Tech

CHAMPAIGN, Ill. -- By adding infrared capability to the ubiquitous, standard optical microscope, researchers at the University of Illinois at Urbana-Champaign hope to bring cancer diagnosis into the digital era.

Pairing infrared measurements with high-resolution optical images and machine learning algorithms, the researchers created digital biopsies that closely correlated with traditional pathology techniques and also outperformed state-of-the-art infrared microscopes.

Led by Rohit Bhargava, a professor of bioengineering and the director of the Cancer Center at Illinois, the group published its results in the Proceedings of the National Academy of Sciences.

"The advantage is that no stains are required, and both the organization of cells and their chemistry can be measured. Measuring the chemistry of tumor cells and their microenvironment can lead to better cancer diagnoses and better understanding of the disease," Bhargava said.

The gold standard of tissue pathology is to add dyes or stains so that pathologists can see the shapes and patterns of the cells under a microscope. However, it can be difficult to distinguish cancer from healthy tissue or to pinpoint the boundaries of a tumor, and in many cases diagnosis is subjective.

"For more than a century, we have relied on adding dyes to human tissue biopsies to diagnose tumors. However, the shape and color induced by the dye provide very limited information about the underlying molecular changes that drive cancer," Bhargava said.

Technologies like infrared microscopy can measure the molecular composition of tissue, providing quantitative measures that can distinguish cell types. Unfortunately, infrared microscopes are expensive and the samples require special preparation and handling, making them impractical for the vast majority of clinical and research settings.

Bhargava's group developed its hybrid microscope by adding an infrared laser and a specialized microscope lens, called an interference objective, to an optical camera. The infrared-optical hybrid measures both infrared data and a high-resolution optical image with a light microscope - the kind ubiquitous in clinics and labs.

"We built the hybrid microscope from off-the-shelf components. This is important because it allows others to easily build their own microscope or upgrade an existing microscope," said Martin Schnell, a postdoctoral fellow in Bhargava's group and first author of the paper.

Combining the two techniques harnesses the strengths of both, the researchers said. It has the high resolution, large field-of-view and accessibility of an optical microscope. Furthermore, infrared data can be analyzed computationally, without adding any dyes or stains that can damage tissues. Software can recreate different stains or even overlap them to create a more complete, all-digital picture of what's in the tissue.

The researchers verified their microscope by imaging breast tissue samples, both healthy and cancerous, and comparing the results of the hybrid microscope's computed "dyes" with those from the traditional staining technique. The digital biopsy closely correlated with the traditional one.

Furthermore, the researchers found that their infrared-optical hybrid outperformed state-of-the-art in infrared microscopes in several ways: It has 10 times larger coverage, greater consistency and four times higher resolution, allowing infrared imaging of larger samples, in less time, with unprecedented detail.

"Infrared-optical hybrid microscopy is widely compatible with conventional microscopy in biomedical applications," Schnell said. "We combine the ease of use and universal availability of optical microscopy with the wide palette of infrared molecular contrast and machine learning. And by doing so, we hope to change how we routinely handle, image and understand microscopic tissue structure."

The researchers plan to continue refining the computational tools used to analyze the hybrid images. They are working to optimize machine-learning programs that can measure multiple infrared wavelengths, creating images that readily distinguish between multiple cell types, and integrate that data with the detailed optical images to precisely map cancer within a sample. They also plan to explore further applications for hybrid microscope imaging, such as forensics, polymer science and other biomedical applications.

"It is very intriguing what this additional detail can offer in terms of pathology diagnoses," Bhargava said. "This could help speed up the wait for results, reduce costs of reagents and people to stain tissue, and provide an 'all-digital' solution for cancer pathology."

HOUSTON - (Feb. 12, 2020) - You don't need a big laser to make laser-induced graphene (LIG). Scientists at Rice University, the University of Tennessee, Knoxville (UT Knoxville) and Oak Ridge National Laboratory (ORNL) are using a very small visible beam to burn the foamy form of carbon into microscopic patterns.

The labs of Rice chemist James Tour, which discovered the original method to turn a common polymer into graphene in 2014, and Tennessee/ORNL materials scientist Philip Rack revealed they can now watch the conductive material form as it makes small traces of LIG in a scanning electron microscope (SEM).

The altered process, detailed in the American Chemical Society's ACS Applied Materials & Interfaces, creates LIG with features more than 60% smaller than the macro version and almost 10 times smaller than typically achieved with the former infrared laser.

Lower-powered lasers also make the process less expensive, Tour said. That could lead to wider commercial production of flexible electronics and sensors.

"A key for electronics applications is to make smaller structures so that one could have a higher density, or more devices per unit area," Tour said. "This method allows us to make structures that are 10 times denser than we formerly made."

To prove the concept, the lab made flexible humidity sensors that are invisible to the naked eye and directly fabricated on polyimide, a commercial polymer. The devices were able to sense human breath with a response time of 250 milliseconds.

"This is much faster than the sampling rate for most commercial humidity sensors and enables the monitoring of rapid local humidity changes that can be caused by breathing," said the paper's lead author, Rice postdoctoral researcher Michael Stanford.

The smaller lasers pump light at a wavelength of 405 nanometers, in the blue-violet part of the spectrum. These are less powerful than the industrial lasers the Tour Group and others around the world are using to burn graphene into plastic, paper, wood and even food.

The SEM-mounted laser burns only the top five microns of the polymer, writing graphene features as small as 12 microns. (A human hair, by comparison, is 30 to 100 microns wide.)

Working directly with ORNL let Stanford capitalize on the national lab's advanced equipment. "That's what made this joint effort possible," Tour said.

"I did a lot of my Ph.D. research at ORNL, so I was aware of the excellent facilities and scientists and how they could help us with our project," Stanford said. "The LIG features we were creating were so small that they would have been next to impossible to find if we were to lase the patterns and then search for them in the microscope later."

Tour, whose group recently introduced flash graphene to instantly turn trash and food waste into the valuable material, said the new LIG process offers a new path toward writing electronic circuits into flexible substrates like clothing.

"While the flash process will produce tons of graphene, the LIG process will allow graphene to be directly synthesized for precise electronics applications on surfaces," Tour said.

WASHINGTON, D.C.--The emergency department is being increasingly utilized as a patient's best or only treatment option for opioid use disorder (OUD). New analysis in Annals of Emergency Medicine shows that the prevalence of patients who visited emergency departments at four Indiana hospital systems for repeat opioid-related emergencies jumped from 8.8 percent of all opioid-related visits in 2012 to 34.1 percent in 2017--nearly a four-fold increase in just five years.

"Emergency departments are vital partners in treatment for opioid disorders. Less frequently discussed is the value of emergency department data that can be applied to predict and prevent emergencies among at-risk patients," said Casey P. Balio, PhD candidate at IU Richard M. Fairbanks School of Public Health at IUPUI and lead study author. "Because the ED is such an important site for care, we need to identify opportunities for treatment and support that help increase efficiency across systems of care and benefit patients."

Patients with greater numbers of previous opioid-related ED visits, previous unique number hospital systems for which they've had an ED encounter, heroin use being documented at the encounter, those insured by Medicaid or uninsured relative to privately insured were more likely to have a future emergency department encounter for opioid-related emergencies, according to the analysis.

The analysis of 9,295 patients in four Indiana hospital systems was conducted with data from a statewide regional Health Information Exchange system that examined prescription history, visit detail, and community characteristics.

"Consolidating patient information from multiple emergency departments can improve risk assessment and help identify more opportunities to provide patients with treatment, particularly those who have multiple ED visits for opioid-related health emergencies. More effective use of health information can enable more efficient care for these individuals," said Balio.

The cover for issue 6 of Oncotarget features Figure 3, "The effect of NCs treatments on routine lab results during disease and recovery progress," by Ben-Nun-Shaul, et al.

Numerous previous attempts to develop therapeutic treatments, directed at discreet targets of the sepsis cascade, could not cope with the complex pathophysiology of sepsis and failed.

Studies in a severe rat sepsis model showed that pre-treatment by NCs led to a dramatic increase in survival, from zero to 75%.

Further studies are needed to determine whether when applied after sepsis onset, the NCs still improve outcomes.

Dr. Arieh Eden from the Department of Anesthesiology, Critical Care and Pain Medicine at the Lady Davis Carmel Medical Center in Haifa, Israel said in their Oncotarget Research Paper, "Sepsis affects millions of individuals annually worldwide, with a mortality of >25%" and according to the Cancer | Sepsis Alliance "Having cancer and undergoing certain treatments for cancer, such as chemotherapy, can result in a weakened immune system, putting you at higher risk for developing an infection that could lead to sepsis. Sometimes incorrectly called blood poisoning, sepsis is the body's often deadly response to infection." https://www.sepsis.org/sepsisand/cancer/

"Having cancer and undergoing certain treatments for cancer, such as chemotherapy, can result in a weakened immune system, putting you at higher risk for developing an infection that could lead to sepsis. Sometimes incorrectly called blood poisoning, sepsis is the body's often deadly response to infection."

- DR. ARIEH EDEN, DEPARTMENT OF ANESTHESIOLOGY, CRITICAL CARE AND PAIN MEDICINE AT THE LADY DAVIS CARMEL MEDICAL CENTER IN HAIFA, ISRAEL

It accounts for more than 50% of hospital deaths, with mortality rates of 10 20% for sepsis, 20 40% for severe sepsis, and 40 80% for septic shock.

In the present study the authors tested the hypothesis, based on their earlier unpublished research, that empty SV40 capsids would improve the outcome of sepsis.

Twenty years ago we established a procedure for the production of empty SV40 capsid, in order to develop a safe gene delivery vector, to be assembled in vitro from empty capsids and plasmid DNA of choice.

The underlying mechanism was up-regulation of Hsp/c70 and induction of the PI3K/Akt survival pathway, both seen exclusively in kidney tissue of NCs treated mice.

That study revealed that SV40 and/or its NCs elicit concurrently opposing pathways: cellular stress response, pro-apoptotic host defense, and Akt-1 survival pathway.

The Eden Research Team concluded in their Oncotarget paper, that these findings, and the dynamic adjustment of the therapeutic pathways to the recovery course, lead them to suggest that the effect of the NCs is tailored both to the type and to the temporal course of the injury, implying a general homeostatic activity.

The homeostatic nature of the NC activity is also manifested in their negligible effect on the normal control rats.

Over a quarter of the remaining endangered Asian elephants in the world live in some form of captivity. The Asian elephant is particularly threatened, its population having halved since the 1950s and its range now only 5 per cent of its original size. The Asian elephant as a species, however, is in a unique position with 24-29 per cent of their remaining population living among humans, in captive or semi-captive conditions. Whilst the conservation priority lies in protecting the dwindling wild population, it is also important to protect these large human-managed populations. The largest of these populations is the semi-captive population of elephants working in the timber industry in Myanmar.

Past studies have highlighted that one of the factors most limiting the growth of this population is high juvenile mortality. Researchers from the University of Turku, Finland, together with the veterinarians responsible for the MTE elephants, have been investigating mortality during a particularly vulnerable time for these juveniles, the taming procedure they go through at the age of four years.

Calf Mortality at Taming Age Differs from Wild Elephants

The researchers first compared the survival of the semi-captive elephants to rates seen in a wild population of African elephants. They found that whilst the semi-captive elephants saw a more than 50 per cent rise in mortality at the taming age of four, this was not the case for the wild elephants.

-- This suggests that the rise in mortality we see at the age of four in the semi-captive elephants is a symptom of their management rather than a natural biological phenomenon, explains Doctoral Candidate Jennie Crawley, lead author of the study.

According to Crawley, a really promising finding is that calf survival has massively improved for taming aged calves in the last few decades. Calf mortality is now a third of the number witnessed in the 1970s. This suggests that changes introduced to the management of the calves have been successful in improving survival.

-- It is important to note these management measures to also improve rates elsewhere. In Myanmar, this population has at least one veterinarian attending the calves daily for the duration of the taming, the calves are provided with constant fodder collected from their natural forest habitat, and they get to walk daily to a natural water source to drink and bathe.

Calves with Less Experienced Mothers at Highest Risk of Death

The research group also studied whether certain calves were more at risk of death than others. These calves could then be the focus of veterinary attention to improve survival further.

-- We found that calves that were born later in the year, and therefore were younger at the onset of taming, were more likely to die, as were calves born to less experienced mothers, likely indicating calves in worse condition, says Professor Virpi Lummaa, the senior scientist on the study.

-- In the past we have found that calves of mothers caught from the wild had lower survival than those of captive born mothers, but here we saw no effect of mother origin on calf survival during taming, which is good news considering over 40 per cent of the individuals from our study period originated from the wild, explains Postdoctoral Researcher and co-author of the study Mirkka Lahdenperä.

According to Jennie Crawley, it is essential to actually monitor calves during this difficult period, rather than avoiding studying it as a controversial, taboo topic.

-- This way, we can try to understand the dynamics surrounding mortality during taming in the hopes of improving survival.

Today, nanoparticles are not only in cosmetic products, but everywhere, in the air, in water, in the soil and in food. Because they are so tiny, they easily enter into the cells in our body. This is also of interest for medical applications: Nanoparticles coated with active ingredients could be specifically introduced into cells, for example to destroy cancer cells. However, there is still much to be learned about how nanoparticles are distributed in the cells, what they do there, and how these effects depend on their size and coating.

New insights have come from a study at BESSY II, where Prof. Gerd Schneider's team can take X-ray microscopy images with soft, intensive X-rays. Researchers from the X-ray microscopy group led by HZB biophysicist Dr. James McNally investigated cells with differently coated nanoparticles. The nanoparticles were exactly the same size, but were coated with different active ingredients.

"X-ray microscopy offers significantly better resolution than light microscopy, and a much better overview than electron microscopy," emphasizes Schneider. For the first time, the team obtained complete, three-dimensional, high-resolution images of the nanoparticle-treated cells with the organelles contained therein: including lipid droplets, mitochondria, multivesicular bodies and endosomes. Lipid droplets act as energy stores in the cell, while mitochondria metabolize this energy.

The analysis of the images showed: The nanoparticles accumulate preferentially in a subset of the cell organelles and also change the number of certain organelles at the expense of other organelles. The changes in organelle numbers were similar regardless of the nanoparticle coating, suggesting that many different kinds of nanoparticle coatings may induce a similar effect. To evaluate how general this effect is, further studies with other nanoparticle coatings and with other cell types must be performed.

"X-ray microscopy allows us to see the cell as a whole, so we were able to observe this behavior for the first time," explains McNally. "We found that the absorption of such nanoparticles increases the number of mitochondria and endosomes, while other organelles, namely lipid droplets and multivesicular bodies, decrease," says Burcu Kepsutlu, who carried out the experiments for her doctorate."When we go on a starvation diet or run a marathon, we see similar changes in the cell - namely an increase in mitochondria and a decrease in lipid droplets," says McNally. "Apparently it takes energy for the cell to absorb the nanoparticles, and the cell feels like it has just run a marathon."

Research involving the University of Liverpool has revealed the effect of climate warming on the complex interactions between tree masting and the insects that eat their seeds.

Masting, the process by which trees vary the amount of seeds they produce year by year, is a characteristic of many forest tree species, including oaks, beeches, pines and spruces. It is beneficial because during `famine years', seed-eating animals (such as moths) are starved so their numbers decrease, while in the `bumper years', seed production is so high that it satiates insects and seed predators, so that some seeds can survive to establish the next generation of trees.

However, a study of beech tree seed production published in the journal Nature Plants, found that increased seed production due to warmer temperatures was accompanied by a reduction in the degree of year-to-year variability in seed production, and specifically a reduction in the frequency of the 'famine years'. Thus the main beneficiaries of climate-driven increases in seed production are seed predators, and not the plants themselves.

Co-author of the paper, Dr Andrew Hacket-Pain, from the University of Liverpool's School of Environmental Sciences, said: "This study is important for understanding how beech trees are responding to changes in the climate: Climate change is leading to an increase in the seed production of beech trees - but we show that any benefit the trees might gain from this increased reproductive effort has been almost entirely offset by higher seed consumption by the moth larvae.

"The trees are producing more seeds but gaining almost no return on their increased investment. It is an excellent example of how the overall response of forests to climate change is dependent on a complex web of interactions between species - it is far from straightforward."

Dr Jonathan Lageard, from Manchester Metropolitan University, added: "In this research, we use data from four decades of long-term monitoring to investigate how climate change has affected the reproduction of one of the UK's most widespread trees, beech. We show that seed production has increased over that time period - but this does not tell the whole story."

Lead author of the paper, Dr Micha? Bogdziewicz from Adam Mickiewicz University, Poland, said: "This study focused on the main seed predator of beech,a specialist moth (Cydia fagiglandana), whose larvae feed on the developing beech seeds. Frequent 'famine years' enable the beech trees to suppress populations of this seed-eating insect.

"However, the disappearance of the characteristic 'boom and bust' seed production patterns in UK beech trees has led to an increase in moth populations. As a result, we have seen a dramatic increase in the percentage of the seeds that are eaten by the larvae - up from around 1% in the 1980s to 40% in recent years."

By far the largest proportion of soybeans grown worldwide is used for animal feed. This is particularly problematic because soybean cultivation inflicts massive environmental damage on supplier countries. The Institute of Agricultural and Nutritional Sciences at Martin Luther University Halle-Wittenberg (MLU) is therefore currently researching domestic alternatives as part of the SilaToast project. This project is conducted jointly with the Saxon State Office for the Environment, Agriculture and Geology (LfULG), with the aim of determining what special handling alternative feedstuffs will require to equal the nutritional value of soybeans.

Soy is a popular feedstuff mainly due to its high protein content. However, its cultivation has been criticized on several grounds. For one, most soybeans, grown primarily in South America, are genetically modified, a practice which European consumers increasingly object to. Soybean cultivation also destroys important ecological areas such as rainforests, and their transport over long distances pollutes the environment. The overall poor environmental footprint of soya has led the Federal Ministry of Agriculture and Food (BMEL) to support research into substitutes. It funds the joint MLU and LfULG SilaToast project for testing two native legumes, the pea and the field bean. "Our main goal is to improve the feed value of regionally produced feedstuffs by fermentation and thermal treatment so they can replace soy protein both quantitatively and qualitatively," states Prof. Dr. Olaf Steinhöfel, MLU honorary professor and the LfULG's project lead. However, this is not the only motivation. "Domestic legumes also benefit agriculture, the environment, and the climate in multiple ways," according to Annette Zeyner, professor of animal nutrition at the MLU. They loosen the soil and store nitrogen from the air, which other plants are incapable of.

Peas in particular contain copious amounts of protein and starch. "But at this point they don't measure up to soy, partly because they contain many so-called anti-nutritive factors," Zeyner explains. These are substances that hinder the absorption of valuable nutrients. However, the problem is relatively easy to solve, as Zeyner's working group has discovered. For one, anti-nutritive ingredients are largely degraded by normal agricultural ensiling practices. Another method for boosting the legume's nutritional properties, although not yet widely used in combination with ensiling, is heat exposure. Thermal treatment does more than just further degrade the anti-nutritive factors in peas.

In a recent study, Zeyner and her collaborator Dr. Martin Bachmann were able to show that it also keeps the proteins from being decomposed as quickly by bacteria in the rumen of cows and other ruminants. Decomposition that happens too soon is problematic for two reasons: one, a large amount of nitrogen is excreted via the fecal matter and can thus enter the groundwater as a nitrate or the air as nitrous oxide, a potent greenhouse gas, and, two, valuable essential amino acids are lost in the process. These need to survive the passage to the small intestine to be absorbed there. This is particularly important in order for dairy cows to achieve sufficient production.

"The sticking point is that overheating in turn damages the proteins", says Zeyner. The project therefore determined the optimal temperature, length of thermal treatment, and silage moisture content. In laboratory testing, Bachmann was able to show that ensiling and thermal treatment did not impact gas and methane production. Scanning electron microscope imaging moreover showed that starch molecules were not altered by heating.

DURHAM, N.C. -- Biomedical engineers at Duke University have demonstrated that while different wearable technologies, like smart watches and fitness trackers, can accurately measure heart rate across a variety of skin tones, the accuracy between devices begins to vary wildly when they measure heart rate during different types of everyday activities.

As wearable technologies are increasingly used to monitor patients' health and collect digital biomarkers for clinical research and health care, this study highlights the need to better understand their accuracy and determine how measurement errors may affect research conclusions and inform medical decisions, according to the researchers.

The study results appear online on February 10 in the journal NPJ Digital Medicine.

"We started this study because we were seeing some evidence, both in research and anecdotally, that indicated that wearable devices weren't working as well for people with darker skin tones," said Jessilyn Dunn, an assistant professor of biomedical engineering at Duke. "People would compare a reading on a chest strap to their smart watch and get different heart rate values. The companies that manufacture these devices don't put out any metrics about how well they work across skin tones, so we wanted to collect evidence about how well they work and identify potential circumstances where they may not work well."

The study enlisted a group of 53 individuals with different skin tones to test the six different devices. To establish an accurate baseline, each participant wore an electrocardiogram (ECG) patch to measure their true heart rate during each activity.

Fitness trackers currently measure heart rate using a process called photoplethysmography, or PPG. This involves shining a specific wavelength of light, which usually appears green, from a pulse oximeter sensor on the underside of the device where it touches the skin on the wrist. As the light illuminates the tissue, the pulse oximeter measures changes in light absorption and the device then uses this data to generate a heart rate measurement.

"Previous research demonstrated that inaccurate PPG heart rate measurements occur up to 15 percent more frequently in dark skin as compared to light skin," says Dunn. "That's because darker skin has a higher melanin content, and melanin absorbs the wavelength of light that PPG uses."

As a second focus of the study, Dunn and her team measured how the devices performed during various types of activity. "There is evidence that people who work at their desk typing all day tend to have worse readings than people who have more stable wrist motion," Dunn said. "We knew that these devices suffer from motion artifact issues, but it wasn't clear to what extent."

Dunn and her lab tested both research-grade and commercial-grade wearable devices to track how diverse skin types, user activity and device type affected the accuracy of heart rate measurements. They tested commercial devices including the Apple Watch 4, Fitbit Charge 2, Garmin Vivosmart 3 and Xiaomi Midband, and research devices including the Empatica E4 and the Biovotion.

In the first round of the experiment, participants wore the Empatica on one wrist and the Apple Watch on the other. They first sat still to measure their baseline heart rate for four minutes before practicing paced deep breathing for one minute. Then they walked for five minutes before returning to a seated rest station for two minutes. Finally, they performed a typing task for one minute. In the second round, the participants repeated these steps while wearing the Fitbit, and in the third round they wore the Garmin, the Xiaomi and the Biovotion.

"Although we did not find statistically significant differences in wearable HR measurement accuracy across skin tones, it doesn't invalidate past concerns with technology equity," said graduate student Brinnae Bent, the first author on this study. "Wearable device software is updated frequently and it appears previous concerns have been addressed in current software versions."

Although the heart rate measurements were more accurate at rest than during activity, each tested device reported a higher heart rate than the ECG during physical activity across all skin tones. The team also found that the commercial devices were more accurate at measuring heart rate than the research devices. Maintaining the sensor's contact with skin can also improve device performance, as the sensor can wiggle around and catch motion artifacts if it's too loose.

Overall, the Apple Watch demonstrated the most accurate measurements of all tested devices, followed by the Garmin.

"We found that there was a bigger drop in accuracy during activities that involved wrist motion that could introduce motion artifacts, like typing, and we saw a drop in accuracy during deep breathing, which could indicate the devices locking onto cyclic behavior, like breathing, rather than heart rate," said Dunn. "We were initially surprised that the commercial devices were more accurate, but they also have huge user bases, so they're able to use lots of data to clean up their signals and improve their algorithms. The research wearables are just using raw data, which is important for researchers and clinicians to be aware of."

The study points the way to improving devices for clinical and research use, she added.

"We want to use these devices to measure digital biomarkers and predict disease outcomes, so if there are disparities in how these devices work we need to identify them," said Dunn.

"We've shown that we have equivalent-enough accuracy that we're not worried that there is a disparity due to skin tone in these devices, but we're hoping this puts out the call to companies that make wearables to share more information about how they evaluate the devices so that disparities can be more readily identified and corrected," Dunn said.

The News in Brief:

Individuals with schizophrenia begin to experience a decline in overall mental health once symptoms onset. This gradual decline often continues for many decades, regardless of when treatment begins.

Early intervention in schizophrenia has been thought to slow or stop further declines. This study, however, suggests that typical interventions do not improve long-term outcomes, even if administered early.

Studies of treatments for schizophrenia need to take into account how long study participants have been symptomatic, otherwise the effects of treatment may appear greater than they are.

STONY BROOK, February 12, 2020 -- A Stony Brook University-led study reveals that, despite the common view that early intervention in schizophrenia slows or stops mental decline, those who receive early intervention eventually experience the same declines as those whose treatment started later. The finding, published online in The American Journal of Psychiatry, suggests that studies of schizophrenia should take into account how long study participants have been symptomatic, otherwise treatments may appear more effective than they actually are.

"Our finding is somewhat counterintuitive. There has been a good amount of evidence suggesting that if you get people who are having their first psychotic episode into treatment as soon as possible, you can avert irreversible declines," said Lead Author Katherine Jonas, PhD, Postdoctoral Fellow in the Department of Psychiatry in the Renaissance School of Medicine at Stony Brook University. "We found that if you compare people who got into treatment early with those who did not, the early treatment group only appears to have better outcomes because they are often younger, and haven't been sick as long."

Jonas and colleagues point out that comprehensive pharmacological and psychosocial treatment has shown to be effective in reducing symptoms and improving quality of life in schizophrenia. However, many patients in the US do not get these treatments. Most receive only antipsychotic medications, which help with hallucinations and delusions but not with other symptoms. Therefore, they caution that "while starting 'treatment as usual' earlier may not halt the disease process, comprehensive and sustained care has been shown to improve overall mental health for those with schizophrenia."

The study evaluated duration of untreated psychosis (DUP) - defined as the amount of time that elapses between psychosis onset and treatment initiation. Data came from the Suffolk County Mental Health Project and included 287 individuals with schizophrenia or schizoaffective disorder. More than 2,000 patient observations spanning from childhood to 20 years after first hospital admission are included in the dataset. Overall mental health was evaluated at multiple points and related to DUP.

The association between long DUP and poor outcomes is well known in the treatment of patients with schizophrenia. Yet Jonas and colleagues found that in this study the association can be explained by lead-time bias.

"Lead-time bias is a phenomenon in which early detection - such as early screening for breast cancer or another disease - appears to improve outcomes because it enlarges the observation window of the disease," she explained.

The authors conclude in their study that the association between DUP and psychosocial function in schizophrenia may be an artifact of early detection, creating the illusion that early detection is associated with improved outcomes. Given this finding, they emphasize that shortening DUP does not necessarily change long-term illness course. DUP may be more of an indicator of illness stage than a predictor of course.

ANN ARBOR--If you're an environmentally conscious consumer, you've probably heard that today's highly efficient dishwashers use less energy and water than traditional hand-washing techniques.

While that's true in most cases, there's one manual washing technique--the two-basin method, in which dishes are soaked and scrubbed in hot water and then rinsed in cold water--that is associated with fewer greenhouse gas emissions than machine dishwashing.

That's one of the surprising findings of a new study from University of Michigan researchers that includes a list of tips for greener dishwashing. The study was published online Feb. 12 in the journal Environmental Research Communications and is the result of a collaboration between U-M researchers and Michigan-based Whirlpool Corp.

The study also found that:

Avoiding pre-rinsing and deselecting the "heated dry" setting can significantly reduce the greenhouse gas emissions associated with machine dishwashers.

The common "running tap" method of manual dishwashing used more energy and more water than any other dishwashing method tested.

If by-hand dishwashers switched from the running tap to the two-basin method, they could reduce associated greenhouse gas emissions by about two-thirds.

"This is the first comprehensive life cycle assessment of manual washing and machine washing, and it provides useful guidance to households on how to improve environmental performance of both methods," said study senior author Greg Keoleian, director of the Center for Sustainable Systems at the U-M School for Environment and Sustainability.

The study builds on a SEAS master's thesis by lead author Gabriela Porras. Data were collected at Whirlpool's dishwasher manufacturing plant in Findlay, Ohio, and a small-scale laboratory study was conducted at the company's headquarters in Benton Harbor, Michigan. Whirlpool also provided funding.

Several previous studies have concluded that consumers can save time, energy and water by using a machine dishwasher instead of washing by hand. But many of those studies failed to account for real-world behavior--such as pre-rinsing and varying the cycle selection--by those who rely on machine dishwashers.

And while the earlier studies compared the in-the-kitchen environmental impacts of manual versus machine dishwashing, most of them did not consider lifetime, cradle-to-grave environmental costs, including the manufacture and disposal of dishwashers.

The new U-M-led study took a comprehensive look at the environmental burdens of manual and machine dishwashing, including greenhouse gas emissions, water and energy consumption, solid waste production and cost. The study also compared recommended best practices for hand and machine washing with typical behaviors observed during the Benton Harbor lab study.

When typical manual and machine practices were followed, machine dishwashers were associated with less than half the greenhouse gas emissions and used less than half the water. Most of the emissions are tied to the energy used to heat the water.

The common "running tap" method of manual dishwashing, which involves washing and rinsing dishes beneath a steady stream of hot water, used more energy and water than any other method tested.

The outcome changed dramatically when the less-common two-basin method of manual dishwashing was used. Under that scenario, manual dishwashing produced lower greenhouse gas emissions than any other alternative examined in the study--18% lower than machine washing using recommended best practices.

Not ready to give up the time-saving convenience of a machine dishwasher? The new study offers several tips to reduce the environmental impact of your appliance, including three key "don'ts": Don't pre-rinse before loading dishes into the dishwasher; don't select the "heat dry" setting; and don't choose the "heavy" cycle over a normal wash, except for tougher loads.

In the observational study, 38 Whirlpool employees were asked to load a dishwasher as they typically would at home, to manually wash dishes as they would at home, and to answer survey questions related to their dishwashing behaviors. The testing room at Whirlpool's Benton Harbor campus was designed to replicate a common kitchen sink area in an average household.

The study assumed that natural gas is used to heat the water. Lifetime greenhouse gas emissions increase significantly if an electric water heater is used.

Porras conducted the study for her master's thesis at the Center for Sustainable Systems at the U-M School for Environment and Sustainability. The other authors are Keoleian, Geoffrey Lewis of the Center for Sustainable Systems and Nagapooja Seeba of Whirlpool Corp.

Many amphibians and fish are able to change their color in order to better adapt to their environment. Munich-based scientists have now investigated the molecular mechanisms in the cytoskeleton necessary for this and revealed potential evolutionary paths.

All cells of higher organisms are permeated by a cytoskeleton that essentially consists of actin filaments and small protein tubes called microtubules. For a long time science considered the actin or microtubule networks as independent systems.

Today it is known that the two network types communicate with each other and thereby make vital cellular processes such as cell division or cell migration possible in the first place. However, it was still unknown how this collaboration works at the molecular level.

Dr. Zeynep Ökten from the Chair of Molecular Biophysics at the Technical University of Munich (TUM)and Erwin Frey, Professor of Statistical and Biological Physics at the Ludwig-Maximilian-Universitaet (LMU) in Munich - with their teams - have now for the first time identified a molecular mechanism by the example of change of color among animals which explains the communication between both network systems, and revealed potential evolutionary paths.

Transport pathways in the cell

Many functional components of a cell, such as the organelles, must be brought to the right place at the right time in the cell. For this purpose they are actively transported by molecular motors on the microtubules and actin filaments.

Studies have shown that motors which were long regarded as highly specific for one of the two network systems can in reality also be redirected to the other filament type. In mice, for example, scientists found an adapter protein that regulates this redirection.

Myosin transports its freight via the actin network, but the adapter protein also interacts with the microtubules and can redirect the transport on this network. Which network is preferred is controlled by a chemical modification to a specific binding site of the adapter protein.

Adapter protein with shifting mode

Fish and amphibians also have a protein corresponding to the mammalian adapter. The evolutionarily older fish and amphibians use it to adapt their skin color to environmental factors by redirecting pigment organelles within specialized cells.

That is why the research team used zebrafish and clawed frogs for experimental investigations in Ökten's laboratory to examine the origin and the molecular mechanisms of interaction between the microtubule network and the actin network.

Evolution of a molecular switch

The scientists found out that the mouse adapter protein as well as the clawed frog adapter protein has a specific domain which enables the switching between the transport of actin and microtubules.

Zebrafish, the evolutionarily oldest of examined animals, do not yet have this domain. "Here the motor proteins which move the pigments organelles are subject to different regulatory mechanisms, and there is no interaction between the different cytoskeleton networks", says Ökten.

"In contrast, switching between the networks is absolutely necessary among the clawed frogs so that the animal can change color - and this ability to switch has also been preserved in the further course of evolution from amphibian to higher vertebrates", explains Ökten further.

Theoretical model explains pigment redistribution

Moreover, the experimental results showed that the environmental signals which bring about the redistribution of pigment organelles in the organism of clawed frogs are associated with a change of probability with which the individual motor proteins from the actin filaments switch to the microtubule filaments.

"We have developed a theoretical model that correlates the switching probability of an individual motor protein with the cell-wide redistribution of pigment organelles", says Frey. Computer simulations revealed that the variation of switching probability is actually sufficient as the only parameter to provide a redistribution of organelles in the simulated cells.

"It is notable that our simulations remarkably precisely reflect the redistribution of organelles observed in the living organism", says Frey. "As a result, the theoretical approach underscores the functional importance of experimental results, and shows that the interaction between actin network and microtubule network, which has developed among lower vertebrates, exhibits a particularly high regulatory efficiency."

WASHINGTON - The landmark Food Quality Protection Act requires the Environmental Protection Agency to protect children's health by applying an extra margin of safety to legal limits for pesticides in food. But an investigation by EWG, published this week in a peer-reviewed scientific journal, found that the EPA has failed to add the mandated children's health safety factor to the allowable limits for almost 90 percent of the most common pesticides.

The study in Environmental Health examined the EPA's risk assessments for 47 non-organophosphate pesticides since 2011, including those most commonly found on fresh fruits and vegetables, and found that the required additional tenfold safety factor was applied in only five cases.

"Given the potential health hazards of pesticides in our food, it is disturbing that the EPA has largely ignored the law's requirement to ensure adequate protection for children," said the study's author, Olga Naidenko, Ph.D., vice president for science investigations at EWG. "The added safety factor is essential to protect children from pesticides that can cause harm to the nervous system, hormonal disruption and cancer."

The Food Quality Protection Act of 1996, or FQPA, requires the EPA to set allowable levels for pesticides in a way that would "ensure that there is a reasonable certainty that no harm will result to infants and children from aggregate exposure to the pesticide chemical residue." It was hailed as a revolutionary recognition of the fact that children are more vulnerable to the effects of chemical pesticides than adults.

"Based on the strong consensus of the pediatric and the public health communities, the FQPA stated unequivocally that regulation of toxic pesticides must focus, first and foremost, on protecting infants and children," said Dr. Philip Landrigan, a pediatrician and epidemiologist who is director of the Program in Global Public Health and the Common Good at Boston College. "When the EPA fails to apply this principle, children may be exposed to levels of chemical pesticides that can profoundly harm their health."

Landrigan chaired the committee that authored "Pesticides in the Diets of Infants and Children," a 1993 report from the National Academy of Sciences. The groundbreaking study led to the FQPA's passage with bipartisan support and the backing of both industry and environmentalists.

"The FQPA was a revolution in how we think about pesticides' effects on children, but it does no good if the EPA doesn't use it," said EWG President Ken Cook. "It's not only necessary to protect kids' health, it's the law, and the EPA's failure to follow the law is an egregious betrayal of its responsibility."

Naidenko's study also examined EPA risk assessments for a particularly toxic class of pesticides called organophosphates, which act in the same way as nerve gases like sarin and are known to harm children's brains and nervous systems. She found that under the Obama administration, the tenfold children's health safety factor was proposed for all organophosphate insecticides.

By contrast, in four assessments of pyrethroid insecticides, the EPA under the Trump administration has proposed adding the FQPA safety factor to none. In human epidemiological studies conducted in the U.S. and in Denmark, exposure to pyrethroid insecticides was associated with increased risk of attention deficit hyperactivity disorder.

In 2017, the EPA reversed the Obama administration's FQPA determination for chlorpyrifos, the most widely used organophosphate pesticide in the U.S. Despite the Trump EPA's decision, in the wake of bans by Hawaii, California and New York, the main U.S. chlorpyrifos manufacturer recently announced it will stop making this chemical. It remains to be seen whether the Trump EPA will uphold the tenfold FQPA determination for the entire group of organophosphates.

The study also found that the Trump EPA has proposed to increase by 2.6-fold the allowable exposure to the herbicide metolachlor. The use of metolachlor has been on the rise for the past decade, with more than 60 million pounds sprayed annually, according to the U.S. Geological Survey.

Biomonitoring studies conducted by the Centers for Disease Control and Prevention and by independent researchers reported the presence of multiple pesticides and their byproducts in the American population, including herbicides such as glyphosate and 2,4-D, the bee-killing neonicotinoid insecticides, organophosphate and pyrethroid insecticides, and fungicide metabolites.

Many amphibians and fish are able to change their color in order to better adapt to their environment. Munich-based scientists have now investigated the molecular mechanisms in the cytoskeleton necessary for this and revealed potential evolutionary paths.

All cells of higher organisms are permeated by a cytoskeleton that essentially consists of actin filaments and small protein tubes called microtubules. For a long time science considered the actin or microtubule networks as independent systems.

Today it is known that the two network types communicate with each other and thereby make vital cellular processes such as cell division or cell migration possible in the first place. However, it was still unknown how this collaboration works at the molecular level.

Dr. Zeynep Ökten from the Chair of Molecular Biophysics at the Technical University of Munich (TUM) and Erwin Frey, Professor of Statistical and Biological Physics at the Ludwig-Maximilians-Universität München - with their teams - have now for the first time identified a molecular mechanism by the example of change of color among animals which explains the communication between both network systems, and revealed potential evolutionary paths.

Transport pathways in the cell

Many functional components of a cell, such as the organelles, must be brought to the right place at the right time in the cell. For this purpose they are actively transported by molecular motors on the microtubules and actin filaments.

Studies have shown that motors which were long regarded as highly specific for one of the two network systems can in reality also be redirected to the other filament type. In mice, for example, scientists found an adapter protein that regulates this redirection.

Myosin transports its freight via the actin network, but the adapter protein also interacts with the microtubules and can redirect the transport on this network. Which network is preferred is controlled by a chemical modification to a specific binding site of the adapter protein.

Adapter protein with shifting mode

Fish and amphibians also have a protein corresponding to the mammalian adapter. The evolutionarily older fish and amphibians use it to adapt their skin color to environmental factors by redirecting pigment organelles within specialized cells.

That is why the research team used zebrafish and clawed frogs for experimental investigations in Ökten's laboratory to examine the origin and the molecular mechanisms of interaction between the microtubule network and the actin network.

Evolution of a molecular switch

The scientists found out that the mouse adapter protein as well as the clawed frog adapter protein has a specific domain which enables the switching between the transport of actin and microtubules.

Zebrafish, the evolutionarily oldest of examined animals, do not yet have this domain. "Here the motor proteins which move the pigments organelles are subject to different regulatory mechanisms, and there is no interaction between the different cytoskeleton networks", says Ökten.

"In contrast, switching between the networks is absolutely necessary among the clawed frogs so that the animal can change color - and this ability to switch has also been preserved in the further course of evolution from amphibian to higher vertebrates", explains Ökten further.

Theoretical model explains pigment redistribution

Moreover, the experimental results showed that the environmental signals which bring about the redistribution of pigment organelles in the organism of clawed frogs are associated with a change of probability with which the individual motor proteins from the actin filaments switch to the microtubule filaments.

"We have developed a theoretical model that correlates the switching probability of an individual motor protein with the cell-wide redistribution of pigment organelles", says Frey. Computer simulations revealed that the variation of switching probability is actually sufficient as the only parameter to provide a redistribution of organelles in the simulated cells.

"It is notable that our simulations remarkably precisely reflect the redistribution of organelles observed in the living organism", says Frey. "As a result, the theoretical approach underscores the functional importance of experimental results, and shows that the interaction between actin network and microtubule network, which has developed among lower vertebrates, exhibits a particularly high regulatory efficiency."

TORONTO, February 12, 2020 - New Yorkers are more trusting of others compared to Alabamans or Texans. While this regional divide between southerners and the rest of Americans is well documented, the gap is wider than perceived, a study from York University reveals.

"If you take into consideration the internal migration of southerners to the northern region and vice versa, and exclude migrants in the calculation, the gap in trust levels between the two groups would be significantly bigger. This is because the trust levels don't change much if someone moved out of their native place after age 16," said Professor Cary Wu in the Department of Sociology, Faculty of Liberal Arts & Professional Studies, who conducted the study.

"The south is more collectivist than the other parts of the country, and that tends to generate lower trust compared to the individualist social relations seen in the rest of America."

Wu's study "Does Migration Affect Trust? Internal Migration and the Stability of Trust among Americans," published in The Sociological Quarterly, examined whether people are trusting because that's how they were raised from an early age or whether they constantly adjusted their trust throughout their life according to social experiences gained along the way.

"My research concludes that people tend to retain the trust they formed since childhood through lived experiences and cultural heritage," said Wu.

The sociologist analyzed migration history using cross-sectional data from the General Social Survey between 1972 and 2018. His study also sheds light on the possible reasons for regional differences in social institutions and individual wellbeing. For example, the higher rates of poverty and lower levels of political engagement in the south than other regions of the country could be direct results of the southerners' low trust levels, Wu said.

The regional gap in trust is not a result of the higher percentage of Black Americans - who tend to have lower trust - living in the south, he said. Instead, the distrust is deeply rooted in the unique social and political culture shaped by the defeat in the Civil War, history of slavery, poverty, and prominence of religion in the southern United States.

"Ultimately, trust - or the belief in the benevolence of the world - is an individual's core value and identity, acquired at an early age and remains relatively stable in later life," Wu concluded.