The algorithm, available online in the journal Neurology, uses data from a kind of brain scan known as amyloid positron emission tomography (PET) to gauge brain levels of the key Alzheimer’s protein amyloid beta.

In those who eventually develop Alzheimer’s dementia, amyloid silently builds up in the brain for up to two decades before the first signs of confusion and forgetfulness appear. Amyloid PET scans already are used widely in Alzheimer’s research, and this algorithm represents a new way of analyzing such scans to approximate when symptoms will arise. Using a person’s age and data from a single amyloid PET scan, the algorithm yields an estimate of how far a person has progressed toward dementia — and how much time is left before cognitive impairment sets in.

“I perform amyloid PET scans for research studies, and when I tell cognitively normal individuals about positive results, the first question is always, ‘How long do I have until I get dementia?’,” said senior author Suzanne Schindler, MD, PhD, an assistant professor of neurology. “Until now, the answer I’d have to give was something like, ‘You have an increased risk of developing dementia in the next five years.’ But what does that mean? Individuals want to know when they are likely to develop symptoms, not just whether they are at higher risk.”

Schindler and colleagues analyzed amyloid PET scans from 236 people participating in Alzheimer’s research studies through Washington University’s Charles F. and Joanne Knight Alzheimer Disease Research Center. The participants were an average of 67 years old at the beginning of the study. All participants underwent at least two brain scans an average of 4½ years apart. The researchers applied a widely used metric known as the standard uptake value ratio (SUVR) to the scans to estimate the amount of amyloid in each participant’s brain at each time point.

The researchers also accessed over 1,300 clinical assessments on 180 of the participants. The assessments typically were performed every one to three years. Most participants were cognitively normal at the start of data collection, so the repeated assessments allowed the researchers to pinpoint when each participant’s cognitive skills began to slip.

Schindler spent years trying to figure out how to use the data in amyloid PET scans to estimate the age at which symptoms would appear. The breakthrough came when she realized that amyloid accumulation has a tipping point and that each individual hits that tipping point at a different age. After this tipping point, amyloid accumulation follows a reliable trajectory.

“You may hit the tipping point when you’re 50; it may happen when you’re 80; it may never happen,” Schindler said. “But once you pass the tipping point, you’re going to accumulate high levels of amyloid that are likely to cause dementia. If we know how much amyloid someone has right now, we can calculate how long ago they hit the tipping point and estimate how much longer it will be until they are likely to develop symptoms.”

People in the study who reached the tipping point at younger ages took longer to develop cognitive symptoms than those who reached it later in life. Participants who hit the tipping point at age 50 typically took nearly 20 years to develop symptoms; those who hit it at age 80 took less than 10 years.

“When we look at the brains of relatively young people who have died with Alzheimer’s, they typically look pretty healthy, other than Alzheimer’s,” Schindler said. “But older people more frequently have damage to the brain from other causes, so their cognitive reserves are lower, and it takes less amyloid to cause impairment.”

The power of this new technique is that it requires just one brain scan, plus the person’s age. With that data, the model can estimate the time to symptom onset, plus or minus several years. In this study, the correlation between the expected age of symptom onset and the true age at diagnosis was better than 0.9 on a scale of 0 (no correlation) to 1 (perfect correlation).

After age, the genetic variant APOE4 is the strongest risk factor for Alzheimer’s dementia. People who carry one copy of the variant are two to three times more likely to develop Alzheimer’s dementia than the general population, and people who carry two copies are 10 times more likely. In this study, people with the high-risk variant hit the tipping point younger, but once that point was passed, they followed the same trajectory as everyone else.

“APOE4 seems to have a seeding effect,” Schindler said. “At very low levels, below the tipping point, you see amyloid rising in people with APOE4 while it’s not changing in people without APOE4. That means APOE4 carriers are going to hit the tipping point sooner. People with two copies of APOE4 hit the tipping point about 10 years earlier than people with no copies. But after that point, we see no difference between the APOE4 carriers and noncarriers.”

At an out-of-pocket cost of about $6,000, amyloid PET brain scans are too expensive for routine clinical use. However, this algorithm could help accelerate the pace of drug development by streamlining clinical trials.

“Most participants in clinical trials designed to prevent or slow Alzheimer’s symptoms do not develop symptoms during the trials,” Schindler said. “That’s a lot of time and effort — for the participants as well as the researchers — that doesn’t yield useful data. If we could do trials only on people who are likely to develop symptoms in the next few years, that would make the process of finding therapies much more efficient.”

Now, a new technique for measuring turbulent flows has been developed by an international collaboration of scientists from the Okinawa Institute of Science and Technology Graduate University (OIST) in Japan, along with the University of Genova, Italy, KTH Stockholm, Sweden and ETH Zurich, Switzerland. By using fibers rather than particles — the usual method of measurement — the researchers could get a more detailed picture of turbulent flows. Their method was reported on 17th September in the journal, Physical Review X.

“Turbulence is a very unique and complicated phenomena, it’s even been called the last unsolved problem in classical physics,” said Dr. Stefano Olivieri, a postdoctoral researcher from the Complex Fluids and Flows Unit at OIST, who was an author of the study. “It’s difficult to predict, difficult to simulate, and difficult to measure.”

Measuring turbulent flows is a pressing challenge for physicists for numerous reasons. Not only is turbulence characterized by its chaotic and random nature, but it also occurs across many scales at once. In turbulent flows, the swirling vortices of fluid break down into eddies that are smaller and smaller in scale, until eventually the eddies are so small and viscous that the kinetic energy of the fluid is transferred to the environment as heat.

Currently, the most common way to measure turbulent flows is by tracking the movement of particles, called tracers, that are added to the fluid. These particles are tiny and of similar density to the fluid, and so move at the same speed and in the same direction as the flow.

But in order to observe how each swirl of fluid is moving, looking at how one particle moves isn’t enough. Physicists need to be able to determine how two particles that are a specific distance apart move in relation to each other. The smaller the eddy, the closer together the two particles need to be to characterize the motion of the vortex.

To make matters more challenging, one of the defining features of turbulence is its diffusivity — a turbulent flow will spread apart over time, and so too will the tracers, especially in open flows, like an ocean current. In many cases, tracers can quickly spread too far apart to measure how the eddies are behaving.

“Every tracer particle is moving independently of each other, so you need lots of tracer particles in order to find ones that are the right distance apart,” explained Professor Marco Rosti, who leads the OIST Complex Fluids and Flows Unit.

“And too many tracer particles can actually disrupt the flow,” he added.

To circumvent this issue, the research team developed an innovative and easy solution to the problem: using fibers instead of tracer particles.

The researchers created a computer simulation where fibers of different lengths were added to a turbulent flow. These fibers were rigid, which kept the ends of each fiber a fixed distance apart. By tracking how each fiber moved and rotated within the fluid over time, the researchers were able to build up a picture that encompassed the full scale and structure of the turbulent flow.

“By using rigid fibers, we can measure the difference in the speed and the direction of the flow at two points a fixed distance apart, and we can see how these differences change depending on the scale of the eddy. The shortest fibers also allowed us to accurately measure the rate at which the kinetic energy of the fluid is transferred from the largest to the smallest scales, where it is then dissipated by heat. This value, called the energy dissipation rate, is a crucial quantity in the characterization of turbulent flows,” said Prof. Rosti.

The researchers also performed the same experiment in the laboratory. They manufactured two different fibers, one made from nylon and the other from a polymer called polydimethylsiloxane. The team tested both these fibers by adding them to water tank containing turbulent water and found that the fibers gave similar results to the simulation.

However, using rigid fibers comes with one important caveat, the scientists emphasized, as the overall movement of the fiber ends is restricted.

“Due to the fiber rigidity, the fiber ends can’t move towards each other, even if that’s the direction of the flow. That means that a fiber cannot fully represent the movement of the flow in the same way that tracer particles can,” explained Dr. Olivieri. “So before we even began simulations or lab experiments, we first needed to develop a suitable theory that took these limitations of movement into account. This was perhaps the most challenging part of the project.”

The researchers also measured the same turbulent flow in the laboratory the conventional way, by adding a high concentration of tracer particles to the water tank. The results obtained from the two different methods were similar, verifying that the fiber method and the newly developed theory gave accurate information.

Moving forward, the researchers hope to expand their method to incorporate flexible fibers that have less restriction on how they move. They also plan to develop a theory that can help measure turbulence in more complex non-Newtonian fluids that behave differently from water or air.

“This new technique has a lot of exciting potential, especially for scientists studying turbulence in large, open flows like ocean currents,” said Prof. Rosti. “And being able to easily measure quantities that were previously difficult to obtain moves us one step closer to fully understanding turbulence.”

In new research published in Nature Communications, co-authors Andrew J. Conith, postdoctoral researcher in the UMass Amherst biology department, and Craig Albertson, professor of biology at UMass Amherst, focus on the jaws of cichlids — which are notable because they have two sets of them.

“Remember the movie ‘Alien,'” asks Conith, “when the alien is about to eat Sigourney Weaver’s character? It opens its mouth and out comes a second set of jaws. Fast forward twenty years, and here I am, studying animals that have jaws in their throats.”

Cichlids, thankfully, don’t eat humans, but, thanks to their twin pairs of jaws, they are a phenomenally successful group of fishes from an evolutionary standpoint. In Lake Malawi alone, more than 1,000 different species of cichlids have evolved over the last 1 to 2 million years. One set of jaws, the oral jaw, is similar to our own, and its role is to capture food. But cichlids, like the Xenomorph from ‘Alien,’ have a second set of jaws, deeper in their throats, that’s made to process food once it has been captured by the first set. Having two pairs of jaws means that each jaw can specialize in a specific role, a feature that should increase their feeding efficiency and make them more evolutionarily successful.

Given the success of cichlids, understanding the evolution of these two jaws has become an important line of inquiry for biologists. “We’re trying to gain a better understanding of the origins and maintenance of biodiversity,” says Albertson. Researchers have long thought that the two sets of jaws are evolutionarily decoupled and can evolve independently of one another, pushing the boundaries of morphological evolution. However, Conith and Albertson demonstrated that such decoupling does not appear to be the case for cichlids, challenging a quarter-century-old assumption. “What we’ve found is not just that the evolution of the two sets of jaws is linked, but that they’re linked across multiple levels, from genetic to evolutionary,” says Albertson

These findings are a significant step forward in better understanding how evolution works. For instance, many models of evolution theorize both that organisms are constructed from repeated units — digits on your hand or teeth in your mouth — and that these individual units evolve independently from one another. “It is this ‘modularity’ of organisms that is thought to facilitate the evolutionary process,” Albertson notes.

Linked systems are usually thought to lack evolutionary potential. “They just cannot evolve in as many dimensions,” Conith says. This is referred to as an evolutionary constraint, and it plays an important role in shaping biodiversity. Constraints determine what body structures are possible.

Remarkably, this constraint seems to be the key to cichlid’s success by promoting rapid shifts in jaw shapes and feeding ecology, all of which is likely to be an advantage in a dynamic and fluctuating environment, like the East African Rift Valley, where Lake Malawi is located. “The constraint is actually facilitating cichlid evolution, rather than impeding it,” says Conith.

“This tells us that we need to rethink the fundamentals of evolutionary mechanisms,” says Albertson. “Perhaps constraints play a wider role in the evolutionary success of species around the world.”

Five peer-reviewed papers in the journal Nature highlight the opportunities to leverage the vast diversity of aquatic, or “blue,” foods in the coming decades to address malnutrition, lower the environmental footprint of the food system, and provide livelihoods.

“People are trying to make more informed choices about the food they eat, in particular the environmental footprint of their food,” said Ben Halpern, a marine ecologist at UC Santa Barbara’s Bren School of Environmental Science & Management, who with colleagues examined the environmental sustainability of aquatic foods, the potential for the growth of small-scale producers and the climate risks that face aquatic food systems. “For the first time we pulled together data from hundreds of studies on a wide range of seafood species to help answer that question. Blue foods stack up really well overall and provide a great option for sustainable food.”

The research projects that global demand for blue foods will roughly double by 2050, and will be met primarily through increased aquaculture production rather than by capture fisheries.

Investing in innovation and improving fisheries management could increase consumption even more and have profound effects on malnutrition. For instance, a “high growth” modeling scenario showed that increasing supply by 15.5 million tons (8%), causing a drop in prices, would reduce cases of nutrient deficiencies by 166 million, especially among low-income populations.

“Small-scale fishers — the individuals and small boats that fish in places all around the world — are a huge part of the global seafood system and are incredibly diverse in who they are and how they fish,” said Halpern, who also directs the National Center for Ecological Analysis & Synthesis at UCSB. “That diversity creates both opportunities and challenges for sustainably managing the oceans. We unpacked this diversity to help guide better management.”

Blue foods were found to rank more highly than terrestrial animal-source foods in terms of their nutritional benefits and potential for sustainability gains.

Many blue food species are rich in important nutrients. Compared to chicken, trout has approximately 19 times more omega-3 fatty acids; oysters and mussels have 76 times more vitamin B-12 and five times more iron; and carps have nine times more calcium.

“For the first time we got to see what more aquatic food production would mean for human health globally,” said Bren School marine ecologist and assistant researcher Christopher Free, who with fellow UCSB marine scientist Jacob Eurich co-authored a study that examines the nutritional potential of blue foods. “What we project is that by making aquatic foods cheaper to the consumer, there’s likely going to be a shift away from land-based foods like chicken, beef and dairy. I think what made us really excited is knowing that aquatic food could be a useful solution to combating malnutrition, and really showing that comprehensively for the first time.”

The nutritional benefits of blue foods are especially important for women, who were found to benefit more than men from increased consumption in nearly three times the number of countries studied.

On average, the major species produced in aquaculture, such as tilapia, salmon, catfish and carp, were found to have environmental footprints comparable to chicken, the lowest-impact terrestrial meat. Small pelagic species like sardines and anchovies, bivalves and seaweeds all already offer lower stressors than chicken.

Further investments to improve the sector’s efficiency and reduce its environmental footprint can have sector-wide benefits, including for less commonly raised species like European bass, weakfish, flatfish, sea breams and milkfish.

The research found that blue food systems facing the highest risk from climate change are also typically located in those regions where people rely on them most and where they are least equipped to respond and adapt to climate hazards.

“Climate change is creating all sorts of risks to humanity, including to our food,” Halpern said. “Blue foods are no different and in fact face some unique risks from things like acidifying and warming waters. But not all foods are equally vulnerable to these risks — in our work we show where, how and why different blue foods face different risks from climate change.”

These five papers are the first in a series produced by the Blue Food Assessment (BFA), a group of more than 100 leading researchers led by Stanford University’s Center for Ocean Solutions & Center on Food Security and the Environment, the Stockholm Resilience Centre at Stockholm University and EAT.

“Blue foods are much more diverse than typically thought, and so too are the many communities of small-scale fishers who are often overlooked despite providing the majority of blue food people eat,” said Beatrice Crona, co-chair of the BFA and deputy science director at the Stockholm Resilience Centre.

“Few, if any, countries are developing their blue food sector to provide ecological, economic, and health benefits to its full potential,” said Rosamond Naylor, BFA co-chair and founding director of the Center on Food Security and the Environment at Stanford University. “This assessment aims to provide the scientific foundation for decision-makers to evaluate trade-offs and implement solutions that will make blue foods an instrumental part of an improved food system from local to global scales.”

“The BFA assessment emphasizes the enormous diversity of blue foods, all of which carry important nutritional, cultural, economic and environmental value,” said Fabrice DeClerck, EAT science director. “To realize its potential, policymakers should put in place better governance, including participation of small producers, women and other marginalized groups, better stewardship of the natural resources on which blue foods rely; and investment in building resilience to climate change.”

“We are nine fishing seasons away from the deadline for achieving the 2030 Sustainable Development Goals so the urgency is high,” said Jim Leape,co-director of the Stanford Center for Ocean Solutions. “This research can help policymakers, companies, financiers, fishers and consumers capitalize on the immense potential of blue foods to help achieve those goals.”

More than 2,500 species or species groups of fish, shellfish, aquatic plants and algae are caught or cultivated globally for food, providing livelihoods and incomes for more than 100 million and sustenance for one billion.

Because B cells are responsible for antibody production, patients’ ability to produce antibodies that prevent the virus from entering and infecting a person’s cells is significantly muted when the B cells are depleted with aCD20 treatment. But the same patients are nonetheless able to mount very good responses of the second protective arm of their immune system, which uses T cells to eliminate cells once infected (thereby preventing viral spread to other cells), according to new research from the Perelman School of Medicine at the University of Pennsylvania in a new paper published in Nature Medicine.

“The message from this study is clear — it is worthwhile for patients with MS receiving aCD20 treatment to get a COVID-19 vaccine, which will prevent severe illness,” said one of the senior authors E. John Wherry, PhD, chair of Systems Pharmacology and Translational Therapeutics and director of the Penn Institute for Immunology. “Based on this body of evidence, we urge patients with MS receiving aCD20 treatment to get a COVID-19 vaccine if they haven’t already.”

The study measured both the antibody and T cell responses in 20 patients with MS who were undergoing aCD20 treatment, compared to those in a group of healthy controls. None of the participants in the study had prior clinical signs or symptoms of COVID-19. Researchers analyzed plasma and peripheral blood mononuclear cell samples five times over the study period: prior to the first vaccine dose, 10-12 days following the first vaccine dose, prior to the second vaccine dose, 10-12 days following the second vaccine dose, and 25-30 days following the second vaccine dose.

All healthy control subjects generated both anti-spike and anti-receptor-binding domain (RBD) antibodies following the first dose of mRNA vaccine, and the level of antibody increased further after the second dose. However, in patients with MS, the antibody response was far more varied. By 30 days after the second vaccine dose, 85% of participants developed anti-spike antibodies, and 50% mounted anti-RBD responses. For those subjects who did have detectable antibodies, the magnitude of response was generally lower, and the response was delayed compared to the control group.

The timing of a patient’s last aCD20 infusion — typically administered every six months — played a significant role in the immune response mounted. Patients with MS with higher percentages of circulating B cells prior to the vaccine had more robust antibody responses to the vaccine.

“This data not only reveal that patients undergoing anti-CD20 infusions are still able to mount important COVID-19 vaccine responses which are likely to protect from severe illness, but also informs our clinical practices in how we advise patients with MS and other autoimmune disorders on such therapies,” said another of the paper’s senior authors Amit Bar-Or, MD, FRCPC director of the Center for Neuroinflammation and Experimental Therapeutics and chief of the Division of MS and Related Disorders. “For example, knowing that responses are weakest immediately following an anti-CD20 infusion, we can now advise patients to wait a number of months after their therapy to get a COVID-19 vaccine.”

Researchers found that patients who had undergone aCD20 treatments had subpopulations of T cells that responded similarly to vaccination as healthy control subjects. Patients who underwent aCD20 therapy generated robust CD4 and CD8 T cell responses to the COVID-19 vaccination. Further, the CD8 T cell response was especially robust among the subgroup of patients with MS who didn’t generate RBD antibodies. This observation reveals that even without circulating B cells, the COVID-19 vaccine effectively primed patients’ immune response to the virus.

“Often when determining if a patient mounted a proper response to an mRNA vaccine, we test for the presence of antibodies, but this method neglects an entire arm of a person’s immune response,” said one of the lead authors Sokratis A. Apostolidis, MD, a fellow in the Department of Rheumatology. “Measuring both antibodies and T-cell response gives us a more complete picture of a patient’s immune response, and reveals that patients who can’t generate antibodies as well as a healthy person are actually still protected by the COVID-19 vaccine.”

The researchers do note that due to the limited antibody responses mounted by patients receiving aCD20 treatments, they might not be able to neutralize the virus as quickly before it infects other cells, which could result in them being contagious carriers of the virus for a longer period of time.

This work was supported by grants from the NIH (AI105343, AI082630, AI108545, AI155577, AI149680, AI152236, P30-AI0450080, R01 AI118694, UC4 DK112217, T32 AR076951-01, T32 CA009140, U19AI082630, UM1 AI144288, NMSS SI-2011-37160). This work was also supported by NIH contract (Nr. 75N9301900065).

Funding was also provided by the Allen Institute for Immunology, Chen Family Research Fund, the National Multiple Sclerosis Society-American Brain Foundation Clinician Scientist Award, the Parker Institute for Cancer Immunotherapy, the Penn Center for Research on Coronavirus and Other Emerging Pathogens, the University of Pennsylvania Perelman School of Medicine COVID Fund, the University of Pennsylvania Institute for Immunology Glick COVID-19 research award, the University of Pennsylvania Perelman School of Medicine 21st Century Scholar Fund, a philanthropic gift from Jeffrey Lurie, Joel Embiid, Josh Harris, and David Blitzer, the Penn Center for Neuroinflammation and Experimental Therapeutics and the Melissa and Paul Anderson Fund.