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UI Health validates cure for sickle cell in adults

Ieshea Thomas


Ieshea Thomas was the first adult to be cured of sickle cell disease with the chemotherapy-free procedure at UI Health. Credit: Image courtesy of University of Illinois at Chicago

 

Physicians at the University of Illinois Hospital & Health Sciences System have cured 12 adult patients of sickle cell disease using a unique procedure for stem cell transplantation from healthy, tissue-matched siblings. The transplants were the first to be performed outside of the National Institutes of Health campus in Maryland, where the procedure was developed. Physicians there have treated 30 patients, with an 87 percent success rate. The results of the phase I/II clinical trial at UI Health, in which 92 percent of treated patients were cured, are published online in the journal Biology of Blood & Marrow Transplantation. The new technique eliminates the need for chemotherapy to prepare the patient to receive the transplanted cells and offers the prospect of cure for tens of thousands of adults suffering from sickle cell disease.

 

 

 

About 90 percent of the approximately 450 patients who have received stem cell transplants for sickle cell disease have been children. Chemotherapy has been considered too risky for adult patients, who are often more weakened than children by the disease. “Adults with sickle cell disease are now living on average until about age 50 with blood transfusions and drugs to help with pain crises, but their quality of life can be very low,” says Dr. Damiano Rondelli, chief of hematology/oncology and director of the blood and marrow transplant program at UI Health, and corresponding author on the paper. “Now, with this chemotherapy-free transplant, we are curing adults with sickle cell disease, and we see that their quality of life improves vastly within just one month of the transplant,” said Rondelli, who is also the Michael Reese Professor of Hematology in the UIC College of Medicine. “They are able to go back to school, go back to work, and can experience life without pain.” Sickle cell disease is inherited. It primarily affects people of African descent, including about one in every 500 African Americans born in the U.S. The defect causes the oxygen-carrying red blood cells to be crescent shaped, like a sickle. The misshapen cells deliver less oxygen to the body’s tissues, causing severe pain and eventually stroke or organ damage. Doctors have known for some time that bone marrow transplantation from a healthy donor can cure sickle cell disease. But few adults were transplanted because high-dose chemotherapy was needed to kill off the patients’ own blood-forming cells — and their entire immune system, to prevent rejection of the transplanted cells, leaving patients open to infection. In the new procedure, patients receive immunosuppressive drugs just before the transplant, along with a very low dose of total body irradiation — a treatment much less harsh and with fewer potentially serious side effects than chemotherapy. Next, donor cells from a healthy and tissue-matched sibling are transfused into the patient. Stem cells from the donor produce healthy new blood cells in the patient, eventually in sufficient quantity to eliminate symptoms. In many cases, sickle cells can no longer be detected. Patients must continue to take immunosuppressant drugs for at least a year.

 

 

 

 

In the reported trial, the researchers transplanted 13 patients, 17 to 40 years of age, with a stem cell preparation from the blood of a tissue-matched sibling. Healthy sibling donor-candidates and patients were tested for human leukocyte antigen, a set of markers found on cells in the body. Ten of these HLA markers must match between the donor and the recipient for the transplant to have the best chance of evading rejection. In a further advance of the NIH procedure, physicians at UI Health successfully transplanted two patients with cells from siblings who matched for HLA but had a different blood type. In all 13 patients, the transplanted cells successfully took up residence in the marrow and produced healthy red blood cells. One patient who failed to follow the post-transplant therapy regimen reverted to the original sickle cell condition. None of the patients experienced graft-versus-host disease, a condition where immune cells originating from the donor attack the recipient’s body. One year after transplantation, the 12 successfully transplanted patients had normal hemoglobin concentrations in their blood and better cardiopulmonary function. They reported less pain and improved health and vitality. Four of the patients were able to stop post-transplantation immunotherapy without transplant rejection or other complications.

 

 

 

“Adults with sickle cell disease can be cured without chemotherapy – the main barrier that has stood in the way for them for so long,” Rondelli said. “Our data provide more support that this therapy is safe and effective and prevents patients from living shortened lives, condemned to pain and progressive complications.”

 

 

Source: University of Illinois at Chicago

 

 

Published on   21st September 2015

Satellites peer into rock 50 miles beneath Tibetan Plateau

Gravity data captured by satellite has allowed researchers to take a closer look at the geology deep beneath the Tibetan Plateau.

 

The analysis, published in the journal Nature Scientific Reports, offers some of the clearest views ever obtained of rock moving up to 50 miles below the plateau, in the lowest layer of Earth’s crust.


There, the Indian tectonic plate presses continually northward into the Eurasian tectonic plate, giving rise to the highest mountains on Earth—and deadly earthquakes, such as the one that killed more than 9,000 people in Nepal earlier this year.

 

The study supports what researchers have long suspected: Horizontal compression between the two continental plates is the dominant driver of geophysical processes in the region, said C.K. Shum, professor and Distinguished University Scholar in the Division of Geodetic Science, School of Earth Sciences at The Ohio State University and a co-author of the study.

 

 

“The new gravity data onboard the joint NASA-German Aerospace Center GRACE gravimeter mission and the European Space Agency’s GOCE gravity gradiometer missionenabled scientists to build global gravity field models with unprecedented accuracy and resolution, which improved our understanding of the crustal structure,” Shum said. “Specifically, we’re now able to better quantify the thickening and buckling of the crust beneath the Tibetan Plateau.”

 

 

 

Shum is part of an international research team led by Younghong Shin of the Korea Institute of Geosciences and Mineral Resource. With other researchers in Korea, Italy and China, they are working together to conduct geophysical interpretations of the Tibetan Plateau geodynamics using the latest combined gravity measurements by the GOCE gravity gradiometer and the GRACE gravimeter missions.

 

Satellites such as GRACE and GOCE measure small changes in the force of gravity around the planet. Gravity varies slightly from place to place in part because of an uneven distribution of rock in Earth’s interior.

 

The resulting computer model offers a 3-D reconstruction of what’s happening deep within the earth.

 

As the two continental plates press together horizontally, the crust piles up. Like traffic backing up on a congested freeway system, the rock follows whatever side roads may be available to relieve the pressure.

 

But unlike cars on a freeway, the rock beneath Tibet has two additional options for escape. It can push upward to form the Himalayan mountain chain, or downward to form the base of the Tibetan Plateau.

 

The process takes millions of years, but caught in the 3-D image of the computer model, the up-and-down and side-to-side motions create a complex interplay of wavy patterns at the boundary between the crust and the mantle, known to researchers as the Mohorovičić discontinuity, or “Moho.”

 

“What’s particularly useful about the new gravity model is that it reveals the Moho topography is not random, but rather has a semi-regular pattern of ranges and folds, and agrees with the ongoing tectonic collision and current crustal movement measured by GPS,” Shin said.

 

As such, the researchers hope that the model will provide new insights into the analysis of collisional boundaries around the world.

 

Co-author Carla Braitenberg of the University of Trieste said that the study has already helped explain one curious aspect of the region’s geology: the sideways motion of the Tibetan Plateau. While India is pushing the plateau northward, GPS measurements show that portions of the crust are flowing eastward and even turning to the southeast.

 

“The GOCE data show that the movement recorded at the surface has a deep counterpart at the base of the crust,” Braitenberg said. Connecting the rock flow below to movement above will help researchers better understand the forces at work in the region.

 

Those same forces led to the deadly Nepal earthquake in April 2015. But Shum said that the new model almost certainly won’t help with earthquake forecasting—at least not in the near future.

 

“I would say that we would understand the mechanism more if we had more measurements,” he said, but such capabilities “would be very far away.”

 

Even in California—where, Shum pointed out, different tectonic processes are at work than in Tibet—researchers are unable to forecast earthquakes, despite having abundant GPS, seismic and gravity data. Even less is known about Tibet, in part because the rough terrain makes installing GPS equipment difficult.

 

Other co-authors on the study included Sang Mook Lee of Seoul National University; Sung-Ho Na of the University of Science and Technology in Daejeon, Korea;

 

Kwang Sun Choi of Pusan National University; Houtse Hsu of the Institute of Geodesy & Geophysics, Chinese Academy of Sciences; and Young-Sue Park and Mutaek Lim of the Korea Institute of Geosciences and Mineral Resource.

 

 

 

 

This research was supported by the Basic Research Project of the Korea Institute of Geoscience and Mineral Resources, funded by the Ministry of Science, ICT and Future Planning of Korea. Shum was partially supported by NASA’s GRACE Science Team Program and Concept in Advanced Geodesy Program. Braitenberg was partially supported by the European Space Agency’s Center for Earth Observation as part of the GOCE User ToolBox project.

 

 

 

 

Source: University of Illinois at Chicago

 

 

Published on   24th July 2015

Predicting Tree Mortality

A combination of drought, heat and insects is responsible for the death of more than 12 million trees in California, according to a new study from UC Santa Barbara’s National Center for Ecological Analysis and Synthesis (NCEAS). Members of the NCEAS working group studying environmental factors contributing to tree mortality expect this number to increase with climate change.


 

Forest die-off Colorado

 

The western U.S. has been a hotspot for forest die-offs such as this one in Colorado.

 

Credit: Courtesy of William M. Ciesla, Forest Health Management

 

The study is the first of its kind to examine the wide spectrum of interactions between drought and insects. Lead author William Anderegg, a postdoctoral researcher at the Princeton Environmental Institute, and his coauthors first devised a framework to look at the effects that each stressor can have on tree mortality and then examined interactions among them. The researchers’ findings appear in New Phytologist.

 

“We wanted to be able to get a sense of how these die-off patterns will shift with climate change,” explained study coauthor Naomi Tague, an associate professor at UCSB’s Bren School of Environmental Science & Management. “Are there huge forests that will be at higher risk of dying sooner?”

 

The western U.S. has been a hotspot for forest die-offs. Local economies in states like California and Colorado are highly dependent on the nature-based tourism and recreation provided by forests, which offer a scenic backdrop to the skiing, fishing and backpacking opportunities that draw so many people to live and play in the West. But lingering drought, rising temperatures and outbreaks of tree-killing pests such as bark beetles have spurred an increase in widespread tree mortality — especially within the past decade.

 

“Very often both drought and insects together are responsible for tree mortality,” explained Anderegg, “but there are several good examples of trees dying because of one impact and not the other. We’ve worked to detail the spectrum of interactions between drought and insects and examine how they go hand in hand to affect tree die-offs.”

 

Forest mortality has also been shown to impact everything from real estate to clean water. Property values in Colorado plummeted after swaths of coniferous forests were damaged by pine beetle infestations. Water purification services provided by forests continue to be disrupted when hectares of forests are lost to pests and drought. What’s more, forest die-off events are projected to increase in frequency and severity in the coming decades.

 

“If we want to account for forest die-off events at local and global scales, we need some way of estimating how often they are likely to occur,” Tague said. “We’re putting together the pieces of how climate conditions can affect that mortality and how to identify the specific stressors that cause it.”

 

The study’s framework is a first step toward developing the tools that resource managers need to better predict the impacts of climate change on forests. Scientists and forest specialists are now tasked not only with determining what conditions prompt tree mortality but also how they will shape forested landscapes in the years to come. Being able to predict forest mortality in a changing climate is key to conservation and land use planning.

 

“Ultimately, forests are a critical part of western U.S. landscapes and state economies,” Anderegg said. “They are also a canary in the coal mine for climate change. These massive forest die-offs that we are starting to see are a sign that climate change is already having major impacts in our backyard.”

 

 

 

Source:- University of California – Santa Barbara.

 

 

Published on 15th June 2015

Rapid Testing for TB Aims to Reduce Drug Resistance, Lower Mortality Rate

Researchers at University of California, San Diego School of Medicine have documented the accuracy of three new tests for more rapidly diagnosing drug-resistant forms of tuberculosis (TB), which are much harder and more expensive to treat and which, experts say, represent a major threat to global public health.


The study is published online in the current issue of PLOS ONE.

 

“Our study shows that TB testing that once took two to three months can now be done in as little as a day,” said co-author Richard Garfein, PhD, professor in the Division of Global Public Health at UC San Diego School of Medicine. “This means we can put people on the right medications sooner, spare them the toxic effects of drugs that are ineffective and prevent the development of drug resistant forms of TB that can occur when the wrong medications are given.”

 

Although rates of TB are declining in the United States due to effective control measures, it  remains one of the world’s deadliest infectious diseases, causing (or contributing to) an estimated 1.5 million deaths in 2013, according to the World Health Organization. TB is also the leading killer of people who have HIV.

 

For the study, sputum (a mixture of saliva and mucus coughed up from the lungs) from 1,128 study participants at TB clinics in India, Moldova and South Africa were examined using three rapid tests for detecting drug-resistant forms of TB. Two of these tests use molecular techniques to look for genetic mutations in the pathogen’s DNA that confer resistance to antibiotics. The third test employs a low-cost and easy-to-use version of the standard bacterial culture technique, making it suitable for resource-limited community clinics and hospitals. An estimated 95 percent of TB deaths globally occur in low- and middle-income countries.

 

Results from the rapid tests were then compared to the reference standard technique for detecting resistance to seven of the most important anti-TB drugs. These comparisons showed that all three rapid assays accurately identified resistance to first- and second-line oral antibiotic treatments (isoniazid, rifampin, moxifloxacin and ofloxacin). They were less accurate but still very good at detecting resistance to injectable antibiotics (amikacin and capreomycin) typically administered to those with multi-drug resistant TB. The rapid tests performed poorly in detecting resistance to only one drug, the injectable antibiotic kanamycin, which is also used to treat multi-drug resistant TB.

 

The study also documented the time it took to obtain results. The molecular techniques showed themselves to be superior, with a mean time of 1.1 days for both DNA testing methods; 14.3 days for the rapid culture method; and 24.7 days for the reference standard test.

 

“The results from this international collaboration take us one step closer to achieving the World Health Organization’s goal of reducing deaths due to TB by 95 percent by 2050,” said lead author Antonino Catanzaro, MD, Professor Emeritus in the Division of Pulmonary, Critical Care and Sleep Medicine. “Rapid, accurate drug susceptibility tests are critical for physicians. They help us ensure that patients receive the appropriate anti-TB drugs to combat their specific form of tuberculosis. When patients receive the proper drug treatment, we see a large reduction in TB mortality.”

 

Source: University of California – San Diego.

 

Published on  9th  September  2015

Sex and violence may not really sell products

If there’s one thing advertisers think they know, it is that sex and violence sell.


A new analysis, however, provides some of the best evidence to date that this widely accepted adage just isn’t true.

 

Researchers analyzed the results of 53 different experiments (a so-called meta-analysis) involving nearly 8,500 people, done over 44 years. All of these experiments examined some facet of the question of whether sexual or violent media content could help sell advertised products.

 

When all the results are considered together, the overall conclusion, with some caveats, is that programs featuring violence and sex aren’t the ideal context for effective advertising, said Brad Bushman, co-author of the study and professor of communication and psychology at The Ohio State University.

 

It’s not that people don’t pay attention to sex and violence in the media, Bushman said. In fact, an evolutionary perspective would say it is just the opposite.

 

“People are so focused on the sex and violence they see in the media that they pay less attention to the advertising messages that appear along with it,” Bushman said.

 

“Advertisers shouldn’t be so sure that sex and violence can help them sell their products.”

 

 

Bushman conducted the study with Robert Lull, who just earned his Ph.D. in communication at Ohio State. The results were published online yesterday in the journal Psychological Bulletin and will be featured in a future print edition.

 

Their analysis included studies involving a variety of types of media, including print, TV, movies and even a few video games. They examined studies in which the ads themselves contained sex or violence and studies in which only the media surrounding the ads contained such content.

 

In all cases, the researchers had studied whether sex and violence affected brand memory, brand attitudes and people’s intention to buy the products advertised.

 

 

They found that memory for brands and ads was significantly impaired in programs containing sex, violence, or both sex and violence.

 

Overall, people had less favorable attitudes toward brands that advertised in violent media compared to neutral media. Only one study examined attitudes toward brands in sexual media and that pointed toward less favorable attitudes as well.

 

And people reported less intention to buy brands that were advertised in media containing violence, sex or both, compared to the same brands in media containing no sex or violence.

 

But what about ads that themselves featured sex and violence? Here, the findings were not as clear-cut. Overall, memory for brands that featured sex and violence was not impaired.

 

But attitudes toward brands that featured sexual ads were significantly lower than those same brands in neutral ads. Only one study examined attitudes toward brands in violent ads and those results also trended toward less favorable attitudes.

 

Overall, buying intentions did not depend on whether the ad contained sex or violence.

 

While these overall conclusions were clear, Lull and Bushman found several nuances in the studies they examined.

 

Memory for ads and buying intentions were both improved when the ad content and the media content were matching in terms of sex and violence. For example, violent ads worked best when they were paired with violent programs, Lull said.

 

“If a TV program prompts violent or sexual thoughts, an ad that prompts similar thoughts will be better remembered,” Lull said.

 

Sexual ads didn’t hurt brand attitudes and buying intentions overall. But the higher the levels of sexual content in the ads, the more negative the attitude people had toward the brand and the less likely they were to say they would buy the product.

 

Older people in the studies were less likely to say they would buy products featured in violent or sexual ads, compared to younger people.

 

Men’s brand memory was more impaired than women’s when watching media content or ads featuring sexual or violent imagery.

 

“This fits in with evolutionary theory that suggests males pay more attention to violence and sex than women do,” Lull said. “Because they’re paying more attention to this content, they are less likely to remember the ads.”

 

Another interesting finding was that memory impairments and negative attitudes toward brands featured in violent or sexual ads have actually decreased over the past decades.

 

This study can’t say for sure, but one explanation is that people have started to become desensitized to sex and violence in ads, Bushman said

 

“Viewers are so accustomed to seeing violent and sexual media content that they don’t respond as much today to the attention-grabbing impact as they did in previous decades,” he said.

 

Bushman said he is continuing work in his laboratory to examine the effects of violent ads on memory.

 

 

 

 

Source: University of Illinois at Chicago

 

 

Published on   24th July 2015

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