Tech

Scientists are a step closer to understanding which genes are responsible for early onset Alzheimer's disease in people with Down syndrome, thanks to a new study led by researchers at the Francis Crick Institute and UCL along with an international group of collaborators.

The findings could pave the way for future medicines to prevent the disease in these individuals, and provide insights into the mechanisms that cause dementia in the general population.

Around 1 in 800 people are born with Down syndrome, which arises in people carrying an extra copy of chromosome 21. By the time they reach their 60s, around two thirds of those with Down syndrome will have early onset Alzheimer's.

The high rates of Alzheimer's in people with Down syndrome were previously thought to be caused by a particular gene on chromosome 21 called APP. Chromosome 21 contains 231 genes, but APP was the prime suspect because it produces amyloid precursor proteins. These are involved in generating amyloid beta proteins, which build up in the brain in Alzheimer's patients.

In this study, published in the journal Brain, researchers found that extra copies of other genes on chromosome 21 increase Alzheimer's-like brain pathology and cognitive impairments in a mouse model of Down syndrome.

Dr Frances Wiseman, Senior Research Fellow at UCL, and first author of this study, said: "We've shown for the first time that genes other than APP are playing a role in early-onset Alzheimer's disease in our model of Down Syndrome. Identifying what these genes are, and what pathways are involved in the earliest stages of neurodegeneration, could help us to one day intervene with these pathways to prevent the disease in people with Down syndrome."

The team compared mice that produce APP amyloid protein with, and without, the presence of human chromosome 21, to tease apart the contributions of APP and other genes in Alzheimer's disease.

They found that mice with an extra copy of all the genes on chromosome 21 had more signs of Alzheimer's disease than mice without. The mice with extra copies of all genes on chromosome 21 had greater levels of amyloid beta and more protein clumps or 'plaques' inside part of the brain that controls memory, and performed worse on memory tests.

The team then looked at what was causing the increased build-up of amyloid-beta and plaques in the brains of mice with extra copies of all the genes on human chromosome 21. They found that these mice produced more of a particular type of amyloid beta protein that is more prone to forming clumps.

Dr Victor Tybulewicz, Group Leader at the Francis Crick Institute and co-senior author of the paper, said: "Down syndrome has historically been very difficult to model in a mouse, because the genes that we have on chromosome 21 are spread across three different chromosomes in mice. Only after years of refining our mouse models can we study the earliest stages of Alzheimer's, and other diseases, in the context of Down syndrome."

Elizabeth Fisher, Professor of Neurogenetics at UCL, and co-senior author of the paper, added: "Although we're looking at Alzheimer's disease through the lens of Down syndrome, this international collaboration provides insight into the earliest stages of disease progression, which may be applicable to modulating Alzheimer's disease in the general population."

An international team of researchers, led by Harvard University, have developed a dynamic surface with reconfigurable topography that can sculpt and re-sculpt microscale to macroscale features, change its friction and slipperiness, and tune other properties based on its proximity to a magnetic field.

Made by infusing a magnetic fluid in a solid microtexture, the researchers demonstrated how the surface could be used to direct the movement and assembly of micro-scale particles, regulate the flow and mixing of millimeter-size droplets, or turn adhesive properties on and off at the macroscale.

"Multifunctional materials capable of performing various tasks is a new, promising area of research," said Joanna Aizenberg, the Amy Smith Berylson Professor of Materials Science and Professor of Chemistry & Chemical Biology at the Harvard John A. Paulson School of Engineering and Applied Sciences and senior author of the paper. "The demonstrated applications - new forms of reversible, hierarchical particle self-assembly, manipulation and transport of non-magnetic matter in a magnetic field by topography-induced hydrodynamic forces, precisely timed chemical reactions, and rewritable, spatial addressing of directional adhesion, friction, and biofilm removal - are only a small representative sample of ample possibilities this new concept opens up to the imagination."

Aizenberg is also Core Member of the Wyss Institute for Biologically Inspired Engineering at Harvard University.

The research, published in Nature, was the result of an interdisciplinary collaboration between chemists, physicists, fluid mechanicists, materials scientists, applied mathematicians and marine biologists.

The surface is nicknamed FLIPS, short for Ferrofluid-containing liquid-infused porous surfaces. FLIPS is a composite surface, made up of two distinct parts: a micro-structured solid substrate and a ferrofluid, which consists of magnetic particles suspended in a liquid. Without a magnetic field, the surface is flat, slick and smooth. But when a magnetic field is applied, the ferrofluid responds, taking on the shape of the underlying topography. The combination of a structured solid surface with a responsive liquid allows the surface to be endlessly re-writable, a kind of dynamic Etch-a-Sketch with reconfigurable patterning, directional friction, adhesion and more.

The specific topographical patterns of the surface can be finely tuned at the micron, millimeter and centimeter scales by controlling the properties of the ferrofluid, the geometry of the substrate, the strength of the magnetic field and the distance of FLIPS from the magnets.

That level of tunablility means FLIPS can do a lot across a range of scales. The researchers demonstrated that FLIPS can:

Direct the movement of microscopic objects such as bacteria and colloidal particles, which would be useful for micro-scale manufacturing and for investigating the individual and collective behaviors of mobile micro-organism

Remove biofilm that accumulates on its surface

Coat droplets of liquid and use the controllable topography of FLIPS to control their movement and delay mixing for precisely-timed chemical reactions in small scale diagnostics

Be used in pipes for continuous liquid pumping.

Act as a reversible adhesive between two large-scale objects.

FLIPS is compatible with all kinds of surfaces and can even be integrated with another technology developed in the Aizenberg Lab, SLIPS, the ultra-slick surface coating.

"Each of these applications can be further extended," said Wendong Wang, first author of the paper and former postdoctoral fellow at SEAS. "Our results suggest that FLIPS allows much more diverse combinations of functions and capabilities than surfaces that have only a simple, single-scale topographical response. This could be a platform for a lot of future technologies."

Wang is currently a postdoctoral researcher at the Max Planck Institute for Intelligent Systems in Germany. This research was a collaboration between SEAS, the Wyss Institute, the Max Planck Institute, Aalto University School of Science in Finland, and the University of Oslo.

PHILADELPHIA - A first-in-human study presented at the 2018 Annual Meeting of the Society of Nuclear Medicine and Molecular Imaging (SNMMI) demonstrates the benefits and safety of a new, long-lasting type of radionuclide therapy for patients with advanced, metastatic neuroendocrine tumors (NETs).

Lutathera-177 (177Lu)-DOTATATE (trade name Lutathera), a peptide receptor radionuclide tharapy (PRRT) with radiolabeled somatostatin analogues (peptides), was recently approved by the U.S. Food and Drug Administration for the treatment of NETs. It is the therapeutic part of a nuclear medicine theranostic pairing. Gallium-68 (68Ga)-DOTATATE is the diagnostic agent used in positron emission tomography/computed tomography (PET/CT) scans that first locates and marks the lesions for follow-up with targeted PRRT delivery directly to the tumor cells which express high levels of somatostatin receptors (SSTRs). Because the PRRT binds to receptors expressed by the tumor cells, healthy cells are unharmed.

However, the peptide quickly clears from the blood through the kidneys limiting the accumulation of radioactivity within tumors and making additional treatment cycles necessary to provide the therapeutic dose.

This first-in-human, first-in-class, Phase I trial (ID: NCT03308682) investigated the safety and dosimetry of a novel long-lasting radiolabeled somatostatin analogue that adds an albumin-binding Evans blue (EB, an azo dye) derivative to 177Lu-DOTATATE. Albumin, the most abundant plasma protein in human blood, is a natural transport protein and has a long circulatory half-life.

"177Lu-DOTA-EB-TATE is a "three-in-one" therapeutic compound, with an octreotate peptide to find the tumor, an Evans blue motif, which uses endogenous albumin as a reversible carrier to effectively extend the half-life in the blood and substantially increase targeted accumulation and retention within the tumor, and a therapeutic radionuclide to kill the tumor cells, to finally provide effective treatment of NETs," explains Shawn(Xiaoyuan) Chen, PhD, senior investigator, of National Institute of Biomedical Imaging and Bioengineering at the National Institutes of Health , Bethesda, Maryland.

For the study, conducted in collaboration with researchers at the U.S. National Institute of Biomedical Imaging and Bioengineering, 8 patients (6 men and 2 women ranging in age from 27 to 61 years old) with advanced metastatic neuroendocrine tumors were recruited from Peking Union Medical College Hospital and the Chinese Academy of Medical Sciences in Beijing, China.

Each patient underwent whole-body 68Ga-DOTATATE PET/CT. Five of the patients then accepted intravenous injection with a single dose of 0.35-0.70 GBq of 177Lu-DOTA-EB-TATE within one week, and were monitored at 2, 24, 72, 120 and 168 hours after 177Lu-DOTA-EB-TATE administration with serial whole-body planar and single photon emission computed tomography (SPECT)/CT images acquired. The other 3 patients accepted a dose of 0.28-0.41 GBq of 177Lu-DOTATATE and were monitored at 1, 3, 4, 24 and 72 hours with the same imaging procedures. Complete physical examinations, including vital signs, blood count, biochemistry, and immunology analyses were performed immediately before and 1, 3, and 7 days, as well as 3 months, after treatment.

Administration of 177Lu-DOTA-EB-TATE was well tolerated, with no adverse symptoms reported throughout the procedure and follow-up. The total effective dose equivalent and effective dose were 0.2048 ± 0.1605 and 0.0804 ± 0.0500 mSv/MBq for 177Lu-DOTA-EB-TATE and 0.1735 ± 0.0722 and 0.0693 ± 0.0317 mSv/MBq for 177Lu-DOTATATE. The liver, kidneys, bone marrow and total body received slightly higher doses (mGy/MBq) with 177Lu-DOTA-EB-TATE than with 177Lu-DOTATATE, while the spleen received lower doses with 177Lu-DOTA-EB-TATE. Blood clearance of 177Lu-DOTA-EB-TATE was also slower. Most importantly, 177Lu-DOTA-EB-TATE lasted in the tumors more than 4 times longer than 177Lu-DOTATATE.

Jingjing Zhang and Zhaohui Zhu of Peking Union Medical College Hospital point out, "By introducing an albumin binding moiety, this long-lasting radiolabeled somatostatin analogue has remarkably enhanced uptake and retention in SSTR-positive tumors, which is important to increase the therapeutic efficacy in patients. With proper selection of patients with advanced metastatic neuroendocrine tumors, 177Lu-DOTA-EB-TATE has great potential to be a highly effective treatment, while providing a safe dose with less frequency of administration than is possible with 177Lu-DOTATATE."

Abstract 118: "Safety, Pharmacokinetics and Dosimetry of a Long-lasting Radiolabeled Somatostatin Analogue 177Lu-DOTA-EB-TATE in Patients with Advanced Metastatic Neuroendocrine Tumors: A Phase 1 First-in-human Study," Jingjing Zhang, MD,PhD, Yuejuan Cheng, MD,Hao Wang, MD, Jie Zang, PhD, Fang Li, MD, Chunmei Bai, MD, and Zhaohui Zhu, MD, Peking Union Medical College Hospital; Gang Niu, MD, Orit Jacobson, PhD4, and Xiaoyuan Chen, PhD, U.S. National Institutes of Health, Bethesda, MD. SNMMI's 65th Annual Meeting, June 23-26, Philadelphia.

Link to Abstract

NOTE: See Abstract 2 of the SNMMI 2018 Annual Meeting on an improved PSMA-targeting agent for prostate cancer imaging and therapy, also an NIH study using Evans blue platform technology.

As World Cup fever sets in, increased hooliganism and football related violence are legitimate international concerns. Previous research has linked sports-related hooliganism to 'social maladjustment' e.g. previous episodes of violence or dysfunctional behaviour at home, work or school etc. However, social bonding and a desire to protect and defend other fans may be one of the main motivations not only for football hooliganism, but extremist group behaviour in general, according to new Oxford University research.

The study, published in Evolution & Human Behaviour, canvassed 465 Brazilian fans and known hooligans, finding that members of super-fan groups are not particularly dysfunctional outside of football, and that football-related violence is more of an isolated behaviour.

Lead author and Postdoctoral researcher at Oxford's Centre for Anthropology and Mind, Dr Martha Newson, said: 'Our study shows that hooliganism is not a random behaviour. Members of hooligan groups are not necessarily dysfunctional people outside of the football community; violent behaviour is almost entirely focused on those regarded as a threat - usually rival fans or sometimes the police.

'Being in a super fan group of people who care passionately about football instantly ups the ante and is a factor in football violence. Not only because these fans tend to be more committed to their group, but because they tend to experience the most threatening environments, e.g. the target of rival abuse,, so are even more likely to be 'on guard' and battle ready.'

While the findings were linked to Brazilian football fans, the authors believe that they are not only applicable across football fans and other sports-related violence, but to other non-sporting groups, such as religious groups and political extremists.

Martha adds: 'Although we focused on a group of Brazilian fans these findings could help us to better understand fan culture and non-sporting groups including religious and political extremists. The psychology underlying the fighting groups we find among fans was likely a key part of human evolution. It's essential for groups to succeed against each other for resources like food, territory and mates, and we see a legacy of this tribal psychology in modern fandom.'

Although the research does not suggest that either reducing membership to extreme football super groups will necessarily prevent or stop football-related violence, the authors believe that there is potential for clubs to tap into super-fans' commitment in ways that could have positive effects.

The findings reinforce the research team's previous work to understand the role of identity fusion in extreme behaviour. They also suggest that fighting extreme behaviour with extreme policing, such as the use of tear gas or military force, is likely counterproductive and will only trigger more violence, driving the most committed fans to step up and 'defend' their fellow fans.

'As with all identify fusion driven behaviours, the violence comes from a positive desire to 'protect' the group. Understanding this might help us to tap in to this social bonding and use it for good. For example, we already see groups of fans setting up food banks or crowd funding pages for chronically ill fans they don't even know." Project director, Professor Harvey Whitehouse added: 'We hope this study spurs an interest in reducing inter-group conflict through a deeper understanding of both the psychological and situational factors that drive it.'

Generally, children who experience recurrent destructive conflicts between their parents are at a higher risk of later developing mental health problems. However, a new longitudinal study published in Child Development finds that strong sibling bonds can offset the negative effects of parental strife.

Conducted by researchers from the University of Rochester, the University of Nebraska-Lincoln, and the University of Notre Dame, the study finds that adolescents who witnessed high levels of acrimony between their parents had greater distressed responses to parental conflict a year later. Those responses, in turn, predicted mental health problems in the subsequent year. Yet, the researchers show that teens with strong sibling relationships are protected from experiencing this kind of distress in response to later parental disagreements and fights.

The researchers looked at 236 adolescents and their families recruited through local school districts and community centers in a moderately sized metropolitan area in the northeastern United States and a small city in the midwestern United States. The families were followed over the course of three years--with families' being measured at three intervals when their children were first 12, then 13, and finally 14 years old. The study's multi-method design relied on observations, semi-structured interviews with mothers about the relationship of the closest-aged siblings, and surveys.

The researchers caution that the families studied were mostly white and middle class, hence their findings should not be generalized to families of all races or socioeconomic status.

"Children may be using their siblings as sources of protection and emotional support--that is, as attachment figures," says lead author Patrick Davies, a professor of psychology at the University of Rochester.

However, Davies notes, "if this were the primary reason for the protective effects, one might expect that younger siblings would benefit significantly more from being able to access support from an older sibling who is more capable as serving as a source of support. But this wasn't the case."

That's why Davies and his team reason that most likely other mechanisms are at work. For example, siblings serve many of the same functions as peers. They may be involved in joint activities such as sports and introduce each other to settings and relationships outside the family that help to distract them from the distress in high conflict homes, says Davies. "Additionally, siblings may develop friendship bonds that involve shared warmth, disclosure about concerns, and support and corrective feedback--such as becoming a sounding board--for their perceptions about family life."

In a nutshell, Davies says, "We showed that having a good relationship with a brother or sister reduced heightened vulnerability for youth exposed to conflicts between their parents by decreasing their tendencies to experience distress in response to later disagreements between their parents."

The study, funded by the National Institute of Mental Health, defines a good sibling relationship as one which is characterized by warmth, closeness, and problem solving, and shows low levels of antagonism, conflict, and detachment.

In order to translate these findings into effective interventions, subsequent studies should investigate whether siblings serve as attachment or parent figures who protect or support each other in times of distress, or if they act as peers who engage in shared activities that distract them from the stresses of home life. Another line of investigation, Davies notes, might be a look at whether the shared warmth between siblings helps develop a sense of solidarity that guards against experiencing distress in high-conflict homes.

While Tropical Storm Bud was lashing parts of western Mexico and causing flooding that extended into the American Southwest, a tropical disturbance was spinning over the Gulf of Mexico and straddling southeastern Texas. This system sat in place for almost a week bringing extremely heavy rainfall and causing a flash flood emergency. More than 15 inches (381 mm) of rain fell in Hidalgo County, Texas between June 18 and 22.

With streets being overrun by rain waters, the Governor of Texas declared a state of emergency for six counties in south Texas Thursday afternoon, June 21, two days after rain began. The heaviest rain from the system had ended by Friday morning, June 22, but the weather service was still calling for more "occasional showers" in the area. At 1:37 p.m. CDT on June 22, 2018 the National Weather Service in Hidalgo County, Texas issued this warning: "Flood Warning for Southeastern Hidalgo County in Deep South Texas and Northwestern Cameron County in Deep South Texas until 1:30 a.m. CDT, Saturday [June 23]. Local Emergency Management and Department of Transportation continued to report residual flooding occurring across the warned area. Multiple roads remain impassable due to ongoing flooding from resent heavy rainfall that ranged from 10 to14 inches over the past few days. In addition some locations that will experience flooding include: Harlingen, Weslaco, San Juan, Alamo, Donna, Mercedes, La Feria, Elsa, Progreso and Edcouch."

Integrated Multi satellitE Retrievals for GPM (IMERG) data were used in this space based estimate of rainfall accumulation over Texas and northern Mexico during the period from June 18 to 22, 2018. These IMERG estimates were derived from various satellite space-borne passive microwave sensors, including the GPM (Global Precipitation Measurement mission) satellite's Microwave Imager (GMI). GPM is a joint mission between NASA and the Japan Aerospace Exploration Agency, JAXA.

IMERG estimates showed extremely heavy precipitation fell over southern Texas and the northwestern Gulf of Mexico. IMERG estimates indicated that the heaviest rainfall occurred in the northwestern Gulf of Mexico where over 21 inches (533.4 mm) of rain fell. IMERG data also indicated that more than 9 inches (228.6 mm) fell in large areas from south Texas to western Louisiana. This extreme rainfall resulted in the worst Texas flooding since Hurricane Harvey in August 2017.

TORONTO, June 21, 2018--A preference for male children persists among second-generation mothers of South Asian descent, according to new study that found a skewed ratio of male-to-female babies born to these women in Ontario.

The findings, published today in the Journal of Epidemiology and Community Health, came from the same group of researchers who reported in 2016 that more male babies than expected were being born to Indian-born women living in Canada.

Today's publication shows the gender imbalance persisted among second-generation mothers of South Asian descent, (women born in Canada) and was associated with previous abortions.

The study was led by Dr. Susitha Wanigaratne, a social epidemiologist and post-doctoral fellow at the Centre for Urban Health Solutions of St. Michael's Hospital and the Institute for Clinical Evaluative Sciences. The study was co-authored with several second-generation Punjabi women, including Manvir Bhangoo, founder of Laadliyan Celebrating Daughters, a non-profit organization promoting gender equity among the South Asian community in the Greater Toronto Area.

In most of the world, between 103 and 107 boys are born for every 100 girls. Canadian-born women of non-South Asian ethnicity give birth to about 104 boys for every 100 girls.

Earlier research published by Dr. Wanigaratne's group showed that women born in India, who already had two daughters, gave birth in Ontario to 196 boys for every 100 girls. The sex ratio increased significantly if the mothers had at least one abortion prior to the third birth. They also found that the male-biased ratio was driven by mothers whose mother tongue was Punjabi or Hindi and that the bias remained even after the mother resided in Canada for more than 10 years. The findings suggested the practice of sex selective abortion, which is common in India, is also happening in Canada.

Noting that Indian immigrants began arriving to Canada as early as the 1890s and in larger numbers since the late 1960s, Dr. Wanigaratne set out to see whether son-biased sex ratios were also occurring among subsequent generations of mothers.

She compared 10,273 live births to second-generation mothers of South Asian ethnicity and 36,687 live births to first-generation mothers from South Asian countries who gave birth between 1993 and 2014. She used data housed by ICES, the Immigration, Refugees and Citizenship Canada permanent resident database and the Canadian Institute for Health Information's Discharge Abstract Database.

In today's publication she reported important similarities and differences between first- and second-generation mothers of South Asian ethnicity:

Among second-generation mothers of South Asian ethnicity with two previous daughters and at least one prior abortion, 280 boys were born for every 100 girls, which was similar to the male-to-female ratio among first-generation mothers. This finding suggests that both groups of mothers are likely taking part in sex-selective abortion in Ontario.

However, among second-generation mothers of South Asian ethnicity with two previous daughters and no prior abortion, the male-to-female ratio was not elevated. Among first-generation mothers with two previous daughters and no reported abortions, 142 boys were born for every 100 girls. This second finding suggests that first-generation mothers are possibly leaving the province or country for an abortion while second-generation mothers are not.

Dr. Wanigaratne suggests that developing and supporting culturally acceptable and community-driven interventions are crucial next steps to tackle son preference in South Asian families, particularly for those originating from India.

(Madison, Wis.) June 21, 2018--For many students, essay tests are a source of dread and anxiety. But for professors, these tests provide an excellent way to assess a student's depth of knowledge and critical-thinking skills. At the American Physiological Society's (APS's) Institute on Teaching and Learning in Madison, Wis., Andrew Petzold, PhD, of the University of Minnesota Rochester Center for Learning Innovation, will discuss how a game of chance can lead to increased student preparation and motivation.

"Students often have negative associations with essay-only exams, either due to writing phobia, discomfort answering open-ended questions or being unsure of expectations or concepts being covered," Petzold said.

Petzold developed an assessment called "Exam Roulette" that allows students to preview potential essay questions a week before sitting for an exam. Students are allowed to ask clarifying questions about the potential essay topics, but they can't receive specific information about the content in essay responses. On the day of the exam, a 12-sided dice is used to assign students the question they will need to answer.

The additional preparation and novel approach may lead to a better experience and outcome for essay test takers. "Students report a greater motivation in studying, better retention of knowledge prior to and following the exam, and reduction in associated stress," Petzold said.

Andrew Petzold, PhD, an assistant professor at the University of Minnesota Rochester Center for Learning Innovation, will present the poster "Roll for essay: A mechanism for increasing self-accountability within summative assessment" on Thursday, June 21, at the Madison Concourse Hotel.

The first comprehensive study comparing the outcomes of robotic surgery to those of traditional open surgery in any organ has found that the surgeries are equally effective in treating bladder cancer. The seven-year study, conducted at 15 institutions, including Sylvester Comprehensive Cancer Center, and directed by Dipen J. Parekh, M.D., chair of urology and director of robotic surgery at the University of Miami Miller School of Medicine, is published in the June 23 issue of The Lancet.

The Randomized Open Versus Robotic Cystectomy (RAZOR) trial showed lower blood loss and blood transfusion rates and shorter hospital stays for patients who received minimally invasive surgery, but there were no differences in complication rates and the two-year progression-free survival was nearly the same.

"We have done more than 4 million surgeries with the robotic approach since the device came into existence, and on average we do close to a million robotic surgeries a year globally," said Parekh, who is chief clinical officer of the University of Miami Health System. "There are close to 5,000 robotic systems installed all over the world - each one costs about $2 million - and yet until we did this study there was not a single Phase 3 multicenter randomized trial comparing this expensive new technology to the traditional open approach of doing surgeries."

A total of 350 patients were involved in the bladder cancer study. Half received the open surgical approach and half received robotic surgery, and they were followed for two to three years so that outcomes could be compared.

"No one had followed these patients over a period of time to find out if you are impacting their cancer outcomes with this robotic approach," Parekh said. "We were able to prove unequivocally that we are not compromising patient outcomes by using robotic surgery."

The most important lesson from the study, Parekh said, is that more trials should be done, on other organs. "It is possible to do well-designed Phase 3 multicenter surgical trials comparing new technology and surgical innovations to traditional ones before proclaiming superiority or success of one over the other," he said. "There's a steep cost to robotic technology, and there is a learning curve, so we need to build on this in terms of making rational, data-based decisions."

Patients will also have more solid information as a result of this study and future research, Parekh said. "The patients will ask better questions, and the physicians for the first time will be able to answer these questions, based on data rather than based on intuition. This is the highest level of data one can get."

There has been an assumption that patients who receive robotic surgery will perceive a better quality of life than patients who have open surgery. Patients participating in the RAZOR study were asked about their quality of life at three and six months after surgery, and while both groups reported a significant return to their previous quality of life, there was no advantage of one group over the other.

Some critics of robotic surgery have expressed concern about the lack of tactile feedback - an important guide in open surgery. "When you do robotic surgery you don't feel anything," Parekh said. "It's more by visual cues. If you're doing open surgery you have the organs in your hands, you can feel them, and you assess and do these surgeries accordingly."

Parekh has extensive experience performing robotic surgeries with the da Vinci Xi Surgical System at UHealth Tower. It provides a magnified, three-dimensional view of the organs, and a wide range of motion and flexibility. Robotic surgery has become particularly popular with prostate cancer patients - 90 percent of them choose it - which would make it difficult if not impossible to do a randomized study of surgical results in prostate cancer. But Parekh says that because robotic surgery is being used in many other organs, including kidney, colorectal, OB/GYN and lung cancer, more studies are needed.

And while there are improvements in perioperative recovery with robotic technology, operating room time is significantly longer for robotic surgery.

"The findings of this study provide high-level evidence to inform a discussion between patients and their physicians regarding the benefits and risks of various approaches for a complex and often morbid surgery, like radical cystectomy," the trial description says. "It also underscores the need for further high-quality trials to critically evaluate surgical innovation prior to adoption into practice."

New Rochelle, NY, June 20, 2018--Tissue-engineered articular cartilage (AC) for repairing cartilage damaged by trauma or disease can be made to more closely mimic natural AC if mechanical stimulation of particular magnitude and duration is applied during the development process. A detailed review of the different stimulation techniques used and how to determine optimal loading parameters for improving the mechanical, structural, and cellular properties of AC is published in Tissue Engineering, Part B (Reviews), a peer-reviewed journal from Mary Ann Liebert, Inc., publishers . The article is available free on the Tissue Engineering website until July 20, 2018.

In "A Guide for Using Mechanical Stimulation to Enhance Tissue-Engineered Articular Cartilage Properties ," coauthors Evelia Salinas, Jerry Hu, PhD, and Kyriacos Athanasiou, PhD, University of California, Irvine, provide a comprehensive overview of the significant progress that has been made in the optimization of loading parameters in AC constructs. The researchers have developed a guide to the qualitative and quantitative effects that can be achieved when various loading parameters are used in tissue-engineered AC, including direct compression, hydrostatic pressure, shear, and tensile loading.

"The translation of tissue-engineered products into clinical reality is a main goal for the field. Improvement of existing protocols and SOP development with focus on achieving full implant functionality, as well as validation and GLP/GMP conformity, are key aspects," says Tissue Engineering Part B Editor Katja Schenke-Layland, MSc, PhD, Eberhard Karls University, Tübingen. "This review is an important guide for derivation of functional in vitro-engineered articular cartilage."

A new study from the University of Waterloo has found that Ontario could save millions by implementing simple measures to help prevent vehicle accidents involving wildlife.

The Waterloo study focused on Ontario. It concluded that many of the thousands of wildlife-vehicle collisions -- some fatal -- occurring each year could be prevented if authorities implemented a few, cost-effective strategies to minimize the occurrences.

Implementing strategies such as better signage, wildlife detection systems, fencing and wildlife crossings could help reduce financial and health-related impacts for people, emergency services and the insurance industry. The measures could also help prevent unnecessary loss in the wildlife populations.

"These collisions cost Canadians hundreds of millions a year in vehicle damage and medical costs, as well as traffic delays, emergency services use and increases in insurance premiums," said Waterloo's Associate Professor Michael Drescher, who co-authored the study with graduate student Kristin Elton. "Ontario is missing an opportunity here. The most efficient way to prevent these accidents is to integrate effective measures in wildlife conflict zones every time major road work is undertaken."

The study looked specifically at Southern Ontario, which has the highest concentration of roads in Canada. With ever-expanding infrastructure having a significant impact on wildlife and their habitat, many of the cost-effective measures that could help reduce wildlife-vehicle collisions are underdeveloped in Ontario.

"Within Canada, the Rocky Mountain region is renowned as a leader in the management of wildlife-road conflicts, said Drescher, who estimates five to 10 per cent of car insurance premiums go to animal-related incidents. "They've realized the economics are simple. Adding measures to road construction projects only marginally impacts the overall budget, while saving millions in taxpayer money, insurance costs, and potentially lives.

"Governments have to balance many competing factors next with the technical elements of this problem, such as perceived financial constraints, public opinion and political motivations," added Drescher. "When these factors are not managed right, wildlife management measures are delayed or never started."

CHAPEL HILL, NC - When cells grow and divide to ensure a biological function - such as a properly working organ - DNA must be unwound from its typical tightly packed form and copied into RNA to create proteins. When this process goes awry - if too little or too much RNA is produced - then the result could be diseases such as cancers. UNC School of Medicine researchers have discovered that a protein called Spt6, previously known to have a key role in making RNA and repackaging DNA after RNA copying, also facilitates RNA degradation so that cells have just the right amount of RNA for the creation of proteins.

The discovery, published in Molecular Cell, represents a revolutionary new understanding of gene expression control and suggests a potential target for treating cancers and other diseases.

"By revealing and understanding this mechanism, we can start to think about targeting parts of it therapeutically in diseases in which Spt6 isn't working properly," said study senior author Brian D. Strahl, PhD, the Oliver Smithies Investigator, Professor, and Vice Chair in the Department of Biochemistry & Biophysics at UNC-Chapel Hill.

Every human cell carries a large amount of DNA - called the genome - composed of roughly 3.5 billion letters that assemble into the genetic code. Researchers have been studying how large genomes fit into the tiny confines of cells. We know that proteins called histones carefully organize and package DNA in cells. Much like wrapping yarn around its spool, the DNA wraps around the histones to be condensed into a smaller space. Although histones help to keep DNA packaged, this packaging creates a barrier to "reading" the genetic information housed within DNA. The DNA needs to be "opened" much like a book needs to be opened for the pages to be read - except that "opening DNA" is a little complicated.

Accessing DNA information is a highly controlled process that involves temporarily removing the histones so the genetic code can be copied into RNA and the RNA can then be used to create proteins. Normally, cells destroy the copied RNA "messages" once they are no longer needed. Diseases such as cancer may arise when the ability of cells to either produce or destroy the messages goes awry.

When a gene is copied into a strand of RNA, the DNA in and around the gene must be loosened from its normal tightly wound configuration. Scientists have known that Spt6 has the crucial job of helping DNA become tightly re-wound when the copying process is completed. But that's not its only function.

"Spt6 seems to be a bit like a Swiss Army Knife," said Strahl, a member of the UNC Lineberger Comprehensive Cancer Center. "Spt6 has many functions, from helping the cell create messenger RNAs, to putting histones back onto the DNA after they were removed. Our study now shows that Spt6 also helps control how much of the messenger RNA remains after it's copied from DNA."

The first thing Strahl's lab investigated was how Spt6 binds to RNA Polymerase II, which is the enzyme machine that copies DNA into RNA. The function of this Spt6-Polymerase II interaction has been unclear. So the Strahl lab wanted to determine whether a non-binding version of Spt6 still performed its DNA-histone rewrapping function.

"To our surprise, we found that Spt6 was still able to get to genes, although at sub-optimal levels," Strahl said. "But Spt6 still did its job of adding back histones."

Although Spt6 still functioned, the researchers witnessed a big problem: the RNA amounts were extremely high, and these high RNA amounts did not occur because there was more copying with the defective form of Spt6.

"It dawned on us that there is more to Spt6 function than just re-wrapping the DNA around histones and facilitating RNA Polymerase copying of DNA," said first author Raghuvar Dronamraju, PhD, research assistant professor in Strahl's lab.

The researchers measured the amounts of all the RNAs in cells that had the mutant form of Spt6 and found abnormal amounts of many RNAs. This suggested there was a loss of the usual control mechanism that maintained just the right amount of each RNA.

It wasn't clear at first how the disruption of Spt6's binding to the polymerase caused RNA misregulation, but further experiments revealed a completely unexpected mechanism.

Normally, RNAs in the process of being made are exposed to enzymes that protect or degrade them so that the cumulative actions of these enzymes create a precise amount of RNA that a cell needs for protein synthesis. The UNC scientists found that the form of Spt6 that could not bind to RNA Polymerase II disrupted this balance between RNA protection and RNA degradation, specifically the degradation side. They found that many RNAs survived in cells longer than they normally would have, allowing the RNA levels to rise to abnormal levels.

Strahl's team went further and connected the dots to show that Spt6 interacted with one of the cell's major RNA degradation machineries - a protein complex called Ccr4-Not. Strahl's team showed that Spt6 used its interaction with RNA Polymerase II to recruit Ccr4-Not during gene expression to ensure the proper balance of enzymes that protect and degrade RNA.

Moreover, the researchers discovered that mutant Spt6 did not affect the levels of all RNAs. A large number of affected RNAs encode proteins that control cell division. Ordinarily, RNAs that contribute to cell division are rapidly degraded as cells pass from one part of the cell division cycle to another. But the abnormal failure to remove these RNAs in the mutant Spt6 cells caused the cells to develop profound growth and cell division defects.

The study by the Strahl lab thus revealed a previously unknown, fundamental mechanism of RNA degradation, and the results suggest that defects in the RNA degradation function of Spt6 may underlie some diseases, particularly cancers, which feature uncontrolled cell division.

"Given Spt6 in humans is sometimes found mutated or misregulated in cancers, it will be important to examine this RNA control mechanism further to determine whether its failure contributes to cancer," Strahl said. His team will turn to researching this with the hope that future studies could identify new therapeutic targets to treat human disease.

The researchers still have many questions about Spt6's involvement in regulating RNAs. But already it's apparent that Spt6's influence on RNA stability represents "a new twist in transcription," as Strahl calls it.

This research was performed with baker's yeast, a classic basic science organism that researchers use to investigate the intricate details of how cells perform and control many biological functions. Importantly, the yeast studies can be extended to human cells because the same proteins occur in yeast and humans.

DURHAM, N.C. - Exposure to fracking chemicals and wastewater promotes fat cell development, or adipogenesis, in living cells in a laboratory, according to a new Duke University-led study.

Researchers observed increases in both the size and number of fat cells after exposing living mouse cells in a dish to a mixture of 23 commonly used fracking chemicals. They also observed these effects after exposing the cells to samples of wastewater from fracked oil and gas wells and surface water believed to be contaminated with the wastewater. The findings appear June 21 in Science of the Total Environment.

"We saw significant fat cell proliferation and lipid accumulation, even when wastewater samples were diluted 1,000-fold from their raw state and when wastewater-affected surface water samples were diluted 25-fold," said Chris Kassotis, a postdoctoral research associate at Duke's Nicholas School of the Environment, who led the study.

"Rather than needing to concentrate the samples to detect effects, we diluted them and still detected the effects," he said.

Previous lab studies by Kassotis and his colleagues have shown that rodents exposed during gestation to the mix of 23 fracking chemicals are more likely to experience metabolic, reproductive and developmental health impacts, including increased weight gain.

Kassotis said further research will be needed to assess whether similar effects occur in humans or animals who drink or come into physical contact with affected surface waters outside the laboratory.

More than 1,000 different chemicals are used for hydraulic fracturing across the United States, many of which have been demonstrated through laboratory testing to act as endocrine disrupting chemicals in both cell and animal models.

To conduct this study, Kassotis and colleagues collected samples of fracking wastewater and wastewater-contaminated surface water near unconventional (aka, fracked) oil and gas production sites in Garfield County, Colorado, and Fayette County, West Virginia, in 2014.

Laboratory cultures of mouse cells were then exposed to these waters at varying concentrations or dilutions over a two-week period. The researchers measured how fat cell development in the cultures was affected. They performed similar tests exposing cell models to a mix of 23 fracking chemicals.

Within each experiment, other cells were exposed to rosiglitazone, a pharmaceutical known to be highly effective at activating fat cell differentiation and causing weight gain in humans.

The results showed that the 23-chemical mix induced about 60 percent as much fat accumulation as the potent pharmaceutical; the diluted wastewater samples induced about 80 percent as much; and the diluted surface water samples induced about 40 percent as much.

In all three cases, the number of pre-adipocytes, or precursor fat cells, that developed was much greater in cell models exposed to the chemicals or water samples than in those exposed to the rosiglitazone.

The tests also provided insights into the mechanisms that might be driving these effects.

"Activation of the hormone receptor PPAR-gamma, often called the master regulator of fat cell differentiation, occurred in some samples, while in other samples different mechanisms such as inhibition of the thyroid or androgen receptor, seemed to be in play," Kassotis explained.

Researchers more than doubled the ability of a material to convert heat into electricity, which could help reduce the amount of wasted heat, and thus wasted fossil fuel, in daily activities and industries.

Researchers from Hokkaido University and their colleagues in Japan and Taiwan have improved the ability to transform wasted heat into usable electricity by significantly narrowing the space through which spread electrons move, according to a new study published in the journal Nature Communications.

More than 60 percent of energy produced by fossil fuels is lost as waste heat. One way to address this problem is to convert the wasted heat into electricity, known as thermoelectric energy conversion. However, improving the conversion rate has been difficult because of a trade-off relationship between the required properties within the material.

Thermoelectric materials convert heat into electricity when there is a temperature difference, a phenomenon known as the Seebeck effect. Scientists have been investigating ways to confine electrons to a narrow space as a way to enhance conversion rates. In 2007, researchers built an artificial superlattice composed of conducting ultrathin layers sandwiched by thick insulating layers. This method yielded higher voltage but did not improve conversion rates. Researchers have predicted that performance can be significantly improved if electrons with longer de Broglie wavelength, which means they are more spread, are confined into a narrow conducting layer, but it had not yet been proven experimentally.

The research team, led by Hiromichi Ohta of Hokkaido University, designed a superlattice in which electrons are spread by 30 percent wider as compared to previous experiments. This resulted in much higher voltage and doubled the thermoelectric conversion rate recorded from previous methods.

"This is a significant step forward towards reducing the amount of heat wasted by power plants, factories, automobiles, computers, and even human bodies" says Hiromichi Ohta of Hokkaido University.

The UK's first energy-positive classroom, designed with research expertise from Swansea University, generated more than one and a half times the energy it consumed, according to data from its first year of operation, the team has revealed.

The findings were announced as the researchers launched the next phase of their research, gathering data and evidence on an office building, constructed using similar methods.

Buildings currently account for around 40% of UK energy consumption. This new building, known as the Active Office, points the way to a new generation of low-carbon offices which produce their own supply of clean energy.

It was designed by SPECIFIC, a UK Innovation and Knowledge Centre led by Swansea University.

Professor Dave Worsley, Research Director for SPECIFIC and Swansea University College of Engineering, explained how the work of SPECIFIC involves a two-way link between research and real-world application:

'SPECIFIC's research focuses on developing solar technologies and the processing techniques that take them from the lab to full-scale buildings.

With our building demonstration programme we are testing and proving the 'buildings as power stations' concept in real buildings, which are used every day. The data obtained from these buildings is then fed back into our fundamental research into solar energy technologies and used to accelerate and steer their development.'

The Active Office combines a range of innovative technologies that will enable it to generate, store and release solar energy in one integrated system, including:

A curved roof with integrated solar cells - showing the flexible nature of the laminated photovoltaic panel;

A Photovoltaic Thermal system on the south facing wall - which is capable of generating both heat and electricity from the sun in one system

Lithium ion batteries to store the electricity generated and a 2,000 litre water tank to store solar heat

The 'buildings as power stations' concept has already been shown to work. Right next to the Active Office is the Active Classroom, the UK's first energy-positive classroom. Also built by SPECIFIC, this was recently named Project of the Year by the RICS Wales. In its first year of operation, the Active Classroom generated more than one and half times the energy it consumed.

The Active Office and Classroom will be linked together and able to share energy with each other and electric vehicles, demonstrating how the concept could be applied in an energy-resilient solar-powered community.

They will provide functional teaching and office spaces, as well as building-scale development facilities for SPECIFIC and its industry partners.

Energy positive buildings could benefit the UK significantly. A 2017 analysis showed that it would mean:

Lower energy costs for the consumer

Less need for peak central power generating capacity and associated reduction in stress on the National Grid, leading to improved energy security

Reduced carbon emissions

The Active Office has been designed to be easy to reproduce. It is quick to build, taking only one week to assemble, with much of the construction taking place off site. It also uses only technologies that are commercially available now, which means there is no reason why they could not be used on any new building.

Kevin Bygate, chief operating officer of SPECIFIC, said:

"Offices are enormous consumers of energy, so turning them energy-positive has the potential to slash fuel bills and dramatically reduce their carbon emissions.

Turning our buildings into power stations is a concept that works, as the Active Classroom shows. This new building will enable us to get data and evidence on how it can be applied to an office, helping us refine the design further.

The Active Office is a first, but it isn't a one-off. It is quick to build using existing supply chains, and uses only materials that are already available. This is tomorrow's office, but it can be built today."

Ian Campbell, Executive Chair of Innovate UK, said:

"It's difficult to overstate the potential of developing a building that powers itself. The concept could genuinely revolutionise not only the construction sector but completely change how we create and use energy, so the opening of the Active Office in Swansea is an exciting step forward.

Developing technologies like those demonstrated in the SPECIFIC Active Office can play a strong role in the Government's modern industrial strategy to create 'clean growth' and fulfil our mission to halve the emissions of new buildings by 2030."

Alun Cairns, Secretary of State for Wales, said:

"The Active Office is a living example of how a building can make a difference to us and our environment using innovative technologies -and equally importantly creating jobs in Wales.

"Research and innovation has a proven track record to stimulate our economy. The UK Government has been a proud supporter of the project, and last year awarded £800,000 of funding towards it via Innovate UK.

"The UK Government is ambitious for Swansea, and the Swansea Bay City Region deal is expected to deliver more than 9,000 jobs and £1.3billion of investment across the region.

"I have no doubt that I'll be back to Swansea University in the near future because of the great strides they are taking in the science and research field which are being recognised around the world."