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New Rochelle, NY, April 24, 2018--Researchers have incorporated therapeutic microRNAs (miRNAs) into bioresorbable, silk-based medical devices such as screws and plates to achieve local delivery of factors that can improve bone growth and mineralization at the site of bone repair. The study, which demonstrated the promise of silk-based orthopedic devices combined with bioactive miRNA-based therapeutics, is published in Tissue Engineering, Part A, peer-reviewed journal from Mary Ann Liebert, Inc., publishers. The article is available free on the Tissue Engineering website until May 24, 2018.

Eric James, Emily Van Doren, Chunmei Li, and David Kaplan, Tufts University, Medford, MA describe the method they used to deliver the antisense therapeutic miR-214 in the article entitled "Silk Biomaterials-Mediated miRNA Functionalized Orthopedic Devices." The article is part of an upcoming special issue of Tissue Engineering on "RNA Therapeutics for Tissue Engineering" led by Guest Editors Elizabeth Balmayor, PhD, Technical University of Munich, Germany and Christopher Evans, PhD, DSc, Mayo Clinic, Rochester, MN.

The researchers coated the surface of bioresorbable silk-based devices used in bone repair with antisense-miR-214 and also studied the use of antisense-miR-214 silk films seeded with human mesenchymal stem cells (hMSCs). The results showed that miR-214 was released continuously for up to 7 days in vitro and could block the production of proteins that downregulate new bone formation.

"This study leverages tissue engineering principles for the design of medical devices with enhanced biocompatibility," says Tissue Engineering Co-Editor-in-Chief Antonios G. Mikos, PhD, Louis Calder Professor at Rice University, Houston, TX.

Have you ever wondered why animals avoid dangers by sensing some "signs" possibly related to the danger? A simple form of this phenomenon is called "fear conditioning", which is a type of learning commonly seen in every animal on the earth. By manipulating activity of specific neurons of the zebrafish brain, scientists at the National Institute of Genetics (NIG) in Japan have elucidated a neuronal population essential for fear conditioning in zebrafish. The study, published in the April 25 issue of BMC Biology, suggests that such a neural circuit essential for fear conditioning exists and is conserved during vertebrate evolution.

How can animals avoid dangers to survive? If animals experienced dangerous events together with some "signs", animals memorize the sign, became in fear of it, and perform fear responses, for instance an escape behavior. This is a type of learning, which is called "fear conditioning". In mammals including humans, the amygdala, one of the structures of the brain, plays an important role in fear conditioning. However, how the brain structure and neural circuits essential for fear conditioning have been conserved (or changed) during vertebrate evolution has not been known. Zebrafish, a popular model animal in biological studies, can perform fear conditioning as well as human and other mammals. Professor Kawakami's group has succeeded in developing technologies for visualizing and manipulating specific brain neurons in zebrafish by employing the yeast transcription factor Gal4, the green fluorescent protein (GFP), and the botulinum neurotoxin (BoTx). They have generated a collection of transgenic fish lines being used to study brain functions as well as other various organs by zebrafish researchers all over the world. Of the nearly 2,000 such transgenic fish lines in his lab, one played an important role in the current study that labels neurons in the dorsomedial (Dm) area of the telencephalon of zebrafish.

"In mammals including human and mouse, fear conditioning is mediated by a brain area called the amygdala. The amygdala integrates information about dangerous events, like electric shock, and some signs, such as visual or auditory stimuli. However, in fish, such neurons have not been found." Prof. Kawakami said.

"It is important to explore such neurons in fish because we can increase the knowledge about fundamental neural circuits for animals to perform evolutionary conserved fear conditioning"

For this purpose, Dr. Lal, a former graduate student in his lab, developed a behavioral analysis system. Fish are placed with a small tank with two compartments. Green LEDs are not harmful to fish. They gave electric shocks while green LEDs are on ten times a day for five consecutive days. Finally, when green LEDs are on, fish learned to escape from the compartment which was illuminated, and moved to another compartment.

"It is fun to see how smart they are" Dr. Lal said.

Using these technologies and resources, they have found that neurons in the region called Dm of the telencephalon of fish are essential for fear conditioning. Namely, these neurons are a functional equivalent of the amygdala of mammals. This result is a clue to clarify the structure and evolution of the neural circuit essential for fear conditioning.

Prof. Kawakami showed us his zebrafish facility where thousands of fish tanks can be seen, each of which contains genetically different fish that can turn on, or drive the GFP or BoTx expression in different types of neurons in the brain or in the body.

"This work showcases a successful application of our genetic resources in the study of the brain function. It is also expected to be the basis for clarifying the causes and treatment of diseases involving fear and anxiety and PTSD.", Prof. Kawakami said.

Researchers at Carnegie Mellon University have used an inexpensive 3-D printer to produce flat plastic items that, when heated, fold themselves into predetermined shapes, such as a rose, a boat or even a bunny.

Lining Yao, assistant professor in the Human-Computer Interaction Institute and director of the Morphing Matter Lab, said these self-folding plastic objects represent a first step toward products such as flat-pack furniture that assume their final shapes with the help of a heat gun. Emergency shelters also might be shipped flat and fold into shape under the warmth of the sun.

Self-folding materials are quicker and cheaper to produce than solid 3-D objects, making it possible to replace noncritical parts or produce prototypes using structures that approximate the solid objects. Molds for boat hulls and other fiberglass products might be inexpensively produced using these materials.

Yao will present her group's research on this method, which she calls Thermorph, at CHI 2018, the Conference on Human Factors in Computing Systems, April 21-26 in Montreal, Canada.

Other researchers have explored self-folding materials, but typically have used exotic materials or depended on sophisticated processing techniques not widely available. Yao and her research team were able to create self-folding structure by using the least expensive type of 3-D printer -- an FDM printer -- and by taking advantage of warpage, a common problem with these printers.

"We wanted to see how self-assembly could be made more democratic --accessible to many users," Yao said.

FDM printers work by laying down a continuous filament of melted thermoplastic. These materials contain residual stress and, as the material cools and the stress is relieved, the thermoplastic tends to contract. This can result in warped edges and surfaces.

"People hate warpage," Yao said. "But we've taken this disadvantage and turned it to our advantage."

To create self-folding objects, she and her team precisely control this process by varying the speed at which thermoplastic material is deposited and by combining warp-prone materials with rubber-like materials that resist contracture.

The objects emerge from the 3-D printer as flat, hard plastic. When the plastic is placed in water hot enough to turn it soft and rubbery -- but not hot enough to melt it -- the folding process is triggered.

Though they used a 3-D printer with standard hardware, the researchers replaced the machine's open source software with their own code that automatically calculates the print speed and patterns necessary to achieve particular folding angles.

"The software is based on new curve-folding theory representing banding motions of curved area. The software based on this theory can compile any arbitrary 3-D mesh shape to an associated thermoplastic sheet in a few seconds without human intervention," said Byoungkwon An, a research affiliate in HCII.

"It's hard to imagine this being done manually," Yao said.

Though these early examples are at a desktop scale, making larger self-folding objects appears feasible.

"We believe the general algorithm and existing material systems should enable us to eventually make large, strong self-folding objects, such as chairs, boats or even satellites," said Jianzhe Gu, HCII research intern.

April 24, 2018 - About 2.6 million American children and adolescents had diagnosed anxiety and/or depression in 2011-12, reports an analysis of nationwide data in the Journal of Developmental & Behavioral Pediatrics, the official journal of the Society for Developmental and Behavioral Pediatrics. The journal is published by Wolters Kluwer.

The number of children with diagnosed anxiety - but not depression - has increased in recent years, according to the new report. The lead author was Rebecca H. Bitsko, PhD, of the National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention.

Study Shows High Rates and Impact of Anxiety and Depression in American Youth

The researchers analyzed data from the nationally representative National Survey of Children's Health for the years 2003, 2007, and 2011-12. In the most recent year, more than 65,000 parents were asked about problems with anxiety and/or depression (diagnosed by a doctor or other healthcare professional) in their children aged six to 17 years.

In the 2011-12 survey, 5.3 percent of children and teens had current anxiety or depression. The prevalence of current anxiety increased significantly between surveys: from 3.5 percent in 2007 to 4.1 percent in 2011-12. By comparison, the prevalence of current depression showed no significant change: 2.5 and 2.7 percent, respectively.

"These estimates correspond with approximately two million children aged six to 17 years in 2011-12 with current anxiety, 1.4 million children with current depression, 2.6 million with current anxiety or depression, and 760,000 children with both," Dr. Bitsko and coauthors write. The percentage of children who had ever been diagnosed with anxiety or depression increased from 5.4 percent in 2003 to 8.4 percent in 2011-12.

Children with anxiety and/or depression were more likely to have other diagnosed chronic health conditions as well, including neurobehavioral disorders and obesity. Even after adjustment for other health problems, the presence of anxiety or depression was associated with increased use of healthcare services, more problems at school, and higher levels of aggravation for parents.

"Despite significant healthcare needs, nearly 20 percent of children with anxiety or depression did not receive mental health treatment in the past year," Dr. Bitsko and coauthors write. Only about one-third of the children with anxiety or depression had a "medical home" - that is, a usual source of healthcare with referrals and care coordination, if needed.

Based on repeated surveys of a nationwide sample of parents, the study provides new information on the burden of anxiety and depression among US children and adolescents. The reasons for the increase in parent-reported anxiety are unclear. This trend may reflect improved identification or increased use of mental health services, or an increase in the number of children experiencing anxiety symptoms, the authors suggest.

Based on repeated surveys in nationally representative samples, the study provides new insights into the prevalence and burden of anxiety and depression in children and teens. The researchers note that the national estimates are lower than data from community-based studies, "suggesting that child anxiety may be under-diagnosed."

"Children with anxiety and depression may have needs that go beyond diagnosis and mental health treatment," Dr. Bitsko comments, "Anxiety and depression are associated with school problems, parenting stress, and unmet medical needs. Parents, healthcare providers, and teachers can look for ways to support children with anxiety and depression in all areas of the child's life." The researchers emphasize the need for further research to identify factors associated with the increased prevalence of anxiety, and to evaluate how improved care coordination and other strategies can improve the health and well-being of children with anxiety and depression.

Ratings, ride assignments and other aspects of Uber's ride-sharing computer platform in some ways subtly serve as the manager for the company's drivers, according to an international team of researchers.

In a study of Uber drivers' discussions, the researchers said that the ride-sharing company's platform seems to perform similar roles to human managers. However, the drivers have little ability to voice grievances, pitch ideas to work better with customers, or influence policy changes as they might with a human manager, said Benjamin Hanrahan, assistant professor of information sciences and technology.

"There has been some work on algorithms as managers and how people interact with algorithmic management, but this looks more deeply at how the platform embodies the management philosophy and how you can judge the ethical nature of that management philosophy," said Hanrahan.

According to the researchers, Uber's platform primarily addresses the needs of people who are looking for a ride, which may mean that drivers' concerns do not have equal weight.

"All of Uber's different management decisions are embodied in the platform as the company's platform is actually doing the management," said Hanrahan. "When we looked at it, Uber's platform seems to focus on one user -- the person who wants a ride -- somewhat at the expense of the drivers."

Most Uber drivers indicated they joined the ride-share service because of the autonomy it offered. However, the platform reinforces the idea that the job is a blur between employee and independent contractor, said Hanrahan.

"Uber -- at least legally -- views drivers as independent from the company," said Hanrahan. "But if you look at the way the platform relates to the drivers, they are treated as employees, in some ways, and as contractors in others. The drivers, who identify as independent, tend to chafe when they perceive the platform is trying to manage them."

For example, if drivers are independent, they should have more say in who they choose as riders, but the platform does not allow drivers to make those choices, Hanrahan added.

The researchers, who present their findings at the CHI Conference today (April 24) in Montreal, studied posts on an active Uber internet forum, which is independent from the company. The site has 93,000 active members and 150,000 discussions. They focused mainly on the most relevant posts in the advice, complaints and technology sections from January 2014 to April 2017.

"What we were really looking at is what were these drivers dealing with -- what did they like about driving, what did they not like about driving, and what role did the platform have in this," said Hanrahan.

The researchers framed their study in stakeholder theory, a management ethics concept that suggests that a company's managers should make decisions based on the considerations of all parties, including workers, rather than just basing their initiatives exclusively on stockholders.

In the future, the researchers will study using interfaces to improve the relationship between the driver and rider, said Ning F. Ma, doctoral student in information sciences and technology, who worked with Hanrahan.

"We want to present the driver, not just as a driver, but as a person with the back stories of the area and present them as someone who is a local expert," said Ma. "The drivers could recommend places to riders through the interface, for example. We're thinking of installing a tablet in the dashboard of the vehicle as one possible interface for this."

Hanrahan said this is a step toward making the driver more integral in Uber's stakeholder structure.

"This is one of the grander directions we're taking," said Hanrahan. "How can you make the stakeholder structure simpler and make it more driver- and rider-run?"

Bipartisan users, who try to bridge the echo chambers, need to pay a price for their work: they become less central in their own network, lose connections to their communities and receive less endorsements from other users.

A recent study of more than 2.7 billion tweets between 2009 and 2016 confirms that Twitter users are exposed mainly to political opinions that agree with their own. It is the largest study to characterise echo chambers by both the content in them and the networks they comprise. The findings indicate a strong correlation between biases in the content people both produce and consume. In other words, echo chambers are very real on Twitter.

'An echo chamber exists if the leaning of the content received by Twitter users is in par with the leaning of the content they share. An opinion echoes back to the user when it is being shared by others in the chamber, the social network around the user,' explains professor Aristides Gionis from Aalto University.

The study identifies three essential roles for Twitter users. Partisan users both consume and produce content with only a one-sided leaning and enjoy high appreciation measured by both network centrality and content endorsement. Gatekeepers have a central role in the formation of echo chambers because they consume content with diverse leanings but choose to produce only content with a one-sided leaning. Bipartisan users produce content with both leanings and make an effort to bridge the echo chambers, but they are less valued in their networks than their partisan counterparts.

The researchers from Aalto University, University of Helsinki and Qatar Computing Research Institute have created machine learning algorithms to predict the roles of users in several datasets. They were able to predict partisan users with nearly 80% accuracy and gatekeepers with 70% accuracy based on their tweets and network. Network centrality was measured in the underlying social network of Twitter users, and endorsement was measured in terms of the number of times a user's message is either re-posted or rated positively by other users in the network.

'Gatekeepers are a small group of users who have higher than average network centrality. However, the users that gatekeepers follow are not always connected with each other; instead, they belong to opposing sides. Finding and connecting the gatekeepers would help spread information to both sides, even though they are more challenging to identify than partisan users,' explains postdoctoral researcher Kiran Garimella, currently working at EPFL in Lausanne.

The price to pay for being bipartisan was studied for the first time on social networks. Producing content that expresses opinions aligned with both sides of a political divide has a price in terms of various aspects including network position, community connections, and content endorsement.

'In other words, the content produced by bipartisan users receives less attention - their tweets are re-posted less frequently by other users,' says professor Michael Mathioudakis from the University of Helsinki.

For all the datasets, in order to ensure that bot accounts were not included in the study, the researchers removed accounts with less than one year of activity at the time of data collection or with any abnormal features, such as suspiciously high number of connections.

'The study was aimed at understanding the interplay between the structure of echo chambers and the role of Twitter users on a scale larger than ever before,' adds Garimella.

'Our motivation was to understand how the social media users perceive the world through their Twitter feed. In future work, we are going to look more closely into different user roles and try to understand who are the users that shape online debates and how, adds Mathioudakis.

The study is presented at this year's international Web Conference (WWW2018) in Lyon, France.

A new RAND Corporation paper finds that artificial intelligence has the potential to upend the foundations of nuclear deterrence by the year 2040.

While AI-controlled doomsday machines are considered unlikely, the hazards of artificial intelligence for nuclear security lie instead in its potential to encourage humans to take potentially apocalyptic risks, according to the paper.

During the Cold War, the condition of mutual assured destruction maintained an uneasy peace between the superpowers by ensuring that any attack would be met by a devastating retaliation. Mutual assured destruction thereby encouraged strategic stability by reducing the incentives for either country to take actions that might escalate into a nuclear war.

The new RAND publication says that in coming decades, artificial intelligence has the potential to erode the condition of mutual assured destruction and undermine strategic stability. Improved sensor technologies could introduce the possibility that retaliatory forces such as submarine and mobile missiles could be targeted and destroyed.

Nations may be tempted to pursue first-strike capabilities as a means of gaining bargaining leverage over their rivals even if they have no intention of carrying out an attack, researchers say. This undermines strategic stability because even if the state possessing these capabilities has no intention of using them, the adversary cannot be sure of that.

"The connection between nuclear war and artificial intelligence is not new, in fact the two have an intertwined history," said Edward Geist, co-author on the paper and associate policy researcher at the RAND Corporation, a nonprofit, nonpartisan research organization. "Much of the early development of AI was done in support of military efforts or with military objectives in mind."

He said one example of such work was the Survivable Adaptive Planning Experiment in the 1980s that sought to use AI to translate reconnaissance data into nuclear targeting plans.

Under fortuitous circumstances, artificial intelligence also could enhance strategic stability by improving accuracy in intelligence collection and analysis, according to the paper. While AI might increase the vulnerability of second-strike forces, improved analytics for monitoring and interpreting adversary actions could reduce miscalculation or misinterpretation that could lead to unintended escalation.

Researchers say that given future improvements, it is possible that eventually AI systems will develop capabilities that, while fallible, would be less error-prone than their human alternatives and therefore be stabilizing in the long term.

"Some experts fear that an increased reliance on artificial intelligence can lead to new types of catastrophic mistakes," said Andrew Lohn, co-author on the paper and associate engineer at RAND. "There may be pressure to use AI before it is technologically mature, or it may be susceptible to adversarial subversion. Therefore, maintaining strategic stability in coming decades may prove extremely difficult and all nuclear powers must participate in the cultivation of institutions to help limit nuclear risk."

RAND researchers based their perspective on information collected during a series of workshops with experts in nuclear issues, government branches, AI research, AI policy and national security.

"Will Artificial Intelligence Increase the Risk of Nuclear War?" is available at http://www.rand.org.

The perspective is part of a broader effort to envision critical security challenges in the world of 2040, considering the effects of political, technological, social, and demographic trends that will shape those security challenges in the coming decades.

Funding for the Security 2040 initiative was provided by gifts from RAND supporters and income from operations.

The research was conducted within the RAND Center for Global Risk and Security, which works across the RAND Corporation to develop multi-disciplinary research and policy analysis dealing with systemic risks to global security. The center draws on RAND's expertise to complement and expand RAND research in many fields, including security, economics, health, and technology.

OAK BROOK, Ill. - A novel technique that delivers high doses of radiation to tumors while sparing the surrounding normal tissue shows promise as a curative treatment option for patients with early-stage liver cancer, according to a study published online in the journal Radiology.

Curative treatment options for early-stage hepatocellular carcinoma (HCC), the most common type of liver cancer, include surgery, liver transplantation and radiofrequency ablation. However, many patients are not candidates for these therapies due to the presence of other conditions. In addition, these treatments carry significant costs and potential complications.

Radiation segmentectomy (RS) is a minimally invasive option that uses the radioisotope yttrium-90 (Y90) to destroy tumors. The isotope is embedded into tiny beads that are delivered through a catheter into a blood vessel in the liver. They then travel to the site of the tumor, where they come to rest and deliver their radioactive effect while sparing much of the surrounding healthy tissue.

The procedure's name derives from the fact that surgeons divide the liver into a number of segments. Using an imaging approach called cone beam CT, interventional radiologists gain a detailed view of the complex liver vasculature and can focus delivery of the Y90 to the relevant segment.

"Cone beam CT has revolutionized our ability to perform segmental injections isolated to very small tumors, sparing the majority of normal tissue," said study senior author Riad Salem, M.D., chief of vascular interventional radiology in the Department of Radiology at the Northwestern University Feinberg School of Medicine in Chicago. "Before cone beam CT, we had the ability to focus radiation, but not with this level of accuracy."

Dr. Salem and colleagues studied long-term outcomes in 70 early-stage HCC patients who had undergone RS between 2003 and 2016. They analyzed the patients' responses to treatment based on two commonly used sets of criteria.

Based on one criteria, 90 percent of patients showed positive response to the therapy, of which 59 percent showed complete response. Based on a second criteria, 71 percent achieved positive response, of which 16 percent achieved complete response.

RS controlled the target tumor, slowed the time to disease progression and improved survival outcomes at rates comparable to radiofrequency ablation, surgery and transplantation for early-stage HCC patients.

Almost three-quarters of patients had no progression of cancer in the target tumor five years after treatment. Median overall survival was 6.7 years, and one-, three-, and five-year survival probabilities were 98 percent, 66 percent and 57 percent, respectively. One-, three-, and five-year overall survival probability was 100 percent, 82 percent and 75 percent in patients with a baseline tumor size of 3 centimeters or less.

"The results show that we are able to impart curative outcomes to these patients," Dr. Salem said. "Our numbers with radiation segmentectomy match or outperform those of other curative treatments in terms of tumor control, survival rate and recurrence."

RS is performed on an outpatient basis, is minimally invasive and has a low toxicity profile, Dr. Salem said. Given the potency of the radiation, RS outperforms transarterial chemoembolization, another minimally invasive procedure in which cancer-killing drugs are injected into the liver's main artery under imaging guidance and travel to the tumor microvasculature. Transarterial chemoembolization has the additional disadvantage of requiring hospitalization.

The researchers continue to follow the patients from the study group as they work on ways to optimize the treatment.

"We want to see these outcomes validated in patients over the longer term," Dr. Salem said. "We also want to minimize the time from clinic visit to treatment, and fine-tune dosimetry so that we can find the optimal dose that will kill the tumor. In the right patient setting, RS can be considered curative."

PHILADELPHIA - Unnecessary emergency department visits and hospitalizations are debilitating for patients with cancer and far too common - and costly - for the United States health care system. To reverse the trend, researchers at the Abramson Cancer Center, the Leonard Davis Institute of Health Economics, and the Wharton School, all at the University of Pennsylvania, have identified the five best practices to reduce unnecessary emergency department (ED) visits and hospitalizations, which they call "unplanned acute care." Taken together, these strategies are the playbook for cancer centers and hospital seeking to improve health care quality in oncology.

The five strategies are: 1) identify patients at high risk of unplanned acute care; 2) enhance access and care coordination among health professionals; 3) standardize clinical pathways for symptom management; 4) develop urgent cancer care tactics, and 5) employ early palliative care. Researchers published their findings and recommendations this month in the Journal of Oncology Practice.

Unplanned acute care for patients with cancer is a major driver of unnecessary health care utilization and cost in the United States. The total cost of cancer care in the U.S. is projected to hit almost $160 billion by 2020, up from $125 billion in 2010, a number that includes great regional variation in spending-per-person. Acute cancer care accounts for 48 percent of all spending and 67 percent of per-capita variation.

Medicare has initiated the Oncology Care Model partly to help reduce unplanned acute care for Medicare beneficiaries with cancer and will soon release an important new measure that could ultimately affect hospitals' outpatient Medicare payments. "We endorse these five strategies as most promising to reduce unplanned acute care for patients with cancer, whether implemented separately or, with possibly more success, as an integrated program," said the study's lead author Nathan R. Handley, MD, a Hematology Oncology fellow in Penn's Perelman School of Medicine and an MBA candidate at the Wharton School.

Handley led this exhaustive review of research, evidence, and quality guidelines on reducing unnecessary ED visits and hospitalizations and an evaluation of selected care delivery models. The research team then categorized and assessed each of the five strategies based on outcomes such as reductions in ED visits, hospitalizations, and rehospitalizations within 30 days, and defined gaps in knowledge for future study.

"These recommendations put the patient at the center of how we give cancer care by leveraging advanced big data analytics, team-based care, alternative care settings, and care pathways," said Justin E. Bekelman, MD, an associate professor of Radiation Oncology and Medical Ethics and Health Policy, and a senior fellow in the Leonard Davis Institute for Health Economics. "Together, these strategies help avoid the need for the emergency department or hospital in the first place or target our highest-touch resources to those at highest risk of experiencing an emergency visit during cancer treatment."

Penn Medicine and the Abramson Cancer Center are using some of these strategies with promising results. For example, the Abramson Cancer Center has developed new pathways that divert cancer patients from the ED to a more specialized urgent care clinic. Research shows more than half of cancer patients who show up to the ED are admitted to the hospital, often during normal clinical hours. As an alternative, the researchers recommend developing sites that give these patients an alternative to seek care.

"We've seen excellent results with this approach here at Penn with our Oncology Evaluation Center, an urgent care-type clinic specifically for our cancer patients," said study co-author Lynn Schuchter, MD, chief of Hematology Oncology.

Other recommendations are underutilized throughout cancer centers in the U.S. For example, the researchers say that while treatment goals and end-of-life planning are an expected part of the conversation for patients with life threatening illnesses like advanced cancer, these conversations often occur too late.

"While patients are hearing more and more that these conversations should happen early, we still see many cases where this doesn't happen until after patients are already in the hospital due to complications that could be devastating," Handley said. "The oncology community would benefit from more robust training and new efforts to initiate palliative care planning earlier in the course treatment."

Schuchter says this training is also already ongoing at Penn.

The researchers also say that because of the large investment required to implement these recommendations, further research and evaluation is needed to identify the optimal strategies for different types of care settings and cancer centers.

"These strategies will improve patients' experience with their cancer care, but they are not only good for patients," Bekelman said. "Health care providers should move in these directions now, especially as new payment models for health and medical care amplify the need for cancer programs to focus on reducing unnecessary emergency department visits and hospitalization."

Each of us carries in our genomes about 10 million genetic variations called single nucleotide polymorphisms (SNPs), which represent a difference of just one letter in the genetic code. Every human's pattern of SNPs is unique and quite stable, as they are inherited from our parents and are rarely mutated, making them a kind of "natural barcode" that can identify the cells from any individual. A group of researchers from the Wyss Institute for Biologically Inspired Engineering at Harvard University and Harvard Medical School (HMS) has developed a new genetic analysis technique that harnesses these barcodes to create a faster, cheaper, and simpler way to track what happens to cells from different individuals when they are exposed to any kind of experimental condition, enabling large pools of cells from multiple people to be analyzed for personalized medicine. The research is reported in Genome Medicine.

As the Big Data revolution in healthcare gallops apace, it is becoming possible and more attractive to perform experiments on cells from multiple people simultaneously, as differences in how the cells respond can indicate that genetic variances between the individuals are conferring some kind of effect. However, keeping track of which cells belong to which person throughout such a multiplexed experiment currently requires that a unique tag or barcode be added to each individual's cells, a time-consuming and costly process that frequently involves integrating a barcode (e.g., a unique DNA sequence) into each cell line separately so that they can identify the cells during testing. By taking advantage of all humans' unique SNP profiles, the Wyss/HMS team achieved the same cell tracking without the cumbersome labeling process.

While SNPs have been known to science for almost two decades, unlocking their utility as barcodes has proven extremely difficult. SNPs are distributed sparsely throughout the genome (approximately one SNP occurs in 1,000 base pairs), meaning that any one SNP can only distinguish between two individuals. Current, commonly used high-throughput sequencing technologies have sequencing read-lengths of less than 1,000 base pairs, making it nearly impossible to ascribe each of the sequencing reads to any particular person based on SNPs.

To overcome this problem, the team's new method combines genomic DNA extraction from a mixed pool of cells, whole-genome sequencing of the extracted DNA, and a computational algorithm that predicts the proportion of each individual within the pool based on the entire SNP allele profile of every known person's cells. Many of the cell lines publicly available for research already have whole-genome SNP allele profiles associated with them, and a given individual's profile can be determined with the use of genotyping arrays or low-coverage whole-genome sequencing.

SNP allele profiles can be used to track cells' identities across any number of different experiments in which the pool of multiple cell samples is subjected to two or more different conditions (usually a "control" condition and an "experimental" condition), and then analyzed. Yingleong Chan, Ph.D., a Postdoctoral Fellow in the laboratory of George Church at the Wyss Institute and HMS, and his coworkers have developed an algorithm that predicts the proportions of each person's cells in the pool before and after the experiment, and compares them to determine which cells are expressed differently when exposed to the condition tested. "The change in the proportion of the individuals' cells in the experimental group when compared to the control group tells you what happened to those cells during the experiment, and whether cells from any particular person might have a genetic advantage," says Chan.

The researchers first tested their method by simulating a pool of cells and varying the number of samples, quantity of SNPs analyzed, and number of times that the pool was sequenced. They found that, over several iterations, the algorithm converged to a fixed estimated proportion for each SNP profile in the pool that closely matched the simulated proportions. The algorithm was able to accurately estimate the proportions of pools of up to 1,000 different individuals by analyzing 500,000 SNPs, and could handle samples of event more cell lines if either the number of SNPs analyzed or the depth of sequencing were increased.

Next, the researchers tested their algorithm on actual human B-lymphocytes whose genomes had been sequenced as part of the Harvard Personal Genome Project, and found that it accurately predicted the proportion of the individuals within a pool of 50 different cell lines. "There are numerous experiments that this technique could be applied to," says Chan. "You can test a cancer drug against different cell lines from different people, see whether a particular patient's cell line responded well to the drug, and then use that drug for a targeted approach to treatment. We've effectively built a discovery tool to enable personalized medicine."

The authors point out that their method will not work on samples where the different cell types come from the same person, because the SNP profiles would be identical, but it holds great promise for multiplexed testing of genetic variation among many human samples.

"Testing the effects of drugs on multiple cancer cell lines is one application that can be implemented immediately," says co-corresponding author George Church, Ph.D., who is a Founding Core Faculty member of the Wyss Institute, a Professor of Genetics at HMS, and Professor of Health Sciences and Technology at Harvard and MIT. "You can test a lot more people at once, which not only gives you more data, but translates into significant time and cost savings."

"This new technology harnesses the very core of what makes us who we are - the unique variations in our DNA - and crafts it into a tool that can accelerate discovery by obviating the need for analyzing individual responses in multiple parallel, time consuming, and expensive experiments. It also opens up an entirely new approach to personalized medicine," says Wyss Founding Director Donald Ingber, M.D., Ph.D., who is also the Judah Folkman Professor of Vascular Biology at HMS and the Vascular Biology Program at Boston Children's Hospital, as well as Professor of Bioengineering at the Harvard John A. Paulson School of Engineering and Applied Sciences.

A new study by Murtuza Jadliwala, assistant professor of computer science at The University of Texas at San Antonio, examines wearable technology and whether it affects drivers' concentration. Jadliwala and his collaborators discovered that while a driver texting with a wearable device can marginally reduce their level of distraction, it ultimately makes texting while driving just as dangerous as with an ordinary cell phone.

"Dr. Jadliwala's research on evaluating the influence of technology on consumer safety and privacy is timely and significant," said Rajendra Boppana, chair of the UTSA Department of Computer Science. "His work on wearable technologies is a great example of impactful research driven by experiments, an approach highly valued by computer scientists."

More than a quarter of car accidents reported each year are attributed to some form of distraction among drivers, often the result of talking or texting while driving. Nine people are estimated to die every day in the U.S. from distracted driving and 330,000 injuries occur each year because of texting while driving, which is also the most common cause of death in teenagers.

Jadliwala worked with Jibo He, associate professor of psychology at Wichita State University and Jason S. McCarley, professor of psychology at Oregon State University, to create a safe environment where distracted driving could be measured.

"We recruited about 20 volunteers on a university campus," Jadliwala said. "They used a driving simulator in a laboratory that included a three-screen display, a wheel and pedals."

Student volunteers were tasked with "driving" in the simulator, using either a smart phone or Google Glass. Jadliwala and his collaborators sent the participants text messages and challenged them to drive safely while receiving and responding to the messages. The simulator recorded deviations in the steering wheel and whether the volunteers drifted out of their lane.

"We found that the Google Glass distracts the driver slightly less," he said. "But that also gave the participants a false sense of safety."

Because the wearable device responded quicker and used voice-activated controls, the drivers noticed the increased efficiency but also were more likely to engage with the device, which negated the marginal safety difference between the smart phone and the wearable device.

While Google stopped producing Google Glass in 2015, wearable technology is becoming increasingly popular. Jadliwala noted that wrist wearables such as Apple Watch has been very successful and that more modern head-mounted displays like Google Glass are in development.

"It's important to keep asking these questions as technology becomes a bigger part of our everyday lives," he said. "A wearable device feels more accessible because it's on your body, which is why it's important to study how it could impact tasks like driving."

Using a technology that provides a 'high-resolution view' of the status of individual cells, a team of researchers has gained new insights into the embryonic development of the mouse heart. They discovered that during development, when progenitor heart cells progressively differentiate into various cell types, the Hippo pathway is essential to coordinate the development of these cell types into a working heart. The study appears in the journal Developmental Cell.

"The Hippo pathway is known for its role as an inhibitor of adult heart regeneration," said corresponding author Dr. James Martin, professor of molecular physiology and biophysics and Vivian L. Smith Chair in Regenerative Medicine at Baylor College of Medicine. "If you take the Hippo pathway away, then the heart can regenerate."

In this study, Martin and his colleagues asked whether the Hippo pathway also was involved in the embryonic development of the heart. Specifically, they investigated the role the pathway played in regulating the development of a group of cardiac progenitor cells called epicardial cells. During development and heart injury, these cells become essential supporters of the cardiomyocytes, the beating muscle cells of the heart.

The researchers genetically engineered mice to lack two essential components of the Hippo pathway, and then determined how the hearts developed when compared with those of normal mice. Martin and his colleagues looked at the structure of the heart blood vessels and also analyzed nearly 18,200 cells taken from heart tissue during a period of development.

The Hippo pathway is essential for normal heart development

The hearts of the mice with a defective Hippo pathway were smaller than normal hearts. Unexpectedly, blood vessel development was also defective; blood vessel coverage was reduced and less dense. These and other results suggested that the Hippo pathway is required for normal heart and blood vessel development.

"In addition, we analyzed thousands of cells from developing heart tissue with a technology called single cell transcriptomics," said Martin, who also is director of the Cardiomyocyte Renewal Lab at the Texas Heart Institute. "This technology allowed us to determine the status of thousands of cells individually. For instance, we learned what genes were turned on and what molecules the cells were expressing. This high level of detail shed light into the cellular and molecular processes leading to an adult heart and how they are coordinated."

The researchers learned of a number of genes and pathways they had not thought would be linked to the Hippo pathway during the heart's embryonic development, for instance, the retinoic acid or vitamin A pathway. They also discovered that when the Hippo pathway is defective during the heart's embryonic development, cardiac fibroblasts do not advance through their normal developmental program.

"We found cells suspended in intermediate states and producing factors important for regulating growth and proliferation of vascular endothelial cells," Martin said. "That was all unexpected."

These new insights suggest that during heart development, when cells progress through transition states, the Hippo pathway regulates the production of factors that regulate normal growth of vascular endothelial cells. Importantly, the Hippo pathway plays an essential role in this process, much like an 'orchestra director' coordinating the development of several types of cells in the heart.

"We know that the Hippo pathway is involved in regeneration of the adult heart, but also controls the size of the developing heart," Martin said. "As the heart grows, more vascular cells need to move into the heart to provide blood vessels to sustain its growth and later support the function of the adult heart. We think that the Hippo pathway can sense the size of the growing heart and, by regulating a number of secreted factors, determine how many cardiac fibroblasts and endothelial cells develop in the heart."

Martin and his colleagues are applying these findings to better understand regeneration of the adult heart.

"If we can figure out ways to improve the blood vessels' ability to regenerate in the adult heart, we would open new possibilities to improve the treatment of heart disease in the future," Martin said.

CHAPEL HILL - Cancer that has spread, or metastasized, from its original site to other tissues and organs in the body is a leading cause of cancer death. Unfortunately, research focused on metastatic disease has been limited by a lack of experimental systems that mimic the way metastatic cancers grow in people.

Now, researchers at the University of North Carolina Lineberger Comprehensive Cancer Center report they have developed a laboratory model for studying metastatic cancer by applying techniques used in tissue engineering, a field in which scientists make enhanced or replacement tissue or organs. Researchers believe their method better reflects the environment in and around tumors that have metastasized.

In the journal Nature Biomedical Engineering, UNC Lineberger's Andrew Wang, MD, and colleagues report they have developed tissue-engineered models for cancer metastases that reflect the microenvironment around tumors that promotes their growth. They believe their models, which were developed to study colorectal cancer that had spread to the liver and lung, will help scientists studying why cancers tend to spread to certain organs rather than others.

"When cancer tumors metastasize, they go to some organs and not to others - we've known this for many years," said Wang, who is associate professor in the UNC School of Medicine Department of Radiation Oncology. "The hypothesis is this is caused by both 'seed and soil' - that the cancer cells have something in them that drive them to a particular organ, and the soil has to be right for them to grow. Most of the focus has been on studying the cancer cell, or the seed, and not as closely looking at the soil, which is the organs that they go to. Our models will help us understand to better understand the conditions of the soil that help promote cancer metastasis."

Researchers in the past have employed a number of techniques to study metastatic disease. Gels and other techniques have been used to create three-dimensional environments in a dish to reflect the environment that might be found in an organ, but researchers report they can be dissimilar to the environment found in different types of tissues, such as the lung or the liver. Genetically engineered animal models of metastatic cancer are also available, but researchers report they can be costly and difficult to use.

Wang and his colleagues created new models of cancer metastasis by constructing organ-like structures made up of "decellularized" tissue. To create these models, researchers removed the individual cells within a mouse organ, but left the remaining structural proteins and signaling molecules that would remain to give the organ structure.

"We're using cutting-edge tissue engineering -- which is being used to study new organs for people who need them for transplants -- and applying it to cancer research," Wang said.

They created liver and lung organ models in the study, and when they grew colorectal cancer cells on these models, they reported that they closely mimicked human tissue samples, spontaneously forming three-dimensional tumor colonies that reflected characteristics of metastasis according to molecular tests, behavior patterns, and when studied the samples under a microscope.

One key characteristic that they saw was the formation of "signet ring cells," which have been linked to poor cancer prognosis.

"To the best of our knowledge, this has not been seen before in cultured cancer cells grown in a dish," Wang said. "By supplying the native organ microenvironment, we're more closely recapitulating the phenotype of human metastasis."

People who feel in control of their lives and who find purpose and meaning in life are less likely to have anxiety disorders even when going through the toughest times, according to a study led by the University of Cambridge.

The study, published today in BMJ Open, found that women who had these traits did not have anxiety, even if they were living in the most deprived circumstances, but women who did not feel that they were in control of their lives and who lacked purpose and meaning in life had high levels of anxiety when facing the hardships of living in deprivation. The study could help researchers develop new ways of teaching women how to overcome anxiety.

Anxiety disorders can manifest as fear, restlessness, an inability to concentrate on work or school tasks, and difficulty in falling asleep at night. In some cases, anxiety can arise out of the blue as in a panic attack, when sudden spikes of intense anxiety make the sufferer think they are having a heart attack, 'going mad', or even dying. In other cases, it is triggered by specific situations, such as being on a bus or at a social gathering, and symptoms such as sweating, gastrointestinal discomfort, dizziness, and chest pains may ensue.

Anxiety disorders are some of the most common mental health problems and their annual cost in the United States is estimated to be $42.3 billion. In the European Union, they affect over 60 million people in a given year.

Despite anxiety disorders being common and costly, few studies have looked at what makes some people have anxiety when going through tough times, while others facing the exact same situations are able to maintain good mental health. National Institute for Health Research (NIHR)-funded researchers from the Cambridge Institute of Public Health used data from over 10,000 British women who had responded to a structured health and lifestyle questionnaire. The questionnaire included a measure of Sense of Coherence, which is a personality disposition.

Women living in deprivation but who reported the following traits were less likely to have anxiety: believing they were in control of their lives, believing their lives made sense, and having a purpose and meaning in life. Women living in deprivation but without these desirable traits had high levels of anxiety. In fact, women in deprived communities without these traits were almost twice as likely to have anxiety as women living in more affluent communities.

"This study sheds light on inner strengths or qualities that we may have which can protect us from anxiety when we're exposed to hardships, such as living in deprivation," says first author and PhD candidate Olivia Remes. "Fostering such strengths or traits may be useful for people who do not respond well to medication or other therapies for anxiety, and further research would be needed on this."

The researchers say that living in deprivation can lead to a sense of meaninglessness among individuals, and can give rise to poor mental health and suicide. In deprived communities, people are more fearful of their neighbours, assaults are more likely to happen, and it is difficult to form close relationships with others. The total number of people living in deprivation worldwide is large; as such, the results of this study are particularly important.

"This study takes a different approach to mental health," continues Professor Carol Brayne, Director of the Cambridge Institute of Public Health. "Up until now, most studies have looked at what makes someone prone to disease, and the risk factors for ill health. But we have taken a different approach. Instead of looking at risk factors for disease, we are looking at traits or strengths that we have within us that can help us maintain good mental health and overcome adversity.

"The study could help researchers develop new ways to approach how women can be helped to overcome anxiety, and also highlights the key role of context in our mental health."

Dr Louise Lafortune, Senior Research Associate at the institute, explains: "Anxiety disorders are common, debilitating, and impairing. Now we know that people who feel that they are in control of their lives, who believe that life makes sense, and who have found purpose and meaning are less likely to have anxiety even if they are going through hardships, such as living in deprivation."

Researcher Profile: Olivia Remes

Anxiety is one of the most common mental health problems, and if left untreated, can lead to substance abuse, depression, and risk of suicide. Yet little seems to known about its causes and consequences.

It is to address this gap in our knowledge that Olivia Remes, originally from Canada, is carrying out research for her PhD. She has been looking at who is most affected by anxiety, some of the factors that can give rise to it, and the impact that untreated illness can have on society.

"Anxiety is not only very costly for society in terms of high health service use, work absenteeism and decreased work productivity, but it can cause much suffering to those affected," she says.

To carry out her research, Olivia uses data from the European Prospective Investigation of Cancer in Norfolk, one of the largest cohort studies looking at chronic diseases, mental health, and the way people live their lives.

Olivia is keenly aware of the importance of sharing her research with other academics, policy-makers and the public, often through the media. This led to significant interest when she published her findings on the burden of anxiety around the world, with radio and TV interviews across the BBC and other media outlets.

"It was truly exhilarating. Knowing that I had done something to increase awareness about anxiety and that I was able to reach people with key messages from my research was very rewarding," she says.

"As I started received personal messages from people suffering from anxiety, I felt that all the hard work I had done to bring this condition to light was truly worthwhile. It made me persevere in my research and gave me hope that, through my work, I can have a positive impact on people's lives."

Olivia hopes her research will help inform prevention and intervention efforts directed to help those suffering from anxiety, but also that it will lead to greater awareness of the condition. "I hope that, as more studies on anxiety come out, more people will start talking about this condition and will seek help if experiencing symptoms without feeling embarrassed or ashamed."

Studying at Cambridge has given her the opportunity to work with and learn from some of the brightest minds in the field, she says.

"The postgrad community is also very welcoming - the Colleges organize many events for students throughout the year, providing opportunities to meet many wonderful people from all over the world," she says. "I have made many friendships here that I will treasure for many years to come. Cambridge is an inspiring place steeped in history, and is dedicated to inspiring innovation. I have enjoyed and continue to enjoy every minute here."

The southwest Indian Ocean cyclone season started on November 15, 2017 and will officially end on April 30, 2018. A tropical cyclone called Fakir formed on April 23 near northeastern Madagascar and the Global Precipitation Measurement mission or GPM core satellite looked at the storm's rainfall rates.

Fakir is expected to intensify as it moves toward the southeast and could be a significant tropical cyclone tomorrow. This cyclone season has already seen Madagascar battered and drenched by tropical cyclones Ava, Dumazile, and Eliakim.

The GPM core observatory satellite flew above the forming late season tropical cyclone near northeastern Madagascar on April 22, 2018. The satellite's Microwave Imager (GMI) and Dual Frequency Precipitation Radar (DPR) instruments revealed the locations of heavy rainfall associated with the forming tropical cyclone. GPM showed that bands of extremely heavy rainfall were spiraling into the tropical low's southeastern side. GPM's radar (DPR Ku Band) showed that precipitation was falling at a rate of over 219 mm (8.6 inches) per hour in some of the strong convective storms that were moving toward Madagascar.

A 3-D view of precipitation in forming tropical cyclone Fakirwas developed with data collected by GPM's radar (DPR Ku Band). A computer simulated 3-D cross section generated at NASA's Goddard Space Flight Center in Greenbelt, Maryland used GPM's radar scans to show the heights of cloud tops and radar reflectivity values within the forming tropical cyclone. GPM's radar indicated that a few of the tallest intense convective storms were reaching heights of almost 16 km (9.9 miles). GPM is a joint mission between NASA and the Japan Aerospace Exploration Agency, JAXA.

On April 23, 2018 at 1500 UTC (11 a.m. EDT), Fakir had maximum sustained winds near 40 knots (46 mph/74 kph). Fakir was centered near 6.5 degrees south latitude and 53.2 east longitude, about 313 nautical miles north-northwest of St Denis, la Reunion. Fakir was moving southeastward.

The Joint Typhoon Warning Center noted "Satellite imagery depicts a rapidly consolidating system with improved deep convective banding wrapping into a well-defined low-level circulation center. Another image showed tightly-curved banding wrapping into a microwave eye feature."

The system is forecast to continue tracking southeastward over the next two days, but is expected to peak in strength in one day, April 24.