate electricity by loosely mimicking the natural process of photosynthesis in plants, except they ultimately use the energy of the sun to create electricity rather than convert carbon dioxide and water into glucose. When a light particle, or photon, hits a solar cell, an electron is excited by the light and leaves behind a ‘hole’ in the material’s electronic structure. The combination of this excited electron and hole is known as an exciton. If the mutual attraction between the negatively charged electron and the positively charged hole in the exciton, akin to the attraction between the positive and negative poles of a magnet, can be overcome, it is possible to harvest these electrons and holes as an electrical current.×280&!1&btvi=1&fsb=1&xpc=iogpXESfCO&p=https%3A//

However, electrons in solar cells can be lost through a process called recombination, where electrons lose their energy—or excitation state—and fall back into the empty ‘hole’ state. As there is a stronger attraction between the electron and hole in carbon-based materials than in silicon, organic solar cells are more prone to recombination, which in turn affects their efficiency. This necessitates the use of two components to stop the electron and hole from recombining rapidly: an electron ‘donor’ material and an electron ‘acceptor’ material.

Using a combination of spectroscopy and computer modeling, the researchers were able to track the mechanisms at work in organic solar cells, from the absorption of photons to recombination. They found that a key loss mechanism in organic solar cells is caused by recombination to a particular type of exciton, known as a triplet exciton.

In organic solar cells, triplet excitons present a difficult problem to overcome, as it is energetically favorable for them to form from the electrons and holes. The researchers found that by engineering strong molecular interactions between the electron donor and electron acceptor materials, it is possible to keep the electron and hole further apart, preventing recombination into triplet excitons from occurring.

Computational modeling suggests that by tuning the components of the organic solar cells in this way, the timescales of recombination to these triplet exciton states could be reduced by an order of magnitude, allowing for more efficient solar cell operation.

“The fact that we can use the interactions between components in a solar cell to turn off the triplet exciton loss pathway was really surprising,” said Gillett. “Our method shows how you can manipulate molecules to stop recombination from happening.”

“Now, synthetic chemists can design the next generation of donor and acceptor materials with strong molecular interactions to suppress this loss pathway,” said co-author Dr. Thuc-Quyen Nguyen from the University of California, Santa Barbara. “The work shows the path forward to achieve higher device efficiency.”

The researchers say their method provides a clear strategy to achieve organic solar cells with efficiencies of 20% or more by stopping recombination into triplet exciton states. As part of their study, the authors were also able to provide design rules for the electron donor and electron acceptor materials to achieve this aim. They believe that these guidelines will allow chemistry groups to design new materials which block recombination into triplet excitons, enabling organic solar cells with efficiencies closer to silicon to be realized.

Explore furtherHybrid materials could smash the solar efficiency ceiling

More information: The role of charge recombination to triplet excitons in organic solar cells, Nature (2021). DOI: 10.1038/s41586-021-03840-5 , information:NatureProvided by University of Cambridge

A new study points to the power of wearables to predict even presymptomatic infections, suggesting use one day against Covid-19

By Maddie Bender Sept. 29, 2021Reprints

Apple watch with red band

Anew study that infected willing participants with common cold and flu viruses provides the most rigorous evidence yet that wearable health monitors could predict infections, even before a person starts experiencing symptoms.

If the wearables can similarly predict infections in real-world conditions, the technology could add to existing disease surveillance and testing methods. But unresolved issues with standardizing wearables and testing them on diverse populations raise questions about their immediate utility.

The new study, published Wednesday in JAMA Network Open, took aim at a research problem that has plagued other efforts to study wearables as infection detectors: small sample size. In two previous studies that looked at wearable devices like Apple Watches and Fitbits, tens of thousands of enrolled individuals corresponded to around 50 cases of Covid-19. In these studies and similar ones, it wasn’t clear when infected people first contracted the virus, further constraining the possibility of making predictions.


Here, researchers recorded biometric data from young people before and after they were inoculated with H1N1 influenza and human rhinovirus. By comparing each participant to their uninfected baseline metrics, researchers detected infection with up to 92% accuracy and distinguished between mild and moderate disease with up to 90% accuracy.

“The beauty of the challenge study is that we know the time of exposure to the pathogen, which is not true in these real-world studies. That makes this study uniquely powerful,” said Dunn, who was the senior author of the new study.


The study participants were given an E4 wristband, made by the company Empatica, which records information on a wearer’s heart rate, skin temperature, movement, and electrodermal activity — a measure of electrical activity on the skin. Once exposed to the viruses, they reported daily symptoms and researchers quantified their viral shedding.NEWSLETTERS

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A machine learning algorithm then predicted the presence of infection and its severity based on the change of each participant’s biometric data after exposure compared to their baselines. When the data were pooled, the algorithm correctly predicted the presence of infection 12 hours after exposure with 78% accuracy when the median time of symptom onset was 48 hours for flu and 36 hours for rhinovirus. These accuracies rose to 92% for flu alone after 24 hours, and 88% for rhinovirus after 36 hours, or at the median time symptoms began. The model also predicted severity of illness (moderate, mild, or asymptomatic/noninfected) with at least 80% accuracy 12 hours after viral exposure.

The study design was particularly useful for studying presymptomatic and asymptomatic cases, said Jennifer Radin, an epidemiologist at the Scripps Research Translational Institute who was not involved in the research. Being able to recognize these infections would be “a very useful public health tool” for a disease like Covid-19, she added.

In fact, the E4 wristband is already part of a Covid-19 detection system from Empatica that has been backed and deployed by the U.S. Army. The system, called Aura, couples the wearable with an algorithm and app to give users a daily risk assessment, and the company plans to apply for Food and Drug Administration approval to use the device to diagnose Covid-19, in parallel with an ongoing prospective clinical trial.Related: 

‘It’s hard to know what’s trustworthy’: A new research effort aims to vet digital health data from wearables

Still, the authors of the new research stressed that further work is needed to evaluate any wearable as a Covid-19 detector. Biometric data follow a circadian rhythm, making it difficult to tease out signals from noise without enough baseline readings, said Emilia Grzesiak, the first author of the study and a data scientist at Lawrence Livermore National Laboratory. Machine-learning algorithms will also have to be trained on samples that are representative of the devices’ target populations, she added: For instance, people tend to have elevated skin temperature when menstruating, which could result in false positives if not factored into an algorithm’s training.

Additionally, commercial wearables vary in performance — some use lights to collect biometric data that have been shown to perform worse on people with darker skin. Representation must also cross the “digital divide” and include people who have difficulty accessing and affording wearable technology, said Geoffrey Ginsburg, a study co-author and director of the Duke Center for Applied Genomics and Precision Medicine.Related: 

Early data suggest wearables can catch some cases of Covid-19 before symptoms emerge

Even if approved and standardized, biometric sensors would not be a replacement for diagnostic tests, but rather a way to augment and prioritize their allocation. Ginsburg likened using interpretations from sensors as a way for a person to “stack the deck” as a sign to get a viral antigen or PCR test.

“I don’t think that this is going to be a standalone tool, but when we’re talking about resource allocation and triage, this can provide some very useful insight for how to go about prioritizing who should be tested and who should get what care when,” Dunn said.