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Team finds bovine kobuvirus in US
University of Illinois at Urbana-Champaign, News Bureau Share Print E-Mail IMAGE IMAGE: University of Illinois veterinary clinical medicine professor Dr. Leyi Wang led the team that detected bovine kobuvirus in the U.S. view more Credit: Photo by L. Brian Stauffer CHAMPAIGN, Ill. -- A virus that afflicts cattle that was first discovered in Japan in 2003 has made its way to the U.S., researchers report in the journal Emerging Infectious Diseases. Bovine kobuvirus is fairly new to science, so its ill effects are not fully understood. It belongs to a family of viruses known as Picornaviridae, which includes Rhinovirus, a source of head colds and sinus infections in humans; and Poliovirus, which causes polio. Previous studies conducted elsewhere in the world have found bovine kobuvirus in fecal samples of cattle with diarrhea. The new study confirmed this association by sequencing the microbial DNA in samples from cattle in the U.S. and analyzing the intestines of two calves that died after infection. "Only bovine kobuvirus was detected in both cases," said University of Illinois veterinary clinical medicine professor Dr. Leyi Wang, who led the new study. "This provides evidence that this virus is the causative agent for calf diarrhea." So far, no other negative associations with bovine infection have been observed. However, since almost no one in North America is looking for the virus in cattle or other species, it remains to be seen how this emerging disease agent influences health, Wang said. "Continued surveillance of bovine kobuvirus is urgently needed to determine how widespread it is," Wang said. "Scientists have access to only a few genetic sequences of this virus in public databases. We need to be sequencing these viruses to learn more about their genetic diversity and evolution." Four of nine samples tested at the U. of I. Veterinary Diagnostic Laboratory were found to harbor bovine kobuvirus, the team reported. All of the infected cows were from the state of Illinois. Elsewhere in the world, bovine kobuvirus has been detected in about 10 countries in Asia, Europe, South America and Africa. |
Salmonella the most common cause of foodborne outbreaks in the European Union
Nearly one in three foodborne outbreaks in the EU in 2018 were caused by Salmonella, say the European Centre for Disease Prevention and Control and the European Food Safety Authority (EFSA) European Centre for Disease Prevention and Control (ECDC) Share Print E-Mail Nearly one in three foodborne outbreaks in the EU in 2018 were caused by Salmonella. This is one of the main findings of the annual report on trends and sources of zoonoses published today by the European Food Safety Authority (EFSA) and the European Centre for Disease Prevention and Control (ECDC). In 2018, EU Member States reported 5 146 foodborne outbreaks affecting 48 365 people. A foodborne disease outbreak is an incident during which at least two people contract the same illness from the same contaminated food or drink. Slovakia, Spain and Poland accounted for 67% of the 1581 Salmonella outbreaks. These outbreaks were mainly linked to eggs. "Findings from our latest Eurobarometer show that less than one third of European citizens rank food poisoning from bacteria among their top five concerns when it comes to food safety. The number of reported outbreaks suggests that there's room for raising awareness among consumers as many foodborne illnesses are preventable by improving hygiene measures when handling and preparing food" said EFSA's chief scientist Marta Hugas. Salmonellosis was the second most commonly reported gastrointestinal infection in humans in the EU (91 857 cases reported), after campylobacteriosis (246,571). West Nile virus and STEC infections at unusually high levels By far the highest increase in the zoonoses covered by this report was in the number of West Nile virus infections. Cases of this zoonotic mosquito-borne disease were seven times higher than in 2017 (1605 versus 212) and exceeded all cases reported between 2011 and 2017. "The reasons for the peak in 2018 are not fully understood yet. Factors like temperature, humidity or rainfall have been shown to influence seasonal activity of mosquitoes and may have played a role. While we cannot predict how intense the next transmission seasons will be, we know that the West Nile virus is actively circulating in many countries in the EU, affecting humans, horses and birds. ECDC is stepping up its support to countries in the areas of surveillance, preparedness, communication and vector control", said ECDC's chief scientist Mike Catchpole. Most locally acquired West Nile virus infections were reported by Italy (610), Greece (315) and Romania (277). Czechia and Slovenia reported their first cases since 2013. Italy and Hungary have also registered an increasing number of West Nile virus outbreaks in horses and other equine species in recent years. Shiga toxin-producing E. coli (STEC) has become the third most common cause of foodborne zoonotic disease with 8 161 reported cases - replacing yersiniosis with a 37% increase compared to 2017. This may be partly explained by the growing use of new laboratory technologies, making the detection of sporadic cases easier. The number of people affected by listeriosis in 2018 is similar to 2017 (2 549 in 2018 against 2 480 the previous year). However, the trend has been upward over the past ten years. Of the zoonotic diseases covered by the report, listeriosis accounts for the highest proportion of hospitalised cases (97%) and highest number of deaths (229), making it one of the most serious foodborne diseases. |
Paving the way to healing complex trauma
La Trobe University Share Print E-Mail A major study led by researchers at La Trobe University in Australia has identified key themes that will be used to inform strategies to support Australian Aboriginal and Torres Strait Islander parents in the first years of their children's lives. The Healing the Past by Nurturing the Future project aims to break the cycle of intergenerational and complex trauma experienced by Aboriginal and Torres Strait islander people, by co-designing strategies for new parents. The international research team, led by Associate Professor Catherine Chamberlain of La Trobe's Judith Lumley Centre and published today in the journal PLOS ONE, reviewed more than 20,000 scholarly articles to build a comprehensive understanding of pregnancy and birth for parents who have experienced trauma in their own childhood. The study identified seven themes, derived from studying interviews with more than 350 parents who experienced trauma as children, relate to parents' experiences during pregnancy, birth and the first few weeks after birth. Associate Professor Catherine Chamberlain said the research is critical for informing discussions with Aboriginal parents and communities to create a strong foundation for work to heal complex trauma. "This gives us a thorough and deep understanding needed to help co-design support strategies with communities to improve the lives of Aboriginal and Torres Strait Islander people and their babies," Associate Professor Chamberlain said. "We have shared these themes in discussions with Aboriginal and Torres Strait Islander parents and community members to see if any are relevant. Doing so also helps parents to understand these experiences are shared, even in other countries. "The next stage of our Healing the Past by Nurturing the Future project will use these themes to examine what support strategies have been evaluated in research. We will look at whether this research reflects what support parents say they want and what they feel works." The seven themes are: • New beginnings: Becoming a parent is an opportunity for 'a fresh start', to put the past behind them and move forward with hope for the future to create a new life for themselves and their child. • Changing roles and identities: Becoming a parent is a major life transition, influenced by perceptions of the parenting role. • Feeling connected: The quality of relationships with self, baby and others has major impacts on the experiences of becoming a parent. • Compassionate care: Kindness, empathy and sensitivity enables parents to build trust and feel valued and cared for. • Empowerment: Control, choice and 'having a voice' are critical to fostering safety. • Creating safety: Parents perceive the 'world as unsafe' and use conscious strategies to build safe places and relationships to protect themselves and their baby. • 'Reweaving' a future: Managing distress and healing while becoming a parent is a personal ongoing and complex process requiring strength, hope and support. Associate Professor Chamberlain said the seven themes also resonated strongly with Aboriginal and Torres Strait Islander parents and she was grateful to the research team for all their hard work and expertise, and to Lowitja Institute and the NHMRC for funding this phase of her work. |
News Release 13-Dec-2019
Breast-conserving treatment without surgery not supported at this time Results of NRG Oncology study BR005 NRG Oncology Share Print E-Mail SAN ANTONIO, TX - Results from NRG Oncology's BR005 study show that breast-conserving treatment without surgery cannot be recommended, based on the study criteria of clinical complete response, radiological complete response (rCR)/near rCR, and negative tumor bed biopsies. These findings were presented at the 2019 San Antonio Breast Cancer Symposium, held December 10-14. This phase II study, which opened in June 2017, was designed as a two-stage trial to assess the accuracy of tumor bed biopsies in predicting pathologic response in patients with clinical complete and radiological complete/near complete response after neoadjuvant chemotherapy to determine if they could avoid surgery. All patients had received chemotherapy for their breast cancer, but had not yet had surgery. All underwent an image-guided biopsy after receiving chemotherapy. A total of 105 patients were enrolled from August 2017 through June 2019, with 98 being evaluable for analysis. Accrual was temporarily closed for futility analysis on June 26, 2019, because 36 of the evaluable patients had residual disease at surgery, which actually met the numbers for the primary analysis. The negative predictive value of the biopsy was 77.5% (95%CI: 66.8% to 86.1%) which did not meet the pre-specified threshold of >90% required to support the feasibility of initiating a study in which surgery could be omitted. "Further analysis including central review of tri-modality imaging and assessment of an imaging algorithm with and without the addition of biopsy are underway. Once these are combined with information on biologic subtypes, a new prediction model will be defined," according to Mark Basik, MD, from Jewish General Hospital, and lead investigator of the study. ### NRG Oncology BR005 was supported by grants U10CA180868 (NRG Oncology Operations), and U10CA180822 (NRG Oncology SDMC). Clinicaltrials.gov identifier: NCT03188393. Citation Basik M, Cecchini RS, De Los Santos JF, Umphrey HR, Julian TB, Mamounas EP, White J, Lucas PC, Balanoff C, Tan AR, Weber JJ, Edmonson DA, Brown-Glaberman UA, Diego EJ, Teshome M, Matsen CB, Seaward SA, Wapnir IL, Wagner JL, Tjoe JA, Thompson AM, Wolmark N. Primary analysis of NRG-BR005, a phase II trial assessing accuracy of tumor bed biopsies in predicting pathologic complete response in patients with clinical/radiological complete response after neoadjuvant chemotherapy to explore the feasibility of breast-conserving treatment without surgery. San Antonio Breast Cancer Symposium 2019. Prog #: GS5-05. About NRG Oncology NRG Oncology conducts practice-changing, multi-institutional clinical and translational research to improve the lives of patients with cancer. Founded in 2012, NRG Oncology is a Pennsylvania-based nonprofit corporation that integrates the research of the legacy National Surgical Adjuvant Breast and Bowel Project (NSABP), Radiation Therapy Oncology Group (RTOG), and Gynecologic Oncology Group (GOG) programs. The research network seeks to carry out clinical trials with emphases on gender-specific malignancies, including gynecologic, breast, and prostate cancers, and on localized or locally advanced cancers of all types. NRG Oncology's extensive research organization comprises multidisciplinary investigators, including medical oncologists, radiation oncologists, surgeons, physicists, pathologists, and statisticians, and encompasses more than 1,300 research sites located world-wide with predominance in the United States and Canada. NRG Oncology is supported primarily through grants from the National Cancer Institute (NCI) and is one of five research groups in the NCI's National Clinical Trials Network. http://www.nrgoncology.org |
News Release 13-Dec-2019
Taking shape: Scientists propose new structure for shell of HIV-1 virus A newly proposed model for the shape of the HIV-1 viral shell may change how we understand the disease University of Alberta Share Print E-Mail IMAGE IMAGE: A new study proposes a new structure for the shell of the HIV-1 virus, pictured here. Image credit Marcelo Marcet. view more Credit: Marcelo Marcet The matrix shell of the HIV-1 virus may have a different shape than previously thought, and a newly proposed model has significant implications for understanding how the virus functions, according to a new study by University of Alberta scientists. The research suggests that the HIV-1 virus is housed within a spherical matrix shell. When it infects a healthy cell, the shell fuses to the outside of the target cell and then releases the viral capsid inside where it attacks the cell. "Our new proposed structure for the HIV-1 virus has a very peculiar shape, almost like petals of a flower," said Sean Graves, instructor in the Department of Mathematical and Statistical Sciences and co-author on the study. "A better structural knowledge of the matrix shell may help us understand the fusing and infection process." Graves is also coordinator of the Decima Robinson Support Centre, providing support to more than 1000 undergraduate students each term. The research shows that the previous model used to describe the structure of the HIV-1 matrix shell was mathematically impossible and provides a viable alternative. While it is too early to anticipate whether the model will translate into new treatment for HIV, the research will help scientists to better understand and make predictions about the behaviour of the HIV-1 virus. Around the world, nearly 38 million people suffer from HIV or AIDS. "Our contribution uses mathematical principles to help guide the scientific community in the right direction," added Marcelo Marcet-Palacios, adjunct professor of medicine in the Faculty of Medicine & Dentistry and co-author. "If our model is correct, then we can begin investigating ways we could block or interrupt the mechanism of viral entry. For example, by using a medication that could cross-link the 'petals' of the structure together to prevent the opening of the particle and thus stopping entry of the viral genome into the host cell." The model is available to anyone, anywhere in the world online. This research is the result of the work of an interdisciplinary team from the fields of biology, mathematics and computing science. One such collaborator is Weijie Sun, Faculty of Science alumnus and a former student of Graves'. "This collaboration made it possible to come up with a new model consistent with previously observed evidence and allowed us to develop a computer program freely accessible online that other scientists around the world can use to recreate our work and further develop this new model," said Sun. "It is incredible what can be achieved in science when experts from different disciplines get together and collaborate." ### |
News Release 12-Dec-2019
Ultrasound blasts potent glioblastoma drug into brain tumor Treatment successfully delivers drug across the blood-brain barrier directly to brain tumor in mice Northwestern University Share Print E-Mail • Glioblastoma currently has no cure. New treatments urgently needed • Powerful drug is 1,400 times more potent than current treatment against the brain tumor • Scientists applying to FDA for approval to test this novel treatment in patients with recurrent glioblastoma CHICAGO --- One of most potent drugs for treatment of glioblastoma, the most deadly type of brain tumor, can't be used in patients because of two problems. First, it can't reach its target because it's blocked by the blood-brain barrier, a microscopic structure that protects the brain from toxins in the blood. And the conventional formulation for this drug is toxic to the brain. But now Northwestern Medicine scientists have used a novel technology for opening the blood-brain barrier with an implantable ultrasound, and have delivered the powerful drug to the tumor in mice. In a new paper, they report on their findings of extensive preclinical research. The scientists also discovered brain toxicity for the conventional formulation for this drug - paclitaxel -to the brain was caused by the solution required to dissolve the drug (cremophor.) Scientists tested a new formulation of the drug that uses albumin as opposed to cremophor, and it was not harmful to the brain. Opening of the blood-brain barrier with an ultrasound increased the concentrations of this paclitaxel in the brain by five-fold. The study also showed that the brain tumor-bearing mice live much longer when treated with the powerful cancer-fighting drug paclitaxel, and survival was even further extended when treated in combination with ultrasound to open the blood-brain barrier. The study will be published Dec. 12 in Clinical Cancer Research, a journal of the American Association for Cancer Research. In the laboratory, paclitaxel is much more potent than the currently used chemotherapy temozolomide. When paclitaxel was tested against the brain tumor in a dish outside an organism, a 1,400-fold lesser drug concentration was necessary to kill same number of tumor cells, compared to the conventional chemotherapy used for this cancer. The scientists are now applying to the U.S. Food & Drug Administration to launch a clinical trial to test this concept of a new formulation of paclitaxel in combination with the novel ultrasound technology to open the blood-brain barrier in patients. The planned trial aims to determine if the treatment is safe, and if it prolongs survival of patients with brain cancer. "Glioblastoma currently has no cure, and when the tumor recurs there are not many treatment options," said the principal investigator for this study, Dr. Adam Sonabend, an assistant professor of neurological surgery at Northwestern University Feinberg School of Medicine and a Northwestern Medicine physician. "We urgently need effective new treatments." The ultrasound technology may have broader benefits. "This ultrasound technology now will enable us to use many agents established in other cancers for patients with brain tumors," said co-investigator Roger Stupp, chief of neuro-oncology and the Paul C. Bucy Professor of Neurological Surgery at Feinberg. Other clinical trials are testing ultrasound-based opening of the blood brain barrier with various chemotherapy agents, but none are using such a potent drug as paclitaxel. How does it work? The tiny ultrasound would be implanted during surgery into a window in the skull that does not contain bone. It is used in combination with microscopic gas bubbles injected into the blood at the same time the ultrasound begins. When the bubbles hit the sound waves, these vibrate and mechanically disrupt the blood-brain barrier. The opening is immediate, allowing penetration of the drug molecules. The blood-brain barrier opening is reversible and lasts for several hours after the sonication. The ultrasound emitter remains in the skull for repeated delivery of the drug. |
News Release 12-Dec-2019
The mathematics of prey detection in spider orb-webs Society for Industrial and Applied Mathematics Share Print E-Mail Spider webs are one of nature's most fascinating manifestations. Many spiders extrude proteinaceous silk to weave sticky webs that ensnare unsuspecting prey who venture into their threads. Despite their elasticity, these webs possess incredible tensile strength. In recent years, scientists have expressed increased interest in the spider orb-web as a biological-mechanical system. The web's sensory mechanisms are especially fascinating, given that most web-weaving spiders--regardless of their vision level--use generated vibrations to effectively locate ensnared prey. "The spider orb-web is a natural, lightweight, elegant structure with an extreme strength-to-weight ratio that is rarely observed among other structures, either natural or manmade," Antonino Morassi said. "Its primary functions are catching prey and gathering sensory information, and study of the mechanisms that guide these processes through web vibration has been one of the main research goals in the field." To understand the mechanics of orb-webs, researchers have previously utilized simplified patterns of wave propagation or relied upon numerical models that reproduce a spider web's exact geometry via one-dimensional elements. While these numerical models adequately handle wind, prey movement, and other sources of vibration, they fall short of providing insight into the physical phenomena responsible for web dynamics. In an article publishing this week in the SIAM Journal on Applied Mathematics, Morassi and Alexandre Kawano present a theoretical mechanical model to study the inverse problem of source identification and localize a prey in a spider orb-web. Due to structural interconnectivity between the circumferential and radial threads, vibrations in an orb-web spread laterally and move beyond the stimulated radius. This observation led Kawano and Morassi towards realistic mechanical models that measure a fibred web's two-dimensionality, rather than more limiting one-dimensional models. "There was no mechanical model--even a simplified one--that described the web as it really is: a two-dimensional vibrating system," Morassi said. "We decided to use a continuous membrane model since theoretical models often permit a deeper insight in the physical phenomena through analysis of the underlying mathematical structure of the governing equations." These equations are also useful in identifying the most relevant parameters that dictate a web's response. The authors classify their model as a network of two intersecting groups of circumferential and radial threads that form an uninterrupted, continuous elastic membrane with a specific fibrous structure. To set up the inverse problem, they consider the spider's dynamic response to the prey's induced vibrations from the center of the web (where the spider usually waits). For the sake of simplicity, Kawano and Morassi limit the model's breadth to circular webs. The geometry of their model allows for a specific fibrous structure, the radial threads of which are denser towards the web's center. The researchers note that the minimal data set to ensure uniqueness in the prey's localization seems to accurately reproduce real data that the spider collects right after the prey makes contact with the web. "By continuously testing the web, the spider acquires the dynamical response of the web approximately on a circle centered at the web's origin, and with radius significantly small with respect to the web dimensions," Kawano said. "Numerical simulations show that identification of the prey's position is rather good, even when the observation is taken on the discrete set of points corresponding to the eight legs of the spider." Ultimately, the authors hope that their novel mechanical model will encourage future research pertaining to nearly periodic signals and more general sources of vibration. They are already thinking about ways to further expand their model. "We believe that it may be of interest to generalize the approach to more realistic geometries -- for example, for spider webs that deviate a little from the circular axisymmetric shape and maintain only a single axis of symmetry," Morassi said. "Furthermore, here we considered the transversal dynamic response caused by orthogonal impact of a prey on the web. In real-world situations, impact can be inclined and cause in-plane vibrations to propagate throughout the web. The analysis of these aspects, among others, may provide novel and important insights, not only for the prey's catching problem but also for bioinspired fibrous networks for sensing applications involving smart multifunctional materials." |
News Release 11-Dec-2019
Virtual reality and drones help to predict and protect koala habitat Queensland University of Technology Share Print E-Mail Volume 90% VIDEO: QUT researchers have used a combination of virtual reality (VR), aerial thermal-imaging and ground surveys to build a better statistical model for predicting the location of koalas and, ultimately, protecting... view more Credit: QUT QUT researchers have used a combination of virtual reality (VR), aerial thermal-imaging and ground surveys to build a better statistical model for predicting the location of koalas and, ultimately, protecting their habitat. In the study, published in the journal PLoS ONE, researchers from QUT and the ARC Centre of Excellence for Mathematical and Statistical Frontiers (ACEMS) used the mashup of high-tech 360-degree imagery and heat-seeking drone cameras along with traditional techniques of ground surveys to develop a model that could be used to identify areas most likely to be home to koalas, which are facing population decline. Lead author Dr Catherine Leigh, who is also an Associate Investigator with ACEMS, said the advantage of the multi-pronged approach was that it greatly increased the accuracy of the statistical model. "It's about building a model that tells us with confidence where koalas are and where they're not," Dr Leigh said. "When you start building up a model with all of that data, you get a much better idea about where the koalas are likely to be. "If you can predict where koalas are, and the types of habitats they are hanging around in, then you know not only where to go to keep monitoring them but also the areas you need to protect." In the study, the researchers used ground survey information captured between 2102 and 2017 from Alexander Clarke Park in Loganholme, south-east Queensland, which is an area that has vegetation ranging from dense forest to grass fields and contains facilities including playgrounds and a dog park. Dr Leigh said one of the challenges with ground survey observations was that they could show a statistical bias of higher koala populations close to paths and other areas easily accessible by observers. "When you're out in the field as an experienced koala observer or a citizen scientist, you really are restricted where you can walk. And koalas are hard to see, even by trained observers," Dr Leigh said. "They are slow moving and often hidden high in the canopy." To counteract that, the researchers surveyed the area from the air using thermal cameras near sunrise, when the body heat of the koalas is detectable against the surrounding foliage. The third part of the study involved sending researchers out to some of the 82 specific locations in the area where koalas were known to either be or not be, to take 360-degree images. Those images were then shown to a panel of koala experts wearing VR headsets, with the experts asked to state how likely the environment they were viewing in was 'good koala habitat'. Dr Leigh said the advantage of using VR for the survey was it enabled them to bring the environment to the experts rather than having to take the experts to the field. "They're called immersive experiences," Dr Leigh said. "A lot of the research done on immersive experiences suggests that it helps to bring back the memories associated with when that expert has been in the field in the past, so they can be more cognizant of making the decision about the likelihood that a koala would be there." The researchers found that the three-pronged system of VR-prompted expert information, thermal imagery and ground surveys proved to be 75 per cent more accurate at predicting koala locations than ground surveys alone. "You put all three together and you get a much better model," Dr Leigh said. Dr Leigh said the methods could be used by councils and town planning authorities to obtain critical information needed for koala protection. |
Volume 90%
VIDEO: QUT researchers have used a combination of virtual reality (VR), aerial thermal-imaging and ground surveys to build a better statistical model for predicting the location of koalas and, ultimately, protecting... view more Credit: QUT QUT researchers have used a combination of virtual reality (VR), aerial thermal-imaging and ground surveys to build a better statistical model for predicting the location of koalas and, ultimately, protecting their habitat. In the study, published in the journal PLoS ONE, researchers from QUT and the ARC Centre of Excellence for Mathematical and Statistical Frontiers (ACEMS) used the mashup of high-tech 360-degree imagery and heat-seeking drone cameras along with traditional techniques of ground surveys to develop a model that could be used to identify areas most likely to be home to koalas, which are facing population decline. Lead author Dr Catherine Leigh, who is also an Associate Investigator with ACEMS, said the advantage of the multi-pronged approach was that it greatly increased the accuracy of the statistical model. "It's about building a model that tells us with confidence where koalas are and where they're not," Dr Leigh said. "When you start building up a model with all of that data, you get a much better idea about where the koalas are likely to be. "If you can predict where koalas are, and the types of habitats they are hanging around in, then you know not only where to go to keep monitoring them but also the areas you need to protect." In the study, the researchers used ground survey information captured between 2102 and 2017 from Alexander Clarke Park in Loganholme, south-east Queensland, which is an area that has vegetation ranging from dense forest to grass fields and contains facilities including playgrounds and a dog park. Dr Leigh said one of the challenges with ground survey observations was that they could show a statistical bias of higher koala populations close to paths and other areas easily accessible by observers. "When you're out in the field as an experienced koala observer or a citizen scientist, you really are restricted where you can walk. And koalas are hard to see, even by trained observers," Dr Leigh said. "They are slow moving and often hidden high in the canopy." To counteract that, the researchers surveyed the area from the air using thermal cameras near sunrise, when the body heat of the koalas is detectable against the surrounding foliage. The third part of the study involved sending researchers out to some of the 82 specific locations in the area where koalas were known to either be or not be, to take 360-degree images. Those images were then shown to a panel of koala experts wearing VR headsets, with the experts asked to state how likely the environment they were viewing in was 'good koala habitat'. Dr Leigh said the advantage of using VR for the survey was it enabled them to bring the environment to the experts rather than having to take the experts to the field. "They're called immersive experiences," Dr Leigh said. "A lot of the research done on immersive experiences suggests that it helps to bring back the memories associated with when that expert has been in the field in the past, so they can be more cognizant of making the decision about the likelihood that a koala would be there." The researchers found that the three-pronged system of VR-prompted expert information, thermal imagery and ground surveys proved to be 75 per cent more accurate at predicting koala locations than ground surveys alone. "You put all three together and you get a much better model," Dr Leigh said. Dr Leigh said the methods could be used by councils and town planning authorities to obtain critical information needed for koala protection. |
News Release 13-Dec-2019
How a protein in your brain could protect against Alzheimer's disease New research sets the stage for new therapeutic strategies for Alzheimer's disease University of Alberta Share Print E-Mail Research shows that white blood cells in the human brain are regulated by a protein called CD33--a finding with important implications in the fight against Alzheimer's disease, according to a new study by University of Alberta chemists. "Immune cells in the brain, called microglia, play a critical role in Alzheimer's disease," explained Matthew Macauley, assistant professor in theDepartment of Chemistry and co-author on the paper. "They can be harmful or protective. Swaying microglia from a harmful to protective state could be the key to treating the disease." Scientists have identified the CD33 protein as a factor that may decrease a person's likelihood of Alzheimer's disease. Less than 10 percent of the population have a version of CD33 that makes them less likely to get Alzheimer's disease. "The fact that CD33 is found on microglia suggests that immune cells can protect the brain from Alzheimer's disease under the right circumstances," said Abhishek Bhattacherjee, first author and postdoctoral fellow in the Macauley lab. Now, Macauley's research shows that the most common type of CD33 protein plays a crucial role in modulating the function of microglia. "These findings set the stage for future testing of a causal relationship between CD33 and Alzheimer's Disease, as well as testing therapeutic strategies to sway microglia from harmful to protecting against the disease--by targeting CD33," said Macauley. "Microglia have the potential to 'clean up' the neurodegenerative plaques, through a process called phagocytosis--so a therapy to harness this ability to slow down or reverse Alzheimer's disease can be envisioned." Macauley is an investigator with GlycoNet, a Canada-wide network of researchers based at the University of Alberta that is working to further our understanding of biological roles for sugars. GlycoNet provided key funding to get this project off the ground in the Macauley lab and continues to support the ongoing applications of the project. According to the Alzheimer's Association, 747,000 Canadians are currently living with Alzheimer's or another form of dementia. The disease affects more than 44 million people around the world. |
News Release 13-Dec-2019
Growing carbon nanotubes with the right twist Researchers synthetize nanotubes with a specific structure expanding previous theories on carbon nanotube growth Institute for Basic Science Share Print E-Mail IMAGE IMAGE: (a) Carbon nanotubes (CNTs) could be viewed as single-atom layer thick graphene sheets rolled into a cylinder. Different directions of rolling determine CNTs' properties. (b) Schematic diagram showing a carbon... view more Credit: IBS In a recently published paper in Science Advances, Feng Ding of the Center for Multidimensional Carbon Materials, within the Institute of Basic Science (IBS, South Korea) and colleagues, have achieved the creation of a specific type of carbon nanotubes (CNTs) with a selectivity of 90%, and expanded the current theory that explains the synthesis of these promising nano-cylinders. CNTs are incredibly strong and light nanomaterials made of carbon with superior current carrying capacity and very high thermal conductivity, making them ideal for electronic applications. Although CNTs are considered as some of the most interesting materials for the future, scientists are still struggling for their controllable synthesis. The CNTs' shape can be compared to paper tubes: in the same way as a cylinder can be created by rolling a sheet of paper, so CNTs can be imagined as a single layer of graphite rolled up on itself. Similarly, as different tubes can be produced by rolling a paper around its long side, its short side, or diagonally at different angles. Depending on the rolling direction, a graphite layer can produce different CNT structures, some are conducting and others are semiconducting, thus selectively creating a specific type of CNT will be key for their future use, such as building energy efficient computer chips. However, CNTs are not produced by rolling, but are grown nanometer after nanometer, adding carbon at the rim of nano-cylinders, one atom at a time. Despite various studies during the last three decades, the understanding on CNT growth remains very limited and rational experimental design for the growth of specific types of CNTs is challenging. One of the most promising manufacturing methods for CNT is the chemical vapor deposition (CVD). In this process, metal nanoparticles combined with carbon-containing gases form CNTs inside a high-temperature furnace. On the tip of the tubes, the metal nanoparticles play a critical role as catalysts: they dissociate the carbon source from the gases, and assist the attachment of these carbon atoms to the CNT wall, making the tubes longer and longer. The growth of the CNT terminates once the catalyst particle is encapsulated by graphitic or amorphous carbon. Carbon atoms are inserted onto the interface between a growing CNT and a catalyst nanoparticle, in active sites of the rim, and are available to incorporate new atoms. A previous model of CNT's growth rate showed that the latter is proportional to the density of these active sites at the interface between CNT and the catalyst, or the specific structure of the CNT. In this study, the researchers monitored the steady growth of CNTs on a magnesium oxide (MgO) support with carbon monoxide (CO) as the carbon feedstock and cobalt nanoparticles as catalysts at 700oC. The direct experimental measurements of 16 CNTs showed how to expand the previous theory. "It was surprising that the growth rate of a carbon nanotubes only depends on the size of the catalyst particle. This implies that our previous understanding on carbon nanotubes growth was not complete," says Maoshuai He, the first author of the paper. More specifically, carbon atoms that are deposited on the catalyst particle surface can be either incorporated on the active side of the CNT or removed by etching agents, such as H2, H2O, O2, or CO2. To explain the new experimental observations, the team included the effects of carbon insertion and removal during CNT growth and discovered that the growth rate depends on the catalyst's surface area and tube diameter ratio. "Compared to the previous model, we added three more factors: the rate of precursor deposition, the rate of carbon removal by etching agents, and the rate of carbon insertion into a carbon nanotube wall. When feedstock dissociation cannot be balanced by carbon etching, the rate of carbon nanotube growth will no longer depend on the structure of the carbon nanotube. On the other hand, the previous theory is still valid if the etching is dominating," explains Ding, a group leader of the Center for Multidimensional Carbon Materials. Interestingly, the new theory of CNT growth leads to a new mechanism to selectively grow a specific type of CNTs, denoted as (2n, n) CNTs, which is characterized by the maximum number of active sites at the interface between the CNT and the catalyst. This CNT structure would correspond to rolling a sheet of graphite diagonally at an angle of around 19 degrees. "If there is no carbon etching and the carbon nanotubes growth is slow, carbon atoms on the catalyst surface will accumulate," says Jin Zhang, co-author of the study and professor of Peking University, China. "This may lead to the formation of graphitic or amorphous carbon, which are established mechanisms of carbon nanotube growth termination. In this case, only carbon nanotubes which are able to add carbon atoms on their walls, that is with the highest number of active sites, can survive." Guided by the new theoretical understanding, the researchers were able to design experiments that produced (2n, n) CNTs with a selectivity of up to 90%: the highest selective growth of this type of CNT was achieved in the absence of any etching agent and with a high feedstock concentration. |
News Release 13-Dec-2019
Nanoscience breakthrough: Probing particles smaller than a billionth of a meter Tokyo Institute of Technology Share Print E-Mail IMAGE IMAGE: Tin oxide SNCs finely prepared by a dendrimer template method are loaded on the thin silica shell layers of plasmonic amplifiers, such that the Raman signals of the SNCs are... view more Credit: Science Advances Scientists at Tokyo Institute of Technology (Tokyo Tech) developed a new methodology that allows researchers to assess the chemical composition and structure of metallic particles with a diameter of only 0.5 to 2 nm. This breakthrough in analytical techniques will enable the development and application of minuscule materials in the fields of electronics, biomedicine, chemistry, and more. The study and development of novel materials have enabled countless technological breakthroughs and are essential across most fields of science, from medicine and bioengineering to cutting-edge electronics. The rational design and analysis of innovative materials at nanoscopic scales allows us to push through the limits of previous devices and methodologies to reach unprecedented levels of efficiency and new capabilities. Such is the case for metal nanoparticles, which are currently in the spotlight of modern research because of their myriad potential applications. A recently developed synthesis method using dendrimer molecules as a template allows researchers to create metallic nanocrystals with diameters of 0.5 to 2 nm (billionths of a meter). These incredibly small particles, called "subnano clusters" (SNCs), have very distinctive properties, such as being excellent catalyzers for (electro)chemical reactions and exhibiting peculiar quantum phenomena that are very sensitive to changes in the number of constituent atoms of the clusters. Unfortunately, the existing analytic methods for studying the structure of nanoscale materials and particles are not suitable for SNC detection. One such method, called Raman spectroscopy, consists of irradiating a sample with a laser and analyzing the resulting scattered spectra to obtain a molecular fingerprint or profile of the possible components of the material. Although traditional Raman spectroscopy and its variants have been invaluable tools for researchers, they still cannot be used for SNCs because of their low sensitivity. Therefore, a research team from Tokyo Tech, including Dr. Akiyoshi Kuzume, Prof. Kimihisa Yamamoto and colleagues, studied a way to enhance Raman spectroscopy measurements and make them competent for SNC analysis (Figure). One particular type of Raman spectroscopy approach is called surface-enhanced Raman spectroscopy. In its more refined variant, gold and/or silver nanoparticles enclosed in an inert thin silica shell are added to the sample to amplify optical signals and thus increase the sensitivity of the technique. The research team first focused on theoretically determining their optimal size and composition, where 100-nm silver optical amplifiers (almost twice the size commonly used) can greatly amplify the signals of the SNCs adhered to the porous silica shell. "This spectroscopic technique selectively generates Raman signals of substances that are in close proximity to the surface of the optical amplifiers," explains Prof. Yamamoto. To put these findings to test, they measured the Raman spectra of tin oxide SNCs to see if they could find an explanation in their structural or chemical composition for their inexplicably high catalytic activity in certain chemical reactions. By comparing their Raman measurements with structural simulations and theoretical analyses, they found new insights on the structure of the tin oxide SNCs, explaining the origin of atomicity-dependent specific catalytic activity of tin oxide SNCs. The methodology employed in this research could have great impact on the development of better analytic techniques and subnanoscale science. "Detailed understanding of the physical and chemical nature of substances facilitates the rational design of subnanomaterials for practical applications. Highly sensitive spectroscopic methods will accelerate material innovation and promote subnanoscience as an interdisciplinary research field," concludes Prof. Yamamoto. Breakthroughs such as the one presented by this research team will be essential for broadening the scope for the application of subnanomaterials in various fields including biosensors, electronics, and catalysts. |
News Release 13-Dec-2019
City College leads new photonics breakthrough City College of New York Share Print E-Mail IMAGE IMAGE: Light localized in space inside the topological crystal, entangled by interaction and topology. view more Credit: ITMO University A new approach to trapping light in artificial photonic materials by a City College of New York-led team could lead to a tremendous boost in the transfer speed of data online. Research into topological photonic metamaterials headed by City College physicist Alexander B. Khanikaev reveals that long-range interactions in the metamaterial changes the common behavior of light waves forcing them to localize in space. Further, the study shows that by controlling the degree of such interactions one can switch between trapped and extended (propagating) character of optical waves. "The new approach to trap light allows the design of new types of optical resonators, which may have a significant impact on devices used on a daily basis, said Khanikaev. "These range from antennas in smartphones and Wi-Fi routers, to optical chips in optoelectronics used for transferring data over the Internet with unprecedented speeds." Entitled "Higher-order topological states in photonic kagome crystals with long-range interactions," the research appears in the journal Nature Photonics published today. It is a collaboration between CCNY, the Photonics Initiative at the Graduate Center, CUNY; and ITMO University in St. Petersburg, Russia. As the lead organization, CCNY initiated the research and designed the structures, which were then tested both at CCNY and at ITMO University. Khanikaev's research partners included: Andrea Alù, Mengyao Li, Xiang Ni (CCNY/CUNY); Dmitry Zhirihin (CCNY/ ITMO); Maxim Gorlach, Alexey Slobozhanyuk (both ITMO), and Dmitry Filonov (Center for Photonics and 2D Materials, Moscow Institute of Physics and Technology. Research continues to extend the new approach to trap visible and infra-red light. This would further expand the range of possible applications of the discovery. |
News Release 13-Dec-2019
Colliding molecules and antiparticles A new theoretical study of the interaction between positrons and simple tetrahedral and octahedral molecules agrees with experimental work and could have useful implications for PET scanning techniques. Springer Share Print E-Mail Antiparticles - subatomic particles that have exactly opposite properties to those that make up everyday matter - may seem like a concept out of science fiction, but they are real, and the study of matter-antimatter interactions has important medical and technological applications. Marcos Barp and Felipe Arretche from the Universidade Federal de Santa Catarina, Brazil have modelled the interaction between simple molecules and antiparticles known as positrons and found that this model agreed well with experimental observations. This study has been published in EPJ D. Positrons, the antimatter equivalent of electrons, are the simplest and most abundant antiparticles, and they have been known and studied since the 1930s. Particle accelerators generate huge quantities of high-energy positrons, and most lab experiments require this energy to be reduced to a specific value. Typically, this is achieved by passing the positrons through a gas in an apparatus called a buffer-gas positron trap, so they lose energy by colliding with the molecules of the gas. However, we do not yet fully understand the mechanisms of energy loss at the atomic level, so it is difficult to predict the resulting energy loss precisely. Some of this energy is lost as rotational energy, when the positrons collide with gas molecules and cause them to spin. Barp and Arretche developed a model to predict this form of energy loss when positrons collide with molecules often used in buffer-gas positron traps: the tetrahedral carbon tetrafluoride (CF4) and methane (CH4), and the octahedral sulphur hexafluoride (SF6). They found that this model compared very well to experimental results. This model can be applied to collisions between positrons and any tetrahedral or octahedral molecules. Barp and Arretche hope that this improved understanding of how positrons interact with molecules will be used to improve techniques for positron emission tomography (PET) scanning in medicine, for example. |
News Release 13-Dec-2019
Better studying superconductivity in single-layer graphene An existing technique is better suited to describing superconductivity in pure, single-layer graphene than current methods Springer Share Print E-Mail Made up of 2D sheets of carbon atoms arranged in honeycomb lattices, graphene has been intensively studied in recent years. As well as the material's diverse structural properties, physicists have paid particular attention to the intriguing dynamics of the charge carriers its many variants can contain. The mathematical techniques used to study these physical processes have proved useful so far, but they have had limited success in explaining graphene's 'critical temperature' of superconductivity, below which its' electrical resistance drops to zero. In a new study published in EPJ B, Jacques Tempere and colleagues at the University of Antwerp in Belgium demonstrate that an existing technique is better suited for probing superconductivity in pure, single-layer graphene than previously thought. The team's insights could allow physicists to understand more about the widely varied properties of graphene; potentially aiding the development of new technologies. Typically, the approach they used in the study is used to calculate critical temperatures in conventional superconductors. In this case, however, it was more accurate than current techniques in explaining how critical temperatures are suppressed with lower densities of charge carriers, as seen in pure, single-layer graphene. In addition, it proved more effective in modelling the conditions which give rise to interacting pairs of electrons named 'Cooper pairs', which strongly influence the electrical properties of the material. Tempere's team made their calculations using the 'dielectric function method' (DFM), which accounts for the transfer of heat and mass within materials when calculating critical temperatures. Having demonstrated the advantages of the technique, they now suggest that it could prove useful for future studies aiming to boost and probe for superconductivity in single and bilayer graphene. As graphene research continues to be one of the most diverse, fast-paced fields in materials physics, the use of DFM could better equip researchers to utilise it for ever more advanced technological applications. |
News Release 13-Dec-2019
Research calls for new measures to treat mental illness and opioid use University of Waterloo Share Print E-Mail Opioid use among psychiatric hospital patients needs to be addressed through an integrated approach to managing mental illness, pain and substance use, a study by researchers at the University of Waterloo has found. The study found that 7.5 per cent of 165,434 patients admitted to psychiatric hospitals in Ontario between 2006 and 2017 had used opioids in the year prior to admission, which compares to estimates that 2 per cent of the general population used opioids in 2015. Among patients who said they experience daily pain, the percentage who reported opiate use jumped to 22 per cent. "The patterns of use we saw are problematic," said Christopher Perlman, a public health researcher. "Opiate use is strongly linked to pain, mental health conditions and use of other drugs. While we don't know how many patients were initially prescribed an opioid for pain, we do know that a large number of patients reporting pain in psychiatry also have an addiction concern." The study highlights the challenging circumstances faced by those who use opioids. For instance, opiate use was almost twice as common among those whose employment or education was at risk (10.5 per cent) compared to those not at risk (5.8 per cent). Many patients who had used opiates did not have a partner or spouse, and individuals living in rural and northern communities were more likely to use opiates, as were young people, and males rather than females. "If we are serious about supporting people with mental and physical health concerns, we need an integrated approach to service delivery, which includes assessing and addressing the risk of addiction," said Perlman, who is a professor in the School of Public Health and Health Systems at the University of Waterloo. "Right now, the way our health system is structured and funded, it's not easy to integrate physical, mental and substance use services." "This study was able to shed some light on the needs of persons who use opioids, but this is really the tip of the iceberg. Because we lack integrated health information systems across various health providers, we really don't know the extent of the physical and health needs of individuals who use opioids across the population. That means they are either getting help elsewhere, which would be good - or more likely, that they are not getting care they need." The paper, "Factors Associated With Opiate Use Among Psychiatric Inpatients: A Population-Based Study of Hospital Admissions in Ontario, Canada" was co-authored by Oluwakemi Aderibigbe (Waterloo), Anthony Renda (independent), and Christopher Perlman (Waterloo), and published in Health Services Insights. |
News Release 13-Dec-2019
Excessive antibiotic prescriptions for children in low-, middle-income countries Many of the prescriptions given from birth through age 5 are unnecessary and might exacerbate resistance Harvard T.H. Chan School of Public Health Share Print E-Mail Boston, MA - Children in low- and middle-income countries (LMICs) are receiving an average of 25 antibiotic prescriptions during their first five years of life, an excessive amount that could harm the children's ability to fight pathogens as well as increase antibiotic resistance worldwide, according to a new study from the Swiss Tropical and Public Health Institute (Swiss TPH) and Harvard T.H. Chan School of Public Health. "We knew children in LMICs are sick more often, and we knew antibiotic prescription rates are high in many countries. What we did not know was how these elements translate into actual antibiotic exposure--and the results are rather alarming," said Günther Fink, lead author of the study and head of the Household Economics and Health Systems Research unit at Swiss TPH. The study--the first to look at total antibiotic prescribing in children under the age of five in LMICs--will be published on 13 December in The Lancet Infectious Diseases. Global health threat Antimicrobial resistance is one of today's biggest threats to global health and development, according to the World Health Organization. One factor contributing to this global health threat is the excessive use of antibiotics worldwide. Previous studies have shown that antibiotics are overprescribed to children in many countries. In Tanzania, for instance, several studies have shown that over 90% of children who visit a health facility receive an antibiotic, although only in about 20% of the cases treatment was actually required. The research team from Swiss TPH and Harvard Chan School analyzed data from 2007-2017 from health facilities and household surveys from eight countries: Haiti, Kenya, Malawi, Namibia, Nepal, Senegal, Tanzania, and Uganda. The study found that, on average, children received 25 antibiotic prescriptions through age five--a "remarkable" estimate, the authors wrote, given that two antibiotic prescriptions per year is considered excessive in many high-income settings. Results showed that antibiotics were administered in 81% of cases for children with a respiratory illness, in 50% for children with diarrhea, and in 28% for children with malaria. The researchers found that the number of antibiotic prescriptions in early childhood varied from country to country: While a child in Senegal received approximately one antibiotic prescription per year in the first five years of life, a child in Uganda was prescribed up to 12. In comparison, a prior study showed that children under five in Europe receive less than one antibiotic prescription per year on average. "This number is still high given that the vast majority of infections in this age group are of viral origin," said Valérie D'Acremont, a study co-author and head of the Management of Fevers group at Swiss TPH. "What is unique about this study is that it provides a much more comprehensive picture of pediatric antibiotic exposure in LMICs than what has been reported previously. It combines both household data on where and when children are brought for care with data from direct observations of health care workers caring for sick children," said Jessica Cohen, the Bruce A. Beal, Robert L. Beal, and Alexander S. Beal Associate Professor of Global Health at Harvard Chan School and senior author of the study. Impact on children "The consequences of antibiotic overprescription not only pose a huge threat to global health, but can also result in a concrete health impact for these children," said Valérie D'Acremont. "Excess antibiotic use destroys the natural gut flora which is essential to fighting pathogens." A Swiss TPH research project is underway to better comprehend the health impact of overusing antibiotics on children. "Understanding the concrete impact on individual children is crucial to achieve a policy change," said Fink. His research team is currently comparing policies at a country level to identify best practices that lead to lower antibiotic prescription rates. |
13-Dec-2019
Mayo Clinic researchers present findings at the 2019 San Antonio Breast Cancer Symposium Mayo Clinic Share Print E-Mail SAN ANTONIO -- Mayo Clinic researchers will present findings at the San Antonio Breast Cancer Symposium Dec. 10-14 in San Antonio. New Mayo Clinic studies to be presented include: •"Women at Elevated Risk of Developing Breast Cancer May Benefit From Taking Anti-inflammatory Drugs" •Embargoed until Friday, Dec. 13, at 6 p.m. EST •Research from Mayo Clinic investigators suggest that some women with an elevated risk of developing breast cancer may benefit from taking anti-inflammatory medications. "Several studies have evaluated whether the use of anti-inflammatory medications such as aspirin, ibuprofen and naproxen affect a woman's risk of developing breast cancer," says Amy Degnim, M.D., a breast surgical oncologist at Mayo Clinic in Minnesota, "but little is known about how use of these drugs might affect their risk after a benign breast biopsy." Dr. Degnim says about one million women receive a diagnosis of benign breast disease annually in the U.S. and having this history increases their risk of developing breast cancer. Researchers surveyed women who had undergone a benign breast biopsy at Mayo Clinic between 1992 and 2001, and asked them to report which types of these medications they had used and for how long. Researchers also obtained information on which women had developed breast cancer at any point in the years after their initial benign biopsy. "We found that women who reported using ibuprofen or naproxen had an approximately 40% reduction in breast cancer risk, while women who reported using aspirin had no reduction in breast cancer risk," says Dr. Degnim. "Women who used the drugs more frequently on a regular basis also had greater protection from breast cancer." Dr. Degnim says the findings suggest that women who have had a benign breast biopsy may benefit from medications that reduce inflammation, except for aspirin, in terms of reducing later breast cancer risk. She cautions that this study was not a clinical trial and she does not recommend that all women should take these medications to reduce their breast cancer risk. "Our results support the need for a clinical trial to further investigate the risks and benefits of taking these medications to lower breast cancer risk." "Young Women With Breast Cancer May Help Preserve Fertility by Avoiding Intensive Chemotherapy" Embargoed until Thursday, Dec. 12, at 8 a.m. EST Young women with HER 2-positive breast cancer may help preserve their fertility by choosing one type of chemotherapy over another according to the findings of a study led by Kathryn Ruddy, M.D., an oncologist at Mayo Clinic. "Ovarian dysfunction is an important issue after cancer treatment because it can be associated with infertility and menopausal symptoms, such as hot flashes and impaired sexual function," says Dr. Ruddy. Dr. Ruddy and her team surveyed study participants taking part in a randomized clinical trial testing the efficacy of T-DM1 versus a combination of paclitaxel and trastuzumab. Participants were asked questions about menstrual periods. "We found that young women with HER 2-positive breast cancer may be more likely to resume menstruation after receipt of two relatively new treatments, T-DM1 or a combination of paclitaxel and trastuzumab, than we have seen previously in young women who received older, more intensive chemotherapy regimens." Dr. Ruddy says the findings should be good news for women who want to maintain fertility after treatment for breast cancer and that menopausal symptoms such as hot flashes may be less burdensome for patients treated with the newer regimens. Dr. Ruddy and her colleagues will perform additional analyses on the effect of tamoxifen on these results before publishing a paper on this study. "Researchers Develop Tool to Identify Patients at Higher Risk of Heart Damage From Breast Cancer Therapy" Embargoed until Friday, Dec. 13, at 6 p.m. EST Researchers at Mayo Clinic in Florida have developed a tool to help identify patients who may be at higher risk of developing heart damage from anti HER 2 breast cancer therapy at an early stage. "Cardiac toxicity is a known complication of anti-HER 2 therapy," says Pooja Advani, M.B.B.S., M.D., a Mayo Clinic oncologist. Dr. Advani says clinical studies have confirmed that the use of anti-HER 2 therapy in breast cancer patients can have a profound effect on patient survival. "The most common manifestation of cardiac toxicity in breast cancer patients receiving anti-HER 2 therapy is a reduction in the ejection fraction without any symptoms," says Dr. Advani. Ejection fraction is a measurement of the percentage of blood leaving the heart each time it contracts. Dr. Advani says risk factors, such as older age; a lower ejection fraction prior to the start of treatment; and the use of anthracycline chemotherapy, such as doxorubin or Adriamycin, have been consistently associated with a higher risk of cardiac toxicity from anti-HER 2 therapy. Dr. Advani and her colleagues followed 604 breast cancer patients who were treated with anti-HER 2 agents at Mayo Clinic. They collected patient data, including, age, race, gender, body mass index, smoking history, medical comorbidities, use of heart medications, baseline heart function, thickness of the heart muscle and prior use of anthracycline chemotherapy. Researchers identified patients who developed cardiac toxicity -- asymptomatic, symptomatic, or both. They performed a statistical analysis to identify risk factors that were associated with a high risk of developing cardiac dysfunction. "We found that patients with certain risk factors including being over the age of 55, having a lower baseline heart function (ejection fraction less than 60 percent), having received anthracycline chemotherapy or patients having enlargement and thickening of the heart walls were most significantly associated with an increased risk of developing cardiac toxicity," says Dr. Advani. "This is consistent with previously reported studies." Dr. Advani says patients receiving radiation therapy as a part of their breast cancer treatment were not found to be at a significantly higher risk of developing cardiac toxicity from anti-HER 2 therapy based on their findings. Dr. Advani and her colleagues created a risk prediction model by assigning a score to each factor mentioned above and found that the cumulative risk score was a highly significant predictor of cardiac toxicity in patients. "Using a risk prediction model at therapy initiation may help us identify patients who may benefit from an early referral to a cardiologist for close cardiac monitoring and treatment with medications to protect their heart function," says Dr. Advani. |
News Release 13-Dec-2019
Research calls for new measures to treat mental illness and opioid use University of Waterloo Share Print E-Mail Opioid use among psychiatric hospital patients needs to be addressed through an integrated approach to managing mental illness, pain and substance use, a study by researchers at the University of Waterloo has found. The study found that 7.5 per cent of 165,434 patients admitted to psychiatric hospitals in Ontario between 2006 and 2017 had used opioids in the year prior to admission, which compares to estimates that 2 per cent of the general population used opioids in 2015. Among patients who said they experience daily pain, the percentage who reported opiate use jumped to 22 per cent. "The patterns of use we saw are problematic," said Christopher Perlman, a public health researcher. "Opiate use is strongly linked to pain, mental health conditions and use of other drugs. While we don't know how many patients were initially prescribed an opioid for pain, we do know that a large number of patients reporting pain in psychiatry also have an addiction concern." The study highlights the challenging circumstances faced by those who use opioids. For instance, opiate use was almost twice as common among those whose employment or education was at risk (10.5 per cent) compared to those not at risk (5.8 per cent). Many patients who had used opiates did not have a partner or spouse, and individuals living in rural and northern communities were more likely to use opiates, as were young people, and males rather than females. "If we are serious about supporting people with mental and physical health concerns, we need an integrated approach to service delivery, which includes assessing and addressing the risk of addiction," said Perlman, who is a professor in the School of Public Health and Health Systems at the University of Waterloo. "Right now, the way our health system is structured and funded, it's not easy to integrate physical, mental and substance use services." "This study was able to shed some light on the needs of persons who use opioids, but this is really the tip of the iceberg. Because we lack integrated health information systems across various health providers, we really don't know the extent of the physical and health needs of individuals who use opioids across the population. That means they are either getting help elsewhere, which would be good - or more likely, that they are not getting care they need." The paper, "Factors Associated With Opiate Use Among Psychiatric Inpatients: A Population-Based Study of Hospital Admissions in Ontario, Canada" was co-authored by Oluwakemi Aderibigbe (Waterloo), Anthony Renda (independent), and Christopher Perlman (Waterloo), and published in Health Services Insights |
News Release 13-Dec-2019
New methods could help researchers watch neurons compute Stanford University Share Print E-Mail Since the 1950s at least, researchers have speculated that the brain is a kind of computer in which neurons make up complex circuits that perform untold numbers of calculations every second. Decades later, neuroscientists know that these brain circuits exist, yet technical limitations have kept most details of their computations out of reach. Now, neuroscientists reported December 12 in Cell, they may finally be able to reveal what circuits deep in the brain are up to, thanks in large part to a molecule that lights up brighter than ever before in response to subtle electrical changes that neurons use to perform their compuations. Currently, one of the best ways to track neurons' electrical activity is with molecules that light up in the presence of calcium ions, a proxy for a neuron spike, the moment when one neuron passes an electrical signal to another. But calcium flows too slowly to catch all the details of a neuron spike, and it doesn't respond at all to the subtle electrical changes that lead up to a spike. (One alternative is to implant electrodes, but those implants ultimately damage neurons, and it isn't practical to place electrodes in more than a handful of neurons at once in living animals.) To solve those problems, researchers led by Michael Lin, an associate professor of neurobiology and of bioengineering and a member of the Wu Tsai Neurosciences Institute, and Stéphane Dieudonné, an INSERM research director at the École Normale Supérieure in Paris, focused on fluorescent molecules whose brightness responds directly to voltage changes in neurons, an idea Lin and his team had been working on for years. Still, those molecules had a problem of their own: Their brightness hasn't always been that responsive to voltage, so Lin and his team at Stanford turned to a well-known method in biology called electroporation. In that technique, researchers use electrical probes to zap holes in cell membranes, with the side effect that their voltage drops rapidly to zero like a punctured battery. By zapping a library of candidate molecules, Lin and colleagues could then select those whose brightness was most responsive to the voltage shift. The resulting molecule, called ASAP3, is the most responsive voltage indicator to date, Lin said. Dieudonné and his lab focused on another problem: how to scan neurons deep in the brain more efficiently. To make fluorescent molecules such as ASAP3 light up deep in the brain, researchers often use a technique called two-photon imaging, which employs infrared laser beams that can penetrate through tissue. Then, in order to scan multiple neurons fast enough to see a spike, which itself lasts only about a thousandth of a second, researchers must move the laser spot quickly from neuron to neuron -- something hard to do reliably in moving animals. The solution, Dieudonné and colleagues found, was a new algorithm called ultrafast local volume excitation, or ULoVE, in which a laser rapidly scans several points in the volume around a neuron, all at once. "Such strategies, where each laser pulse is shaped and sent to the right volume within the tissue, constitute the optimal use of light power and will hopefully allow us to record and stimulate millions of locations in the brain each second," Dieudonné said. that illuminates multiple points at once. Putting those techniques together, the researchers showed in mice that they could track fine details of brain activity in much of the mouse cortex, the top layers of the brain that control movement, decision making and other higher cognitive functions. "You can now look at neurons in living mouse brains with very high accuracy, and you can track that for long periods of time," Lin said. Among other things, that opens the door to studying not only how neurons process signals from other neurons and how they decide, so to speak, when to spike, but also how neurons' calculations change over time. In the meantime, Lin and colleagues are focused on further improving on their methods. "ASAP3 is very usable now, but we're confident there will be an ASAP4 and ASAP5," he said. |
News Release 13-Dec-2019
Standard pathology tests outperform molecular subtyping in bladder cancer Medical College of Georgia at Augusta University Share Print E-Mail IMAGE IMAGE: Dr. Vinata B. Lokeshwar and graduate students Sarrah S. Lahorewala and Daley S. Morera. view more Credit: Phil Jones, Senior Photographer, Augusta University While trying to develop a comparatively easy, inexpensive way to give physicians and their patients with bladder cancer a better idea of likely outcome and best treatment options, scientists found that sophisticated new subtyping techniques designed to do this provide no better information than long-standing pathology tests. They looked at several sets of data on cancer specimens from patients with muscle invasive bladder cancer, a high-grade cancer associated with high mortality rates. The datasets included the one used to determine emerging molecular subtypes, and had outcome information on patients. They consistently found that molecular subtyping of bladder tumors, which is currently being offered to patients, was outperformed by standard tests long-used by pathologists to characterize cancer as low- or high-grade and to determine the extent of its invasion into the bladder wall, surrounding fat, lymph nodes, blood vessels and beyond, they report in a study featured on the cover of the Journal of Urology. "Muscle invasive bladder cancer is aggressive, it often has a very bad prognosis," says Dr. Vinata B. Lokeshwar, chair of the Department of Biochemistry and Molecular Biology at the Medical College of Georgia at Augusta University. "Everyone is trying to find out how to improve diagnosis, treatment and survival." "Genetic profiling of a patient's tumor definitely has value in enabling you to discover the drivers of growth and metastasis that help direct that individual's treatment, even as it helps to identify new treatment targets," says Lokeshwar, the study's corresponding author and a member of the Georgia Cancer Center. "But using this information to subtype tumors does not appear to add diagnostic or prognostic value for patients." Rather the investigators suggest that more study is needed before molecular subtypes are used to help guide patient care. Evolving diagnostic approaches include compiling databanks on gene expression and mutations present in a cancer type to find patterns of gene expression that are then used to subtype tumors that "pathologically look similar" but are molecularly different. The idea is that molecular subtypes are better equipped to indicate which cancer is more or less aggressive and to help steer treatment options like whether chemotherapy before surgery to remove a diseased bladder is better. It was RNA sequencing, or RNA-Seq, and a federal databank of genetic material from a wide range of cancers that enabled investigators from around the globe to examine gene expression in a particular tumor type, looking for common expression of some genes that correlate with a particular clinical outcome. Two subtypes, luminal, which predicts better survival, and basal, which predicts poor prognosis, were first identified for muscle invasive bladder cancer, and a total of six subtypes have now emerged. The first paper on subtypes in muscle invasive bladder cancer was published in the journal Nature in 2014. But in their search to find a simpler, cheaper, widely available test to provide similar insight, investigators found that these emerging subtypes were outperformed by the usual clinical parameters like the tumor's grade and its spread to lymph nodes or blood vessels, Lokeshwar says. Their work began in earnest with an exhaustive review by graduate students Daley S. Morera and Sarrah S. Lahorewala of the datasets on patients and differing classification methods used to identify the molecular subtypes. They found 11 genes that were common in all subtype classification methods. They thought, if they were going to develop a widely available test, subtyping based on these common genes might suffice. They decided to call their new subtyping panel, MCG-1. Instead of doing RNA-Seq, which costs several thousand dollars, they used the readily available reverse transcription quantitative PCR method costing less than $10, which also looks at gene expression and is actually used to verify RNA-Seq data, Lokeshwar says. They first looked at their own cohort of 52 patients with bladder cancer, 39 of whom had muscle invasive disease. They found MCG-1 was only 31-36% accurate at predicting important indicators like likelihood of metastasis; disease specific survival, meaning surviving bladder cancer; or overall survival, meaning survival from all causes of death from the time of cancer diagnosis or beginning of treatment until the study's end. Recognizing that the dataset they used was comparatively small and that they did not use RNA-Seq for analysis, they then used three patient datasets from the cancer database ONCOMINE which had more patients -- 151 with muscle invasive bladder cancer -- and also used RNA-Seq to look at gene expression. "We found the same thing: MCG-1 could not predict disease-specific mortality," Lokeshwar says. On some patients in this dataset, information on response to chemotherapy, like commonly used cisplatin-based chemotherapy following surgical removal of the bladder, was available but subtypes could not predict chemotherapy response either, she says. Next they looked at the dataset that has been used by a large network of investigators to identify the subtypes, The Cancer Genome Atlas, or TCGA. TCGA is a project of the National Cancer Institute and National Human Genome Research Institute that started in 2006, and has collected genetic material for 33 different cancers. The dataset includes routine pathology information on 402 specimens from patients with muscle invasive bladder cancer. It also includes these patients' overall survival and recurrence-free survival - that is when or if their cancer returned or progressed. "Up until this point, we had been looking at patients that other groups had not looked at," Lahorewala says. In this dataset MCG-1 predicted overall survival similar to findings reported from subtypes in several high profile publications. "We were intrigued why MCG-1 could not predict anything in our cohort or the ONCOMINE dataset but predicted overall survival in the TCGA dataset," says Morera. So they looked again at the 402 patients whose specimens were in the dataset and found that 21 patients' tumors were actually low-grade. Patients with low-grade tumors have higher survivability and a better prognosis than patients with high-grade muscle invasive disease. When they removed the low-grade cases from the TCGA dataset, MCG-1 accurately predicted essentially nothing, not even overall survival. Then they included some patients with low-grade tumors into their own dataset, which they had looked at originally, and MCG-1 was now able to predict metastasis and disease specific survival, the investigators say. All the existing subtypes are categorized as bad or better based on the cancer prognosis, the investigators say. The presence of the low-grade tumors in the classification of subtypes skewed the data to make it look like subtypes were predicting overall survival when really it was the grade of the cancer itself that was predictive. "As investigators the first thing we did was to question our findings, since the results were so different than those reported by others," says Lokeshwar. With the help of MCG biostatistician and coauthor Dr. Santu Ghosh, they also went back and looked at the same patients in the TCGA datasets and the subtypes they had been assigned by three different classification methods established by a network of bladder cancer researchers. "Even with these established classification methods, the subtypes were accurate only about 50% of the time in predicting patients' overall survival. And once again, routine pathology parameters like invasion into lymph nodes or blood vessels were more accurate than the established subtypes in predicting patients' prognosis," says Lahorewala. A recent study by investigators at Sweden's Lund University published in the journal Urologic Oncology supports the MCG investigators' findings. Their study of 519 patients who had their bladders removed because of bladder cancer found subtypes were not associated with cancer-specific survival. Part of the problem with subtyping may be the inherent heterogeneity of tumors, says Morera. There is tremendous heterogeneity in the gene expression of tumors, even among the same tumor type, like bladder cancer, and within different parts of the same tumor as well. Furthermore, this pattern of heterogeneity can change both during tumor growth and treatment. "Just because it's bladder cancer does not mean it's the same in all patients. We know that tumors are very dynamic and so there is heterogeneity," Lokeshwar says. "Because there is heterogeneity, there could be problems when you want to categorize a tumor into a single subtype," says Morera. As the name indicates, muscle invasive bladder cancer has already spread from the lining of the sac-like organ to its muscular wall. High-grade tumors, if not detected early, will spread into bladder muscle, whereas, low-grade tumors are rarely invasive. Painless blood in the urine is the most common sign of bladder cancer although only a small percentage of the individuals with it have cancer. Smoking is the major risk factor for bladder cancer. |
A test of a customized implant for hip replacement
Scientists developed a mathematical model of an 'endoprosthesis-skeleton' system; special attention was paid to the geometry and internal structure of hip bones Peter the Great Saint-Petersburg Polytechnic University Share Print E-Mail IMAGE IMAGE: General distribution of stresses in the "endoprosthesis-skeleton " model of the biomechanical structure when a patient is standing on two legs. The voltage range is from 1 to 100 MPa. view more Credit: Peter the Great St.Petersburg Polytechnic University A team of scientists from the Advanced Manufacturing Technologies Center of the National Technology Initiative (NTI) of Peter the Great St.Petersburg Polytechnic University (SPbPU) (head -- Prof. A.I. Borovkov, the Vice-rector for Advanced Projects of Peter the Great St. Petersburg Polytechnic University) developed a mathematical model of an "endoprosthesis-skeleton" system. Special attention was paid to the geometry and internal structure of hip bones. Using advanced computer modeling technologies, the team assessed the integrity of the biomechanical structure for a typical case (a patient standing on two legs). Currently the team is working on a methodology that would reduce the time of such analysis to several days. The results of the study were published in the Vibroengineering PROCEDIA journal and presented at the 12th All-Russia Congress on Fundamental Issues of Theoretical and Applied Mechanics. Hip joint arthroplasty is a relatively common procedure today. During arthroplasty the upper part of a patient's hip bone is replaced with a metal stem with a spherical joint element, and a cup to allow the head of the joint to rotate inside the pelvis. Medical companies manufacture standard elements with different parameters for ordinary hip replacement operations. However, after some time a certain share of patients experiences issues with implants and requires their replacement. As a rule, this happens due to the insufficient (or excessive) load the endoprosthesis puts on the hip bone causing its tissue to change. Moreover, bone strength can be affected by osteoporosis and other diseases. By the time of the second surgery (the removal of the initial implant and the installation of a revision one) a part of the hip bone becomes unfit as it is unable to bear the load. Therefore, when a patient comes to a secondary operation with a damaged hip bone, standard implants are of no use for them, and a regular cup (even if it is of a bigger size) might not work. The manufacturers produce special sets of elements that can be combined with each other in different ways to be used in revision operations as well as in patients with compound fractures or cancer. However, such surgeries have high risk rates: any issue with a revision structure or additional bone tissue loss may cause grave health issues. It is extremely important to understand if the prosthesis is able to bear the load, and if the damage to the patient's bone can be avoided. Virtual testing before installation could help eliminate numerous post-surgical complications. However, there is currently no universal assessment method to do so. It takes a long time to build a model on the basis of bone CT results, while the patient's health parameters keep constantly changing. Therefore, the window between diagnostics and the surgery should be as short as possible. A team of engineers from the Advanced Manufacturing Technologies Center of the National Technology Initiative (NTI) of Peter the Great St. Petersburg Polytechnic University (SPbPU) analyzed the integrity of an "endoprosthesis-skeleton" system for a case of hip joint revision arthroplasty and assessed the durability of the implanted structure and pelvis bones, as well as the distribution of load when a patient stands on two feet. The work describes the peculiarities of simulation model preparation. Currently, this process takes a long time, but the team is working on a method to reduce the whole calculation to several days. Other groups tend to entirely ignore pelvic bones in their studies or to consider only their simplified models. However, in this case the researchers paid special attention to detailed description of pelvic bones including their external and porous internal layers. This was done due to the fact that the pelvis is often at risk in its entirety. "If we consider the work done by us as a virtual test, the article described the load we put on the patient's skeleton and the implant, as if they were tested in reality. Studies like this help reduce the risk of complications in patients with individually designed implants. Hopefully, they would help prioritize prevention over cure," commented Mikhail Zhmaylo, a lead engineer at the Advanced Manufacturing Technologies Center of the National Technology Initiative (NTI) of Peter the Great St. Petersburg Polytechnic University (SPbPU) |
New assay assesses multiple cellular pathways at once
Baylor College of Medicine Share Print E-Mail IMAGE IMAGE: Synthetic assembly cloning for inserting multiple luciferase reporters into a single vector. Nature Communications/The Venken lab view more Credit: Nature Communications/The Venken lab A novel technological approach developed by researchers at Baylor College of Medicine expands from two to six the number of molecular pathways that can be studied simultaneously in a cell sample with the dual luciferase assay, a type of testing method commonly used across biomedical fields. Published in the journal Nature Communications, the report shows that multiplexed hextuple luciferase assaying, meaning a testing method that can effectively probe six different pathways. It can also be used to monitor the effects of experimental treatments on multiple molecular targets acting within these pathways. The new assay is sensitive, saves time and expense when compared to traditional approaches, reduces experimental error and can be adapted to any research field where the dual luciferase assay is already implemented, and beyond. "One of the interests of our lab is to have a better understanding of the processes involved in cancer. Cancer usually originates through changes on many different genes and pathways, not just one, and currently most cell-based screening assays conduct single measurements," said corresponding author Dr. Koen Venken, assistant professor of biochemistry and molecular biology, and pharmacology and chemical biology at Baylor. To get a more detailed picture of the cellular processes that differentiate normal versus cancer cells, researchers resort to conduct several independent screening assays at the expense of time and additional cost. "Our goal in this study was to measure multiple cellular pathways at once in a single biological sample, which would also minimize experimental errors resulting from conducting multiple separate assays using different samples," said Venken, a McNair Scholar and member of the Dan L Duncan Comprehensive Cancer Center at Baylor. Dr. Alejandro Sarrion-Perdigones, first author of the paper, focused on developing a multiplexed method - a method for simultaneously detecting many signals from complex systems, such as living cells. He developed a sensitive assay using luciferases, enzymes that produce bioluminescence. The assay includes six luciferases, each one emitting bioluminescence that can be distinguished from the others. Each luciferase was engineered to reveal the activity of a particular pathway by emitting bioluminescence. "To engineer and deliver the luciferase system to cells, we used a 'molecular Lego' approach," said co-author Dr. Lyra Chang, post-doctoral researchers at the Center for Drug Discovery at Baylor. "This consists of connecting the DNA fragments encoding all the biological and technological information necessary to express each luciferase gene together sequentially forming a single DNA chain called vector. This single vector enters the cells where each luciferase enzyme is produced separately." Treating the cells with a single multi-luciferase gene vector instead of using six individual vectors, decreased variability between biological replicates and provided an additional level of experimental control, Chang explained. This approach allowed for simultaneous readout of the activity of five different pathways, compared to just one using traditional approaches, providing a much deeper understanding of cellular pathways of interest. "In addition to applications in cancer research, as we have shown in this work, our multiplex luciferase assay can be used to study other cellular pathways or complex diseases across different research fields," Venken said. "For instance, the assay can be adapted to study the effect of drugs on insulin sensitivity in different cells types, the immune response to viral infections, or any other combinations of pathways |
A test of a customized implant for hip replacement
Scientists developed a mathematical model of an 'endoprosthesis-skeleton' system; special attention was paid to the geometry and internal structure of hip bones Peter the Great Saint-Petersburg Polytechnic University Share Print E-Mail IMAGE IMAGE: General distribution of stresses in the "endoprosthesis-skeleton " model of the biomechanical structure when a patient is standing on two legs. The voltage range is from 1 to 100 MPa. view more Credit: Peter the Great St.Petersburg Polytechnic University A team of scientists from the Advanced Manufacturing Technologies Center of the National Technology Initiative (NTI) of Peter the Great St.Petersburg Polytechnic University (SPbPU) (head -- Prof. A.I. Borovkov, the Vice-rector for Advanced Projects of Peter the Great St. Petersburg Polytechnic University) developed a mathematical model of an "endoprosthesis-skeleton" system. Special attention was paid to the geometry and internal structure of hip bones. Using advanced computer modeling technologies, the team assessed the integrity of the biomechanical structure for a typical case (a patient standing on two legs). Currently the team is working on a methodology that would reduce the time of such analysis to several days. The results of the study were published in the Vibroengineering PROCEDIA journal and presented at the 12th All-Russia Congress on Fundamental Issues of Theoretical and Applied Mechanics. Hip joint arthroplasty is a relatively common procedure today. During arthroplasty the upper part of a patient's hip bone is replaced with a metal stem with a spherical joint element, and a cup to allow the head of the joint to rotate inside the pelvis. Medical companies manufacture standard elements with different parameters for ordinary hip replacement operations. However, after some time a certain share of patients experiences issues with implants and requires their replacement. As a rule, this happens due to the insufficient (or excessive) load the endoprosthesis puts on the hip bone causing its tissue to change. Moreover, bone strength can be affected by osteoporosis and other diseases. By the time of the second surgery (the removal of the initial implant and the installation of a revision one) a part of the hip bone becomes unfit as it is unable to bear the load. Therefore, when a patient comes to a secondary operation with a damaged hip bone, standard implants are of no use for them, and a regular cup (even if it is of a bigger size) might not work. The manufacturers produce special sets of elements that can be combined with each other in different ways to be used in revision operations as well as in patients with compound fractures or cancer. However, such surgeries have high risk rates: any issue with a revision structure or additional bone tissue loss may cause grave health issues. It is extremely important to understand if the prosthesis is able to bear the load, and if the damage to the patient's bone can be avoided. Virtual testing before installation could help eliminate numerous post-surgical complications. However, there is currently no universal assessment method to do so. It takes a long time to build a model on the basis of bone CT results, while the patient's health parameters keep constantly changing. Therefore, the window between diagnostics and the surgery should be as short as possible. A team of engineers from the Advanced Manufacturing Technologies Center of the National Technology Initiative (NTI) of Peter the Great St. Petersburg Polytechnic University (SPbPU) analyzed the integrity of an "endoprosthesis-skeleton" system for a case of hip joint revision arthroplasty and assessed the durability of the implanted structure and pelvis bones, as well as the distribution of load when a patient stands on two feet. The work describes the peculiarities of simulation model preparation. Currently, this process takes a long time, but the team is working on a method to reduce the whole calculation to several days. Other groups tend to entirely ignore pelvic bones in their studies or to consider only their simplified models. However, in this case the researchers paid special attention to detailed description of pelvic bones including their external and porous internal layers. This was done due to the fact that the pelvis is often at risk in its entirety. "If we consider the work done by us as a virtual test, the article described the load we put on the patient's skeleton and the implant, as if they were tested in reality. Studies like this help reduce the risk of complications in patients with individually designed implants. Hopefully, they would help prioritize prevention over cure," commented Mikhail Zhmaylo, a lead engineer at the Advanced Manufacturing Technologies Center of the National Technology Initiative (NTI) of Peter the Great St. Petersburg Polytechnic University (SPbPU |
News Release 13-Dec-2019
Researchers reconstruct spoken words as processed in nonhuman primate brains Brown University Share Print E-Mail Volume 90% VIDEO: Using a brain-computer interface, a team of researchers has reconstructed English words from the brain activity of rhesus macaques that listened as the words were spoken. view more Credit: Nurmikko Lab / Brown University PROVIDENCE, R.I. [Brown University] -- A team of Brown University researchers has used a brain-computer interface to reconstruct English words from neural signals recorded in the brains of nonhuman primates. The research, published in the journal Nature Communications Biology, could be a step toward developing brain implants that may help people with hearing loss, the researchers say. "What we've done is to record the complex patterns of neural excitation in the secondary auditory cortex associated with primates' hearing specific words," said Arto Nurmikko, a professor in Brown's School of Engineering, a research associate in Brown's Carney Institute for Brain Science and senior author of the study. "We then use that neural data to reconstruct the sound of those words with high fidelity. "The overarching goal is to better understand how sound is processed in the primate brain," Nurmikko added, "which could ultimately lead to new types of neural prosthetics." The brain systems involved in the initial processing of sound are similar in humans and non-human primates. The first level of processing, which happens in what's called the primary auditory cortex, sorts sounds according to attributes like pitch or tone. The signal then moves to the secondary auditory cortex, where it's processed further. When someone is listening to spoken words, for example, this is where the sounds are classified by phonemes -- the simplest features that enable us to distinguish one word from another. After that, the information is sent to other parts of the brain for the processing that enables human comprehension of speech. But because that early-stage processing of sound is similar in humans and non-human primates, learning how primates process the words they hear is useful, even though they likely don't understand what those words mean. For the study, two pea-sized implants with 96-channel microelectrode arrays recorded the activity of neurons while rhesus macaques listened to recordings of individual English words and macaque calls. In this case, the macaques heard fairly simple one- or two-syllable words -- "tree," "good," "north," "cricket" and "program." The researchers processed the neural recordings using computer algorithms specifically developed to recognize neural patterns associated with particular words. From there, the neural data could be translated back into computer-generated speech. Finally, the team used several metrics to evaluate how closely the reconstructed speech matched the original spoken word that the macaque heard. The research showed the recorded neural data produced high-fidelity reconstructions that were clear to a human listener. The use of multielectrode arrays to record such complex auditory information was a first, the researchers say. "Previously, work had gathered data from the secondary auditory cortex with single electrodes, but as far as we know this is the first multielectrode recording from this part of the brain," Nurmikko said. "Essentially we have nearly 200 microscopic listening posts that can give us the richness and higher resolution of data which is required." One of the goals of the study, for which doctoral student Jihun Lee led the experiments, was to test whether any particular decoding model algorithm performed better than others. The research, in collaboration with Wilson Truccolo, a computational neuroscience expert, showed that recurrent neural networks (RNNs) -- a type of machine learning algorithm often used in computerized language translation -- produced the highest-fidelity reconstructions. The RNNs substantially outperformed more traditional algorithms that have been shown to be effective in decoding neural data from other parts of the brain. Christopher Heelan, a research associate at Brown and co-lead author of the study, thinks the success of the RNNs comes from their flexibility, which is important in decoding complex auditory information. "More traditional algorithms used for neural decoding make strong assumptions about how the brain encodes information, and that limits the ability of those algorithms to model the neural data," said Heelan, who developed the computational toolkit for the study. "Neural networks make weaker assumptions and have more parameters allowing them to learn complicated relationships between the neural data and the experimental task." Ultimately, the researchers hope, this kind of research could aid in developing neural implants the may aid in restoring peoples' hearing. "The aspirational scenario is that we develop systems that bypass much of the auditory apparatus and go directly into the brain," Nurmikko said. "The same microelectrodes we used to record neural activity in this study may one day be used to deliver small amounts of electrical current in patterns that give people the perception of having heard specific sounds." |
News Release 13-Dec-2019
Entrectinib effective, well-tolerated against ROS1 and NTRK lung cancers, especially with brain metastases University of Colorado Anschutz Medical Campus Share Print E-Mail IMAGE IMAGE: Robert C. Doebele, MD, PhD, and colleagues update the effectiveness of entrectinib against ROS1+ and NTRK+ cancers. view more Credit: University of Colorado Cancer Center Pooled analysis of three phase 1 and 2 clinical trials published online ahead of print in the journal Lancet Oncology show that the drug entrectinib is effective and well-tolerated against advanced ROS1 and NTRK fusion-positive non-small cell lung cancers (NSCLC). Results of the trials STARTRK-1 (NCT02097810), STARTRK-2 (NCT02568267), and ALKA, show 77 percent response rate to entrectinib in 53 patients with ROS1+ NSCLC, with a median progression-free survival of 19 months and a median duration of response of 24.6 months. In 54 patients with NTRK+ NSCLC, 57 percent responded to entrectinib, with a median progression-free survival of 11.2 months and a median duration of response of 10.4 months. Based on the early promise of these trials, in August 2019 the U.S. Food and Drug Administration granted entrectinib accelerated approval for the treatment of metastatic ROS1+ NSCLC and for advanced tumors across cancer types defined by NTRK fusion. The current journal articles update these findings that led to approval. "For a drug to get simultaneous approval for use against two different targets is somewhat unique. I don't know of this ever happening before," says Robert C. Doebele, MD, PhD, director of the University of Colorado Cancer Center Thoracic Oncology Research Initiative, senior author on the ROS1 study, and first author on the NTRK study. About 2 percent of lung cancers are driven by the improper fusion of the gene ROS1 with one of a handful of possible genetic partners, resulting in a cancer-causing ROS1 fusion gene. About 1 percent of all solid tumors, including but not limited to lung cancers, are similarly caused by NTRK fusion genes. The FDA-approved drug crizotinib can silence the action of ROS1 fusion genes in some cases, but can't reach cancers that have metastasized to the brain. And, unfortunately, 36 percent of patients with ROS1+ NSCLC already have brain metastases at the time of advanced disease diagnosis, and many more will go on to develop brain metastases during the course of care. "For ROS1+ lung cancer, entrectinib represents a new and better standard of care due to entrectinib's effectiveness against ROS1 in the body and especially due to its activity against ROS1+ brain metastases," Doebele says. "For NTRK cancers, the picture is a little more complex and I think it depends on an NTRK+ cancer's chance of developing brain metastases. Personally, if I were a patient and felt there was any chance of me getting brain mets, I would want this brain-penetrating drug." Included in these phase 1 or 2 studies were adults with locally advanced or metastatic ROS1+ or NTRK+ NSCLC who had received previous treatment not including other ROS1 inhibitors. Patients received entrectinib at a dose of at least 600 mg orally once per day, with at least 12 months follow-up. Doebele describes the drug as "well tolerated with a manageable safety profile," with side effects including weight increase (8%) and neutropenia (4%). Eleven percent of patients had serious treatment-related adverse events, the most common of which were nervous system disorders (3%) and cardiac disorders (2%). No treatment-related deaths occurred. "The genes ROS1 and NTRK are on a growing list of known genetic drivers of non-small cell lung cancer. In addition to showing the benefit of entrectinib against cancers caused by these fusion genes, these results highlight the importance of genetic testing in NSCLC, especially when patients are diagnosed with the condition in the absence of other risk factors," Doebele says. "Only by testing for genes like ROS1 and NTRK can we match these genetic drivers of cancer with drugs like entrectinib." |
News Release 13-Dec-2019
Rapid tissue donation program offers feasible approach to improve research Well-preserved postmortem lung cancer specimens allow for genetic and molecular analyses H. Lee Moffitt Cancer Center & Research Institute Share Print E-Mail TAMPA, Fla. - Precision medicine with targeted therapies has led to improved treatment options and patient outcomes. These approaches were developed by studying tumors grown in laboratories and patient samples obtained before and during their treatment. However, there is often a limited supply of patient samples to adequately study, and the samples that exist do not always tell the complete genetic story of how the patient responded to specific drugs and the reasons why they failed treatment. Researchers need a better way to determine how tumors respond to therapies and evolve to resist drug treatment. In an article published in Cancer Medicine, Moffitt Cancer Center scientists describe a community-based program called the Rapid Tissue Donation (RTD) protocol. It enables patients to consent to donating tumor tissue and blood samples for research purposes after their death. The samples provided by patients postmortem enable researchers to study the genetic and molecular makeup of primary and metastatic tumors after the patient failed treatment, and to compare those finding with what was known about the patient during earlier phases of their therapy. There were several challenges that the Moffitt team had to overcome before embarking on this program, including ethical considerations and logistical challenges, communication with hospice care facilities, locating autopsy facilities in the community and identifying tumors in postmortem specimens. During a two-year span from Nov. 2015 to Nov. 2017, Moffitt researchers were able to gain consent from 21 lung cancer patients from Hillsborough, Pinellas and Pasco counties to participate in the RTD study. They collected 180 tumor tissue and blood specimens from nine deceased patients, while the remaining 12 patients were still alive at the time of the article publication. One of the logistical challenges the researchers faced was the need to preserve the specimens as quickly as possible after death to ensure that the tissue and molecular material remained intact. The average time to collect the specimens for all nine patients was 15.8 hours. Samples were collected within 20 hours of death for eight donors, and by 41 hours from death for one donor due to unavoidable logistic complexities. Analysis of the specimens found that most of the DNA samples taken from the primary and metastatic tumors of the same patient were similar and contained the same DNA mutations. The researchers also discovered an AGK-BRAF fusion in one patient with a known EML4-ALK fusion and resistance to ALK inhibitor therapy. Activated BRAF can promote tumor growth. "This is a compelling finding because, had the AGK-BRAF fusion been detected during treatment, physicians could have adapted therapy to include a BRAF-targeted agent," said Eric Haura, M.D., medical oncologist and director of Moffitt's Lung Cancer Center of Excellence. Analysis of tumor tissue samples for protein biomarkers showed that expression of the protein PD-L1 varied up to 55% among samples taken from the primary tumor and metastatic tumors from the same patient. Levels of PD-L1 are used as a diagnostic assay for lung cancer patients to determine if they should receive certain drugs. "Twenty to sixty percent of individuals in this study would have a different PD-L1 result if different tumor sites were tested," said Haura. "This illustrates the importance of interpreting PD-L1 results with caution because a large number of patients might not be eligible for immunotherapy based on testing of one tumor site but would be eligible based on testing of a tumor in a different location." Haura is pleased with the progress the RTD program has made and is excited for what is to come. He hopes that it can be expanded into other tumor types and even developed in partnership with other institutions. |
News Release 13-Dec-2019
Multi-omics approach offers new insights into peanut allergy severity Findings could improve diagnostics and lead to new treatments The Mount Sinai Hospital / Mount Sinai School of Medicine Share Print E-Mail New York, NY -- Dec 12, 2019 -- Researchers at the Icahn School of Medicine at Mount Sinai have identified novel genes associated with the severity of peanut allergy, as well as ways in which these genes interact with other genes during allergic reactions. The findings, published December 12 in the Journal of Allergy and Clinical Immunology, could lead to better treatments for peanut allergy. Peanut allergy varies widely in severity and is the leading cause of fatal food-related anaphylaxis. The tests used to determine the existence of a peanut allergy don't offer any clues as to whether an individual ingesting a peanut could experience a minor rash, major swelling, or life-threatening issues such as difficulty breathing or cardiovascular complications. The study's senior author, Supinda Bunyavanich, MD, MPH, Associate Professor of Genetics and Genomic Sciences, and Pediatrics, and Associate Director of the Elliot and Roslyn Jaffe Food Allergy Institute at Mount Sinai, was especially curious about why the severity of reactions varies so much, both as a clinician-scientist and as a mother of a child with a peanut allergy. To help address this question, Dr. Bunyavanich and her team used novel multi-omic approaches (the study of the role, relationships, and actions of a system-wide measure of a given molecular type) to identify genes and networks of activity that might be driving the severity of peanut allergy reactions. The approaches included transcriptomics, the study of gene expression across the genome, and epigenomics, the study of reversible modifications to DNA that affect gene expression. The study involved 21 children ages 7-17 with peanut allergy, who were given gradually increasing doses of peanut until they displayed an allergic response. The scientists drew blood from the participants at three times: before they ate, as they reacted, and after their reaction. The team confirmed their findings from the initial cohort by repeating the study in another 19 children. Taking blood samples at multiple times allowed the team to analyze both the transcriptome and epigenome (which can tell scientists which genes are turned on or off through a process called methylation) as the children reacted. Using this genome-wide approach, they identified more than 300 genes and 200 CpG sites (areas where DNA can be activated or inactivated by methylation) associated with reaction severity. Combining these data using integrative networks, the team also characterized key interactions between gene expression, CpG sites, and reaction severity. Not only did they identify novel genes associated with the severity of peanut allergy, but they also managed to characterize ways in which these genes interact with other genes and CpG sites during allergic reactions to regulate biological processes. "It was very exciting to apply multi-omics to uncover how genes and methylation sites interact to affect reaction severity in these peanut allergic kids," says Anh Do, PhD, lead author of the study and postdoctoral fellow in the Bunyavanich Lab. Among the insights is that while the findings support recognized roles for adaptive immunity in allergy, they also suggest that neutrophil (a type of white blood cell)-mediated immunity plays a prominent role in reaction severity. "We know neutrophil-mediated immunity is part of immune responses, and this study suggests it may play a central role in the severity of peanut allergic reactions," said Dr. Bunyavanich. Additionally, one of the reaction severity drivers the team identified, the gene ARG1, can be inhibited by arginase inhibitors, a type of drug under study for many diseases. This study's finding suggests it may be a potential target for treating peanut allergy as well. Dr. Bunyavanich hopes future studies will identify biomarkers that can predict who is likely to have severe responses without having to expose them to peanuts first. But in the meantime, she states that this study "hopefully challenges people to think about food allergy with a broader lens." |
News Release 13-Dec-2019
Bone bandage soaks up pro-healing biochemical to accelerate repair Trapping adenosine at the site of a bone break speeds recovery in mice Duke University Share Print E-Mail IMAGE IMAGE: This graphic shows the healing progress of a fracture in a mouse treated with a new type of bone bandage that traps native adenosine (top), is preloaded with external adenosine... view more Credit: Shyni Varghese, Duke University DURHAM, N.C. -- Researchers at Duke University have engineered a bandage that captures and holds a pro-healing molecule at the site of a bone break to accelerate and improve the natural healing process. In a proof-of-principle study with mice, the bandage helped to accelerate callus formation and vascularization to achieve better bone repair by three weeks. The research points toward a general method for improving bone repair after damage that could be applied to medical products such as biodegradable bandages, implant coatings or bone grafts for critical defects. The results appear online on December 12 in the journal Advanced Materials. In 2014, Shyni Varghese, professor of biomedical engineering, mechanical engineering and materials science, and orthopedics at Duke, was studying how popular biomaterials made of calcium phosphate promote bone repair and regeneration. Her laboratory discovered that the biomolecule adenosine plays a particularly large role in spurring bone growth. After further study, they found that the body naturally floods the area around a new bone injury with the pro-healing adenosine molecules, but those locally high levels are quickly metabolized and don't last long. Varghese wondered if maintaining those high levels for longer would help the healing process. But there was a catch. "Adenosine is ubiquitous throughout the body in low levels and performs many important functions that have nothing to do with bone healing," Varghese said. "To avoid unwanted side effects, we had to find a way to keep the adenosine localized to the damaged tissue and at appropriate levels." Varghese's solution was to let the body dictate the levels of adenosine while helping the biochemical stick around the injury a little bit longer. She and Yuze Zeng, a graduate student in Varghese's laboratory, designed a biomaterial bandage applied directly to the broken bone that contains boronate molecules that grab onto the adenosine. However, the bonds between the molecules do not last forever, which allows a slow release of adenosine from the bandage without accumulating elsewhere in the body. In the current study, Varghese and her colleagues first demonstrated that porous biomaterials incorporated with boronates were capable of capturing the local surge of adenosine following an injury. The researchers then applied bandages primed to capture the host's own adenosine or bandages preloaded with adenosine to tibia fractures in mice. After more than a week, the mice treated with both types of bandages were healing faster than those with bandages not primed to capture adenosine. After three weeks, while all mice in the study showed healing, those treated with either kind of adenosine-laced bandage showed better bone formation, higher bone volume and better vascularization. The results showed that not only do the adenosine-trapping bandages promote healing, they work whether they're trapping native adenosine or are artificially loaded with it, which has important implications in treating bone fractures associated with aging and osteoporosis. "Our previous work has shown that patients with osteoporosis don't produce adenosine when their bones break," Yuze said. "These early results indicate that these bandages could help deliver the needed adenosine to repair their injuries while avoiding potential side effects." Varghese and Yuze see several other paths forward for biomedical applications as well. For example, they imagine a biodegradable bandage that traps adenosine to help heal broken bones and then decomposes into the body. Or for osteoporotic patients, a permanent bandage that can be reloaded with adenosine at sites that suffer from repeated injuries. They also envision a lubricating gel armed with adenosine that can help prevent bone injuries caused by the wear and tear associated with reconstructive joint surgeries or other medical implants. "We've demonstrated that this is a viable approach and filed a patent for future devices and treatments, but we still have a long way to go," said Varghese. "The bandages could be engineered to capture and hold on to adenosine more efficiently. And of course we also have to find out whether these results hold in humans or could cause any side effects." |
News Release 13-Dec-2019
Study probing visual memory, amblyopia unveils many-layered mystery Picower Institute at MIT Share Print E-Mail IMAGE IMAGE: Researchers used a genetic technique to knock out NMDA receptors in layer 4 of the visual cortex of mice. view more Credit: Bear Lab/ Picower Institute for Learning and Memory In decades of studying how neural circuits in the brain's visual cortex adapt to experience, MIT Professor Mark Bear's lab has followed the science wherever it has led, yielding the discovery of cellular mechanisms serving visual recognition memory, in which the brain learns what sights are familiar so it can focus on what's new, and of a potential therapy for amblyopia, a disorder where children born with disrupted vision in one eye can lose visual acuity there permanently without intervention. But this time his lab's latest investigation has yielded surprising new layers of mystery. Heading into the experiments described in a new paper in Cerebral Cortex, Bear and his team expected to confirm that key proteins called NMDA receptors act specifically in neurons in layer 4 of the visual cortex to make the circuit connection changes, or "plasticity," necessary for both visual recognition memory and amblyopia. Instead, the study has produced unexpectedly divergent results. "There are two stories here," said Bear, co-senior author and Picower Professor of Neuroscience in The Picower Institute for Learning and Memory. "One is that we have further pinpointed where to look for the root causes of amblyopia. The other is that we have now completely blown up what we thought was happening in stimulus-selective response potentiation, or SRP, the synaptic change believed to give rise to visual recognition memory." The cortex is built like a stack of pancakes, with distinct layers of cells serving different functions. Layer 4 is considered to be the primary "input layer" that receives relatively unprocessed information that arises from each eye. Plasticity that is restricted to one eye has been assumed to occur at this early stage of cortical processing, before the information from the two eyes becomes mixed. However, while the evidence demonstrates that NMDA receptors in layer 4 neurons are indeed necessary for the degradation of vision in a deprived eye, they apparently play no role in how neural connections, or synapses, serving the uncompromised eye strengthen to compensate, and similarly don't matter for the development of SRP. That's even though NMDA receptors in visual cortex neurons have directly been shown to matter in these phenomena before, and layer 4 neurons are known to participate in these circuits via telltale changes in electrical activity. "These findings reveal two key things," said Samuel Cooke, co-senior author and a former member of the Bear Lab who now has his own at King's College London. "First, that the neocortical circuits modified to enhance cortical responses to sensory inputs during deprivation or to stimuli that have become familiar reside elsewhere in neocortex, revealing a complexity that we had not previously appreciated. Second, the results show that effects can be clearly manifest in a region of the brain that are actually echoes of plasticity occurring elsewhere, thereby illustrating the importance of not only observing biological phenomena but also understanding their origins by locally disrupting known underlying mechanisms." 'We were stunned' To perform the study, Bear Lab postdoc and lead author Ming-fai Fong and used a genetic technique to specifically knock out NMDA receptors in excitatory neurons in layer 4 of the visual cortex of mice. Armed with that tool, she could then investigate the consequences for visual recognition memory and "monocular deprivation," a lab model for amblyopia in which one eye is temporarily closed early in life. The hypothesis was that knocking out the NMDA receptor in these cells in layer 4 would prevent SRP from taking hold amid repeated presentations of the same stimulus, and would prevent the degradation of vision in a deprived eye as well as the commensurate strengthening of the unaffected eye. "We were gratified to note that the amblyopia-like effect of losing cortical vision as a result of closing an eye for several days in early life was completely prevented," Cooke said. "However, we were stunned to find that the two enhancing forms of plasticity remained completely intact." Fong said that with continued work, the lab hopes to pinpoint where in the circuit NMDA receptors are triggering SRP and the compensatory increase in strength in a non-deprived eye after monocular deprivation. Doing so, she said, could have clinical implications. "Our study identified a crucial component in the visual cortical circuit that mediates the plasticity underlying amblyopia," she said. "This study also highlights the ongoing need to identify the distinct components in the visual cortical circuit that mediate visual enhancement, which could be important both in developing treatments for visual disability as well as developing biomarkers for neurodevelopmental disorders. These efforts are ongoing in the lab." The search now moves to other layers, Bear said, including layer 6, which also receives unprocessed input from each eye. "Clearly this is not the end of the story," Bear said. |
News Release 13-Dec-2019
Moongoose females compete over reproduction University of Helsinki Share Print E-Mail IMAGE IMAGE: A group of banded mongooses (Mungos mungo) enjoying morning sunshine at the study site, the Mweya peninsula in Western Uganda. view more Credit: Emma Vitikainen A new study on wild banded mongooses reveals that females may use spontaneous abortion to cope with reproductive competition, and to save their energy for future breeding attempts in better conditions. Researchers at the University of Exeter, UK, followed a population of wild banded mongooses (Mungos mungo) in western Uganda for 15 years, using ultrasound imaging to track which females became pregnant and which carried to full term. They discovered that there were more abortions during the dry season when food was scarce, and also when more females were competing over reproduction in the same group. Individual females were less likely to carry to term if they were young, in poor condition, or carrying smaller fetuses. "Reproduction takes a lot of energy, and for a female whose offspring may have slim chances at survival, it makes sense to delay that investment until times are better. Spontaneous abortion may be an adaptive strategy in this species because it enables females to save energy for the next breeding attempt," says researcher, and senior author of the study, Emma Vitikainen from the University of Helsinki. Banded mongooses are cooperative breeders that live in family groups where several females give birth at the same time to a litter that is jointly cared for by all the group members. Underneath this seemingly harmonious surface, co-breeding females compete over whose offspring do best. Pups that are born bigger have more help from their group members, grow faster and outcompete their littermates. This study revealed that females adjust their own investment in response to the competition, and that females whose offspring would be more likely to lose out are more likely to cut their losses by aborting their fetuses mid-pregnancy. Banded mongooses also curb competition by evicting younger females. To focus on spontaneous pregnancy loss the researchers only looked at breeding events where no violent eviction events occurred. "Female competition over reproduction is easily overlooked," explains lead author Emma Inzani from the University of Exeter, UK. "Males fight with horns and antlers over access to females, whereas female competition can be much more subtle. Our study shows that even in the absence of overt aggression, females adjust their reproductive decisions in response to competition from other females. " All research was done under ethical permits from University of Exeter and Uganda Wildlife Authority and study methods caused no harm to pregnant mongooses |
Tracking titin in real time
Max Delbrück Center for Molecular Medicine in the Helmholtz Association Share Print E-Mail IMAGE IMAGE: Collage made from single cells expressing titin-GFP and titin-DsRed. view more Credit: Gotthardt Lab, MDC Using new high-resolution imaging techniques, MDC researchers and colleagues have tracked titin, the body's largest protein, in real time throughout its entire lifecycle. The method and results could provide new insight into muscle development as well as treating damaged muscles and heart disease. As twinkling lights brighten the holiday season, Max Delbrueck Center for Molecular Medicine researchers are cheered by red and green lights for an entirely different reason. Using colorful probes, a team has tracked the full lifecycle of titin, the body's largest protein known to play a key role in muscle tissue. Observing titin from synthesis to degradation has provided novel insight into the formation of sarcomeres, the main contractile units of heart and skeletal muscle. The results were reported in the journal Proceedings of the National Academy of Sciences (PNAS). Titin is such a large molecule that its analysis provides unique challenges. The team attached red and green fluorescent tags to opposite ends of the protein, enabling them to observe titin's precise movements in muscle cells derived from the mouse heart, called cardiomyocytes. "Cardiomyocytes are highly specialized and cannot skip a beat," said Michael Gotthardt, who heads MDC's Neuromuscular and Cardiovascular Cell Biology Lab and spearheaded the research. "We can watch how titin is made and inserted into the myofilament while everything is still working. It's beautiful to see." Not just a pretty picture The insight gained from being able to watch titin in real time is significant. Titin has long been assumed to be the rigid backbone of sarcomeres, the basic functional segments of heart and skeletal muscles that expand and contract. It turns out that titin is much more dynamic than previously thought, Gotthardt said. Heart muscle cells appear to have a pool of soluble titin spread throughout the sarcomere, ready to replace proteins damaged in the repetitive process of muscle expansion and contraction. Overextended proteins are moved out of the cells and then degraded. All of this happens over the course of a few hours, which sounds fast, but is actually much longer than for any other sarcomeric protein. The large amount of titin located outside the sarcomere was as surprise, seen for the first time thanks to the new genetic mouse model and imaging technique, Gotthardt said. Another unexpected finding was the diversity of titin molecules, called isoforms, that were observed. Faster moving proteins are likely different isoforms than slower moving ones. "This is a look at the real life of the sarcomere," Gotthardt said. "We can understand the formation and remodeling of the myofilament structure, which has relevance to human disease and development." Potential applications The fluorescent probes can help researchers study how muscles rebuild themselves after exercise, or how heart muscles remodel after a heart attack. They might also help to better understand heart diseases associated with mutations in other sarcomeric proteins, said Franziska Rudolph, first author of the paper. "This is amazing, to follow endogenous titin variants in real time from start to finish," Rudolph said. "So many experiments are possible with these mouse models and different imaging techniques." For example, the technique could potentially be used to track implanted cells to see how well they are integrating with the native muscle fiber, and if they properly connect with their new neighbors to work as a unit or not. Such insight could show if cell based therapies are effective. Validating the novel tools and establishing methods for image analysis was a challenge and required the collaboration with colleagues from MDC's Berlin Institute for Medical Systems Biology, University Medical Center Goettingen, and the University of Arizona. The team worked hard to show how the fluorescent proteins, which are genetically generated, had no unexpected side effects on muscle or titin development and function. MDC researchers are continuing to investigate titin with the new tools, including how skeletal muscles respond to exercise |
The Max Delbrueck Center for Molecular Medicine (MDC)
The Max Delbrueck Center for Molecular Medicine in the Helmholtz Association (MDC) was founded in Berlin in 1992. It is named for the German-American physicist Max Delbrueck, who was awarded the 1969 Nobel Prize in Physiology and Medicine. The MDC's mission is to study molecular mechanisms in order to understand the origins of disease and thus be able to diagnose, prevent and fight it better and more effectively. In these efforts the MDC cooperates with the Charite - Universitaetsmedizin Berlin and the Berlin Institute of Health (BIH ) as well as with national partners such as the German Center for Cardiovascular Research and numerous international research institutions. More than 1,600 staff and guests from nearly 60 countries work at the MDC, just under 1,300 of them in scientific research. The MDC is funded by the German Federal Ministry of Education and Research (90 percent) and the State of Berlin (10 percent), and is a member of the Helmholtz Association of German Research Centers. http://www.mdc-berlin |
Deck The Halls With Bouts Of Nausea
Lazy/Unhelpful, Non-Dialogue, Pharmacy, Texas, USA | Healthy | December 16, 2019 I have chronic nausea. I take a prescription nausea medication to keep it under control so I can eat and function. The nausea is related to stress, as well as my diagnosed depression and anxiety. Six days ago at the time of writing, two days before Thanksgiving, my grandmother, who has to handle most phone calls for me due to my hearing issues, called the pharmacy to request a refill of my meds because I was almost out. Later, we got a call telling us that the refill request had been denied because my doctor’s office said I had to see the doctor before I could get a refill. I called the doctor the next day and was told that they had sent in an approval, but they would send another one to be sure. Pharmacy still said they had no approvals, only a denial. Thanksgiving came and the office was closed. I checked the pharmacy again, and they still said they only had a denial and couldn’t fill it. Black Friday, same deal, but we got a call from someone at my doctor’s office informing us that they’d be closed until Monday. I only had enough of my meds to get me through Black Friday. I ended up skipping my second dose so I would have one for Saturday morning, and was unable to eat dinner on Friday. Same deal with the pharmacy on both Saturday and Sunday. No approvals received, only one denial, and they still couldn’t fill it even though I was unable to eat or drink without it at this time. I even got on the phone myself and cry and beg the pharmacist to give me an emergency three-day supply that the law allows, and was told no because of the “denial.” This morning, Cyber Monday, after going the entire weekend feeling like I was in Hell since eating was pretty much impossible, my grandmother called my doctor’s office to set up an appointment for the first time slot they could fit me into today. She was informed that they absolutely did not send in a denial, I did not need to see my doctor before getting a refill, and that their system says I don’t have to see my doctor for a refill on my medication until sometime next year. My doctor knows that I need the medication every single day to be able to eat, and I’m about twenty pounds underweight right now due to stress-induced illness that lasted for three months solid, so I need to be able to get a refill at any time until I gain some weight back. It turns out that someone at the pharmacy put it on my file that they were sent a denial and got no approvals whatsoever. A few hours ago, I got a text saying that I had a prescription ready for pickup, which would be done first thing in the morning because we couldn’t get to the store. I have filed a complaint with corporate for the store the pharmacy is in, and my complaint has been forwarded to the store manager with the assurance that the incident will be investigated and that this absolutely should not have happened. The person I conversed with — via chat — was horrified about it. I hope that pharmacist gets fired and feels proud of themselves for giving a disabled woman no less than five panic attacks over the course of three days and causing her a lot of unnecessary stress that has likely set back her recovery from illness. I won’t be able to fully enjoy Christmas with my family now because I’ll still be recovering and having trouble eating much food. |
Just Another Kidney Stoner
Bad Behavior, Hospital, Lazy/Unhelpful, Nurses, USA | Healthy | December 15, 2019 (I have a massive kidney stone trying to pass. I’m in the hospital, waiting for surgery to reduce the size. I suddenly have massive pain, bad enough my vision goes fuzzy. I’m crying, unable to really form words. I press my call button. After a moment, a nurse comes in.) Nurse: “Can I help you?” Me: “Pain… bad…” Nurse: “On a scale of one to ten?” Me: “Ten!” (Because of the pain, I practically shout the number.) Nurse: “You don’t need to raise your voice! I’ll get you something!” (She leaves and comes back a minute later with a pill.) Nurse: “Here’s some Tylenol.” (All I can do is look at her, since that won’t be anywhere near enough for how my pain is.) Nurse: “Well?! Take it!” Me: “Need more…” Nurse: “Ugh, you’re probably just a drug seeker! I’m not giving you anything else!” (At this point, I just break down sobbing. She storms out. A few minutes later, my doctor comes in.) Doctor: “Are you okay?!” Me: “Pain bad… help…” Doctor: “Okay, sweetie, I just need to know if you can tell me what number you’re at.” Me: “Ten…” Doctor: “All right. Do you want me to wait here while I have someone bring you medication?” Me: “Please!” (She does stay with me. After she calls the pharmacy, she holds my hand and talks to me to calm me back down. Once the medication is brought up and put into my IV, she makes sure it starts working.) Doctor: “Your nurse said you were asking for drugs?” Me: “No, I pushed my call light and told her I was in pain. She yelled at me saying that’s all I wanted and then left.” Doctor: “She apparently thought you were faking something to get pain meds for an addiction. There’s no way you could fake a kidney stone on the imaging results. I’ll make sure you don’t have to deal with her anymore.” (True to her word, I didn’t see that nurse for the rest of my stay.) |
That Flu Right Over Her Head
Health & Body, High School, Jerk, Louisiana, Parents/Guardians, USA | Healthy | December 13, 2019 (This event happens more than halfway through my junior year in high school. It’s important to note that prior to this, I have only missed about four or five days of school during my ENTIRE high school career, half of which were from when my grandmother died unexpectedly last year. This one particular morning, I wake up feeling like complete and utter crap. I also just so happen to have two major presentations today after lunch and my parents know about both of them. They basically have to fight to get me out of bed, accusing me of either lying or exaggerating to get out of my presentations. I manage to power through the first half of the day before breaking down at lunch and having my counselor essentially force my mother to come and get me. Naturally, she isn’t happy about it as she still thinks I’m purposefully trying to avoid my presentations.) Mom: *in a very condescending tone* “I hope you’re prepared to go to the doctor. I’m bringing you back right after, too.” (It’s very clear she’s trying to call my “bluff” and scare me into backing down, but I just quietly shrug. And just as she said, she brings me to a walk-in clinic near my school. After going through the standard procedure, the nurse seeing me takes a snot sample for a flu test.) Mom: “I’m thinking it’s just a little cold at most.” Nurse: “If that’s the case, we’ll probably just do a steroid shot, but let’s see the test results first.” (She leaves and returns a few minutes later. To my mother’s surprise, the nurse is now wearing a procedure mask.) Nurse: “So, he has the flu. We’re lucky y’all caught it within the first two days so we can write him a prescription for some Tamiflu that y’all can pick up at your preferred pharmacy. We’ll also give you a doctor’s note that says he can’t go to school until at least next Monday. Until then, make sure he gets plenty of rest and that he doesn’t have a fever for at least 48 hours prior to Monday.” (My mother was horrified and ended up asking to have herself tested, too; she was negative. Although I feel bad for all my friends and classmates who sat by me that morning, I can’t help but gleefully remember my mom’s face when she realized that I wasn’t faking s***.) |
When Laughter Is NOT The Best Medicine
Connecticut, Emergency Services, Punny, Silly, USA | Healthy | December 11, 2019 (I am a paramedic.) Me: *to a patient* “Let me borrow your arm for a blood pressure check, please.” (The patient extends their arm.) Partner: “Don’t worry; she’ll give it back.” Me: “Yeah. I got in way too much trouble last time for not giving it back. The police even chased me!” Patient: “The police chased you?” Me: “Yeah! For armed robbery!” Partner: *groans and slams back doors of the ambulance while walking away |
It’s Not Just The Organs That Are Failing
Doctor/Physician, Hospital, Jerk, Lazy/Unhelpful, Uruguay | Healthy | December 9, 2019 (When my brother is around nine, he wakes up screaming in pain. As we have no vehicle of our own and no way of getting a taxi or a lift, my mother has to walk with a screaming child two kilometers to the hospital. She went to nursing school, but is not currently working as a nurse.) Doctor: *after barely poking him* “Well, seems to be just some gas. He’s probably just using the pain to get attention.” (My mother looks at her like she’s crazy, while my brother still cries and screams.) Mom: “My son is not like that. Look, I am a nurse. I’m pretty sure he has appendicitis.” Doctor: “Oh, nonsense. You don’t know what you are talking about.” Mom: “But I do–” Doctor: “Listen. I am a doctor. You are just a nurse. He is fine. Now leave.” (My mother leaves the hospital furious. Not surprisingly, two days later, my brother’s appendix ruptures. My mom manages to get a passing car to take them to the hospital, and my brother has surgery. Because the hospital has no full anesthesia, they have to use local — the kind that only numbs the area — and my brother is operated on while awake and screaming. While he is still in surgery, my mother runs into the doctor in the hallway.) Doctor: “Oh, you are here again. What, does your son have a headache now? It might be a tumor, don’t you think?” (My mother almost attacked her, but her father entered the hospital on time and stopped her. My brother survived and made a full recovery, and my mother reported the doctor; unfortunately, nothing came out of it at the time, but a few years later she was forced into retirement for repeatedly misdiagnosing patients.) |
Bring Them Back In For A Brain Check
Extra Stupid, Florida, Medical Office, USA | Healthy | December 8, 2019 (I am at the checkout desk of an urgent care medical office.) Coworker: “How was your visit today?” Patient: “Pretty good. I don’t like going to the doctor, but this was a great experience. Everyone was really nice.” Coworker: “Thanks! Glad everything went well. Yeah, I work in a doctor’s office and I don’t really like going to the doctor, either.” Patient: “Oh, really? What kind of doctor’s office do you work in?” My Brain: “Seriously? Did she just ask that?” |
Cheese Addiction Is Becoming A Problem
California, Health & Body, Los Angeles, Medical Office, USA | Healthy | December 5, 2019 (I work at a non-profit rehab for teens as a counselor. During their lunch, a new resident is having a heated argument with other staff over her dietary restrictions.) Teen: “I can’t eat this; it has cheese. I’m vegan.” Staff: “We’re trying to accommodate. The cooks have been made aware and are working on fixing you something else.” Teen: “You shouldn’t be eating this stuff. Do you know how badly dairy and meat harms your body? You guys are all disgusting.” Me: *screaming internally* “You shouldn’t lecture anyone when you smoke meth!” |
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