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In recent years it has been increasingly appreciated that immune cells within the tumor microenvironment contribute to tumor progression and, importantly, to the tumor's response to therapy. To better understand the specific roles different immune cell types play, a multi-institutional team led by researchers at Baylor College of Medicine profiled the immune cell composition of multiple murine models and clinical datasets of triple negative breast cancers.

Focusing on two types of immune cells, neutrophils and macrophages, they found large diversity in the cells' frequency, including neutrophil-enriched and macrophage-enriched groups whose functionality suggested potential roles in immunotherapy. The work highlights that heterogeneity of both tumor cells themselves and immune composition of the microenvironment are important considerations for therapy. The report appears in the journal Nature Cell Biology.

"We know that breast cancer is very heterogeneous. For many years we have recognized different subtypes of breast cancer, for instance, estrogen receptor positive (ER+), ER- and triple negative, and these categories can be further divided into subcategories. To that, we now have to add the diversity of the immune cell component in the tumor microenvironment," said corresponding author Dr. Xiang 'Shawn' Zhang, professor at the Lester and Sue Smith Breast Center and member of the Dan L Duncan Comprehensive Cancer Center at Baylor College of Medicine.

With the goal of better understanding the role immune cells within tumors play in tumor growth and in response to therapy, Zhang and his colleagues conducted a series of analyses to characterize the immune cell composition of tumor microenvironments in eight murine models and in clinical datasets of triple negative breast cancers.

"Focusing on neutrophils and macrophages, we investigated whether different tumors had the same immune cell composition and whether seemingly similar immune components played the same role in tumor growth. Importantly, we wanted to find out whether differences in immune cell composition contributed to the tumors' responses to immunotherapy," said Zhang, a McNair Scholar at Baylor.

The researchers found large diversity in the frequency of neutrophils and macrophages among the tumor samples, including some tumors that preferentially attracted macrophages, while others attracted more neutrophils. The predominance of one cell type over the other can be explained in part by the type of molecules produced by the tumor. As Zhang explained, some tumors secrete molecules that attract macrophages, while other tumors produce other molecules that lure neutrophils to the tumor site.

Interestingly, macrophages and neutrophils seem to work against each other.

"Once one type of cell starts accumulating in the tumor, the other will tend to stay away," Zhang said. "What supports one type of cell, does not seem to support the other."

Exploring the roles macrophages and neutrophils play in tumor growth revealed that in some tumors macrophages favored tumor growth, while in others they helped control it. Neutrophils, on the other hand, tended to promote tumor growth.

"These findings are just the beginning. They highlight the need to investigate these two cellular types deeper. Under the name 'macrophages' there are many different cellular subtypes and the same stands for neutrophils," Zhang said. "We need to identify at single cell level which subtypes favor and which ones disrupt tumor growth taking also into consideration tumor heterogeneity as both are relevant to therapy."

The remarkable ability of a small Australian sea snail to produce a colourful purple compound to protect its eggs is proving even more remarkable for its potential in a new anti-cancer pharmaceutical.

Researchers at Flinders University, Southern Cross University and Monash University in Australia have isolated one compound in the gland secretions from the Australian white rock sea snail (Dicathasis orbita) which has not only antibacterial and anti-inflammatory qualities, but important anti-cancer properties.

"After a decade of work, we have found an active compound derived from the substance produced by the mollusc's gland which could be used as a preventative in bowel cancer," says senior lead scientist Professor Catherine Abbott from Flinders University. "We're very excited about these latest results and hope to attract investment from a pharma company to work on a new drug to reduce development of colorectal cancer tumours."

Using the latest mass spectrometry technology, the research team has been able to pinpoint the lead active compound which, in future, could be put to good work.

Colorectal cancer is the second leading cause of the 9.6 million cancer deaths every year, with the World Health Organization reporting 862,000 deaths in 2018.

Natural compounds from marine and terrestrial plants and animals are valuable sources of current and future medicines for human health, says Southern Cross University marine scientist Professor Kirsten Benkendorff, who is also researching the potential of replicating the snail species' anti-inflammatory compound.

"In this latest research we have not only show that a specific snail compound can prevent the formation of tumours in a colon cancer model, but we were also able to use sophisticated technology to trace the metabolism of the compound inside the body," says Professor Benkendorff. "This is very important for drug development because it helps demonstrate the absence of potentially toxic side-effects".

Along with tracking the active compound inside the body to confirm it reaches the colon where is has the anti-tumor effect - which is important for oral drug delivery - the snail compound comes from a class of compounds called "indoles" which are commonly found in both natural plant medicines and some pharmaceuticals.

"We were able to use the fact that snail compound contains bromine like a unique fingerprint to trace how these types of compounds are metabolised inside the body and identify some potentially toxic metabolites from the crude extracts that were not found with the pure snail compound," Professor Benkendorff adds.

"This research is very important for understanding the safety of these types of natural compounds for human medicine."

Vaccinating older adults against shingles in Canada is likely cost-effective, according to a study in CMAJ (Canadian Medical Association Journal), and the Shingrix vaccine appears to provide better protection than the Zostavax vaccine.

Herpes zoster, or shingles, affects about 1 in every 3 adults, causing a painful rash that can result in long-term pain in 8% to 27% of people.

The study used a model to compare the effectiveness and cost-effectiveness of the recombinant subunit (RZV, Shingrix) and live attenuated zoster (LZV, Zostavax) vaccines in adults aged 50 years and older in Canada. The LZV vaccine has been available in Canada since 2008, and RZV was approved in 2017.

The number of people needed to be vaccinated to prevent one case of shingles was lower for RZV (Shingrix) than for LZV (Zostavax) for all ages. For example, in people aged 60 years, the number needed to vaccinate was 18 for RZV and 78 for LZV.

"Our model predicted that the recombinant subunit zoster vaccine is likely cost-effective in Canada for adults 60 years or older and that it provides greater health benefits than the live attenuated zoster vaccine for all age groups," writes Dr. Marc Brisson, Centre de research du Centre hospitalier de l'Université de Québec and the Université Laval, Québec, Quebec, with coauthors.

The study results are consistent with other economic evaluations in the United States and the Netherlands.

DALLAS, Aug. 26, 2019 -- Survivors of childhood cancer have a higher risk of developing a range of heart disease due to cancer therapy, according to new research published in the American Heart Association's journal Circulation.

Most studies of this survivor group have focused on heart failure related to anthracyclines, a class of chemotherapy medications used to treat many types of cancer. In this new study, researchers used data from Ontario's health care system to investigate the full spectrum of heart disease subtypes in close to 7,300 childhood cancer survivors (diagnosed at an average age of 7) - compared to more than 36,000 people of the same age, gender and postal code without cancer. Heart disease studied included coronary artery disease, arrhythmias, valve abnormalities, cardiomyopathy, heart failure and pericardial disease.

Researchers found that, even at relatively young ages, childhood cancer survivors have up to a threefold increase for any cardiac event and up to a tenfold increased risk for heart failure when compared to their cancer-free peers. Additionally, survivors exposed to higher doses of anthracycline chemotherapy, as well as those diagnosed with diabetes, hypertension or both, are significantly more likely to experience heart disease as adults.

"While anthracycline chemotherapy may induce heart disease, many patients require this cancer treatment to survive," said Paul Nathan, M.D., M.Sc., senior author of the study and staff oncologist in the division of hematology/oncology and senior associate scientist in the Child Health Evaluative Sciences program at The Hospital for Sick Children (SickKids) in Canada.

"Doctors should address heart disease risk factors - such as diabetes and hypertension - that can be modified," said Nathan, who is also a professor in the pediatrics and health policy, management & evaluation departments at the University of Toronto.

Childhood cancer survivors appear to have a higher likelihood of metabolic conditions such as diabetes, hypertension and unhealthy levels of one or more kinds of lipid (fat) in the blood. These modifiable risk factors appear to interact with chemotherapy or radiation that may be toxic to the heart, prematurely age the heart and accelerate the development of heart disease.

"The close connections between lifestyle, metabolic disorders and cardiac disease warrant careful follow-up and monitoring of the childhood cancer survivor population," Nathan said.

Researchers used the Pediatric Oncology Group of Ontario Networked Information System (POGONIS), a provincial pediatric cancer registry, to identify five-year cancer survivors who were diagnosed before age 18 and treated in a pediatric cancer center between 1987 and 2010. Each childhood cancer survivor was matched to five cancer-free peers for the purposes of this comparative study. During an average of 10 years of follow-up, nearly 3% of childhood cancer survivors experienced one or more cardiac events, compared to less than 1% of those without cancer.

Researchers were unable to assess lifestyle factors such as smoking, physical activity, diet and alcohol use. A more comprehensive understanding of these and other modifiable factors and their impact on cardiovascular disease among childhood cancer survivors could be gained through future work involving the use of data from multiple sources.

Since its rediscovery and characterization in 2004, graphene has been the focus of countless research efforts across multiple fields. It is a very versatile material consisting of a two-dimensional (2D) carbon network; in other words, it comprises a thin sheet of carbon that has a thickness of one atom. Graphene is not only stronger than the strongest steels, but also has a myriad of interesting chemical, electronic, and mechanical characteristics that has left scientists wondering if similar 2D networks of other materials could have such useful properties.

One novel 2D material that was recently reported is borophene, an analogue of graphene but consisting of boron atoms instead of carbon atoms. However, as one would expect for 2D sheets of any material, the synthesis of borophene has proved to be challenging. Researchers either require the use of a substrate to make borophene more stable or coupling boron with hydroxyl groups (OH-), which causes the structure to not be atomically flat.

In a recent study conducted at Tokyo Institute of Technology, a research team including Tetsuya Kambe, Akiyoshi Kuzume and Kimihisa Yamamoto was successful in synthesizing atomically flat oxidized borophene sheets through a simple solution-based method. First, they synthesized stacked layers of borophene oxide through a fairly simple process using a potassium borohydride salt (KBH4). An X-ray analysis revealed the 2D-layered structure of the material, in which layers of boron atoms forming a hexagonal 2D network with oxygen atoms as bridges were intercalated with layers containing potassium atoms. Then, the subsequent necessary step was to find a way to exfoliate atomically thin layers of the borophene oxide network. The researchers achieved this by putting the material in dimethylformamide, which is a commonly used organic solvent. Various types of measurements were carried out to verify the structure of the exfoliated sheets, including electron microscopy, spectroscopy, and atomic force microscopy. The results confirmed that the proposed method was effective for producing the desired atomically flat oxidized borophene sheets.

Finally, the researchers performed resistivity measurements to analyze the conducting properties of stacked borophene sheets and found an interesting characteristic referred to as anisotropy. This means that the sheets exhibited different types of conductivity depending on the direction of the current flow. The material behaved like a semiconductor in the inter-plane direction, whereas it exhibited metal-like behavior in the in-plane direction of the boron network. The mechanisms behind these two types of conducting behaviors were elucidated as well. "It is important to note that our boron sheets can be handled easily at ambient conditions," remarks Dr. Kambe, indicating that this pioneering research could be the basis for finding potential applications for borophene.

Finding facile methods for the synthesis of borophene and borophene-based compounds is crucial to conducting further research on this interesting material and its potential uses. "Like graphene, borophene is expected to have unique properties, including extraordinary mechanical characteristics and metallic behavior that could be exploited in a variety of fields," states Dr. Kambe. Hopefully, future findings and developments on 2D materials will enable us to employ their exotic properties and tailor them to suit our needs.

WASHINGTON, D.C., August 23, 2019 -- When energy is added to uranium under pressure, it creates a shock wave, and even a tiny sample will be vaporized like a small explosion. By using smaller, controlled explosions, physicists can test on a microscale in a safe laboratory environment what could previously be tested only in larger, more dangerous experiments with bombs.

"In our case, it's the laser depositing energy into a target, but you get the same formation and time-dependent evolution of uranium plasma," author Patrick Skrodzki said. "With these small-scale explosions in the lab, we can understand similar physics."

In a recent experiment, scientists working with Skrodzki used a laser to ablate atomic uranium, stealing its electrons until it ionized and turned to plasma, all while recording chemical reactions as the plasma cooled, oxidized and formed species of more complex uranium. Their work puts uranium species and the reaction pathways between them onto a map of space and time to discover how many nanoseconds they take to form and at which part of the plasma's evolution.

In their paper, released this week in Physics of Plasmas, from AIP Publishing, the authors discovered uranium forms more complex molecules, such as uranium monoxide, uranium dioxide and other, larger combinations, as it mixes with different percentages of oxygen.

"We used optical emission and looked at excited states decaying into ground states, but that's only a small fraction of the picture," Skrodzki said.

Uranium, with its 92 electrons and approximately 1,600 energy levels, can produce a complicated spectrum that is hard to decipher, even with high-resolution spectroscopy. In the paper, the authors focused on one energy transition in the plasma. They closely examined the morphology of the plasma plume, collisional interactions with various concentrations of oxygen, and other factors, like plume confinement and particle velocities, to create a detailed picture of species evolution from atomic uranium to more complex uranium oxides.

The resulting data has implications for technologies that use lasers to probe materials and detail their elemental composition, such as the laser spectroscopy system on the Mars Curiosity rover. It can also be used for a portable device for verifying nuclear treaty compliance by testing for evidence of enriched uranium production.

"There's still so much work left to do on this topic," Skrodzki said. "It's a scientific question, because nobody knows anything about the optical emission in the visible region from those higher oxides. We want to try to provide data to fill in those gaps."

Many patients with concussion have normal CT scans and are discharged from the hospital without follow-up. But a blood test that is currently under development and costs a fraction of the price of a brain scan may flag concussion in these CT-negative patients, enabling them to be evaluated for long-term complications.

In a study led by UC San Francisco, researchers tracked 450 patients with suspected traumatic brain injury (TBI) -- which includes concussion or mild TBI -- who had been admitted to one of 18 level 1 trauma centers throughout the nation. The patients, whose injuries were mainly attributed to traffic accidents or falls, all had normal CT scans, according to the study publishing in The Lancet Neurology on Aug. 23, 2019.

Within 24 hours of their accidents, the patients had their blood drawn to measure for glial fibrillary acidic protein, a marker correlating to TBI. The study used a device by Abbott Laboratories called i-STAT™ Alinity™, a handheld portable blood analyzer, currently unavailable in the U.S., that produces test results in minutes.

The researchers later confirmed the blood test results against MRI, a more sensitive and expensive scan that is not as widely available as CT but offers a more definitive diagnosis of TBI. They found that 120 of these 450 patients (27 percent) had an MRI that was positive for TBI.

'Patients with TBI Are Not Even Getting a Diagnosis'

"Our earlier research has shown that even in the best trauma centers, patients with TBI are not getting the care they need," said Geoffrey Manley, MD, PhD, senior author of the study, professor of neurosurgery at UCSF and a member of the Weill Institutes for Neurosciences. "Now we know that many of these patients with TBI are not even getting a diagnosis."

Manley is also the principal investigator of TRACK TBI, which has analyzed clinical data on more than 3,300 patients and comparison participants, and previously has linked concussion with major depression, post-traumatic stress disorder and cognitive deficits. Work by other UCSF faculty has found correlations between TBI and Parkinson's disease and TBI and dementia.

To assess the accuracy of the blood test, researchers compared the results of the patients whose CT-negative TBIs were confirmed by MRI, with a group of healthy participants as well as a cohort of patients with orthopedic injuries. They found that the average protein value of the blood samples of patients with positive MRIs was 31.6 times higher than those with orthopedic injuries and nearly 52 times that of the healthy participants. The protein was elevated even in the patients with normal MRIs, suggesting that the test may be sensitive to injury undetectable by MRI, the researchers noted.

In the future, the blood test may help clinicians decide who can safely avoid a CT scan, with the advantage of not exposing patients to radiation from a CT, said first author John Yue, MD, of the UCSF Department of Neurological Surgery. Additionally, the blood test may be a useful tool for those patients in trauma centers and emergency departments, whose symptoms may be altered by substance use, he said. "Patients with concussion may present as confused and disoriented, and may repeat themselves -- symptoms that are similar in people with intoxication. With the blood test, we may be able to discern whether their symptoms are primarily due to brain injury and treat accordingly."

The blood test may also clarify diagnosis in patients with co-existing conditions or those who take medications that may impact speech and behavior, said Yue.

"These blood-based biomarkers are the next step in the evolution of diagnosing and treating TBI," said Manley. "We are finding that not only are they more sensitive than CT in identifying TBI, but they may be more accurate than the current standard of MRI."

The study follows an earlier TRACK-TBI pilot study that found approximately 30 percent of concussion patients with negative CTs and positive MRIs had disability three months post-injury.

For the first time, researchers have managed to view previously inaccessible details of certain chemical processes. They have shown there are significant discrete stages to these processes which build on our knowledge of chemical synthesis. These details could aid in the development of methods to synthesize chemicals with greater control and precision than ever before. Methods such as these could be useful in materials science and in drug development.

"Since 2007 we have been able to realize a dream over 200 years old — the ability to see an individual molecule in motion," said Project Professor Eiichi Nakamura. "But it didn't end there. Our research group has reached beyond this dream to create videos of molecules to see chemical reactions in unprecedented detail."

Nakamura shares a bold ambition with scientists everywhere, to develop new and useful materials for the world. To do this, his team from the University of Tokyo's Department of Chemistry wishes to master control of various chemical processes responsible for material synthesis. However, chemical synthesis is a complicated thing to study.

"Conventional analytical methods such as spectroscopy and crystallography give us useful information about the outcomes of processes, but only hints about what takes place during them," explained Koji Harano, project associate professor in the Nakamura group. "For example, we are interested in metal-organic framework (MOF) crystals. Most studies look at the growth of these but miss the early stage of nucleation, as it is difficult to observe."

The transient stages of complex chemical reactions are difficult to study as there are multiple intermediate processes that occur between the start and end of most reactions. In principle, the individual stages could be seen, but in reality it was impossible to isolate the products at each stage and to see how these changed with time. Nakamura, Harano and team spent over 10 years on this problem and have developed a method called molecular electron microscopy.

"It was a problem of two parts," continued Harano. "On the large scale, there was an engineering challenge to combine a uniquely high-resolution electron microscope with a fast and sensitive imaging sensor for continuous video imaging; while on the small scale, we had to devise a way to capture the molecules of interest and hold them in place so the camera could catch the action."

To isolate and secure particular molecules, the team used a specially modified carbon nanotube. This would snag a passing molecule and hold it in place, but crucially, would not interfere with the reactions of that molecule. This way every stage of the reaction would take place at the tip of the nanotube, which in turn was held in place at the focal point of the electron microscope. The resulting data can be made into real-time videos of the reactions.

"What surprised us much in the beginning was that our plan actually worked. It was a complex challenge but we first visualized these molecular videos in 2013," said Harano. "Between then and now, we worked to turn the concept into a useful tool. Our first success has been to visualize and describe a cube-shaped molecule, which is a crucial intermediate form that occurs during MOF synthesis. It took a year to convince our reviewers what we found is real."

This is just the first step towards the ability to gain control over chemical synthesis in a precise and controlled manner -- a term the researchers call "rational synthesis." It's important to observe details of reactions as they progress so they can effectively be reverse engineered. The dream 200 years ago was to see an atom, the dream now is to control them in order to create things like synthetic minerals for construction or even new drugs to help save lives.

With every unfinished meal since Band Aid, you've heard it: "people are starving in Africa, y'know". True, the UN estimates that rich countries throw away nearly as much food as the entire net production of sub-Saharan Africa - about 230 million tonnes per year. But is it any less a waste to eat the excess food?

Morally, it's equivocal. Nutritionally, it depends. However: the land, water and carbon footprints are just the same.

In fact, researchers in Italy have proposed a way to measure the ecological impact of global food wastage due to excessive consumption. First, they estimated the net excess bodyweight of each country's population - based on BMI and height data - and distributed its energy content among foods groups according to national availability.

Published in Frontiers in Nutrition, the results suggest that direct food waste - thrown away or lost from field to fork - is a mere hors-d'œuvre.

"Excess bodyweight corresponds to roughly 140 billion tonnes of food waste globally," reports group lead Prof. Mauro Serafini, of the University of Teramo. This figure is a snapshot of the current world population's accumulated dietary excesses, not a rate of overconsumption. It is, though, orders of magnitude higher than current annual direct food waste, estimated at 1.3 billion tonnes.

The disproportionate impact of Serafini's so-called 'metabolic food waste' grows when its ecological costs are calculated, using per-kilo values from thousands of food lifecycle assessments. Fruits, vegetables, roots and tubers have the highest direct wastage rates, but excess energy consumption is dominated by more calorie-dense foods. These typically entail more land, water and greenhouse gases to produce.

So much so, that growing the world's metabolic food waste would be expected to generate the equivalent of 240 billion tonnes of CO2. This is roughly the amount mankind released burning fossil fuels over the last seven years combined. Notably the EU, North America and Oceania together contribute as much to this estimate as the rest of the world combined, with meat, eggs and dairy accounting for 75%.

The total land and water figures are more difficult to interpret, as they do not take into account how long land is required to grow different foods - or the redistribution of water, which is not lost per se via agriculture. And though based on public data collected by the UN, WHO, WWF and BCFN - an EU-backed nutrition think tank - the whole approach is fraught with methodological and conceptual uncertainty.

The calculations are based on national availability of the main food commodities, not average food intake or typical sources of excess calories among the overweight and obese. They assumed that bodyweight beyond BMI 21.7 - midpoint of the 'healthy' range associated with lowest all-cause mortality - was all excessive, and all fat. How excess bodyweight is changing over time, or how much of it would vanish if physical activity were increased to healthier levels, are left unaddressed.

So, like Serafini we take metabolic food waste with a pinch of salt. But as back-of-a-napkin estimates of the ecological costs of dietary excess, these figures are close to as good as we'll practically get. And they are monstrously high.

The glaring corollary: overeating is bad for our planet's health, not just our own. And as highlighted by this month's IPCC land-use report, overconsumption of farmed animal products by Westerners is probably the single biggest contributor.

Paris, France - 23 Aug 2019: Heavily polluted areas have a higher rate of angioplasty procedures to treat blocked arteries than areas with clean air, according to research to be presented at ESC Congress 2019 together with the World Congress of Cardiology.(1) Procedures are even more common in winter, the most polluted time of year.

Study author Dr Rafal Januszek of the University Hospital in Krakow, Poland said: "Epidemiological studies have reported negative impacts of pollution on the cardiovascular system but the effects on specific diseases were unclear. We also show for the first time that patients from areas with cleaner air are more sensitive to changes in pollution, while those from more polluted cities can adapt to fluctuations."

Using particulate matter (PM) 10 levels published by the Chief Inspectorate for Environmental Protection in Poland, six unpolluted cities and five polluted cities were selected for the study. PM10 are particles ten micrometres or less in diameter. Sources include industrial processes like iron making and quarrying, lawn mowing, wood and coal stoves, bushfires, dust storms, and vehicle exhaust emissions.

The study enrolled 5,648 patients from unpolluted cities and 10,239 patients from polluted cities. All patients underwent stent insertion (percutaneous coronary intervention; PCI) to open arteries blocked due to acute coronary syndromes (heart attack or unstable angina). PCI data were obtained from the ORPKI Polish National PCI Registry.

Dates of PCI procedures were matched with air quality on the same day during a 52-week period. Analyses were also performed to compare winter versus non-winter weeks because pollution levels rise during winter.

The annual average PM10 concentration was significantly higher in polluted cities (50.95 μg/m3) compared to unpolluted cities (26.62 μg/m3). In both polluted and unpolluted areas, a rise in PM10 concentration was significantly associated with a greater frequency of PCI.

Patients in cities with clean air were more sensitive to pollution rises, with each 1 μg/m3 increase in PM10 concentration linked to 0.22 additional PCIs per week. While in polluted cities, the same rise in PM10 was linked with just 0.18 additional PCIs per week.

Regarding the seasonal effect, the PCI rate was significantly lower in non-winter, compared to winter, weeks in both polluted and clean cities. "The higher incidence of PCI in winter is related to greater air pollution during this period," said Dr Januszek. "This is due to several factors such as artificial heating and the resulting smog."

He concluded: "The study shows that the incidence of acute coronary syndromes treated with PCI was higher in winter and rose along with increasing pollution, and this rise was higher in regions with initially cleaner air, if taking the same increment in pollution into account. This is further evidence that more needs to be done to lower pollution levels and protect the public's health."

A new study finds people who have mild cognitive impairment (MCI), which lies on the continuum of cognitive decline between normal cognition and dementia, are less likely to receive proven heart attack treatment in the hospital.

Researchers found no evidence that those with MCI would derive less benefit from evidence-based treatment that's offered to their cognitively normal peers who have heart attacks, says lead author Deborah Levine, M.D., MPH.

"Patients should get the treatments they would want if they were properly informed," says Levine, an associate professor of internal medicine and neurology at Michigan Medicine, the academic medical center of the University of Michigan.

Some people with thinking, memory and language problems have MCI. Unlike dementia, which severely interferes with daily functioning and worsens over time, MCI does not severely interfere with daily functioning and might not worsen over time. Although people with MCI have an increased risk of developing dementia, it's not an inevitable next step, Levine says.

"While some may progress to dementia, many will persist in having MCI, and a few will actually improve and revert to normal cognition," says Levine, also a member of the University of Michigan Institute for Healthcare Policy and Innovation. "Many older adults with MCI live years with good quality of life, and so face common health risks of aging like heart attack and stroke.

"Clinicians, patients and families might be overestimating the risk of dementia after a mild cognitive impairment diagnosis even without realizing it. These older adults with MCI should still receive evidence-based treatments when indicated."

The research, published in the Journal of General Internal Medicine, found pre-existing MCI was associated with significantly lower use of guideline-concordant care after a heart attack, whether catheter-based or open surgery. The study measured 609 adults ages 65 and older who were hospitalized for a heart attack between 2000 and 2011.

Levine notes both cardiac catheterization (35% less likely in patients with pre-existing MCI) and coronary revascularization (45% less likely in patients with pre-existing MCI) have been shown to be highly effective at reducing deaths and improving physical functioning after heart attack in multiple large clinical trials.

'A timely issue'

Physicians must weigh the competing risks of all health problems that increase with age, Levine says, including heart disease and cognitive decline. Many families are dealing with both concerns at once in their older loved ones.

"This is a timely issue because as the population ages, the number of seniors 85 years old and older has become the fastest-growing segment of the U.S. population," Levine says. "Seniors 85 and older are most likely to have MCI, and their incidence of heart attack has surged."

However, cardiovascular disease, including heart attack and stroke, is still the leading cause of death and serious morbidity in older adults, whether they have MCI or normal cognitive functioning.

Up to 1 in 5 adults ages 65 and older has MCI, although many may be undiagnosed, Levine says. Since the Affordable Care Act mandated coverage of cognitive impairment assessments for Medicare beneficiaries, MCI diagnoses are expected to increase, she adds.

The need to question decision-making

Although much recent medical literature addresses overtreatment, Levine says this research shows undertreatment with high-value therapies can also be a problem.

Her team's ongoing research finds physicians might not be recommending invasive treatments as often after an older patient with some memory and thinking problems has a heart attack. She encourages clinicians to reflect on the influence of MCI in their decision-making.

"It's important for providers to consider whether they are recommending against treating a patient just because they have MCI," Levine says. "Physicians can think about offering treatments to all patients when clinically indicated."

Invasive treatments may not be indicated in those with advanced dementia or a limited life expectancy, she says, but MCI does not fall in that category.

This potential disconnect in provider recommendations provides an opportunity for patients and families to empower themselves by having conversations about the care they'd want if they become ill, she says. People with MCI can still participate in these types of discussions, and families don't need to wait until an event happens to start the conversation.

"In these discussions, patients and families often think about catastrophic illnesses where life support measures may be used, but heart attacks and stroke are much more common, and they're treatable," Levine says.

"Because dementia is so feared among older adults and their families, it's understandable and appropriate that it may weigh heavily on the decisions for all types of care, including heart attack care," adds co-author Kenneth Langa, M.D., Ph.D., a professor of internal medicine at Michigan Medicine and a member of the Institute for Healthcare Policy and Innovation. "Our study emphasizes the importance of differentiating between MCI and dementia and of educating patients, families and clinicians on the relative risks of further cognitive decline versus common cardiovascular conditions for people with MCI."

An ongoing effort

Levine and colleagues used data from the Health and Retirement Study, a nationally representative longitudinal study of older Americans that's based at U-M.

Heart attack, or acute myocardial infarction, was an appealing lens to research whether patients with MCI receive guideline-based treatment, Levine says. Heart attacks are acute, emergent medical problems that are common in seniors and have robust evidence of effective treatment, she adds.

Levine's team is also studying the effect of pre-existing MCI on treatment for acute ischemic stroke, and the reasons physician recommendations and patient preferences for effective treatment after stroke or heart attack might be different if the patient already has MCI.

"Studies like this are an important first step in raising awareness on MCI so that providers, like cardiologists, can make sure they offer the best therapies available during heart attacks," says senior author Brahmajee Nallamothu, M.D., MPH, an interventional cardiologist and professor of internal medicine at Michigan Medicine.

University of Calgary researchers at the Cumming School of Medicine (CSM) led by Drs. Donna Senger, PhD, Paul Kubes, PhD, and Stephen Robbins, PhD have discovered a new way to stop harmful inflammation in the lungs due to sepsis and injury.

"This work demonstrates the power of collaboration in solving complex health issues to benefit patients," says Robbins, a professor in the departments of Oncology, and Biochemistry & Molecular Biology and Scientific Director of the CIHR Institute of Cancer Research. "The research involved teams from 10 laboratories, nine at UCalgary with investigators from the Arnie Charbonneau Cancer Institute and the Snyder Institute for Chronic Diseases."

One in 18 deaths in Canada is connected to sepsis. It occurs when the body is fighting off severe infection. The immune system goes into overdrive sending white blood cells to clear up the infection. The battle between your immune system and the infection leads to inflammation. A problem occurs when the white blood cells leave the blood stream and move into the tissue to clean up the inflammation. In some cases instead of cleaning up and moving on, they stay, and more white blood cells come in behind them. The accumulation causes damage to internal organs, like the lungs, and can lead to death.

Sepsis is not the only condition that leads to an unhealthy collection of white blood cells in the lungs. Inflammation caused by injury, and other diseases, can also create this harmful response. Acute lung injury is a leading cause of death in critical care in Canada.

The collaboration began about 15 years ago. It was a project based on a similar premise, with two distinct problems to solve. The researchers wanted to know what was causing some cells to bind in the lungs. Senger and Robbins are cancer biologists and were investigating how cancer metastasizes. They knew that some cancer cells target the lungs and somehow stay there and grow. Many people with cancerous tumours do not die from the primary tumour, but rather from where the cancer metastasizes. Meanwhile, Kubes, a specialist in inflammation was investigating why white blood cells collect in the lungs. In conditions like sepsis, victims often die from the body's response to the illness, not from sepsis itself.

Together they started screening for a molecule present in both processes. They targeted the lining of blood vessels in the lungs because they suspected a signal would be present that allows cancer cells and white blood cells to stop and collect there. That's exactly where they found a molecule present during inflammation that could bind with white blood cells and help the cells pass from the blood stream into the tissue. As long as those molecules are present, white blood cells continue to bind them.

Once the scientists understood how and why the white blood cells were entering the tissue, they went in search of an "off switch" to stop the molecule from binding with the white blood cell. The teams developed a drug-like molecule that when introduced into the blood stream prevents white blood cells from binding with the molecule.

"We discovered that by targeting this molecule we can stop the ill effects of sepsis, acute lung injury and death," says Kubes, the director of the Snyder Institute for Chronic Diseases at the CSM and professor in the Department of Physiology and Pharmacology. "It could have an impact on any inflammatory condition in which lung injury is a contributor to worsening a patient's condition."

With this knowledge, the researchers have found a similar process that occurs in the liver. They've now patented two drug-like molecules that can prevent lung and liver damage due to inflammation. While all of the research to date has been performed on mice, a phase I clinical trial is underway to begin human testing.

The researchers are also applying the findings to cancer metastasis in hopes this new understanding could lead to treatments to stop cancer cells from spreading in the body and targeting the liver and lungs.

"The molecule we discovered binds to both white blood cells and certain cancer cells," says Senger, a research associate professor in the Department of Oncology. "We've developed a way to stop the white blood cells from binding and moving into the tissue. Now, we're hoping to find a solution to prevent cancer cells from spreading to these organs."

An international group of scientists studied the effects of 17 different lifespan-extending interventions on gene activity in mice and discovered genetic biomarkers of longevity. The results of their study were published in the journal Cell Metabolism.

Nowadays, dozens of interventions are known that extend the lifespan of various living organisms ranging from yeast to mammals. They include chemical compounds (e.g. rapamycin), genetic interventions (e.g. mutations associated with disruption of growth hormone synthesis), and diets (e.g. caloric restriction). Some targets of these interventions have been discovered. However, there is still no clear understanding of the systemic molecular mechanisms leading to lifespan extension.

A group of scientists from Skoltech, Moscow State University and Harvard University decided to fill this gap and identify crucial molecular processes associated with longevity. To do so, they looked at the effects of various lifespan-extending interventions on the activity of genes in a mouse, a commonly used model organism closely related to humans.

The scientists identified a group of genes, whose activity was associated with longevity in response to various interventions, serving as biomarkers of lifespan extension.

"In our lab, we subjected mice of different sexes and ages to 8 longevity interventions and analyzed gene expression changes induced by these treatments. After aggregating our data with the datasets published by other groups, we obtained gene activity profiles of 17 interventions. Although in general the effects produced by individual treatments turned out to be rather specific, a certain group of genes changed its expression in a similar way in response to different lifespan-extending interventions," says the first author of the study, Alexander Tyshkovskiy.

The scientists then applied the discovered biomarkers to search for other interventions with the same effect on their activity and, therefore, high potential for lifespan extension. In their work, the researchers identified several such treatments, including chronic hypoxia and chemical compounds, such as antioxidant ascorbyl-palmitate and mTOR inhibitor, KU-0063794.

"Currently, we are validating these hits by testing their effect on the mouse lifespan. We hope that our biomarkers will significantly facilitate the search for new longevity interventions and help improve the healthspan and lifespan in rodents and, in the long term, in humans," says Alexander.

In addition to their scientific research, the scientists developed GENtervention, an application that offers fast and user-friendly tools for investigating the associations between the activity of individual genes and longevity.

Stanford, CA (Aug 22, 2019) -- As sea levels rise, many communities will be forced to relocate or be swallowed by the sea. Yet, retreat--relocation of communities in response to natural hazards and climate impacts--remains immensely controversial, and getting people and governments to plan for it is an uphill battle on several fronts. Below, researchers A.R. Siders, Miyuki Hino and Katharine Mach discuss their related article, published in the journal Science, on why, where, when and how communities should plan for retreat. Siders was an Environmental Fellow at the Harvard University Center for the Environment and is now an assistant professor at the University of Delaware. Hino is a Ph.D. candidate in Stanford's Emmett Interdisciplinary Program in Environment and Resources. Mach served as director of the Stanford Environment Assessment Facility and is now an associate professor at the University of Miami.

How can societies change the narrative of failure around retreat?

Siders: Fighting the ocean is a losing battle. The only way to win against water is not to fight. We need to stop picturing our relationship with nature as a war. We're not winning or losing: we're adjusting to changes in nature. Sea levels rise, storms surge into floodplains, so we need to move back. We can do that the hard way, by fighting for every inch and losing lives and dollars in the meantime. Or we can do it willingly and thoughtfully and take the opportunity to re-think the way we live on the coasts. This is why retreat needs to be strategic as well as managed. Retreat is a tool that can help achieve societal goals like community revitalization, equity, and sustainability if it is used purposefully.

Mach: The changing climate has transformations underway and in store, whether it's from risks of fire, drought and desertification, sea level rise, extreme heat, or heavy rain. To keep communities vibrant and safe, changing the narrative may be one of the most empowering tools societies have at their disposal. As Marine Corps Gen. Oliver Smith once said, "We're not retreating, we're just advancing in a different direction."

What are the biggest barriers to managed retreat?

Hino: No matter the circumstances, moving is hard. People have chosen where to live for a reason, and it is often difficult to find a place to move to that meets all their social, cultural, and financial requirements. One major challenge with retreat is that we're so focused on getting people out of harm's way, we miss the chance to help them move to opportunity. There are financial constraints as well. With limited resources, government agencies have to decide whether to try to reach more households, providing less to each, or try to fully support a smaller number of households. But there are certainly opportunities to tackle both of these challenges and find low-cost measures that give people a reason to be excited about their destination.

Siders: The biggest barrier to retreat is that there are short-term benefits to building and living in risk-prone areas. People like living in these areas - along the coasts, on riverbanks, in fire-prone wilderness. Developers make fortunes building new properties in risk-prone areas, which provide local governments with increased property tax revenue. Some people aren't aware of the risks, while others choose to ignore them because they have insurance, believe floodwalls or stilts will protect them, or just feel lucky. Some people don't have much choice because they have jobs nearby or can't afford housing in safer areas. It's a complicated mix of psychological, economic, and social issues. To address these issues, managed retreat needs to be embedded in larger conversations and social programs. Policies that give people incentives to stay need to be reformed. Programs need to give people reasons to leave. Retreat can't be just about avoiding risk: it needs to be about moving towards something better.

What are the social justice concerns regarding retreat?

Hino: One of the enduring questions is whether the residents "get to" relocate or "are forced to" relocate. In some cases, providing financial assistance for the most vulnerable households to move to safer ground will mean a fresh start. In others, it might equate to forced relocation, disrupting the social fabric that ties communities together and reinforcing existing inequities. Implementing retreat equitably requires taking a context-specific approach and putting the households and communities first.

Siders: If people have to move without any government assistance, people with the most resources are likely to move first, leaving the most vulnerable people in the most at-risk areas. When those people finally have to leave, the financial losses could be devastating. This could also happen if retreat is managed in a way that helps the wealthy first or is not paired with other social programs like building affordable housing in safe places.

How do you manage retreat?

Mach: In the United States, the most common approach to date has been buying out homeowners after disasters and then restoring the land to open floodplain. A few communities have aimed to relocate in their entirety in response to cyclones or gradual land loss and erosion. And there are also more subtle nudges: the ways that requiring setback from the ocean or public access to the beach has encouraged development that makes way for tides, storm surge, and seasonal replenishment of sand and sediments on the shore. Moving forward, there are important opportunities to innovate the "how" of retreat, building from these past experiences.

Siders: How you manage retreat depends on what you want to achieve and the local context. Of course, retreat is about adapting to climate change and reducing risk exposure, but is the program meant to help people who survived the last disaster, people who will be at risk in the future, or people with the fewest resources to move on their own? Will the land be used to create one large wetland to absorb floodwaters or a series of small community gardens spread throughout town? Retreat isn't an end in itself. It's a way to achieve other goals.

What future research needs to be done to improve strategic retreat?

Siders: Retreat needs experimentation - creative solutions developed by practitioners and rigorously tested by scientists to learn what works and what doesn't. Retreat is already happening - sometimes strategically, sometimes not. To be more strategic, retreat needs to be included in much larger conversations, such as how we build affordable housing, deal with social justice, integrate green spaces in urban landscapes, and develop larger cities in a more sustainable fashion. Retreat can be a tool in working towards those goals, if it is part of the conversation.

Mach: The story of retreat as a climate response is just beginning. Retreat is compelling because it brings together so many aspects of how societies work, what individuals are trying to achieve, and what it takes to ensure preparedness and resilience in a changing climate. Retreat is an adaptive option at the intersect of changing disaster risk, market forces, societal investments, and community well-being. There are exciting opportunities to better combine these drivers in research. To support deployment, there are intriguing possibilities for integrating data-rich analytics in the participatory processes in which people are defining their goals, assessing their options, and learning through time as they take action.

The first detailed map of individual malaria parasite behaviour across each stage of its complicated life cycle has been created by scientists. Researchers at the Wellcome Sanger Institute and their collaborators used advanced single-cell technology to isolate individual parasites and measure their gene activity. The result is the Malaria Cell Atlas, which gives the highest resolution view of malaria parasite gene expression to date and monitors how individual parasites change as they develop in both the mosquito and human host.

Reported today (22 August) in Science, the team also pinpoint particular stages in the life cycle where each malaria parasite gene is likely to play a key role in parasite development. Knowing when and where a gene is active presents possible targets in the malaria life cycle that are important for developing much-needed antimalarial drugs, vaccines, and transmission blocking strategies.

Malaria affects more than 200 million people worldwide and caused nearly 450,000 deaths in 2017, the majority of which were children under five*. The malaria parasite's ability to become resistant to multiple frontline drugs poses an enormous threat to malaria control. While advances are being made in vaccine development, a barrier to discovering new malaria drugs is the fact that the function of nearly half of the parasite's genes are unknown.

Understanding the diverse behaviours and gene activities of malaria parasites across their complicated life cycle is now possible with the freely available Malaria Cell Atlas data resource, created by scientists at the Wellcome Sanger Institute.

Dr Virginia Howick, joint first author from the Wellcome Sanger Institute, said: "We've created an atlas of gene activity that spans the complete life cycle of the malaria parasite. This is the first atlas of its kind for a single-cell organism. The malaria parasite's life cycle is key to research into this disease and the Malaria Cell Atlas will help us truly understand the parasite in order to effectively control malaria."

To create the map, the team isolated and measured the gene activity of 1,787 individual malaria parasites from 10 stages across the complete life cycle, spanning both the human and the mosquito. For example, the researchers gave mosquitoes infected with malaria a fake blood meal to capture the parasites they released in their spit in order to compare them to parasites that remained in the salivary glands.

The team then measured which genes were active in individual parasites across the entire life cycle. Knowing which genes are critical in each stage of the parasite's life cycle presents weak spots and future drug targets.

By looking at the activity of previously studied genes that showed similar patterns of activity to the 40 percent of genes that currently have no known function, the team could infer potential functions for these unknown genes.

Andrew Russell, joint first author and a PhD student at the Wellcome Sanger Institute, said: "Using the Malaria Cell Atlas, we've inferred the roles of parasite genes that until now were entirely unknown. We do this through 'guilt-by-association': by looking at functions of previously studied genes, we can predict roles of unknown genes if they show similar activity patterns to known genes. This provides a new opportunity to find novel drug targets."

The team expanded the Malaria Cell Atlas by using another single-cell technology to examine a further 16,000 individual parasites from the blood stages of malaria that infect mice, monkeys and humans. This showed similar gene activity behaviour across the three malaria parasite species even though they infect such different hosts. Identifying genes that are essential in multiple species of malaria helps towards building new candidate drug targets, as these targets might be effective in all five of the malaria species that infect humans.

Researchers then collected parasites present in the blood of three Kenyan people who were infected with malaria, just as they were being treated for the disease. Using the Malaria Cell Atlas as a reference, the team were able to examine individual "wild" parasites from two different human malaria parasite species for the first time. This opens the door to understanding which genes are active in natural infections in the real world, and how these might differ to malaria parasites cultured in the laboratory.

Dr Mara Lawniczak, lead author from the Wellcome Sanger Institute, said: "To defeat malaria we need to understand all the tricks the parasite uses throughout its life cycle. The Malaria Cell Atlas is the first detailed map that gives us insight into how different one parasite is from another, even when they are genetically identical. We face the problem of malaria becoming more resistant to current malaria drugs, and as new drugs are introduced, we hope the Malaria Cell Atlas will act as a reference to understand how parasites change their behaviours in response to our efforts to control them. Knowing this will help reveal how to corner the parasites and ultimately eliminate them."