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WASHINGTON -- Inserting air into hot glass to form a bubble has been used to make glass objects since Roman times. In new work, researchers apply these same glass blowing principles on a microscopic scale to make specialized miniature cone-shaped lenses known as axicons.

Axicons are used to shape laser light in a way that is beneficial for optical drilling, imaging and creating optical traps for manipulating particles or cells. These lenses have been known for more than 60 years, but their fabrication, especially when small, is not easy.

"Our technique has the potential of producing robust miniature axicons in glass at a low cost, which could be used in miniaturized imaging systems for biomedical imaging applications, such as optical coherence tomography, or OCT," said research team member Nicolas Passilly from FEMTO-ST Institute in France.

In The Optical Society (OSA) journal Optics Letters, the researchers describe the new fabrication approach, which is based on the same processes used to make large numbers of photonic and electronic circuits in parallel on semiconductor wafers. The researchers used their approach to create glass axicons with diameters of 0.9 and 1.8 millimeters and showed that they successfully generated Bessel beams.

"Wafer-level microfabrication allows the axicons to be integrated into more complex microsystems created also at a wafer-level, leading to a system made of a wafer stack," said Passilly. "This type of integration comes with better optical alignments, high performance vacuum packaging and much lower-costs for the final systems because a large number can be processed simultaneously."

Creating a microlens

When used with a laser, axicons create a beam of light that begins as a Bessel-like beam -- a non-diffracting beam with maximum intensity on its axis -- and then turns into a hollow beam further away from the axicon. Bessel-like beams feature a depth of field that can be orders of magnitude larger than that of a beam focused by a traditional rounded lens with a similar diameter. The beam's high depth of field allows optical drills to reach deeper and creates higher quality OCT images. For optical tweezers, both the Bessel-like and hollow portions of the beam can be used to trap particles or cells.

Techniques traditionally used to make glass axicons can produce only one lens at a time. Although less expensive axicons can be made in polymer, these can't withstand high temperature processes such as wafer-level fabrication or be used in applications that require high levels of light power.

"Polymer axicons can't be used in optical drilling, for example, because the instantaneous light power is comparable to the power of a nuclear plant but with an extremely short duration," said Passilly.

Micro glass blowing has been previously used to make microlenses, but it usually involves gas expansion from a single reservoir. The researchers developed an axicon fabrication method that combines gas expansion from multiple reservoirs to produce the optical component's conical shape. The technique shapes the surface from underneath leaving a high-quality optical surface, unlike commonly used methods like etching transfer from a 3D mask that engrave the wafer from above.

To carry out the new micro glass blowing method, the researchers deposited silicon cavities in concentric rings that were then sealed with glass under atmospheric pressure. Placing the silicon and glass stack in a furnace caused gas trapped in the cavities to expand, creating ring-shaped bubbles. These bubbles pushed out the glass surface to form cone shapes and then the opposite side was polished away to leave only the shaped lenses.

"Although all the processes we used are standard for microfabrication, we applied these techniques in non-standard ways to make miniature glass axicons," said Passilly. "The technique could be applied to create other shapes, even ones without cylindrical symmetry."

ANAHEIM, CA (Embargoed until 9 a.m. PDT, Tuesday, June 25, 2019) - A novel therapy using two targeted treatments for prostate cancer has been shown to maximize efficacy while reducing side effects according to research presented at the Society of Nuclear Medicine and Molecular Imaging (SNMMI) 2019 Annual Meeting.

Prostate cancer is the most commonly diagnosed cancer among men in the United States, other than skin cancer. According to the American Cancer Society, approximately 175,000 new cases of prostate cancer are diagnosed and more than 31,500 men die from the disease annually in the United States.

Although there have been great treatment advances, metastatic castrate resistant prostate cancer (mCRPC) remains a deadly disease. Trials with the targeted radionuclide therapy 177Lu PSMA 617 have proven safe and effective in some men; however, not all respond to treatment, and responses may be limited in duration. To build upon these trials, researchers paired 177Lu PSMA 617 with the tumor-specific radiation sensitizer idronoxil (NOX66) to assess responses in patients with heavily treated mCRPC.

The phase I/II trial enrolled 16 men with progressing mCRPC, despite previous treatments. All men received up to six doses of 177Lu PSMA 617 at six-week intervals. Half the patients (cohort 1) received additional treatment of 400mg NOX66 daily for ten days. Following a safety data review, the remaining patients (cohort 2) received additional treatment of 800mg NOX66 daily.

Researchers found that nearly 70 percent of all patients saw a more than 50 percent reduction in their PSA levels (62.5 percent in cohort 1 and 75 percent in cohort 2) after the combination treatment. Furthermore, adverse side effects, such as fatigue and pneumonitis, were reported in 31 percent of all patients (37.5 percent in cohort 1 and 12.5 percent in cohort 2).

"The initial results of this phase I dose escalation study show that the combination targeted treatments were well tolerated together, with no increase in toxicity from 177Lu PSMA 617, and an apparent high efficacy in men who have already had extensive treatments," said Louise Emmett, MD, associate professor at the University of New South Wales in Sydney, Australia.

She continued, "We are now in a dose expansion phase II stage to further evaluate toxicity and efficacy. This raises the very important possibilities of combining tumor-targeted therapeutic agents to gain synergistic treatment effects without an increase in side effects."

Abstract 465. "Interim Results of a Phase I/II Prospective Dose Escalation Trial Evaluating Safety and Efficacy of Combination 177Lu PSMA 617 and NOX66 in Men with mCRPC Post Androgen Signalling Inhibition and 2 Lines of Taxane Chemotherapy (LuPIN Trial)," Louise Emmett, MD, Megan Crumbaker, MBChb, Andrew Nygen, Bao Ho, MBChB, Charlotte Yin, MBChB, Noah Isheish MBBS, Shikha Sharma, and Anthony M. Joshua, PhD, 390 Victoria St., St. Vincent's Hospital, Sydney, Australia; Arun Azad, PhD, Oncology, Monash University, Melbourne, Australia; and John Violet, John Violet, Radiation Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia. SNMMI's 66TH Annual Meeting, June 22-25, 2019, Anaheim, CA.

About one of every five breast cancers presents with high levels of HER2 proteins. Known as HER2-positive breast cancer, these tumors typically show an aggressive behavior - a greater likelihood of metastasis and relapse and decreased patient survival than HER2 negative types - and are physiologically dependent on the abundance of HER2. These findings prompted the question, if we take HER2 away from 'HER2-addicted' cancers, would cancer slow down?

Extensive research in the 1980s and '90s showed that, indeed, treating HER2-positive breast cancer cells with antibodies that bind specifically to HER2 could slow down the cells' growth in a laboratory dish.

These findings were confirmed in mouse models and subsequently led to the development of a HER2-specific antibody called trastuzumab for use in humans. Trastuzumab blocks the communication between HER2 and the tumor cells and elicits an immune response against the cancer cells by engaging the host's immune system.

Later, three clinical trials showed that metastatic HER2-positive breast cancer treated with trastuzumab plus standard chemotherapy grew more slowly than those treated with chemotherapy alone. Additional clinical trials also showed positive outcomes with early-stage HER2-positive breast cancer.

Can we stop HER2-positive breast cancer without chemotherapy?

"Patient outcome has markedly improved since the U.S. Food and Drug Administration approved trastuzumab in combination with chemotherapy for the treatment of HER2-positive breast cancer," said Dr. Rachel Schiff, associate professor in the Lester and Sue Smith Breast Center and in the departments of molecular and cellular biology and medicine at Baylor College of Medicine. "And outcome can be improved further if two instead of one anti-HER2 therapies, referred now on as dual anti-HER2 therapy, are used, as we and others have shown. The more effectively we block the HER2 cascade of events, the more potent the antitumor effect."

The increased effectiveness of dual anti-HER2 therapy prompted the researchers to investigate in mouse models the outcome of treating HER2-positive breast cancer exclusively with anti-HER2 therapies.

"Our animal studies showed that treating tumors only with dual anti-HER2 therapies and no chemotherapy resulted in complete tumor eradication, which, if translated to the clinic, may spare patients the toxicity and cost associated with chemotherapy," said Schiff, who also is a member of the Dan L Duncan Comprehensive Cancer Center.

Encouraged by these promising results, Dr. Mothaffar F. Rimawi, professor of medicine and executive medical director and co-leader of the breast cancer program at the Dan L Duncan Comprehensive Cancer Center at Baylor, Dr. C. Kent Osborne, professor of medicine, Dudley and Tina Sharp Chair for Cancer Research and director of the Dan L Duncan Comprehensive Cancer Center, Schiff and their colleagues suggested that anti-HER2 therapy alone would suffice for treating a subset of HER2-positive breast cancers that are truly HER2-addicted. Furthermore, they proposed that adding chemotherapy may not offer extra benefit. This novel strategy of sparing chemotherapy, also called treatment de-escalation, was tested by the researchers in the TBCRC006 clinical trial.

In this clinical trial, patients with HER2-positive breast cancer were treated for 12 weeks with lapatinib and trastuzumab, without chemotherapy. Lapatinib is a small molecule, anti-HER2 drug that interrupts molecular pathways triggered by HER2. Combined, trastuzumab and lapatinib disrupt different molecular mechanisms that activate HER2 and thereby block the HER2-mediated cancer-promoting effects.

Twenty-seven percent of the patients with HER2-positive breast cancer achieved pathologic complete response (pCR) - their tumors disappeared in the breast despite a median tumor size of 6 cm (2.4 inches). This clinically meaningful pCR rate has now been confirmed in two similar chemotherapy-sparing trials, TBCRC023 and PAMELA, according to Dr. Jamunarani Veeraraghavan, assistant professor at the Lester and Sue Smith Breast Center at Baylor in the Schiff-Osborne lab.

"Our and others' results showed that not all HER2-positive breast cancers benefit from the de-escalation strategy," Veeraraghavan said. "We needed a plan to differentiate patients who are candidates for de-escalation approach from those needing additional therapy."

In this study published in Annals of Oncology, the researchers looked for signals or biomarkers that would allow them to identify candidates for the de-escalation approach among patients with HER2-positive breast cancer.

Finding the tumors that may not need chemotherapy

Based on preclinical and clinical evidence, the researchers hypothesized that the truly HER2-addicted tumors that may benefit from anti-HER2 therapy alone would need to have high levels of HER2 gene and protein. They further hypothesized that the normal or mutated status of the PI3K pathway, a key molecular pathway that mediates HER2 signaling to promote tumor growth, also would affect the response of these HER2-addicted tumors to anti-HER2 therapies.

Using tissue samples the researchers already had from the TBCRC006 clinical trial, they explored the possibility that looking at two instead of one biomarker (high levels of HER2 and PI3K pathway activation) would enable them to predict which tumors most likely would respond to the dual anti-HER2 therapy without needing chemotherapy.

They found that patients with tumors having both high levels of HER2 and an intact (normal) PI3K pathway had a higher probability to achieve pCR than patients not meeting these criteria ? 44 percent of the patients with high HER2 levels and intact PI3K pathway achieved pCR. On the other hand, only 4 percent of patients not meeting these criteria achieved pCR.

A parallel similar study analyzed tissue specimens from the PAMELA clinical trial looking at levels of HER2 RNA and HER2 signaling. Published in the Journal of the National Cancer Institute, the results of this study support the approach of combining biomarkers HER2 RNA levels and HER2 signaling to better predict which patients would most likely benefit from the dual anti-HER2 treatment.

"Our findings suggest that there is a clinical subtype of breast cancer with high HER2 levels and intact PI3K pathway that is especially sensitive to HER2-targeted therapies without chemotherapy," Schiff said. "Identifying these tumors by measuring the levels of HER2 gene amplification and PI3K pathway status warrants validation."

"Our ultimate goal is to be able to conduct molecular testing at the time of diagnosis to distinguish patients who may need less and those who may need more therapy. This is the future of precision medicine," Rimawi said.

New Rochelle, NY, June 24, 2019--A new systemic review of the literature has shown a clear gap in the understanding of cancer in lesbian, gay, bisexual, transgender and/or intersex (LGBTI) adolescents and young adults (AYA). The knowledge that LGBTI adults with cancer face unique disparities in healthcare access and poorer outcomes, and that LGBTI AYA have difficulty accessing health services, led a group of researchers to propose that LGBTI young people with cancer likely represent an at-risk patient population. The researchers issue a Call to Action aimed at reducing gaps in AYA cancer care, published in a Perspective article in Journal of Adolescent and Young Adult Oncology (JAYAO), a multidisciplinary peer-reviewed publication from Mary Ann Liebert, Inc., publishers. Click here to read the full-text article free on the Journal of Adolescent and Young Adult Oncology (JAYAO) website through July 24, 2019.

The article entitled "Overlooked Minorities: The Intersection of Cancer in Lesbian, Gay, Bisexual, Transgender, and/or Intersex Adolescents and Young Adults" was coauthored by
Mairghread Clarke, Peter MacCallum Cancer Centre (Melbourne), and colleagues from The University of Melbourne and Royal Melbourne Hospital, Melbourne Health, Australia.

The researchers remark on the special challenges that can accompany cancer during the developmental years of adolescence and young adulthood, including issues such as body image, mental health, and youths' emerging independence and autonomy. All of these can further compound the difficulties faced by AYAs with cancer who identify as LGBTI. The article provides a detailed look at broader LGBTI health disparities, discrepancies in access to care, and health service barriers. The Call to Action offers a blueprint for change that begins with acknowledging the risks, identifying the challenges, and specifying recommendations to lessen the gap.

"LGBTI adolescents and teens are already challenged by barriers to healthcare access. Add a life-threatening cancer diagnosis, and you can see that the burden is enormous," says Editor-in-Chief of JAYAO Leonard S. Sender, MD, University of California, Irvine and CHOC Children's Hospital Hyundai Cancer Institute, Orange, CA. "We must not tolerate poorer outcomes for this group with unique needs; we must acknowledge the problem, we must identify the risks, and we must adapt our practice of medicine accordingly."

A prevailing theory in neuroscience holds that people make decisions based on integrated global calculations that occur within the frontal cortex of the brain.

However, Yale researchers have found that three distinct circuits connecting to different brain regions are involved in making good decisions, bad ones and determining which of those past choices to store in memory, they report June 25 in the journal Neuron.

The study of decision-making in rats may help scientists find the roots of flawed decision-making common to mental health disorders such as addiction, the authors say.

"Specific decision-making computations are altered in individuals with mental illness," said Jane Taylor, professor of psychiatry and senior author of the study. "Our results suggest that these impairments may be linked to dysfunction within distinct neural circuits."

Researchers used a new tool to manipulate brain circuits in rats while they were making choices between actions that led to them receiving rewards or no rewards. The authors found decision-making is not confined to the orbital frontal cortex, seat of higher order thinking. Instead, brain circuits from the orbital frontal cortex connecting to deeper brain regions performed three different decision-making calculations.

"There are at least three individual processes that combine in unique ways to help us to make good decisions," said Stephanie Groman, associate research scientist of psychiatry and lead author of the research.

Groman says an analogy would be deciding on a restaurant for dinner. If restaurant A has good food, one brain circuit is activated. If the food is bad, a different circuit is activated. A third circuit records the memories of the experience, good or bad. All three are crucial to decision-making, Groman says.

For instance, without the "good choice" circuit you may not return to the restaurant with good food and without the "bad choice" circuit you might not avoid the restaurant with bad food. The third "memory" circuit is crucial in making decisions such as whether to return to the restaurant after receiving one bad meal after several good ones.

Alterations to these circuits may help explain a hallmark of addiction - why people continue to make harmful choices even after repeated negative experiences, researchers say.

The Yale researchers previously showed that some of the same brain computations were disrupted in animals that had taken methamphetamine.

"Because we used a test that is equivalent to those used in studies of human decision- making, our findings have direct relevance to humans and could aid in the search for novel treatments for substance abuse in humans," Groman said.

They have been called the 'time bomb' of cardiology - ascending aortic aneurysms grow for decades without any warning signs and can be fatal once they rupture. They have taken the lives of well-known actors Alan Thicke and John Ritter and are a leading cause of death in North America.

In a new study published in EBioMedicine, researchers at Western University and Lawson Health Research Institute demonstrate what might be causing these aneurysms and potentially how to treat them.

It is known that these aneurysms are caused by the thinning of the aortic wall which weakens it and makes it silently grow like a balloon over time without any symptoms. If caught early enough, they can be surgically repaired at low risk, but if they go undetected, which many do, they will eventually rupture or cause a tear in the wall of the aorta, called an aortic dissection.

While the phenomenon is well documented, the medical community previously had little evidence to understand the mechanisms causing it to occur or how to prevent it.

Now, researchers at Lawson and Western' s Schulich School of Medicine & Dentistry have shown that a process that is recognized in cancer biology is causing the cells to become destructive and eat away at the surrounding muscle tissue, weakening the aortic wall.

"We discovered that within the wall of the aorta, a small proportion of the muscle cells have undergone remarkably fast aging and they have aged so much that they've gone into a state called senescence. Rather than die, these senescent cells become destructive, secreting enzymes that chew the area around them," said Dr. Geoffrey Pickering, professor at Schulich Medicine & Dentistry, scientist at Robarts Research Institute and associate scientist at Lawson.

This is important because this opens up the possibility for strategies to prevent it from occurring. Dr. Pickering points to a line of research aimed at developing therapies that flush out these inactive cells.

"There are select research groups around the world that are coming up with compounds that have shown promise in clearing out senescent cells. They are thinking about it for certain aging-related diseases, but it could be positioned for this important problem as well," he said.

Partnering with cardiac and aortic surgeon Dr. Michael Chu, Professor at Schulich Medicine and Associate Scientist at Lawson, Dr. Pickering examined human tissue from enlarged aortas that had been surgically removed from patients before they ruptured. This group of patients have a genetic variance that causes them to have bicuspid aortic valve, and puts them at much greater risk for ascending aortic aneurysms. Bicuspid aortic valve disease is the most common congenital valve abnormality, occurring in approximately one to two percent of the general population.

"Half of patients with bicuspid aortic valve disease will develop an ascending aortic aneurysm in their lifetime," said Dr. Chu. "In some patients, their aneurysms grow rapidly, and in others they grow very slowly. Better understanding the mechanism contributing to ascending aortic aneurysm's behaviour and growth will help us not only better prognosticate natural history of these aneurysms, but hopefully, lead us to new treatment options to slow or halt the growth of these aneurysms and hopefully avoid the catastrophic risks of aortic rupture or dissection."

Glioblastomas, the deadliest type of brain tumor in adults, attract "turncoats." These are macrophages, a type of immune cell, which promote tumor progression and mask tumors from the immune system's scrutiny. To better understand the cells that brain tumors recruit, scientists led by Dolores Hambardzumyan, PhD, developed advanced imaging techniques to visualize macrophages found in the brain tumors of living mice.

The results were published Monday, June 24 in PNAS.

The researchers demonstrated that depending on where these macrophages originated, their appearance and behavior vary significantly. Hambardzumyan and her colleagues say their results provide support for a strategy that would block macrophage infiltration into brain tumors as part of cancer treatment.

"This research provides the scientific community with a novel mouse model to study the populations of glioblastoma-associated macrophages both separately and together," Hambardzumyan says. "Our results also demonstrate the efficacy of blocking macrophage infiltration and calls for the use of combination therapies to enhance patient survival."

Hambardzumyan is associate professor of pediatrics at Winship Cancer Institute of Emory University and Aflac Cancer and Blood Disorders Center at Emory and Children's Healthcare of Atlanta.

Tumor-associated macrophages come from two distinct sources. They can come from the peripheral blood supply, or they can be microglia: cells that are already resident within brain tissue. The Hambardzumyan lab has previously demonstrated macrophages coming from the blood are much more prevalent in number and aggressive in behavior, compared to macrophages coming from the brain.

"In order to develop more effective immunotherapies to treat glioblastoma, we must first understand the properties of each of these macrophage populations individually rather than treating them as one homogenous entity," says Zhihong ("Z") Chen, PhD, a postdoctoral instructor and the co-first author of the paper.

The researchers developed a mouse model which allows them to observe infiltrating macrophages in real time inside the tumor. The mice are genetically modified (also, some received bone marrow transplants) so that only particular groups of macrophage cells produce fluorescent proteins, making peripheral blood-derived macrophages or brain microglia visible under a microscope.

The team installed a clear imaging window made of thin glass over the brain tumor and utilized advanced techniques including two-photon imaging to observe macrophages over time as they move through and interact with the tumor. They were able to image cells as deep as 500 micrometers in the tumor and up to several hours at a time.

The researchers found clear morphological and behavioral differences between macrophages coming from the blood and brain resident macrophages. They showed blood derived macrophages are smaller, more motile cells that zip around the tumor along blood vessels. On the contrary, they found brain-resident macrophages to be large, highly branched, and immobile cells that have minimal migratory behavior.

To test the efficacy of blocking the infiltration of the blood derived macrophages, they treated mice with a drug (anti-VEGF antibody or bevacizumab) that normalizes the irregular vasculature of glioblastomas. This drug has been used in the clinic to treat glioblastoma and improve quality of life in patients. The research team observed fewer macrophages in the tumors that were treated, and they observed an increase in survival in these mice. They also observed a morphological switch in the macrophages, indicating that not only can the infiltration of these cells be inhibited but their state of differentiation may also be affected.

Despite aggressive therapeutic strategies, the average survival for patients with glioblastoma is only 12 months. One reason for this dismal outcome is that current therapeutic strategies fail to effectively target properties of other cell types within the tumor, such as tumor-associated macrophages. The Hambardzumyan lab is now actively seeking to find new therapeutic approaches, such as blocking macrophage infiltration in combination with immune checkpoint inhibitors to treat these deadly brain tumors.

Researchers from Aarhus University and Aarhus University Hospital have succeeded in using mice with a transplanted human immune system to study functions in the immune system which are otherwise particularly difficult to study. The method could turn out to be important in further research into e.g. cancer, HIV and autoimmune diseases.

When it comes to research, there can certainly be a long way from mice to humans. So, what are researchers to do when they need to study the immune system's convoluted response when it meets serious diseases, but can't give trial subjects diseases such as HIV, cancer or psoriasis so they can study how the body reacts?

Researchers at Aarhus University and Aarhus University Hospital have succeeded in transplanting human stem cells into mice whose own immune system is disabled, and then triggering a type of reaction in the immune system which normally reacts to meeting a range of viruses and bacteria. These reactions are partly controlled by the protein STING (the stimulator of interferon genes), which can recognise the DNA of foreign microorganisms in infected cells and signal to the immune system that it should react to this and defend the body. The protein plays a role in connection with e.g. cancer, a number of autoimmune diseases such as lupus and psoriasis, and also with viral and bacterial infections.

"The humanised mice are an important tool in understanding how human immune cells behave during diseases and how they react to different medical treatments. So being able to show that it's possible to study human STING in mice is an important step. We hope this will lead to better research into diseases that are related to STING," explains Anna Halling Folkmar Andersen, PhD student at the Department of Clinical Medicine at Aarhus University and one of the researchers behind the study, which has just been published in the scientific journal Immunology.

Hope for new treatments

STING is a central part of the innate immune system, and many researchers are currently looking closely at the protein.

"Within inflammatory research, STING is currently one of the great hopes. Around the world, researchers are working to understand how STING works, so it will be possible to utilise it in the development of a range of new treatments for a wide range of diseases," says Anna Halling Folkmar Andersen.

Autoimmune diseases such as psoriasis and lupus are characterised be an overactive immune system and excessive STING activity, which is why researchers might be interested in studying the effects of curbing STING. On the other hand, others hope to be able to activate STING in cases of cancer diseases, as it could help to fight tumours more effectively. This is because the immune system becomes exhausted by cancer diseases, meaning that STING does not fight the disease by itself and therefore may need a boost in the form of immunotherapy to fight the disease.

When a patient complains about chest pain, diagnosis will usually involve catheter angiography to evaluate the adequacy of blood supply to the heart. Researchers from Charité - Universitätsmedizin Berlin have now established that, in certain cases, the diagnostic reliability of non-invasive coronary computed tomography (CT) angiography is as good as that of coronary angiography - thereby dispensing with the need for invasive procedures. Results from this research have been published in The BMJ*.

Symptoms such as dull chest pain or a feeling of tightness in the chest may be indicative of coronary artery disease (CAD), a condition which develops when a narrowing of the coronary arteries limits the blood supply to the heart muscle. In the worst-case scenario, CAD can lead to a life-threatening heart attack or sudden cardiac death. Prompt diagnosis is therefore essential.

Until now, patients with suspected CAD have often been examined using cardiac catheterization for coronary angiography, a procedure that involves a tube (catheter) being inserted into a blood vessel via a small incision in the groin or arm and then advanced to the heart. The advantage of this method is that it combines diagnosis with treatment: if a narrowed segment is detected, the intervention to open up the affected artery can be performed immediately. However, the procedure is not without its risks, and out of a total of 880,000 patients who undergo the procedure in Germany every year, 58% do not require such an intervention. Led by Charité, an international research consortium has now been able to show that, in certain patients, an equally accurate diagnosis can be achieved using cardiac CT angiography - a non-invasive imaging method.

Research groups from 22 countries worked together to analyze the data of more than 5,300 patients from a total of 65 completed studies. Their analysis revealed that coronary CT angiography is a suitable diagnostic technique in patients with a low to intermediate probability of CAD. "Physicians can determine a patient's probability of having CAD using individual factors such as age, sex and type of chest pain," says study lead Prof. Dr. Marc Dewey, Deputy Head of the Department of Radiology on Campus Charité Mitte. "If this probability is between 7 and 67 percent, coronary CT angiography will provide a reliable diagnosis as to whether or not the patient has narrowed arteries. Cardiac catheterization is indicated in patients with higher probabilities, as these patients are likely to need an intervention."

"Cardiac CT is a gentle technique, which only lasts a few minutes," emphasizes the study's first author, Robert Haase, a doctoral student and member of Prof. Dewey's research group. The technique involves a circular X-ray machine taking 1,000 images per second from various angles. These images are then combined to produce a 3D reconstruction of the heart. Contrast agents are used to make the coronary arteries clearly visible. "Our work shows that, in both men and women, this method is capable of clearly visualizing narrowed segments," adds Robert Haase.

"Our findings will make it easier for physicians to determine which patients may benefit from having a coronary CT angiogram rather than a catheter-based procedure to diagnose coronary artery disease," says Prof. Dewey. The radiologist also hopes that the study will contribute to the harmonization of clinical practice guidelines. Country-specific guidelines continue to vary in terms of courses of action recommended when dealing with suspected CAD.

Understanding how the weather and climate change is one of the most important challenges in science today. A new theoretical study from associate professor, Jan Härter, at the Niels Bohr Institute, University of Copenhagen, presents a new mechanism for the self-aggregation of storm clouds, a phenomenon, by which storm clouds bunch together in dense clusters. The researcher used methods from complexity science, and applied them to formerly established research in meteorology on the behavior of thunderstorm clouds. The study is now published in Geophysical Research Letters.

The life and death of a storm cloud

When the sun warms up the surface of the ocean, warm, humid air rises from the ocean surface, forming tall, columnar thunderstorm clouds, which reach heights of approximately 12 km and measure typically only a few kilometers across. As these clouds produce rain, some of it evaporates and cools the local area under the cloud. By this, the initial circulation of air, forming the cloud, is shut down and the cloud dissipates. If it were this simple, this should be the end of the thunderstorm cloud. However, the dense air below the cloud needs to equilibrate with less dense air surrounding it: "Cold air is denser, and it spreads away from the cloud. Gust fronts are formed which can collide with gust fronts from other clouds. As a consequence the air rises up, and new clouds are produced. This means that areas where sufficiently many clouds are, are more likely to set off additional clouds", Jan Härter explains (Illustration 1). "Areas with fewer clouds exhibit further reduction of clouds. As energy needs to enter the system, and since energy comes from the sunlight, there is a limit to how big the cloud lumps can grow - so we put a constraint into our model. The result is that cloud clusters form, with cloud-free regions in between. This is also seen in observations for the tropical ocean."

Combining theory with real world phenomena

Building models is purely theoretical, but still manages to explain a phenomenon. "It is a theoretical argument, a suggestion for a mechanism that can now be tested. Clustering of thunderstorm clouds has been observed in the real world, but still lacks a scientific explanation. If we contrast two extreme cases, where one cloud is created, it ends up shutting itself down. Then statistical mechanics says no convective self aggregation will take place. Comparing this to another model where two clouds create another one, aggregation can take place. That's basically what the theoretical model can do". Jan Härter goes on: "This type of self organization is hugely interesting and can occur in a range of systems from biology to magnetism.

Preparing for the destructive force of the weather

Tropical meteorology is, due to the strong interaction of clouds with solar irradiation there, relevant for climate change. More clustering in a future climate might affect how much the ocean warms, relative to the rate seen today. Prediction of clustering of storm clouds could affect the weather in Denmark as well, and fairly recent events in Denmark with surprise flash floods, flooded sewers and basements, and damage to infrastructure has prompted questions on the origin of such sudden floods. Deeper understanding of how clouds interact could shed new light on the occurrence of such floods.

WEST HILLS, Calif. (June 25, 2019) - Pharmavite LLC, the makers of Nature Made vitamins, minerals and supplements, announced the publication of a review paper in the May issue of the journal Nutrients, highlighting current research into the roles of choline and docosahexaenoic acid (DHA) in maternal and infant nutrition.

National data shows that most adult Americans, more than 90%, do not have adequate dietary intake of choline and DHA, this is found to be especially true in women of child-bearing age and pregnant women. Choline and DHA play a significant role in infant brain and eye development, with inadequate intakes leading to visual and neurocognitive deficits.

The review paper findings suggest a link between intake of DHA and choline, and that an inadequate intake of one or both nutrients may have an impact on baby's brain and eye development. Furthermore, emerging findings illustrate a synergistic interaction between choline and DHA, indicating that insufficient intakes of one or both could have lifelong impact on both maternal and infant health, particularly brain health. Therefore, supplementation of DHA and choline, particularly for vulnerable populations including women during pregnancy and lactation, should be considered.

"This review paper suggests that prenatal care can be improved with a greater understanding of maternal nutrient needs and how an individual's dietary intake, as well as their genetic and lifestyle factors, may impact metabolism of these important nutrients," said Susan Hazels Mitmesser, PhD, vice president of science & technology at Pharmavite. "As part of prenatal care, it may be beneficial to include testing of key nutrients such as DHA and choline, to ensure adequate intake levels are being met."

Leading health organizations including American Congress of Obstetricians & Gynecologists (ACOG), American Academy of Pediatrics (AAP), Europe Food Safety Authority (EFSA), and World Health Organization (WHO) have highlighted the importance of several key nutrients during pregnancy, including choline and DHA. The 2018 AAP policy statement emphasized the role of nutrition in the first 1000 days of life, including choline and DHA as key nutrients in supporting early neurodevelopment and lifelong mental health.

By analyzing records in countries of the Amazon and Orinoco basins--which include Brazil, Venezuela, Colombia, Bolivia, Peru and Ecuador--a paper published today in Oryx--The International Journal of Conservation, categorized 85 past and present initiatives or projects that work to preserve the South American River Turtle, or charapa (Podocnemis expansa), a critically endangered species. These projects are protecting more than 147,000 female turtles across the basin, an unprecedented figure.

The paper "On the future of the giant South American river turtle, Podocnemis expansa" was drafted by 29 Latin American researchers and scientists, including WCS's German Forero Medina, Camila R. Ferrara, and Camila K. Fagundes, Ruben Cueva, and Brian D. Horne. The collaboration stems from a 2014 workshop held in Balbina, Brazil in which park rangers, indigenous people, and conservationists from the six countries provided information on their work to protect the charapa. The efforts discussed in that continental meeting and subsequent study reveal the serious commitment of public and private entities to conserve the species.

The charapa is considered the largest river turtle in South America. It inhabits the tributaries of the Amazon and Orinoco river basins, and is an important cultural symbol for many communities in the region. It also has great ecological importance for ecosystems, as it helps transport fruits and seeds along the rivers and serves as prey for birds, catfish, foxes, jaguars, alligators, and water dogs. In the twentieth century, hundreds of thousands of turtles spawned on beaches throughout the continent.

Despite their local importance and past abundance, turtle populations are still threatened by the hunting and collection of adults and juveniles, looting of nests, the illegal trafficking of hatchlings to be used as pets, and the use of inappropriate fishing gear which can harm or kill individuals. In addition, broader degradation of their habitat is contributing to their decline.

Germán Forero, Scientific Director with WCS Colombia and lead author, called for the creation of a protection network for the charapa--a regional monitoring program that would link technical information and lessons learned among all the projects in the six countries. He noted the importance of communities in this future network.

"The participation of local communities that live with the charapa is essential to protecting them," said Forero. "They live side by side with the turtles and are interested in controlling or preventing the commercialization of eggs or meat to ensure the ongoing sustainability of the species as a food source and important part of their culture."

Camila Ferrara, co-author and researcher with WCS Brazil, added that the formation of this network would be extraordinary, because it would allow stakeholders to design and assess methodologies for management and conservation of the species, from its gestation and protection of nesting beaches to population monitoring.

In Brazil, the charapa is not considered critically endangered, but a near-threatened species. Ferrara explains that although Brazil is home to important populations of the species, the turtle is still the second most consumed vertebrate group in the Amazon, surpassing even some fish. Therefore, she believes that the network should focus their efforts on strengthening environmental education in Brazil to ensure the sustainability of the reptile's consumption.

Ferrara said: "We are seeing positive results as work progresses, as communities are expressing greater interest in working with turtles. We have seen a decrease in the consumption of eggs, an important achievement that we must replicate throughout the continent."

The paper highlights the importance of the monitoring conducted by the Brazilian Institute of the Environment and Renewable Natural Resources (IBAMA), which provides the only way to assess the trends of populations over time and thus is valuable information for decision-making on the species.

In Colombia, initiatives are working to protect at least two large populations, one in the Caquetá River in the Amazon basin and another in the Meta River in the Orinoco basin. In both areas, local communities are committed to protecting the nesting females at beaches, and these programs are expected to receive continued support over time.

Going forward, the proposed network plans to develop a platform that can serve as an observatory of the species, tracking population trends across the basin over time to prioritize intervention sites and ensure the long term conservation of the species.

This paper reviews a diversity of initiatives that seek to recover these turtle populations. Rick Hudson, President of the Turtle Survival Alliance (TSA), believes that interest in protecting the charapa in South America comes at an opportune moment, as there are still robust populations of river turtles to protect; this is not the case in Asia, where many of turtle species have gone extinct.

Hudson said: "The lesson is clear: protect the habitat and large nesting aggregations of river turtles now and avoid crisis management in the future. This paper makes a strong case for improving levels of protection while there is still time."

Examining fossilised pigments, scientists from the University of Bristol have uncovered new insights into blue colour tones in prehistoric birds.

For some time, paleontologists have known that melanin pigment can preserve in fossils and have been able to reconstruct fossil colour patterns.

Melanin pigment gives black, reddish brown and grey colours to birds and is involved in creating bright iridescent sheens in bird feathers.

This can be observed by studying the melanin packages called melanosomes, which are shaped like little cylindrical objects less than one-thousandth of a millimetre and vary in shape from sausage shapes to little meatballs.

However, besides iridescent colours, which is structural, birds also make non-iridescent structural colours.

Those are, for example, blue colour tones in parrots and kingfishers. Until now, it was not known if such colours could be discovered in fossils.

This blue structural colour is created by the dense arrangement of cavities inside feathers, which scatters the blue light. Underneath is a layer of melanin that absorbs unscattered light.

Paleontologists have shown that the feather itself, which is made of keratin, does not fossilise while the melanin does. Therefore, if a blue feather fossilised, the dark pigment may be the only surviving feature and the feather may be interpreted as black or brown.

Now researchers from the University of Bristol, led by Frane Barbarovic who is currently at the University of Sheffield, have shown that blue feather melanosomes are highly distinct from melanosomes that are from feathers expressing black, reddish-brown, brown and iridescent, but overlap significantly with some grey feather melanosomes.

By looking at plumage colourations of modern representatives of fossil specimen and reconstructing which colour was the most likely present in the fossil specimen, they were able to discriminate between melanosomes significant for grey and blue colour, leading to the reconstruction of prehistoric Eocoracias brachyptera as a predominantly blue bird.

Frane Barbarovic said: "We have discovered that melanosomes in blue feathers have a distinct range in size from most of colour categories and we can, therefore, constrain which fossils may have been blue originally.

"The overlap with grey colour may suggest some common mechanism in how melanosomes are involved in making grey colouration and how these structural blue colours are formed.

"Based on these results in our publication we have also hypothesized potential evolutionary transition between blue and grey colour."

The research team now need to understand which birds are more likely to be blue based on their ecologies and modes of life. The blue colour is common in nature, but the ecology of this colour and its function in the life of birds is still elusive.

Frane Barbarovic added: "We also need to understand how grey colour is made. This is made in a very different way in birds than it is in mammals. We believe it is related to how the melanosome shape can result in a kind of self-assembling process in the feather and the surface tension of the melanosomes pull them into certain configurations inside a feather as it forms."

Millions of acres of pine woodlands once covered a large portion of the Midwest. But as humans logged these trees and suppressed natural fires, the woodlands gave way to dense forests with thick leaf litter and tree species that were less fire-resistant, leading to more intense and unpredictable fires as well as the loss of native bird habitats.

Now, researchers from the University of Missouri have shown in a new study that restoration of pine woodlands, through the combined use of intentional, managed fires and strategic thinning of tree density, has a strikingly beneficial effect on a diverse array of birds, some of which are facing sharp declines from human-driven impacts like climate change and habitat loss.

"Some people might hear the words 'fire' and 'thinning' and immediately imagine charred, flattened wastelands, but that isn't the reality," said Melissa Roach, now a researcher with the U.S. Geological Survey's Bird Banding Lab who carried out the study while completing her master's degree at MU. "Researchers are using these management techniques to restore beautiful open woodlands. In this study, we found that birds that have been struggling elsewhere are positively thriving in these restored areas."

Frank Thompson, a wildlife biologist with the USDA Forest Service and cooperative professor at MU's College of Agriculture, Food and Natural Resources with more than two decades of experience studying Midwestern bird populations, worked with Roach to survey 16 bird species in varying degrees of pine woodland density. These woodlands were located in parts of Missouri, Arkansas and Oklahoma in the Ozark-Ouachita Mountain Complex. Unlike most studies, Roach returned to the same locations three years in a row to monitor the bird populations over time.

The researchers found that the restored pine woodland created an open canopy and a lush ground layer, and was ideal for allowing a balance between species that prefer less tree density and canopy cover with those that prefer more. Several of the birds that were observed thriving in this habitat are in decline elsewhere, including the Red-headed Woodpecker and the Prairie Warbler. Only five species were impacted negatively by restoration, but these remain abundant in the untreated forests that still dominate the Midwest.

Researchers also isolated two management practices--controlled fires and tree thinning--to determine their individual effects on bird abundance. Eight of the 16 species of birds, including the Red-headed Woodpecker, were more numerous in areas with a history of fires, while four species benefitted from thinning. Taken together, Thompson said the results suggest that restoring pine woodlands in conjunction with prescribed fires and tree thinning can create suitable habitats for a wide range of birds.

"Our study shows that restoration using fire and tree-thinning leaves large, widely-spaced trees for canopy-nesting species while allowing the development of grasses and shrubs for ground or shrub-nesting species," Thompson said. "Given that we took care to survey birds with diverse breeding requirements, we can see that restored pine woodlands can support many different birds with different needs, whether they nest on the ground, in shrubs or high in the canopies of mature trees. This is a powerful testament to the need to continue restoring these woodlands, which are also rich in plant diversity and likely more sustainable in many cases than closed forests under climate change."

When you think of national parks, you might picture the vast plateaus of the Grand Canyon, the intricate wetlands of the Everglades, or the inspiring viewscapes of the Grand Tetons. You probably don't envision 100 million pounds of mashed water bottles, barbecue-smudged paper plates, and crumpled coffee cups - but that is the staggering quantity of garbage that is generated in our National Parks each year. And handling that amount of waste is becoming a huge problem.

The quantity of waste produced and how park visitors dispose of it (recycling some materials) is a growing concern for park managers. Handling park waste costs money, involves significant effort, and requires human and natural resources that tax parks to the extreme. And with numbers of visitors increasing, managers are looking for strategies to increase diversion of recyclable materials from landfills and reduce the overall amount of waste produced in national parks.

"Many park managers prefer to take a light-handed approach to these kind of challenges - using strategies like better communication rather than enforcement," said Zach Miller from the Institute of Outdoor Recreation and Tourism at USU, and lead author on recently published research on this topic. "This style of management requires fewer resources, leaves visitors happier, and matches the independent park experience people are seeking in these places."

Waste management has been studied in urban settings, but it is new territory for national parks. That's why the Leave No Trace Center for Outdoor Ethics, the organization leading the Zero Landfill Initiative research project, reached out to Miller and Dr. Derrick Taff at Penn State University to collaborate on studies in three national parks to better understand what kinds of strategies might work to reduce the amount of waste generated in parks while also diverting more recyclable materials away from landfills.

Yosemite, Grand Teton, and Denali National Parks were used as field sites for this study. These iconic parks host millions of visitors each year, and offer stunning flora and fauna, iconic viewscapes, and historic park infrastructures. Each park unit faces unique waste management challenges, and different waste processing and diversion processes (e.g. single stream recycling, source separated recycling, etc.).

There are definable reasons people choose to drop their soda can in a recycling bin rather than a trash can ... moral beliefs, peer pressure, convenience ... and reasons people choose not to recycle. In the survey, Miller and colleagues worked to pinpoint exactly what held people back. They found two issues that had a significant impact on behavioral intentions related to waste: moral norms and perceived difficulty.

"Perhaps the most important finding from this research is that people's perceptions and reported behaviors are largely in line with proper disposal of waste and recyclable materials," said Ben Lawhon, lead researcher with the Leave No Trace Center. "Many visitors are predisposed to be environmentally responsible and follow behaviors that benefit and protect national parks. Parks need to reinforce messages of moral responsibility and make it easy for them to dispose of waste properly."