Culture

Biodiversity hotspot Madagascar is one of the world's biggest islands, and home to some of its biggest insects. Now German scientists have discovered two new species of giant stick insect, living only in the dry forests of Madagascar's northernmost tip.

One giant female measures a whopping 24cm - but it is the smaller males that are most striking. At sexual maturity these daredevils abandon their stick-like camouflage for dazzling blue or many-colored shining armor.

Writing in Frontiers in Ecology and Evolution, the researchers describe their rare and exciting findings, and wonder at the reproductive success of the least stick-like stick insects on the planet.

When two become four

"Nearly all of the 3000+ known species of stick insects try to be inconspicuous and just look like twigs," says senior author Dr. Sven Bradler of the University of Göttingen, Germany. "There are a very few, very large exceptions - and we have just discovered a couple more of them."

The authors re-examined specimens they'd previously identified as odd-looking examples of two existing giant stick insect species, whose adult males remarkably are bright blue or multicolored.

"These were similar in size - 15 to 24cm - but generally less spiny and a bit differently colored than typical examples of their kind," explains Bradler. "Now genetic tests confirm that the quirky individuals are in fact two new species, distinct from the original two but part of the same group." explains Bradler.

Bradler's reclassification places members of this group of species as close evolutionary relatives to other Madagascan stick insects, rather than cousins from overseas as previously thought. This is a potentially major finding, as it challenges the prevailing view that sticks insects colonized Madagascar multiple times.

He who dares, wins

The discovery also prompted the researchers to wonder: what reproductive advantage do these males gain from their bright colors, that is worth exposing themselves to predators?

The first author Dr. Frank Glaw of the Bavarian State Collection of Zoology in Munich, and colleagues bred the new giant stick insect species in captivity to observe their behavior.

"Males of one species started mating attempts only when they achieved their bright blue color."

This might suggest that the males use their bright coloring to attract a mate. However, it is hard to believe the males could find a mate before being eaten - unless their bright coloring acts as a deterrent to predators.

"Males searching for a mate have to move about more, so pretending to be a stick becomes tricky. Better perhaps to plump for the opposite: a brightly colored warning."

Bright colors - suggestive of toxicity - keep safe vivid members of other typically camouflaged species, like lividly colored Madagascan frogs.

"In support of this, all stick insects have neck glands that repellant substances, and these are typically well-developed in brightly colored species. Alternatively, like the Madagascan frogs some giant stick insects may have developed the ability to accumulate toxins from their food."

But testing these hypotheses will be tough, admits Glaw.

Bradler adds "More than one factor may have played a role in the evolution of this remarkably conspicuous coloration. So even with more data on mate selection, habits, predators, natural food plants, toxins produced by defense glands and possible accumulation of toxins among giant stick insects, finding evidence for these ideas may prove difficult."

Colorful stick insects have a bright future

Whatever its function, the splendid coloring of the male giant stick insects could make them a strong flagship species to promote the unique biodiversity of Madagascar, and the need for its protection.

"Already the once-uncertain future of these two new species seems secured, with their forest habitat in northern Madagascar a hotspot for conservation priorities," says Glaw. "It is vital to maintain awareness and motivation to keep logging at bay. This precious area also harbors the highest density of critically endangered reptiles in Madagascar and is home of one of the most threatened primate species in the world, the lemur Lepilemur septentrionalis."

Computing--Broader impacts of bullying

Oak Ridge National Laboratory is using artificial intelligence to analyze data from published medical studies associated with bullying to reveal the potential of broader impacts, such as mental illness or disease. Search results from a computing method known as literature-based discovery could help identify long-term negative consequences of bullying behavior and could inform better-targeted intervention programs. For the study, ORNL's S. M. Shamimul Hasan applied the algorithm, through a biomedical document retrieval system, to the publicly available medical database Semantic MEDLINE to discover various direct and indirect effects of bullying. "The method uses a three-level approach to detect relationships, for example, from bullying to psychological distress--which is a direct impact--to epilepsy, an indirect consequence," Hasan said. While the advanced analytical tool makes intelligent inferences, Hasan said for now the process requires a "human in the loop" to validate the connections. He hopes to further enhance the tool's capabilities. [Contact: Sara Shoemaker, (865) 576-9219; shoemakerms@ornl.gov]

Image: https://www.ornl.gov/sites/default/files/2019-03/bullying_img_1.png

Caption: Using artificial intelligence, Oak Ridge National Laboratory analyzed data from published medical studies to reveal the potential of direct and indirect impacts of bullying. Their results could help identify long-term consequences and could inform better-targeted intervention programs. Credit: S. M. Shamimul Hasan/Oak Ridge National Laboratory, U.S. Dept. of Energy

Grid--Wrap-around sensors

Scientists at Oak Ridge National Laboratory have developed a low-cost, printed, flexible sensor that can wrap around power cables to precisely monitor electrical loads from household appliances to support grid operations. Using an inkjet printer, researchers deposited wires on a flexible plastic substrate, then wove in a magnetic strip to channel the flux produced by an electric current, making the sensor suitable to install in tight spaces. When tested on conductors in the lab and on a building HVAC unit, the sensor measured responses of up to 90 amps of electrical current, and is expected to exceed 500 amps in larger applications. "These inexpensive sensors provide crucial, real-time usage data needed to monitor and control devices such as smart HVAC and water heaters for better power grid efficiency and resilience," said ORNL's Pooran Joshi. The team is currently testing new materials, electronics and packaging to increase the sensor's range and applications while keeping costs low. [Contact: Stephanie Seay, seaysg@ornl.gov; (865) 576-9894]

Image: https://www.ornl.gov/sites/default/files/2019-03/2019-P01298.jpg

Caption: ORNL scientists have created a low-cost, compact, printed sensor that can collect and transmit data on electrical appliances for better load monitoring. Credit: Genevieve Martin/Oak Ridge National Laboratory, U.S. Dept. of Energy

Nuclear--Remote-controlled reactors

Oak Ridge National Laboratory scientists are evaluating paths for licensing remotely operated microreactors, which could provide clean energy sources to hard-to-reach communities, such as isolated areas in Alaska. "Current regulatory guidance was written when remote operations of nuclear reactors were not possible, so this is a new frontier," said ORNL's Randy Belles. The flexibility of microreactors--which could power thousands of homes for a decade without refueling and be easily transported due to their compact size--could allow operators to autonomously control them using advanced computing systems. This would help limit onsite staffing, and increase economic viability. "Our team's evaluations aim to address several licensing questions that come with remote operations, such as handling cybersecurity, staffing and manipulations of the controls," Belles said. The next step is advising Nuclear Regulatory Committee staff about the guidance needed to make deployment possible. [Contact: Jason Ellis, (865) 241-5819; ellisjk@ornl.gov]

Image: https://www.ornl.gov/sites/default/files/2019-04/Micro%20Reactor%202-03%5B1%5D.jpg

Caption: Oak Ridge National Laboratory scientists are evaluating current regulatory guidance to understand the potential challenges in licensing remotely operated microreactors. Microreactors could offer unique mobility and flexibility--opening the possibility for nuclear energy to reach isolated areas. Credit: Adam Malin/Oak Ridge National Laboratory, U.S. Dept. of Energy

Clean Water--Better separations

A team of scientists led by Oak Ridge National Laboratory used carbon nanotubes to improve a desalination process that attracts and removes ionic compounds such as salt from water using charged electrodes. Carbon nanotubes have superior ability to conduct electricity. When applied to the desalination process known as flow-electrode capacitive deionization, the nanotubes boosted electroconductivity by 13.2 times and increased the desalination rate by 34 percent, with only a slight increase in solution viscosity. The result was salt water removal efficiency of 93.6 percent, as detailed in ACS Sustainable Chemistry & Engineering. "The process is particularly good at treating industrial wastewater and could help meet the global challenge of fresh water availability," said ORNL's Costas Tsouris. He added that exploring the use of carbon fiber in the process could result in similar improvements at a lower cost. [Contact: Stephanie Seay, seaysg@ornl.gov, 865-576-9894]

Image: https://www.ornl.gov/sites/default/files/2019-04/DesalDiagram-.jpg

Caption: Scientists used carbon nanotubes that enhanced conductivity and sped up a salt water removal process known as flow-electrode capacitive deionization. Reprinted with permission from Kexin Tang, et al., "Enhanced Water Desalination by Increasing the Electroconductivity of Carbon Powders for High-Performance Flow-Electrode Capacitive Deionization." ACS Sustainable Chemistry & Engineering. Copyright 2019. American Chemical Society.

Using newly discovered archival materials, Igor Fedyukin of the Higher School of Economics, in collaboration with Robert Collis (Drake University) and Ernest A. Zitser (Duke University), sheds light on the significance and context surrounding a Spanish diplomat's initiative which sought to establish an informal men's club called the 'Order of the Anti-Sober' at Peter II's court. Their study was published in The International History Review.

In the late 17th - early 18th centuries, various fraternities, societies and associations were gaining popularity throughout Europe among the elite. Their motives were often not particularly serious: the informal gatherings often served as an occasion for drinking and socializing. However, these associations often provided venues for discussing and solving important political issues, forging political alliances, and laying the groundwork for future political parties.

In 1728, in St. Petersburg, Russia, the Duke of Liria, a Spanish Ambassador, sought to start such a club at Peter II's court. It was to be called the 'Order of the Anti-Sober'.

When James Francis Fitz-James Stuart (1696-1738), Duke of Liria and Spain's first permanent envoy to Russia, was preparing to depart on his diplomatic mission, he knew in advance how he would go about achieving his objectives in St. Petersburg. As he intimated in a letter to his uncle and heir to the British throne James (III) Stuart, the envoy planned to rely on 'the varieties of [his] wines', since 'in that part of the world all affairs are concluded on a bottle'.

Such assumptions should not be too surprising: during the reign of Peter the Great, the Russian court was known for its boisterous feasts and carnivals with heavy drinking. It appears only natural that Liria would have the same stereotype about the court of Peter the Great's teenage grandson, Emperor Peter II (1715-1730, r. 1728-1730), who reigned by the time the envoy arrived.

However, the behavior and alcohol consumption of Russian elites of those times were in fact not so different from their European counterparts. In the 18th-century European royal courts, informal meetings with a narrow circle of confidants were quite popular, where the aroma of wine was an integral element. There is evidence of the existence of such societies as 'The Order of the Wine Grape' (Ordre de la Grappe) in Arles, France, 'The Order of the Medusa' (Ordre de la Meduse) in Toulon, and 'The Order of the Drinks' (Ordre de la Boisson) in Avignon. A 'Collegium of Tobacco Smokers' (Tabakskollegium) existed at the court of King Friedrich Wilhelm I of Prussia. According to the diary by Friedrich Wilhelm von Bergholz, a gentleman of the bedchamber to Duke Karl Friedrich of Holstein-Gottorp, who resided in Russia throughout the early 1720s, the creation of mock orders was a common practice in the context of small northern European courts. These societies were a platform for entertainment and informal interaction for diplomats and the ruling elites. So the Duke of Liria's intention to create a closed club named future 'Order of the Anti-sober' (Ordre des Antisobres) was quite in line with that era's political culture trends.

Rules of the Club

The charter of the 'Order of the Anti-Sober', which was discovered in French archives, mentions the Epiphany of 1728 as the date of the order foundation. It is known that the Duke of Liria, who had come to Russia and had been introduced at the court not long before that, officially participated in a foreign diplomats' assembly for the first time around these dates.

The surviving text of the charter has, of course, a boisterous, mocking tone. For example, the first article mockingly refers to the Old Testament and requires order members to exhibit 'eternal antipathy' towards the 'sect' of teetotalers and all those who practiced the 'vice of sobriety'. Another rule had it that the 'cavaliers' of the order had to be pleasant in their interactions and be able to mock without turning to malice. Pointedly, the lack of these qualities could be forgiven if a candidate had a 'good cook' and 'excellent wines'.

The planned order was intended as a space for socializing, uninterrupted by any personal or political tensions. The members were instructed to leave all their ranks and titles at the door and limit the length of their speeches to two minutes to avoid the 'dread' of 'yawning' and the 'unpardonable crime' of boredom.

No more than three dishes were to be put on the table during the meals, since 'profusion is the irreconcilable enemy of delicacy.' In addition, nobody was to force other members to eat and drink beyond the dictates of their own appetite.

The members of the order were to observe secrecy, in a manner similar to other secretive societies. There would also be special marks, signs, and rituals, allowing a member to recognize his fellows wherever they met. The members were supposed to greet each other by exclaiming 'Long live the Epiphany at the 59th Degree!' - a countersign marking the latitude of St. Petersburg, the location of the order foundation.

Women were barred from entering the order. This was explained by the necessity to temper the 'ardor of certain desires' and contribute to the 'sweet harmony' and 'happiness' to which the prospective members of this 'august and incomparable order' aspired.

Article 11 of the charter mandated that the members maintain sincere, close, and cordial relations with one another and exclude all prejudices, such as those that are caused by religious or national differences. To this end, the charter even banned all 'ceremonial toasts' honouring monarchs and any other 'potentates'.

The violators of these rules were to be condemned to 'travel 20 years in Russia without a bed and without a cook, in winter without a fur jacket, in summer without ice.'

According to the researchers, the exclusion of women and the explicitly apolitical nature of the meetings were very much in the spirit of English Freemasonry, as articulated in 1723 by James Anderson.

Motives to Create the Club

The Duke of Liria was, in fact, a servant to two masters: Philip V, the sovereign who appointed him Spain's first official diplomatic representative in Russia, and James (III) Stuart, the Jacobite claimant to the British throne, with whom the duke maintained secret correspondence and to whom he professed boundless loyalty.

In 1725, Spain signed The Treaty of Vienna with Austria, which opposed the signatories of the Treaty of Hanover, most notably, France, Great Britain, and Prussia. Under such a balance of powers, Philip V commissioned Liria to persuade Russia to join the Treaty of Vienna and, probably, even dispatch a fleet that would land in England, overthrow George I, and restore the Stuart dynasty.

In St. Petersburg, Liria was going to count on Duke Karl Friedrich of Schleswig-Holstein-Gottorp, spouse of tsar's daughter Anna Petrovna, member of Russia's Supreme Privy Council and an important political player at the court of his mother-in-law, Empress Catherine I. Karl Friedrich's claims to both the Holstein territory annexed by the king of Denmark and to the Swedish throne were very much central to the hostility between Russia and Britain. Liria was therefore hoping to talk Karl Friedrich into acting against the Hanoverian Alliance.

But over the course of the Spanish envoy's six-month journey from Madrid to St. Petersburg, the diplomatic situation in Europe changed. In March 1727, the government of George I managed to persuade Sweden to join the Hanover alliance. In June, Catherine I passed away. These conditions led to the expulsion of the Duke of Holstein-Gottorp, whose support was to be instrumental to Liria, from Russia.

The charter of the 'Order of the Anti-Sober' establishes Liria as Grand Master, but it also names Baron Mardefeld, Prussian Ambassador in Russia, 'Protector' of the order. It appears such courtesy towards the Prussian diplomat was made in pursuit of some clear political goals. On the one hand, by the moment of Liria's arrival to Russia in November 1727, Mardefeld had spent a full decade in St. Petersburg and probably knew more about Russian domestic politics than most of the other foreign residents. On the other hand, Mardefeld had been charged with repairing the strategic relationship between Russia and the Hanoverian Alliance, a diplomatic rapprochement that Liria was specifically tasked with preventing. The Prussian diplomat also supported the candidacy of a Saxon prince to the Polish throne, whereas Liria was intriguing in favor of an alternative claimant for the crown. Apparently, some opportunities for close and informal meetings with the Prussian diplomat as part of a mock order would be very useful for Liria.

Meanwhile, researchers have no further evidence on whether the 'Order of the Anti-Sober' was created or not. Neither reports by Liria himself, nor known papers by Mardefeld, include any intentions on creating a closed drinking club in St. Petersburg. But this does not mean that informal interaction over a bottle of wine was not used by diplomats as a political tool. It is known that the Duke of Liria hosted regular dinner parties for diplomats, the young Russian monarch, and his confidants. At such parties, over 500 bottles of wine could be emptied, and, undoubtedly, political talk was an integral part of them. As a result, Liria managed to assume very good positions at Peter II's court. Unfortunately, however, the teenage monarch died soon, and the international political situation quickly changed. As a result, Liria's embassy did not achieve any outstanding diplomatic results. Mock orders as a space for informal socializing for the elites soon started to be replaced by Masonic Lodges: Jacobites, advocates of the overthrown Stuart dynasty in Europe, played a key role in their popularization.

Cold Spring Harbor, NY -- Maize is a staple crop that came from humble beginnings. If you look at its wild ancestor, teosinte, the plant looks nearly unrecognizable. Human selection has persuaded the maize plant to grow in a way that produces higher yields and can be more efficiently harvested. But scientists and farmers are looking for ways, in the face of climate change, population growth, and other factors, to even further optimize maize yields.

Now, researchers at Cold Spring Harbor Laboratory (CSHL) have identified a relationship between crop yield in the maize plant and specific genetic activity associated with one of the plant's metabolic pathways. The discovery has implications for plant breeding, potentially opening the door for increasingly resilient, higher-yield maize plants.

CSHL Professor David Jackson and his team have connected the RAMOSA3 gene to branching, which can affect its yield. When a maize plant has too many branches, it will expend more energy towards making those branches, and less towards making seeds. More branches often means lower or less efficient yields.

Ears, the part of maize that we eat, are normally not branched at all--they just form one straight cob. But maize mutants that don't have the RAMOSA3 gene can end up with gnarly-looking branched ears.

Jackson and his team initially hypothesized that the enzyme that RAMOSA3 encodes, called TPP, and a sugar phosphate called T6P which TPP acts on, are likely responsible for the ear-branching. Although the precise function of T6P remains "largely elusive," the scientists believe that it has signaling properties.

Then, in a surprising twist, they found that a related gene, TPP4, also helps to control branching, but that gene's effect was unrelated to its enzymatic activity. They wondered if the same might be true for RAMOSA3 and its own enzymatic activity. To follow up on this, they blocked only the enzyme activity associated with RAMOSA3, and not the gene itself, and got normal-looking ears of maize. This indicates that although RAMOSA3 controls the activity of the enzyme, it seems the enzyme activity is not responsible for controlling branching. Thus, the gene may be "moonlighting" with a hidden activity, explains Jackson. The question of what that moonlighting may entail is a launching-off point for future research.

The team's findings were published in Nature Plants. Their work could lead to better crop yields and more efficient harvesting for the maize plant, as well as for other crops, like rice and quinoa.

Hamilton, ON (April 1, 2019) - The legalization of medical assistance in dying (MAID) in Canada has resulted in some people choosing to donate their bodies to anatomy programs, but it has raised profound ethical issues, says McMaster University's head of anatomy.

Bruce Wainman, director of the Education Program in Anatomy at McMaster, said the anatomical scientist community needs to establish guidelines around these donations.

The use of MAID, also known as 'active voluntary euthanasia' or 'voluntary euthanasia', is legally obtainable in Belgium, Canada, Colombia, Germany, Luxembourg, the Netherlands, Switzerland, the United States, and some parts of Australia.

As a result, Wainman said, there are issues about the appropriateness of accepting or using MAID body donations; communication with donors including consenting processes, and the transparency surrounding MAID donation with staff, faculty and students.

"These are profound questions that scrape at morals and ethics," Wainman said. "I don't think any of us have the answers right now."

His article on the topic, co-authored with medical ethicist Jon Cornwall of the University of Otago in New Zealand, was published in the journal Anatomical Sciences Education.

"At this point, it is unclear how many anatomical programs have accepted or are accepting bodies of persons who end their life using MAID, as no reliable information exists on this topic," said Wainman, professor of pathology and molecular medicine at McMaster.

"I wrote this discussion paper to raise the potential difficulties and ethical questions facing body donation programs where MAID exists, and to open the conversation. The last thing we would want to do is compromise our association with our community."

The McMaster University body donation program has accepted six MAID bodies between the time the legislation was enacted in June 2016 and November 2018.

"Right after the law was passed in Canada, the bodies began to arrive," Wainman said. "MAID makes up five per cent of our body donations now, but I can see it easily going to 10 per cent before the end of the year. That makes it five to 10 bodies a year."

Wainman said the process of receiving and using bodies from donors who undertake MAID poses many challenges for institutions like McMaster.

"We have a tremendous relationship with many people in the palliative care field, so it comes up as a discussion point: 'Are you interested in donating your body to anatomic study?'" he said. "We find the potential MAID donors are far more likely to want to donate their bodies to science. As a result, we are typically in contact with the donor themselves who reach out to us to talk about donation.

"An ethical question I face is that for these people who are so vulnerable, who are at that moment trying to decide if theirs is a life worth living, are we somehow inducing them to want to donate? Are we providing them with additional impetus to donate? It's a serious issue as the last thing we want to do is to bring about any pressure at this difficult point in their lives."

Then, there's the complexity about how to communicate the circumstances of these body donations with students in anatomy education programs at academic institutions, he noted.

Wainman said he decided upon the arrival of the first MAID body donation that his policy of transparency and openness at McMaster's anatomy program would continue. He said everyone, from faculty members to students, who interact with the body donations know the circumstances. To date, no concerns have been expressed.

"We are having discussions - important discussions - in our anatomy lab on what it means to receive a body that has not died of natural causes," he said. "On the death certificate it lists the cause which compelled them to seek MAID, not from medical assistance in death, but we are aware of the circumstances beyond that. It's important in every possible way to be transparent. Everyone we train here at McMaster has an interest in human health, and this is an additional ethical issue for them to think about.

"Human health is not just about the function of your lungs and kidneys, it's also about the person who lives in that body."

There are guidelines around body donation to anatomy facilities, such as those from the International Federation of Associations of Anatomists (2012) and the American Association of Anatomists (2009).

However, Wainman pointed out these guidelines do not refer directly to the acceptance of MAID bodies, likely due to the newness of euthanasia laws. As such, the current guidelines are silent on the use of MAID bodies in the anatomical sciences.

"Further guidance from local and international recommendations are needed to raise awareness on this sensitive topic and ensure that MAID donors are treated with respect and that good practice around MAID donations can be consistently adopted," said Wainman.

Wainman and Cornwall will be presenting on the issue at a summer meeting of the International Federation of Associations of Anatomists in London, England.

He said he expects there to be significant discussion as a result of the paper and subsequent presentations.

"This is such a new discussion for our field," he said. "I'm sure we're going to ignite a huge discussion, which is exactly the point of this article."

Wainman added that the authors consulted with Sabine Hildebrandt, a medical ethicist and associate professor of pediatrics at Harvard University.

ORLANDO, Fla., March 31, 2019 -- The sugar maple tree yields autumn foliage, maple syrup and Tennessee whiskey. Wood from the tree is chopped into planks, stacked in piles and burned to form charcoal. Freshly distilled, un-aged whiskey is filtered over the charcoal in a mysterious, but necessary step known as the Lincoln County Process (LCP). By law, a product cannot be called Tennessee whiskey without it. Researchers now say they have some clues as to what the process imparts to the final product.

The researchers will present their results today at the American Chemical Society (ACS) Spring 2019 National Meeting & Exposition. ACS, the world's largest scientific society, is holding the meeting here through Thursday. It features nearly 13,000 presentations on a wide range of science topics.

"Although Tennessee whiskey and traditional bourbon both have to be made from 51 percent corn and aged in charred oak barrels, the distinction is really this filtration step," says graduate student Trenton Kerley, who performed the work.

Even in this modern age, whiskey making is still a bit of an art form. Distillers currently adjust their product empirically at the end of a long process of brewing, filtering and aging. They blend different batches to achieve a certain flavor. But until now, no one has systematically studied the effects of the LCP step, so named for the county where the original Jack Daniel's distillery was located. John Munafo, Ph.D., leader of the study at the University of Tennessee, says that by probing the fundamental chemistry of this process, his team could help distilleries achieve the flavor profile they desire and reduce product variability.

Munafo's group partnered with the Sugarlands Distilling Company in Gatlinburg, Tennessee, to figure out how LCP affected the flavor of their Roaming Man Tennessee whiskey. To do that, the researchers first established baseline values for its flavor. They began with unfiltered whiskey provided by the distillery. They identified all of the aroma-active molecules (odorants) of the beverage using a combination of gas chromatography-mass spectrometry and gas chromatography-olfactometry, a technique by which a scientist can smell the individual components of a sample as they are separated. They then determined which of these compounds was important to the whiskey's flavor with a technique called aroma extract dilution analysis, in which aroma-active compounds are diluted until they no longer be smelled. Finally, the key odorants were quantitated by stable isotope dilution assays.

After identifying the compounds that contributed to the unfiltered whiskey's flavor, they exposed it to sugar maple charcoal also obtained from Sugarlands. Based on a procedure established by the distiller, they left the whiskey soaking in the charcoal from one to five days. Afterward, they analyzed samples by spiking them with known quantities of the odorants previously identified so they could quantify how much of each compound was removed by the LCP step.

Kerley says that based on the whiskey's smell before and after filtration, he was not surprised by the change in chemical composition, but he was surprised by how much some of the levels changed. "I was expecting it to have an effect, but I wasn't expecting as large of an effect as we saw in some of the compounds. For example, levels of some compounds declined by up to 30 percent after LCP," he says.

Now that Munafo and his student better understand how LCP changes whiskey chemically, they want to adjust some of the parameters of the filtration process. Munafo says they will run a series of experiments varying the time the unfiltered whiskey is in contact with the charcoal, and another in which the whiskey-to-charcoal ratio is systematically altered. He also wants to investigate the sensory impact of combinations of compounds that are present. "There are some 'strong' flavor compounds present in low concentrations, but then there are 'weaker' aroma-active compounds such as branched alcohols that are present at high concentrations," Munafo says. "Even though they might not be potent aroma-active compounds, they could have an effect like a perception of burning that our senses pick up."

Down the road, the data Munafo and his students collect could be used to advise distillers on exactly what changes to make to their whiskey to produce the best flavor for their unique brand. "We want to give them levers to pull so they are not blindly trying to get the flavor target they want," Munafo says.

ATLANTA -- A combination of chemotherapy and chimeric antigen receptor (CAR) T cells designed to target the protein HER2 was found to be safe and showed clinical responses in pediatric and adult patients with advanced HER2-positive sarcoma, according to results from a phase I clinical trial presented at the AACR Annual Meeting 2019, March 29-April 3.

"Children and adults with recurrent or refractory sarcomas have limited treatment options," said Shoba Navai, MD, assistant professor of pediatrics at the Center for Cell and Gene Therapy at Baylor College of Medicine, Texas Children's Hospital, and Houston Methodist Hospital in Houston. "Depending on the specific type of sarcoma, curative salvage chemotherapy regimens are available, but the chance of success is low and the therapies can be quite toxic."

While it is not known what percentage of sarcomas express HER2 on the tumor surface, osteosarcoma, one of the most common types of sarcoma, has been reported to be HER2-positive in up to 40 percent of patients, and HER2-positivity is associated with a higher likelihood of tumor metastasis, Navai explained. Prior clinical studies have shown that HER2-targeted antibodies such as trastuzumab are not effective for these patients. "Our group has previously shown in the laboratory that HER2-directed CAR T cells are better at targeting low levels of HER2 on tumor cells compared with trastuzumab, so these CAR T cells may have antitumor activity in patients with sarcoma even when HER2-antibody therapies do not," she added.

"Our study shows that HER2-targeted CAR T-cell therapy given in combination with lymphodepletion chemotherapy is safe, and though very early, it shows promising antitumor activity in some patients with advanced HER2-positive sarcomas," Navai said.

In this trial, Navai and colleagues treated 10 patients, ages 4 to 54, with refractory/metastatic HER2-positive sarcoma (five with osteosarcoma, three with rhabdomyosarcoma, and one each with Ewing sarcoma and synovial sarcoma). Patients had received up to five prior salvage therapies.

Patients received up to three infusions of HER2-targeted CAR T cells after lymphodepletion with either fludarabine or fludarabine and cyclophosphamide; those who had responses to this initial treatment received up to an additional five infusions of CAR T cells without lymphodepletion.

The investigators found that the CAR T cells expanded in all but two patients with a median peak expansion on day 7, and that they could detect the CAR T cells in all patients six weeks after infusion.

One pediatric patient whose rhabdomyosarcoma had metastasized to the bone marrow had a complete response (CR) for 12 months, but relapsed later; retreatment with CAR T cells resulted in a CR that has been ongoing for 17 months. Analysis of this patient's blood at multiple time points showed antibody responses against several intracellular proteins involved in the cell cycle, cell growth, cell signaling, and in tumor processes such as invasion and metastasis, Navai said.

"Some antibodies in this patient's blood were newly detected and maintained after CAR T-cell infusions, suggesting that in addition to the expected direct effect of the CAR T cells targeting HER2 on the tumor, they may have engaged the patient's own immune system," she added. "Further studies are needed to identify the specificities and functional significance of these responses."

One pediatric patient with osteosarcoma that had metastasized to the lungs has an ongoing CR for 32 months. Three patients had stable disease, and five had progressive disease.

Navai noted that overall, the patients on this study had limited treatment-related toxicities. All patients had expected decreases in their blood counts following chemotherapy that subsequently improved, and none developed infections secondary to low blood counts, she added.

"Importantly, no patients experienced decreased heart function, which has been reported with other types of HER2-targeted therapies. We also did not observe any pulmonary toxicities in our patients despite expansion of the infused CAR T cells," Navai said.

A limitation to the study is that this is a small phase I trial, and further testing of the HER2-specific CAR T cells in larger cohorts of patients is warranted to define efficacy and optimal dosage, Navai said.

ATLANTA - A new combination of immunotherapy and chemotherapy for pancreatic cancer caused tumors to shrink in the majority of evaluable patients - 20 out of 24 as of an interim analysis of the phase 1b trial data. The early findings provide hope that this strategy involving a CD40 antibody, a checkpoint inhibitor, and standard-of-care chemotherapy could be effective for treating the nation's third deadliest type of cancer. Researchers from the Abramson Cancer Center at the University of Pennsylvania will present the findings today in a clinical trials plenary session at the American Association for Cancer Research 2019 Annual Meeting in Atlanta (Abstract #8060). The ongoing study is being conducted in collaboration with the Parker Institute for Cancer Immunotherapy and its other member institutions and partners. These are the first clinical trial data ever presented as a result of this collaboration.

"These findings give us clues that this new and innovative combination therapy can be effective against pancreatic cancer," said the study's co-lead author Mark H. O'Hara, MD, an assistant professor of Hematology-Oncology at Penn. "Although only time and further research will truly tell, our data are a reason for optimism." O'Hara will present the plenary at 12:45 p.m. in Marcus Auditorium, Bldg A-GWCC.

Pancreatic ductal adenocarcinoma (PDAC) is the most common type of pancreatic cancer, and it kills more Americans each year than any cancer type other than lung and colorectal. Despite the fact that it only accounts for about three percent of new cancer cases, it is responsible for more than seven percent of all cancer deaths, and just 8.5 percent of patients survive five years with the disease. Previous research has shown PD-1 inhibitors are ineffective on their own against PDAC, but preclinical data showed combining PD-1 inhibitors with antibodies that target a different antigen known as CD40 can trigger an immune response.

For this study, patients with metastatic PDAC who were previously untreated received combinations of four different therapies. Each patient received gemcitabine and nab-paclitaxel, which are standard-of-care chemotherapies, as well as an experimental antibody targeting CD40 called APX005M. Half the patients also received the PD-1 inhibitor nivolumab. As of the data cutoff for the interim analysis, 20 of 24 patients (83 percent) saw their tumors shrink. Overall, although the majority of the patients experienced side effects from the treatment, they were expected and manageable, with several patients continuing on treatment for more than a year, which also suggests the combination treatment can produce a durable response.

"Seeing patients continue treatment for this length of time does give us hope that this combination approach holds promise, especially when you consider that for stage 4 pancreatic cancer, the median survival is just two to six months," said senior author Robert H. Vonderheide, MD, DPhil, director of the Abramson Cancer Center and a Parker Institute member researcher. Vonderheide previously led the first-in-human clinical trial of APX005M reported in 2017 that enabled the current study.

The Parker Institute holds the Investigational New Drug application from the U.S. Federal Drug Administration. Patients on this trial were treated at seven Parker member institutions, leveraging a unique ability to develop faster and more efficient clinical studies.

"This study represents the first illustration that our unique collaborative model, which we used to bring together partners from across academia, pharma, and biotech, can help speed the process of translating laboratory findings into efficient, impactful clinical trials in areas with high unmet medical need," said Ramy Ibrahim, MD, the chief medical officer at the Parker Institute for Cancer Immunotherapy. "Based on these early but promising findings, we are excited to see results from the next phase of the study."

In addition to Penn, Parker member institutions who treated patients on this study were Memorial Sloan Kettering Cancer Center; The University of Texas MD Anderson Cancer Center; University of California, Los Angeles; University of California, San Francisco; Stanford University; and Dana-Farber Cancer Institute.

The randomized phase two portion of the trial evaluating chemotherapy, APX005M, and/or nivolumab is currently underway.
Apexigen, which manufactures APX005M, and Bristol-Myers Squibb, which manufactures nivolumab, each supplied the drugs for this study. Additional support was provided by the Cancer Research Institute.

A combination of two common immunotherapy drugs shrinks rare, aggressive neuroendocrine tumors, according to new research results presented at the American Association for Cancer Research Annual Meeting 2019, held March 29-April 3 in Atlanta.

Results from the SWOG Cancer Research Network trial known as DART, short for Dual Anti-CTLA-4 and Anti-PD-1 Blockade in Rare Tumors, show a significant clinical benefit for patients with high-grade neuroendocrine carcinoma, a cancer of the neuroendocrine cells that often forms tumors in the lungs and along the digestive tract. This cancer is rare - about 12,000 people in the U.S. are diagnosed each year - but the general prevalence of the disease grew six-fold between 1973 and 2012. Patients with the high-grade, or rapidly growing, form have few treatment options.

"We saw a benefit in patients with high-grade carcinoma, which is the population that really needs an effective treatment option," said Sandip Patel, MD, the DART clinical study chair, an associate professor of medicine at the University of California at San Diego School of Medicine, and a medical oncologist with Moores Cancer Center at UC San Diego Health.

"These early results are really encouraging - and intriguing," Patel said. "We found a clear difference in response to treatment between the high-grade and low-grade forms of this cancer type. So tumor biology makes a difference. We don't yet know why, but we've opened another treatment arm of the trial to patients with just high-grade neuroendocrine carcinoma to see if we see the same response to the immunotherapy combination."

The DART trial, also known as S1609, is managed by SWOG, the cancer clinical trials group that is part of the National Cancer Institute's National Clinical Trials Network (NCTN). DART features an innovative "basket" design which allows the testing of a single drug or drug combination in a variety of tumor types. DART currently tests the immunotherapy combination of ipilimumab and nivolumab in patients with 37 types of rare cancers, which together make up almost a quarter of all cancers diagnosed worldwide.

Results presented at the AACR Annual Meeting 2019 represent one of the 37 cohorts of DART, in which researchers enrolled 33 patients with neuroendocrine tumors. Of those 33 patients, 19 had high-grade disease. Most patients' tumors were located in the gastrointestinal tract or the lungs. All patients received doses of ipilimumab every six weeks and doses of nivolumab every two weeks, and continue on the treatment for as long as their bodies respond to the drugs.

Results showed that 42 percent of patients with the high-grade form of neuroendocrine carcinomas saw their tumors shrink partially or completely after treatment, while none of the low-grade patients did. For all patients, 70 percent saw their cancer spread within six months. Patients survived a median of at least 11 months after treatment. Some patients are alive more than a year after treatment, and doctors continue to track their progress on the study drugs.

DART has enrolled over 550 patients since it opened in 2017 - an uncommon success for a rare cancers trial. The trial is open at over 800 hospitals, cancer centers, and community clinics across the U.S., widespread availability that is a unique feature of trials run through the NCTN and the NCI's Community Oncology Research Program.

"There's a myth that you can't successfully complete clinical trials in rare cancers," Patel said. "Researchers think it's too hard to find patients. But DART shows us that we can run rare cancer trials, and enroll patients quickly and learn if therapies are effective in rare diseases. Through the NCTN, we can also offer investigational drugs to patients right in their communities. They don't necessarily need to travel to a cancer center to get enrolled in a clinical trial."

ATLANTA -- Adding the investigational MET inhibitor savolitinib to the EGFR inhibitor osimertinib (Tagrisso) yielded clinical responses in patients who had EGFR-mutant non-small cell lung cancer (NSCLC) that had developed resistance to prior EGFR-targeted therapies through MET-gene amplification, according to interim results from two expansion cohorts of the phase Ib clinical trial TATTON, presented at the AACR Annual Meeting 2019, March 29-April 3.

"To date, targeted therapy for lung cancer patients with EGFR mutations has consisted solely of monotherapy with various EGFR tyrosine kinase inhibitors (TKIs), though we have known for more than 10 years that a proportion of resistance to EGFR TKIs results from activation of the MET bypass pathway," said Lecia V. Sequist, MD, MPH, a thoracic medical oncologist and director of the Center for Innovation in Early Cancer Detection at Massachusetts General Hospital Cancer Center.

Prior research has shown that MET amplification is a bypass pathway observed in about 5 to 10 percent of patients whose disease has progressed after treatment with first- or second-generation EGFR TKIs and in about 25 percent of those whose disease has progressed after treatment with third-generation EGFR TKIs, Sequist explained.

Prior clinical trials of combinations of EGFR- and MET-targeted therapeutics have not been successful, partly due to the drug combinations studied, and largely because patients were not chosen based on appropriate biomarkers, Sequist said. "In the TATTON trial, newer TKIs that have increased specificity for EGFR and MET are used, and patients with EGFR-mutant NSCLC are required to have documented MET-driven resistance," she added.

Interim results from two distinct expansion cohorts are presented here. In the first cohort, a combination of osimertinib and savolitinib was tested in patients with EGFR-mutant lung cancer with acquired resistance driven by MET amplification after treatment with a first- or second-generation EGFR TKI; these patients' tumors were also negative for T790M mutation. In the second cohort, the same combination was tested in patients with EGFR-mutant lung cancer with acquired resistance driven by MET amplification after treatment with osimertinib or another experimental third-generation EGFR TKI.

"Data from the TATTON trial demonstrate for the first time the benefit of adding a MET inhibitor to an EGFR inhibitor in patients with EGFR-mutant NSCLC and with MET-driven acquired resistance," Sequist said. "The study has shown efficacy of combination targeted therapy in a patient population for whom chemotherapy is the current primary treatment option.

"This finding illustrates the value of careful patient selection in studies of targeted therapies," Sequist said, adding, "These clinically meaningful responses also demonstrate that as different heterogeneous resistance clones come up, they can in turn be brought under control by tailoring therapy."

In the cohort of 46 patients who had received prior first- or second-generation EGFR TKI, treatment with osimertinib plus savolitinib yielded an objective response rate (ORR) of 52 percent, with 24 partial responses. The median duration of response (DOR) was 7.1 months.

In the cohort of 48 patients who had received prior third-generation EGFR TKI, treatment with osimertinib plus savolitinib yielded an ORR of 28 percent, with 12 partial responses. The median DOR was 9.7 months.

"Overall the regimen was tolerable, though there was added toxicity with the combination of osimertinib and savolitinib compared to osimertinib given alone, and we saw that some patients discontinued treatment due to toxicity," Sequist said. The most frequent adverse events were nausea, diarrhea, and lowered numbers of leukocytes and platelets.

One patient, who had brain metastases, died from kidney failure a few days after starting the combination treatment. The treating investigator considered that this serious adverse event was difficult to evaluate with respect to relation to the study drugs, Sequist said. "Our understanding of the adverse event profile of the osimertinib-savolitinib combination, and how to manage the adverse events, is improving," she added.

Since the initiation of the TATTON trial, osimertinib was approved for treatment in first-line setting for patients with EGFR-mutant NSCLC. Because of this, only a subset of patients in the trial had received prior first-line osimertinib and had developed MET-driven resistance. "The newly opened phase II SAVANNAH study will further explore the combination of osimertinib plus savolitinib in patients whose disease has progressed on osimertinib and is MET-positive," Sequist said.

These are early-phase trials and the findings need confirmation in larger trials, Sequist noted.

ORLANDO, Fla., March 31, 2019 -- As current antibiotics dwindle in effectiveness against multidrug-resistant pathogens, researchers are seeking potential replacements in some unlikely places. Now a team has identified bacteria with promising antibiotic activity against known pathogens -- even dangerous organisms, such as the microbe that causes MRSA infections -- in the protective mucus that coats young fish.

The researchers will present their results today at the American Chemical Society (ACS) Spring 2019 National Meeting & Exposition. ACS, the world's largest scientific society, is holding the meeting here through Thursday. It features nearly 13,000 presentations on a wide range of science topics.

"For us, any microbe in the marine environment that could provide a new compound is worth exploring," says Sandra Loesgen, Ph.D., the group's principal investigator.

According to Loesgen, who is at Oregon State University, while novel chemical reagents have been found in the human microbiome, the marine equivalent remains relatively unstudied. One potential goldmine of microbes is the mucus that coats the surfaces of fish. This viscous substance protects fish from bacteria, fungi, and viruses in their environment, trapping the microbes before they can cause infections. The slime is also rich in polysaccharides and peptides known to have antibacterial activity.

"Fish mucus is really interesting because the environment the fish live in is complex," says Molly Austin, an undergraduate chemistry student in Loesgen's laboratory, who conducted some of the studies. "They are in contact with their environment all the time with many pathogenic viruses." According to Austin, it would be interesting to figure out if anything in the mucus, which protects the fish, could actually help protect humans.

Collaborator Erin (Misty) Paig-Tran, Ph.D., who is at California State University, Fullerton, supplied the mucus, swabbed from juvenile deep-sea and surface-dwelling fish caught off the Southern California coast. The team examined young fish because they have a less-developed immune system and more mucus on the outside of their scales that could contain a greater concentration of active bacteria than adult fish.

Loesgen, Austin and graduate student Paige Mandelare isolated and screened 47 different strains of bacteria from the slime. Five bacterial extracts strongly inhibited methicillin-resistant S. aureus (MRSA), and three inhibited Candida albicans, a fungus pathogenic to humans. A bacteria from mucus derived from a particular Pacific pink perch showed strong activity against MRSA and against a colon carcinoma cell line. Austin is now focusing her work on the Pseudomonas aeruginosa, a Gram-negative bacteria derived from that fish, to study the many potentially interesting phenazine natural products and antibiotics that this bacteria makes.

While the team members are interested in new sources for antibiotics to help humans, they are also looking at other ways to apply this knowledge. For example, the study of fish mucus could also help reduce the use of antibiotics in fish farming by leading to better antibiotics specifically targeted to the microbes clinging to certain types of fish.

But first, the researchers want to understand more fundamental questions. For example, "We don't even know what a healthy microbiome is," Loesgen says. She explains that it's unclear whether the bacteria they studied in the fish slime were typical of their microbiomes and are protecting their hosts, or if these bacteria just happened to hitch a ride on these individual fish. Learning more about healthy fish microbiomes and how environmental factors in the Pacific can affect them could help inform conservation efforts, the researchers say.

ORLANDO, Fla., March 31, 2019 -- The U.S. opioid epidemic is being driven by an unprecedented surge in deaths from fentanyl and other synthetic opiates. Fentanyl's powerful effects are long-lasting, and even tiny amounts of the drug can lead to an overdose. Antidotes, such as naloxone, do not last long enough in the body to fully counter the drug, requiring repeated injections. Now, scientists report that they are developing single-dose, longer-lasting opioid antidotes using polymer nanoparticles.

The researchers will present their results today at the American Chemical Society (ACS) Spring 2019 National Meeting & Exposition. ACS, the world's largest scientific society, is holding the meeting here through Thursday. It features nearly 13,000 presentations on a wide range of science topics.

"We became interested in this problem while trying to make non-addictive pain medications," Saadyah Averick, Ph.D., says. "In that course of research, we realized the limitations of current opioid antidotes."

According to the U.S. Centers for Disease Control, opioids, such as heroin, oxycodone and fentanyl, were implicated in more than 47,000 deaths from overdose in 2017. These drugs all bind to the mu opioid receptor (MOR) in the brain, which is the body's natural pleasure receptor, explains Averick, a scientist at Allegheny Health Network Research Institute. "The drugs bind, turn on the receptor and stimulate a euphoric feeling. The synthetic opioids, such as fentanyl, turn this on really, really well," he says.

And their effects are long-lasting. Fentanyl, which is much stronger than morphine, another opioid, can be absorbed into fat tissue, which protects it from being metabolized right away. It is then slowly released from this tissue, causing effects for several hours. Naloxone, an MOR antagonist and antidote, only stays in the system for about 30 minutes to an hour, however. Because of this mismatch, repeated doses are required to help the patient recover. But not all patients want to undergo the entire treatment course, and they can end up succumbing to an overdose after the naloxone is metabolized.

To overcome this challenge, Averick and his colleagues developed a drug delivery system intended to ensure that a steady, sufficient dose of antagonist is delivered over 24 hours. The researchers reacted naloxone, which has a multi-ringed chemical structure, with polylactic acid (PLA), thus creating a naloxone polymer. They then prepared covalent nanoparticles (CNPs) by adding this polymer to a solution of polyvinyl alcohol. They used a variety of analytical methods to purify and analyze the resulting particles, which are 300 nanometers in diameter.

"In collaboration with the Benedict Kolber laboratory at Duquesne University, proof-of-concept research has shown that these nanoparticles can deliver sufficient naloxone in a linear time-release fashion to block morphine's analgesic effect for 24 hours," Averick notes. "As a next step, the study will be extended to fentanyl." Although the most recent work was performed with mice, future studies will include an animal model that more closely simulates how humans metabolize opioids.

The researchers are also planning to investigate how particle size impacts naloxone release from the nanoparticle. "Ultimately, we hope to develop a therapeutic intervention for fentanyl overdose that can be used in the field, perhaps supplanting short-acting naloxone as an overdose antidote of choice," Averick says. "We anticipate that this drug delivery system will also be effective for other non-fentanyl opioids."

Given the fact that naloxone and the other compounds the team uses are already deemed safe, Averick predicts that the time-to-market could be less than five years for the nanoparticle system.

Yokohama, Japan 30 March 2019: Trips to the toilet at night are a sign of high blood pressure, according to results from the Watari study presented today at the 83rd Annual Scientific Meeting of the Japanese Circulation Society (JCS 2019).

"Our study indicates that if you need to urinate in the night - called nocturia - you may have elevated blood pressure and/or excess fluid in your body," said study author Dr Satoshi Konno, of the Division of Hypertension, Tohoku Rosai Hospital, Sendai, Japan. "If you continue to have nocturia, ask your doctor to check your blood pressure and salt intake."

JCS 2019 takes place from 29 to 31 March in Yokohama. Joint scientific sessions are being held by the European Society of Cardiology (ESC) and JCS as part of the ESC Global Activities programme.1

Previous research from Japan has reported that high salt intake is associated with nocturia.2 Compared to western countries, people in Japan eat more salt and are more likely to be "salt sensitive", meaning that their blood pressure rises more when salt is consumed. Taken together, these two factors mean that people in Japan are at greater risk of developing high blood pressure.

This study examined the link between nocturia and hypertension in the general Japanese population. The study enrolled 3,749 residents of Watari who had an annual health check in 2017. Blood pressure was measured and information on nocturia was obtained by questionnaire. Participants with blood pressure 140/90 mmHg or higher or prescribed antihypertensive drugs were considered hypertensive.

Nocturia (one or more nocturia events per night) was significantly associated with hypertension after controlling for possible confounders (odds ratio 1.4; p

"We found that getting up in the night to urinate was linked to a 40% greater chance of having hypertension," said Dr Konno. "And the more visits to the toilet, the greater the risk of hypertension."

Of the 1,882 participants who answered the questionnaire, 1,295 (69%) had nocturia. Dr Konno said the results do not prove a causal relationship between nocturia and hypertension and may not apply to populations outside Japan. He said: "The relationship may be influenced by various factors including lifestyle, salt intake, ethnicity, and genetic background."

Dr Mutsuo Harada, press coordinator for JCS 2019, said: "Hypertension is a national disease in Japan. The average salt intake in Japan is approximately 10 g/day, which is more than double the average salt intake worldwide (4 g/day). This excessive salt intake is related to our preference for seafood and soy sauce-based food, so salt restriction is difficult to carry out. Early detection and management of hypertension are very important to prevent cardiovascular diseases. We should keep in mind that nocturia is not only caused by urinary organ problems but also by systemic diseases such as hypertension."

ESC President Professor Barbara Casadei said: "More than one billion people have high blood pressure worldwide. High blood pressure is the leading global cause of premature death, accounting for almost ten million deaths in 2015. ESC guidelines recommend medication to reduce the risk of stroke and heart disease.3 A healthy lifestyle is also advised, including salt restriction, alcohol moderation, healthy eating, regular exercise, weight control, and smoking cessation."

A new study published in the April 2019 issue of the American Journal of Roentgenology (AJR) considers several potential factors that might have led to disparities in follow-up imaging rates among patients with indeterminate initial abdominal imaging findings.

The study, "Patient Factor Disparities in Imaging Follow-Up Rates After Incidental Abdominal Findings," reviewed the records of 1588 patients with inconclusive abdominal imaging results consecutively registered between July 1, 2013, and March 20, 2014. Factors studied included distance between the flagship hospital of the health system patients' home zip codes, age, race, and health insurance status.

Of the 1,513 patients included in the study, 554 (36.62%) did not undergo follow-up abdominal imaging within 1 year of the index abdominal imaging. Follow-up rates varied depending on the initial patient setting. More than 60 percent of the emergency department patients in the study did not undergo follow-up imaging, while less than 30 percent of outpatients failed to complete their follow-up imaging.

The study also found that those at the extremes of age had lower rates of follow-up completion. Of the 959 patients who received follow-up imaging, 9.28% were younger than 40 years, compared 13.72% of patients who did not receive follow-up imaging. Only 5.63% of patients who underwent follow-up imaging were older than 80 years, compared with 12.64% patients who did not undergo follow-up imaging.

While the study found emergency department patients and those at the extremes of age had lower rates of follow-up completion, the authors recommend further investigation of additional factors that may influence rates of follow-up imaging. For example, more white patients and fewer black patients were found in the follow-up imaging group, but the authors caution that "confounders may affect this conclusion."

A new study published in the April 2019 issue of the American Journal of Roentgenology (AJR) investigates the safety of uterine artery embolization (UAE) for symptomatic leiomyomas in patients with various autoimmune diseases.

Between January 2007 and June 2018, 1183 consecutive patients underwent UAE for symptomatic leiomyomas at Yonsei University College of Medicine. Nine of those patients with autoimmune disease ranging in age from 34-49 years (mean age of 42.6 years) were included in the study, "Uterine Artery Embolization in Patients With Autoimmune Disease: A Matched Case-Control Study." All UAE procedures were performed by one interventional radiologist with 16 years of UAE experience.

Using the patient registry, researchers randomly generated an age- and disease-matched control group (n = 8) to compare volume reduction rates of the uterus and dominant leiomyoma and the change in C-reactive protein (CRP) levels before and after UAE to evaluate the safety and effectiveness of UAE in patients with autoimmune disease. The authors defined clinical success as "improvement or resolution of symptoms" following UAE and technical success as "successful embolization of the bilateral uterine arteries."

UAE was technically and clinically successful in all patients in both groups. No significant difference was found between the autoimmune and control groups in the volume reduction rates of uterus and dominant leiomyoma. However, CRP level in the autoimmune patient group was found to be significantly higher 1 day after UAE (1.23 ± 0.6 mg/L vs 9.54 ± 6.63 mg/L; p = 0.001).

While the authors conclude UAE appears to be safe and effectual in the management of symptomatic leiomyoma in patients with autoimmune disease that is well controlled, they note that due to the inclusion of a variety of autoimmune diseases in the case series, a small sample size, and the retrospective nature of the study, the results should be interpreted with some caution.