Brain

UCLA researchers are part of an international team that reported the use of a stem cell gene therapy to treat nine people with the rare, inherited blood disease known as X-linked chronic granulomatous disease, or X-CGD. Six of those patients are now in remission and have stopped other treatments. Before now, people with X-CGD – which causes recurrent infections, prolonged hospitalizations for treatment, and a shortened lifespan – had to rely on bone marrow donations for a chance at remission.

“With this gene therapy, you can use a patient’s own stem cells instead of donor cells for a transplant,” said Dr. Donald Kohn, a member of the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA and a senior author of the new paper, published today in the journal Nature Medicine. “This means the cells are perfectly matched to the patient and it should be a much safer transplant, without the risks of rejection."

People with chronic granulomatous disease, or CGD, have a genetic mutation in one of five genes that help white blood cells attack and destroy bacteria and fungus using a burst of chemicals. Without this defensive chemical burst, patients with the disease are much more susceptible to infections than most people. The infections can be severe to life-threatening, including infections of the skin or bone and abscesses in organs such as lungs, liver or brain. The most common form of CGD is a subtype called X-CGD, which affects only males and is caused by a mutation in a gene found on the X-chromosome.

Other than treating infections as they occur and taking rotating courses of preventive antibiotics, the only treatment option for people with CGD is to receive a bone marrow transplant from a healthy matched donor. Bone marrow contains stem cells called hematopoietic, or blood-forming, stem cells, which produce white blood cells. Bone marrow from a healthy donor can produce functioning white blood cells that effectively ward off infection. But it can be difficult to identify a healthy matched bone marrow donor and the recovery from the transplant can have complications such as graft versus host disease, and risks of infection and transplant rejection.

“Patients can certainly get better with these bone marrow transplants, but it requires finding a matched donor and even with a match, there are risks,” Kohn said. Patients must take anti-rejection drugs for six to 12 months so that their bodies don’t attack the foreign bone marrow.

In the new approach, Kohn teamed up with collaborators at the United Kingdom’s National Health Service, France-based Genethon, the U.S. National Institute of Allergy and Infectious Diseases at the National Institutes of Health, and Boston Children’s Hospital. The researchers removed hematopoietic stem cells from X-CGD patients and modified the cells in the laboratory to correct the genetic mutation. Then, the patients’ own genetically modified stem cells — now healthy and able to produce white blood cells that can make the immune-boosting burst of chemicals — were transplanted back into their own bodies. While the approach is new in X-CGD, Kohn previously pioneered a similar stem cell gene therapy to effectively cure a form of severe combined immune deficiency (also known as bubble baby disease) in more than 50 babies.

The viral delivery system for the X-CGD gene therapy was developed and fine-tuned by Professor Adrian Thrasher’s team at Great Ormond Street Hospital, or GOSH, in London, who collaborated with Kohn. The patients ranged in age from 2 to 27 years old; four were treated at GOSH and five were treated in the U.S., including one patient at UCLA Health.

Two people in the new study died within three months of receiving the treatment due to severe infections that they had already been battling before gene therapy. The seven surviving patients were followed for 12 to 36 months after receiving the stem cell gene therapy. All remained free of new CGD-related infections, and six of the seven have been able to discontinue their usual preventive antibiotics.

“None of the patients had complications that you might normally see from donor cells and the results were as good as you’d get from a donor transplant — or better,” Kohn said.

An additional four patients have been treated since the new paper was written; all are currently free of new CGD-related infections and no complications have arisen.

Orchard Therapeutics, a biotechnology company of which Kohn is a scientific co-founder, acquired the rights to the X-CGD investigational gene therapy from Genethon. Orchard will work with regulators in the U.S. and Europe to carry out a larger clinical trial to further study this innovative treatment. The aim is to apply for regulatory approval to make the treatment commercially available, Kohn said.

Kohn and his colleagues plan to develop similar treatments for the other forms of CGD — caused by four other genetic mutations that affect the same immune function as X-CGD.

“Beyond CGD, there are also other diseases caused by proteins missing in white blood cells that could be treated in similar ways,” Kohn said.

Evaluating the effectiveness of therapies for neurodegenerative diseases is often difficult because each patient's progression is different. A new study shows artificial intelligence (AI) analysis of blood samples can predict and explain disease progression, which could one day help doctors choose more appropriate and effective treatments for patients.

Scientists at The Neuro (Montreal Neurological Institute and Hospital) of McGill University and the Ludmer Centre for Neuroinformatics and Mental Health used an AI algorithm to analyze the blood and post-mortem brain samples of 1969 patients with Alzheimer's and Huntington's disease. Their goal was to find molecular patterns specific to these diseases.

The algorithm was able to detect how these patients' genes expressed themselves in unique ways over decades. This offers the first long-term view of molecular changes underlying neurodegeneration, an important accomplishment because neurodegenerative diseases develop over years.

Previous studies of neurodegeneration often used static or "snapshot" data, and are therefore limited in how much they can reveal about the typically slow progression of disease. This study aimed to uncover the chronological information contained in large-scale data by covering decades of disease progression, revealing how changes in gene expression over that time are related to changes in the patient's condition.

Furthermore, the blood test detected 85 to 90 per cent of the top predictive molecular pathways that the test of post-mortem brain data did, showing a striking similarity between molecular alterations in both the brain and peripheral body.

"This test could one day be used by doctors to evaluate patients and prescribe therapies tailored to their needs," says Yasser Iturria-Medina, the study's first author. "It could also be used in clinical trials to categorize patients and better determine how experimental drugs impact their predicted disease progression."

Iturria-Medina says his next steps will be testing these models in other diseases such as Parkinson's disease and amyotrophic lateral sclerosis.

This study was made possible with data made openly available through the Alzheimer's Disease Neuroimaging Initiative (ADNI) and the Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago.

The results were published in the journal Brain on Jan. 28, 2020. It was funded by McGill University's Healthy Brain for Healthy Lives Initiative, the Ludmer Centre, and the Brain Canada Foundation and Health Canada support to the McConnell Brain Imaging Centre at The Neuro.

Researchers at Karolinska Institutet have mapped how different nerve cells in the brain area striatum process information to plan and execute our movements at just the right time and with the right vigour. The results, presented in the journal Cell Reports, show that different cell types in the striatum receive signals from completely different parts of the cerebral cortex and thus respond to different types of information.

Many behaviours occur in response to sensory input from our environment. For example, when playing a new piece on the piano, we adjust our finger movements according to the sound we hear and the sensory feedback from the keys. Researchers at Karolinska Institutet in Sweden aimed to increase our understanding of how this works by studying the neuronal network that allows us to align our planned movements to sensory information such as touch. The nerve cells (neurons) that underlie this function are in the striatum, which is part of a larger structure in the brain called the basal ganglia.

While playing piano, sensory feedback from our fingertips is processed in the somatosensory cortex, the brain area specialised for touch. Movements are planned in a separate part of the brain called motor cortex. Information from the somatosensory cortex, the motor cortex and other brain areas such as thalamus are sent to the striatum, which is the first instance where movement plans and sensory information are combined. Based on the broad information delivered by these inputs, the striatum is able to generate a precisely timed output signal that is sent back to the muscles and allows us to press the next keys correctly on the piano.

"Although it has long been known that the striatum is composed of different types of nerve cells, it is unclear how striatal cells achieve this complex function," says Yvonne Johansson, PhD student at the Department of Neuroscience, Karolinska Institutet. "To address this question, we asked which striatal cell populations process which incoming information."

The researchers have used optogenetics, among other technologies, to analyse which of five important cell types in the striatum are responsible for the communication from the motor cortex, the somatosensory cortex and the thalamus.

Studies on mice revealed that striatal medium spiny neurons strongly respond to sensory inputs representing a sensation of touch. Another class of striatal neurons, the low-threshold spiking interneurons, hardly respond to inputs carrying sensory information but are strongly activated by inputs from motor cortex. In sharp contrast, cholinergic interneurons respond most strongly to thalamic inputs which are thought to notify us that something important is happening in our environment.

The researchers also found that the responses of the different neuron classes are mediated by different receptor compositions. As some receptors open faster than others, the receptors strongly shape the timing of the response.

The findings shed new light on how the striatum is systematically processing the vast amount of information that it receives.

"Our work shows that the flow of information into the striatal network is highly organised and that the properties of the numerous inputs targeting different striatal neuron populations are pathway-specific," says Gilad Silberberg, professor at the Department of Neuroscience, Karolinska Institutet.

When, in 2014, Brazilian researchers stumbled across a never-before-seen red-eyed leafhopper feeding inside the rosettes of bromeliads, growing in the restingas of southeastern Brazil, they were certain it was a one-of-a-kind discovery. Described as new-to-science species, as well as genus (Cavichiana bromelicola) and added to the sharpshooter tribe Cicadellini, it became the first known case of a leafhopper feeding on otherwise nutrition-poor bromeliads in their natural habitat.

Several years later, however, a team of entomologists from Universidade Federal do Rio de Janeiro carried out fieldwork in a mountainous area of southeastern Brazil and, as a result, another bromelicolous leafhopper species of the genus was discovered: Cavichiana alpina. Only, the new one appeared even more spectacular.

The new species, described and illustrated in the open-access journal Zoologia, is known from Itatiaia National Park (state of Minas Gerais, southeastern Brazil), where it can be found at altitudes above 1,800 m a.s.l. In fact, its characteristic mountainous habitat came to determine its species name (alpina). In contrast, its relative was originally described exclusively from sea level regions, even though the latest field trips have recorded it from a site located at 1,250 m a.s.l.

Slightly larger than the previously known C. bromelicola and similarly red-eyed, what most remarkably sets apart the newly-described species is its colouration. Rather than a single large yellow blotch contrasting against the dark-brown to black back of the insect, this sharpshooter sports a motley amalgam of red and blue covering most of its upper side.

In conclusion, the researchers explain that the peculiarity of the two known Cavichiana species is best attributed to a putative common ancestor that had likely once been widely distributed in southeastern and southern Brazil. Later, they speculate, a vicariant event, such as the uplift of the southeastern Brazilian mountain ranges during the latest Eocene and Oligocene, might have caused its diversification into two separate species.

Hamilton, ON (January 28, 2020) - Children who spend time in a neonatal intensive care unit (NICU) at birth have a higher risk of mental health issues later, regardless of their birth weight, say McMaster University researchers.

The study examined the mental health of NICU graduates in childhood (four to 11 years) and adolescence (12 to 17 years), using data from parent and youth psychiatric interviews.

The research builds on previous studies that suggest extremely low birth weight babies who are admitted to the NICU are more likely to develop mental health issues during those years.

The results were published in Archives of Disease in Childhood.

"Advancements in the medical care of patients admitted to the NICU have led to improved outcomes for infants and families, and the need for NICUs has increased in Canada and the U.S.," said study senior author Ryan Van Lieshout, associate professor of psychiatry and behavioural neurosciences at McMaster.

"However, little has been known about the mental health of the broader population of NICU graduates, particularly as they enter late childhood and adolescence."

The study used a provincially representative cohort from the 2014 Ontario Child Health Study, led at McMaster. Parents provided data on psychiatric disorders for 3,141 children aged four to 11 and in 2,379 adolescents aged 12 to 17. Additionally, 2,235 adolescents aged 12 to 17 completed the interview themselves

Children aged four to 11 who had a NICU admission were nearly twice as likely to have any mental disorder or have more than one mental illness. The risk of separation anxiety disorder, specific phobia, attention deficit hyperactivity disorder, or oppositional defiant disorder also increased.

At the age of 12 to 17 years, NICU graduates remained at nearly twice the risk for developing any psychiatric problem, multiple psychiatric problems and oppositional defiant disorder as reported by adolescents and their parents.

"Existing follow-up guidelines of preterm infants suggest monitoring for mental health issues, and this study provides preliminary evidence that in the future it may be prudent to expand this to all infants who stay in a NICU regardless of birth weight status," said Van Lieshout.

Van Lieshout added that additional research and more data are needed to better understand potential causal factors, and further identify at-risk individuals.

The type of salamander called axolotl, with its frilly gills and widely spaced eyes, looks like an alien and has other-worldly powers of regeneration. Lose a limb, part of the heart or even a large portion of its brain? No problem: They grow back.

"It regenerates almost anything after almost any injury that doesn't kill it," said Parker Flowers, postdoctoral associate in the lab of Craig Crews, the John C. Malone Professor of Molecular, Cellular, and Developmental Biology and professor of chemistry and pharmacology.

If scientists can find the genetic basis for the axolotl's ability to regenerate, they might be able to find ways to restore damaged tissue in humans. But they have been thwarted in the attempt by another peculiarity of the axolotl -- it has the largest genome of any animal yet sequenced, 10 times larger than that of humans.

Now Flowers and colleagues have found an ingenious way to circumvent the animal's complex genome to identify at least two genes involved in regeneration, they report Jan. 28 in the journal eLife.

The advent of new sequencing technologies and gene-editing technology has allowed researchers to craft a list of hundreds of gene candidates that could responsible for regeneration of limbs. However, the huge size of the axolotl genome populated by vast areas of repeated stretches of DNA has made it difficult to investigate the function of those genes.

Lucas Sanor, a former graduate student in the lab, and fellow co-first author Flowers used gene editing techniques in a multi-step process to essentially create markers that could track 25 genes suspected of being involved in limb regeneration. The method allowed them to identify two genes in the blastema -- a mass of dividing cells that form at the site of a severed limb -- that were also responsible for partial regeneration of the axolotl tail.

Flowers stressed that many more such genes probably exist. Since humans possess similar genes, the researchers say, scientists may one day discover how to activate them to help speed wound repair or regenerate tissue.

WASHINGTON -- A new approach that uses artificial intelligence to analyze retinal images could one day help doctors select the best treatment for patients with vision loss from diabetic macular edema. This diabetes complication is a major cause of vision loss among working-age adults.

Anti-vascular endothelial growth factor (VEGF) agents are widely used as the first line of therapy for diabetic macular edema, but they don't work for everyone. There's a need to identify who would benefit from the therapy because it requires multiple injections that are costly and burdensome for both patients and physicians.

"We developed an algorithm that can be used to automatically analyze optical coherence tomography (OCT) images of the retina to predict whether a patient is likely to respond to anti-VEGF treatments," said research team leader Sina Farsiu from Duke University. "This research represents a step toward precision medicine, in which such predictions help clinicians better select first-line therapies for patients based on specific disease conditions."

In The Optical Society (OSA) journal Biomedical Optics Express, Farsiu and colleagues show that the new algorithm can analyze just one pre-treatment volumetric scan to accurately predict whether a patient is likely to respond to anti-VEGF therapy.

"Our approach could potentially be used in eye clinics to prevent unnecessary and costly trial-and-error treatments and thus alleviate a substantial treatment burden for patients," Farsiu said. "The algorithm could also be adapted to predict therapy response for many other eye diseases, including neovascular age-related macular degeneration."

Predicting treatment response
The algorithm developed by the researchers is based on a novel convolutional neural network (CNN) architecture, a type of artificial intelligence that can analyze images by assigning importance to various aspects or objects. They used the algorithm to examine images acquired with OCT, a noninvasive technology that produces high-resolution cross-sectional retinal images and is the standard of care for assessing and treating many eye conditions.

"Unlike previously developed approaches, our algorithm requires OCT images from only a single pretreatment timepoint," said Reza Rasti, first author of the paper and a postdoctoral scholar in Farsiu's laboratory. "There's no need for time-series OCT images, patient records or other metadata to predict therapy response."

The new algorithm preserves and highlights global structures in the OCT image while enhancing local features from diseased regions to efficiently use retinal thickness information. To help with treatment decision making, the researchers incorporated an additional step that looks for CNN-encoded features that are highly correlated with anti-VEGF response.

Testing the algorithm
The researchers tested their new algorithm with OCT images from 127 patients who had been treated for diabetic macular edema with three consecutive injections of anti-VEGF agents. They applied the algorithm to analyze OCT images taken before the anti-VEGF injections, then compared the algorithm's predictions to OCT images taken after anti-VEGF therapy to confirm whether the therapy improved the condition.

Based on the results, the researchers calculated that the algorithm would have an 87 percent chance of correctly predicting who would respond to treatment. It exhibited an average precision and specificity of 85 percent and a sensitivity of 80 percent.

Next, the researchers plan to confirm and extend the findings from this pilot study by performing a larger observational trial of patients who have not yet undergone treatment.

January 28, 2020 -- City design combining more public transport and rail networks with smaller, low speed blocks are the best to reduce road transport injuries, according to a new global study co-authored by researchers at Columbia University Mailman School of Public Health. The findings are published in The Lancet Planetary Health.

The research identified the best and worst performing city designs with respect to road injuries. Researchers from Australia, Spain in addition to the United States compared maps of almost 1700 cities across the world with injury data to understand urban design factors that contribute to the most road injuries.

Cities were categorized into nine unique design types ranging from locations with highly organized road and rail network ('High Transit', 'Motor City' and 'Intense' types) to areas with almost no public transport and sparse urban design ('Sparse' and 'Informal' types).

Lead researcher Dr. Jason Thompson of the Melbourne School of Design said the research aims to highlight the importance of urban design and planning as a key factor in reducing transport related injuries across the world.

"The floor plans of our cities matter enormously for the health of residents. Designs that prioritize motor vehicles have huge costs, including more injuries and deaths due to crashes, whereas intelligent designs that promote public transportation can very substantially reduce this burden," said Christopher N. Morrison, PhD, assistant professor of epidemiology at Columbia Mailman School of Public Health.

The study found 'High Transit' cities with strong rail networks like Barcelona, Durban, Jerusalem and Toronto had the lowest rates of road injuries compared to 'Informal' type cities across India, China and Africa where poor urban design contributed to twice the injury rates.

"If reducing the road toll is your ultimate goal, it is better to invest in safer alternative transport options rather than continuing to focus on car-based safety interventions," Dr. Thompson said.

Australian cities like Perth, Adelaide, Newcastle and Melbourne fell under the 'Motor City' category with extensive road networks and suburbs designed around the needs of drivers that create car dependency.

"Australia has successfully reduced road injuries through enforcement and public safety education in the past but a shift away from motor vehicles toward more compact city design and investment in safe, efficient public transport is key to reducing future road injury rates," Dr. Thompson noted.

The study also found that the income of a country did not necessarily relate to road injury rates. High-income countries like Saudi Arabia, the United States and United Arab Emirates were still experiencing high road injury rates due to city designs that encourage motor vehicle use.

The research was conducted at the University of Melbourne's Transport, Health and Urban Design Research Hub in collaboration with Barcelona Institute of Global Health and Columbia University's Mailman School of Public Health.

WASHINGTON, D.C., January 28, 2020--Students' high school grade point averages are five times stronger than their ACT scores at predicting college graduation, according to a new study published today in Educational Researcher, a peer-reviewed journal of the American Educational Research Association.

The authors of the new study, Elaine M. Allensworth and Kallie Clark, both of the University of Chicago, also found that the predictive power of GPAs is consistent across high schools. The relationship between ACT scores and college graduation depends on which high school a student attends; at many high schools there is no connection between students' ACT scores and eventual college graduation.

"It was surprising not only to see that there was no relationship between ACT scores and college graduation at some high schools, but also to see that at many high schools the relationship was negative among students with the highest test scores," said Allensworth, who is the director of the University of Chicago Consortium on School Research.

Across all high schools in the study, each incremental increase in GPA is associated with an increase in the odds of graduating college. The chance of graduating from college ranges from 20 percent for students with high school GPAs under 1.5 to about 80 percent for those with GPAs of 3.75 or higher, after controlling for student backgrounds and college characteristics.

"While people often think the value of GPAs is inconsistent across high schools, and that standardized test scores, like the ACT, are neutral indicators of college readiness because they are taken by everyone under the same conditions, our findings indicate otherwise," Allensworth said. "The bottom line is that high school grades are powerful tools for gauging students' readiness for college, regardless of which high school a student attends, while ACT scores are not."

According to the authors, their study confirms prior research that finds high school GPAs are more predictive than SAT and ACT scores of college freshman GPA and college graduation. This study is the first to explicitly test whether standardized assessments are comparable across high schools as measures of college readiness.

The study examined 55,084 students who graduated from the Chicago public school district between 2006 and 2009 and immediately enrolled in a four-year college. The Chicago district contains schools with varying academic profiles, ranging from extremely high-achieving, selective schools to schools with very low average test scores. At the time the study students were in high school, all students in Illinois took the ACT in the spring of 11th grade.

In the authors' view, the fact that high school GPAs are based on many factors--including effort over an entire semester in many different types of classes, demonstration of academic skills through multiple formats, and different teacher expectations--might be why GPAs are strong indicators of college readiness.

"GPAs measure a very wide variety of skills and behaviors that are needed for success in college, where students will encounter widely varying content and expectations," said Allensworth. "In contrast, standardized tests measure only a small set of the skills that students need to succeed in college, and students can prepare for these tests in narrow ways that may not translate into better preparation to succeed in college."

"Extensive time spent preparing for standardized tests will have much less pay-off for postsecondary success than effort put into coursework, as reflected in students' grades," said Clark, a doctoral student at the University of Chicago. "The more that middle and high school educators can support strong engagement in school--helping students overcome barriers to engagement in class, helping them succeed at different types of academic tasks, so that they earn strong grades--the better these educators are supporting academic skills broadly and preparing students for college."

The authors also note that most states and districts in the United States rely heavily on standardized test scores in their accountability systems as indicators of whether students are meeting state college readiness goals. Because the relationship of test scores with college graduation is not strong or consistent, states and districts that choose this metric may misestimate the effects of policies and school practices on students' college readiness. The authors suggest that measures of students' actual performance in college would provide better information.

Above and beyond students' individual achievement on high school coursework and the ACT, Allensworth and Clark found that students are more likely to graduate college if they come from some high schools rather than others. These school effects may be the result of more rigorous academic programs at some high schools, different non-academic supports for preparing students for college, or simply a tendency of families with more resources for college to send their students to particular high schools.

"There are large high school effects on college graduation that are not explained by students' high school GPA, their individual ACT scores, or the two of them combined," Clark said. "Understanding why students from some high schools succeed in college more than students at other schools is an important next step for better supporting all students' ability to earn a college degree."

NEW ORLEANS, Louisiana (January 27, 2020) -- While transcatheter aortic valve replacement (TAVR) continues to expand its pool of eligible patients, open heart surgery--resulting in excellent patient survival and fewer strokes when compared to TAVR--is the best option for young and middle-aged adults with aortic valve disease--at least for now, according to a scientific presentation at the 56th Annual Meeting of The Society of Thoracic Surgeons.

"Our research favors the use of surgical aortic valve replacement (SAVR) in adults who are younger than 55 years old," said Jennifer S. Nelson, MD, from Nemours Children's Hospital in Orlando, Florida. "Although young and middle-aged adult TAVR candidates do exist, thoughtful patient selection is critical to optimizing triage to SAVR and TAVR."

Using the STS National Database, Dr. Nelson and colleagues from Nemours and the Cleveland Clinic in Ohio examined data from patients who were 18 to 54 years old and received aortic valve replacement (SAVR or TAVR) between 2013 and 2018. Approximately one-sixth of these patients had congenital (present from birth) heart disease (CHD). As a result, researchers combined data from two components of the Database: the STS Adult Cardiac Surgery Database (ACSD) and the STS Congenital Heart Surgery Database (CHSD).

Overall, 1,580 unique CHSD and 44,173 ACSD operations were analyzed, and more than 15% of the operations were related to CHD. When isolated SAVR (no other complex operations were performed at the same time as the aortic valve replacement) was compared to isolated TAVR, the stroke rate was 0.9% versus 2.4%, respectively. The researchers also found that the 30-day mortality rate was slightly better for isolated SAVR than for isolated TAVR--1.9% versus 2.9%.

TAVR had an advantage over SAVR, though, when the researchers looked at the length of hospital stay: SAVR was longer at 6 days versus 4 days for TAVR (with the length of stay for TAVR expected to continue decreasing). This is especially noteworthy because the number of young and middle-aged adult TAVR candidates is increasing, with TAVR becoming more appealing to younger patients who want to minimize downtime and risks, according to Dr. Nelson. "The wisdom of extending TAVR to a younger adult population that mirrors the characteristics of an older population with acquired aortic valve stenosis may be reasonable," she said.

Dr. Nelson explained that there also are challenges associated with TAVR in younger patients. Most concerning is that little is known about long-term valve durability, and so only time will tell how the latest devices fare as TAVR use is expanded into this group. The researchers also found that patients in this study most often had aortic insufficiency (leakage of the aortic valve) rather than aortic stenosis (narrowing of the valve)--the condition for which TAVR valves currently are approved. Therefore, many younger patients may have a type of valve disease that is "not amenable" to treatment currently available for TAVR, explained Dr. Nelson.

"However, as the durability of these valves and the benefits in other types of valve dysfunction become known through longer-term follow up, I expect the TAVR trend will continue toward younger and younger patients," she said.

In addition, caution should be exercised in the application of TAVR to adult patients with CHD. According to Dr. Nelson, TAVR has been used only rarely in young adults and even less in adults with CHD. "Adults with CHD is a large and growing subgroup, but the anatomy of the aorta, aortic valve, and coronary arteries could present challenges for current TAVR devices. However, adults with CHD often have undergone several procedures in their lifetimes, so we must evaluate new therapies that could potentially avoid open, invasive operations. Further study is needed," she added.

Dr. Nelson recognized TAVR as a "disruptive technology" that has changed the way adult cardiac surgery is practiced. "When handled thoughtfully and responsibly, technological advances such as TAVR can help patients lead longer and fuller lives. As a congenital cardiac surgeon, I seek to define which patients will benefit the most from this new therapy and which patients are better served with other modalities," she said.

"Despite the excellent results and less invasive nature of TAVR in older adults, we need to exercise caution before offering this technology to younger patients," said Robbin Cohen, MD, MMM, professor of surgery at the Keck School of Medicine of the University of Southern California in Los Angeles, who was not directly involved with this research. "We just don't know enough about the durability of TAVR in young patients, nor do we know what the best treatment option will be should TAVR valves fail from structural deterioration and need to be replaced."

The heart team approach, including an emphasis on shared decision-making and new collaborations between congenital and adult cardiac surgeons, has become especially important as the number of aortic valve replacement options increases, according to Dr. Nelson. When cardiologists and cardiac surgeons together evaluate aortic valve disease cases, patients receive comprehensive counseling and invaluable insight into all of the viable options for their valve choice, allowing them to make more informed decisions.

"Because each patient is an individual with unique characteristics, deciding on the best valve option means considering the whole picture," said Dr. Nelson. "Taking the time to learn about the risks and benefits of each valve option and sharing in the decision-making process with the heart team is the best way to make the right choice."

Today, modern lasers can generate extremely short light pulses, which can be used for a wide range of applications from investigating materials to medical diagnostics. For this purpose, it is important to measure the shape of the laser light wave with high accuracy. Until now, this has required a large, complex experimental setup. Now this can be done with a tiny crystal with a diameter of less than one millimeter. The new method has been developed by the MPI for Quantum Optics in Garching, the LMU Munich and the TU Wien (Vienna). The advance will now help to clarify important details about the interaction of light and matter.

Looking at Light with Electrons

Extremely short light pulses with a duration in the order of femtoseconds (10-15 seconds) were investigated. "In order to create an image of such light waves, they must be made to interact with electrons," says Prof. Joachim Burgdörfer from the Institute of Theoretical Physics at the TU Wien. "The reaction of the electrons to the electric field of the laser gives us very precise information about the shape of the light pulse".

Previously, the common way to measure an infrared laser pulse was adding a much shorter laser pulse with a wavelength in the X-ray range. Both pulses are sent through a gas. The X-ray pulse ionizes individual atoms, electrons are released, which are then accelerated by the electric field of the infrared laser pulse. The motion of the electrons is recorded, and if the experiment is carried out many times with different time shifts between the two pulses, the shape of the infrared laser pulse can eventually be reconstructed. "The experimental effort required for this method is very high," says Prof. Christoph Lemell (TU Vienna). "A complicated experimental setup is needed, with vacuum systems, many optical elements and detectors."

Measurement in Tiny Silicon Oxide Crystals

To bypass such complications, the idea was born to measure light pulses not in a gas but in a solid: "In a gas you have to ionize atoms first to get free electrons. In a solid it is sufficient to give the electrons enough energy so that they can move through the solid, driven by the laser field", says Isabella Floss (TU Vienna). This generates an electric current which can be directly measured.

Tiny crystals of silicon oxide with a diameter of a few hundred micrometers are used for this purpose. They are hit by two different laser pulses: The pulse which is to be investigated can have any wavelength ranging from ultraviolet light and visible colours to long-wave infrared. While this laser pulse penetrates the crystal, another infrared pulse is fired at the target. "This second pulse is so strong that non-linear effects in the material can change the energy state of the electrons so that they become mobile. This happens at a very specific point in time, which can be tuned and controlled very precisely," explains Joachim Burgdörfer.

As soon as the electrons can move through the crystal, they are accelerated by the electric field of the first beam. This produces an electric current which is measured directly at the crystal. This signal contains precise information about the shape of the light pulse.

Many Possible Applications

At TU Wien, the effect was studied theoretically and analysed in computer simulations. The experiment was performed at the Max Planck Institute for Quantum Optics in Garching. "Thanks to the close cooperation between theory and experiment, we have been able to show that the new method works very well, over a large frequency range, from ultraviolet to infrared," says Christoph Lemell. "The waveform of light pulses can now be measured much more easily than before, with the help of such a much simpler and more compact setup."

The new method opens up many interesting applications: It should be possible to precisely characterize novel materials, to answer fundamental physical questions about the interaction of light and matter, and even to analyze complex molecules - for example, to reliably and quickly detect diseases by examining tiny blood samples.

The design of sophisticated new materials is undergoing brisk technological advancement. Innovations in material science promise transformative improvements in industries ranging from energy to manufacturing.

In a new study, researchers at ASU's Biodesign Institute and their colleagues explore new materials with physical properties that can be custom-tailored to suit particular needs. The work is inspired by mechanisms in nature, where the complex three-dimensional structure of surrounding proteins influences the electrochemical properties of metals at their core.

The advances could have broad implications for the design of many new innovations useful for semiconductor technology, sustainable energy and industrial production.

Material world

Lead author Brian Wadsworth and his collaborators describe techniques for immobilizing metal complexes onto physical supports that are both transparent and conductive. The resulting hybrid materials permit synthetic control over the configuration, allowing researchers to regulate the shuttling of electrons within the composite material.

Precise control over material performance may be accomplished through modification of material interfaces. According to corresponding author Gary Moore, "any time two things touch each other, they form an interface. Material interfaces are central to our work." It is in these regions that modifications designed to adjust a material's physical properties take place.

The current study extends the group's earlier efforts with semiconductor materials, which involved the capture and conversion of solar energy to produce fuels. Accomplishing this requires the ability to control reactions and chemical entities that increase their rate, known as catalysts. "Our use of molecules on surfaces can have a wide range of applications, including solar energy conversion, catalysis, and chemical manufacturing via green chemistry," Moore says.

In addition to Wadsworth and Moore, both researchers in the Biodesign Center for Applied Structural Discovery, the team includes Diana Khusnutdinova and Jennifer M. Urbine, (formerly with the Biodesign Institute and currently at Intel and the doctoral program at UC Irvine, respectively). Ahlea S. Reyes, who began working in the Moore lab as a high school student and is currently an undergraduate at ASU, also contributed to the new study.

The research graces the cover of the latest issue of the journal ACS Applied Materials & Interfaces.

Control center

Catalysts play a vital role in processes involving the conversion of energy and are important in both biology and technology. The current study provides valuable information that could lead to advances in efficiency, reliability and scalability of sustainable energy solutions. The mounting energy crisis puts efforts to better understand the electrochemistry of new materials on the fast track and opens far-reaching possibilities for new technologies.

Conventional catalysts like those used in industry are usually based on two-dimensional surfaces. Here, reactants are brought together in order to produce a desired product. Catalysts speed up the rate of such reactions. One of the most basic transformations is hydrogen production, where electrons and protons are brought together to form molecular hydrogen. In this case, platinum is commonly used as a catalyst.

Nature, however, has found a cheaper and more efficient means of hydrogen production. "Biology doesn't use two dimensional sheets of platinum," Moore explains. Instead, life forms carry out this transformation with the aid of specialized enzymes. "Enzymes often contain metal centers where the reactivity is occurring, but their specificity comes from their unique three-dimensional structures."

Their unique approach results in materials inspired by such three-dimensional architectures in order to guide reactions that bring together multiple substrates-- substances on which catalysts act. Creating three-dimensional soft matter environments, similar to those found in proteins, permits researchers to apply fine-grained control of these reactions in both space and time.

"Brian has worked out an approach to attach relatively thin molecular coatings, including polymers, onto an electrode surface," Moore says. "Now these electrode surfaces have three-dimensional molecular environments, where we can purposefully deposit a metal center." These metal centers are the sites of so-called reduction-oxidation or redox reactions, where electrons are gained or lost.

Overcoming metal fatigue

The method helps overcome one of the primary limiting factors in designing effective catalysts. Conventional catalysts typically use rare earth metals like platinum, which, as their name implies, are scarce and very costly. Instead, by creating a three-dimensional hybrid material consisting of structurally well-defined homogeneous components that are bonded to a heterogeneous support structure, the synthetic material can be made with far cheaper and more earth-abundant metals like cobalt (used in the current study). The authors stress that these innovations can not only reduce the cost of new materials but improve their efficiency and stability as well. "Again, that's the bio-inspired part of our vision for developing these molecular coatings," Moore says.

In order to design the new material, Wadsworth uses some of the sophisticated attachment chemistries developed in earlier work on light-gathering semiconductors. Experiments described in the new paper investigate the effects of applying these chemistries to the surfaces of conducting materials. This enables the researchers to directly probe the electrochemical properties of the embedded metal centers. "We're getting mechanistic information on how the soft material or protein-like environments control the chemistry occurring at the metal center," Wadsworth says.

Once the metal-containing complexes are bound to the electrode surface, the surrounding molecular environment can be subtly modified to alter the redox responses. "Every chemical transformation involves changes in structure and energy that are associated with a chemical potential," Moore says. "The coatings reported in this work enable the surface-immobilized metal centers to operate across a relatively large span of potentials for applications in a range of chemical processes and emerging technologies."

Catalyzing research

Some of these new ideas were recently discussed at the Winter Inter-American Photochemical Society (I-APS) Conference, which took place in Sarasota, Florida, January 2-5, 2020. The lively conference was co-organized by Moore and his colleague Elizabeth Young of Lehigh University and brought together leading scientists in all areas of the photochemical sciences, from North and South America.

At the meeting, Wadsworth presented a poster titled "Bridging Concepts between Heterogeneous-, Homogeneous-, and Bio-Catalysis to Model Photoelectrosynthetic Reactions" and received an award supported by the journal ACS Applied Materials & Interfaces, (the same journal featuring the current research cover story).

The researchers believe one of the strengths of bio-inspired and molecular-based strategies is the diversity in structure and function this approach enables. "Diversity brings increased creativity and promotes innovation. This notion is leveraged not only in the materials we construct, but also in the team of researchers that guide the ongoing evolution of our science," Moore says. "The current work features contributions from high school, undergraduate, graduate, and postgraduate students from across the globe."

Scientists studied the sex lives of 778 individual plants for 21 years

During the study, prescribed, controlled burns took place in nine different years

In the year after a prescribed burn, more plants flowered, annual seed production nearly doubled

EVANSTON, Ill. -- For a prairie plant, a fiery love life isn't just fun -- it's essential.

In a new study, researchers found that prescribed, expert-controlled fires are critically important to successful reproduction in prairie plants. Fires cause prairie plants to flower at the same time, which increases mating opportunities and seed production.

During the study, which ran from 1996 to 2016, researchers observed the sex lives of 778 individual plants on Staffanson Prairie in Minnesota. Throughout the 21-year study, conservation scientists conducted prescribed burns in nine different years.

"In most years, plants are isolated from other plants because few plants flower," said Stuart Wagenius, a Northwestern University conservation scientist, who led the study. "They don't get well pollinated, and they produce few seeds. In the summer right after a fire, however, many plants flower. They are not isolated. They get pollinated and produce many seeds. Synchronized flowering after a fire keeps populations healthy and averts local extinctions."

The study will publish this week in the Proceedings of the National Academy of Sciences. Wagenius is a senior scientist at the Chicago Botanic Garden and an adjunct assistant professor at Northwestern University's Program in Plant Biology and Conservation.

Tallgrass prairie is one of the most threatened and least protected habitats in the world. Over the past several years, native plants have been disappearing from prairies, especially those not managed with prescribed fires. These fires are not the same as the wildfires that make headlines in the news. Prescribed fires are a controlled application of fire by experts under specific conditions. They keep ecosystems healthy and actually prevent wildfires by reducing dried vegetation, which can fuel fires.

To better understand how fires might help revitalize these communities, researchers specifically followed Echinecea angustifolia, or the narrow-leaved purple coneflower. Widespread in the prairie and plains west of the Mississippi River, the purple coneflower is a model organism to study perennial plants in grasslands.

An individual purple coneflower plant lives for many years, without flowering every year. It's important for plants within the same location to flower at the same time as one another. This synchronization improves opportunities for bees to move pollen among plants.

"Fires serve as a signal for plants to flower, which we expected," said Gretel Kiefer, scientist at the Chicago Botanic Garden and coauthor of the study. "However, we didn't know that, within a season, flowering times would overlap a lot more after a burn compared to most years. This synchronized flowering improves pollination by bees, which is required to make seeds."

The researchers hope their findings will encourage more prescribed fires in prairies and other fire-prone habitats with a history of fire suppression.

"Rekindling fires may have widespread benefits for plant reproduction and diversity in fire-dependent ecosystems worldwide," Wagenius said. "Usually people think that fires help plants compete for better resources. This experiment uncovers a totally different additional benefit -- more mating and better pollination."

COLUMBIA, Mo. - Hormonal changes, different schools, more teachers and changing expectations are just some of the challenges families face when a child enters middle school. Now, researchers from the University of Missouri have found that 94% of middle school teachers experience high levels of stress, which could contribute to negative outcomes for students. Researchers say that reducing the burden of teaching experienced by so many teachers is critical to improve student success -- both academically and behaviorally.

The new study, which expands on work looking at stress among elementary school teachers, provides additional evidence that teacher stress might lead to negative outcomes for students.

"Many studies of teacher stress have used samples from elementary schools," said Keith Herman, professor in the MU College of Education. "However, middle school is a particularly important time in students' lives as they transition from elementary school and have many different teachers. It's critical that we understand how stress impacts middle school teachers so we can find ways to support them."

Herman, along with fellow MU researchers Wendy Reinke, Sara Prewett, Colleen Eddy and Alyson Savale, studied data collected from nine middle schools in two neighboring urban school districts in the Midwest. Factors that went into the analysis included self-reported levels of teacher stress and coping, student disruptive and prosocial behavior, and parent involvement.

The researchers found that nearly all teachers reported high stress. They also found that teachers varied in how they coped with stress.

The largest group, 66%, reported high stress and high coping.

Nearly one-third of the participants, 28%, reported high stress and low coping.

Only 6% of middle school teachers reported low levels of stress and high coping ability.

"Unfortunately our findings suggest many teachers are not getting the support they need to adequately cope with the stressors of their job," Herman said. "The evidence is clear that teacher stress is related to student success, so it is critical that we find ways to reduce stressful school environments while also helping teachers cope with the demands of their jobs."

Herman suggests that school districts provide access to initiatives and programs that promote mental health to improve conditions for middle school teachers. This can include wellness programs, organizational support for teachers and mental health interventions.

"There are research-based tools that can help screen and identify teachers who might be at risk for problems with stress, coping and the risk of burnout," Herman said. "Knowing what we know about how teacher stress can impact students, it is imperative that district and school leaders examine policies and practices that make the job less burdensome while also supporting teacher well-being.

Imagine a device that could swiftly analyze microbes in oceans and other aquatic environments, revealing the health of these organisms - too tiny to be seen by the naked eye - and their response to threats to their ecosystems.

Rutgers researchers have created just such a tool, a portable device that could be used to assess microbes, screen for antibiotic-resistant bacteria and analyze algae that live in coral reefs. Their work is published in the journal Scientific Reports.

The tool, developed initially to assess algae, can determine in the field or in laboratories how microbes and cells respond to environmental stresses, such as pollution and changes in temperature or water salinity.

"This is very important for environmental biology, given the effects of climate change and other stressors on the health of microorganisms, such as algae that form harmful blooms, in the ecosystem," said senior author Mehdi Javanmard, an associate professor in the Department of Electrical and Computer Engineering in the School of Engineering at Rutgers University-New Brunswick.

"Our goal was to develop a novel way of assessing cell health that did not rely on using expensive and complex genomic tools," said co-senior author Debashish Bhattacharya, a distinguished professor in the Department of Biochemistry and Microbiology in the School of Environmental and Biological Sciences. "Being able to assess and understand the status of cells, without having to send samples back to the lab, can allow the identification of threatened ecosystems based on a 'stress index' for their inhabitants."

The research focused on a well-studied green microalga, Picochlorum. The tool can quickly reveal whether a cell is stressed, robust or unaffected by environmental conditions. Microbes pass one by one through a micro-channel, thinner than the diameter of a human hair. Impedance, or the amount an electrical field in the tool is perturbed when a cell passes through the channel, is measured. Impedance varies among cells in a population, reflecting their size and physiological state, both of which provide important readouts of health.

The researchers showed that electrical impedance measurements can be applied at the single cell and population levels. The scientists plan to use the tool to screen for antibiotic resistance in different bacteria and algae that live in symbiosis with coral reefs, which will help give them a better idea of coral health.