United Response: workforce innovation award runner-up

United Response Stamp of Support programme encourages carers to allow people with disabilities to take sensible risks.

A disabled woman made herself a cup of tea for the first time after her support workers realised providing her with a surface-mounted cup and a hot water dispenser meant she was no longer in danger of scalding herself.

Staff at the charity United Response came up with the solution because they realised that the benefit of making a cup of tea far outweighed the possibility of her being scalded. The support workers felt confident that it was a risk worth taking.

A young adult with a learning disability now travels to work by bus on his own, rather than taking expensive taxis. The staff knew there was a possibility that he could get lost on the way, so they gave him a mobile phone to ring them if needed. Staff realised that the financial and personal benefits were greater than the chances of him getting off the bus at the wrong stop.

Both cases illustrate the success of the charity's Stamp of Support initiative – which is encouraging "positive risk-taking" by staff in the organisation, which supports 1,300 adults with learning disabilities, physical disabilities or mental ill-health.

The charity wanted its 3,500 support staff to have the confidence to take a calculated risk when making decisions which would help service users achieve their "hopes and dreams".

"We didn't want them to risk their safety, but we wanted them to know that so long as they have acted reasonably then we will support them all the way," says Shonagh Methven, the charity's senior business partner for risk management.

The Stamp of Support slogan now appears on all its health and safety material and on a staff keyring.

Staff guidance and advice to support them to make a positive risk decision – even if it ends in failure – has been written into the charity's risk management strategy.

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Glioblastoma response to anti-angiogenesis therapy revealed by new MR analysis technique

Main Category: Cancer / Oncology
Also Included In: MRI / PET / Ultrasound;  Neurology / Neuroscience
Article Date: 20 Aug 2013 - 1:00 PDT Current ratings for:
Glioblastoma response to anti-angiogenesis therapy revealed by new MR analysis technique

A new way of analyzing data acquired in MR imaging appears to be able to identify whether or not tumors are responding to anti-angiogenesis therapy, information that can help physicians determine the most appropriate treatments and discontinue ones that are ineffective. In their report receiving online publication in Nature Medicine, investigators from the Martinos Center for Biomedical Imaging at Massachusetts General Hospital (MGH), describe how their technique, called vessel architectural imaging (VAI), was able to identify changes in brain tumor blood vessels within days of the initiation of anti-angiogenesis therapy.

"Until now the only ways of obtaining similar data on the blood vessels in patients' tumors were either taking a biopsy, which is a surgical procedure that can harm the patients and often cannot be repeated, or PET scanning, which provides limited information and exposes patients to a dose of radiation," says Kyrre Emblem, PhD, of the Martinos Center, lead and corresponding author of the report. "VAI can acquire all of this information in a single MR exam that takes less than two minutes and can be safely repeated many times."

Previous studies in animals and in human patients have shown that the ability of anti-angiogenesis drugs to improve survival in cancer therapy stems from their ability to "normalize" the abnormal, leaky blood vessels that usually develop in a tumor, improving the perfusion of blood throughout a tumor and the effectiveness of chemotherapy and radiation. In the deadly brain tumor glioblastoma, MGH investigators found that anti-angiogenesis treatment alone significantly extends the survival of some patients by reducing edema, the swelling of brain tissue. In the current report, the MGH team uses VAI to investigate how these drugs produce their effects and which patients benefit.

Advanced MR techniques developed in recent years can determine factors like the size, radius and capacity of blood vessels. VAI combines information from two types of advanced MR images and analyzes them in a way that distinguishes among small arteries, veins and capillaries; determines the radius of these vessels and shows how much oxygen is being delivered to tissues. The MGH team used VAI to analyze MR data acquired in a phase 2 clinical trial - led by Tracy Batchelor, MD, director of Pappas Center for Neuro-Oncology at MGH and a co-author of the current paper - of the anti-angiogenesis drug cediranib in patients with recurrent glioblastoma. The images had been taken before treatment started and then 1, 28, 56, and 112 days after it was initiated.

In some patients, VAI identified changes reflecting vascular normalization within the tumors - particularly changes in the shape of blood vessels - after 28 days of cediranib therapy and sometimes as early as the next day. Of the 30 patients whose data was analyzed, VAI indicated that 10 were true responders to cediranib, whereas 12 who had a worsening of disease were characterized as non-responders. Data from the remaining 8 patients suggested stabilization of their tumors. Responding patients ended up surviving six months longer than non-responders, a significant difference for patients with an expected survival of less than two years, Emblem notes. He adds that quickly identifying those whose tumors don't respond would allow discontinuation of the ineffective therapy and exploration of other options.

Gregory Sorensen, MD, senior author of the Nature Medicine report, explains, "One of the biggest problems in cancer today is that we do not know who will benefit from a particular drug. Since only about half the patients who receive a typical anti-cancer drug benefit and the others just suffer side effects, knowing whether or not a patient's tumor is responding to a drug can bring us one step closer to truly personalized medicine - tailoring therapies to the patients who will benefit and not wasting time and resources on treatments that will be ineffective." Formerly with the Martinos Center, Sorensen is now with Siemens Healthcare.

Study co-author Rakesh Jain, PhD, director of the Steele Laboratory in the MGH Department of Radiation Oncology, adds, "This is the most compelling evidence yet of vascular normalization with anti-angiogenic therapy in cancer patients and how this concept can be used to select patients likely to benefit from these therapies."

Lead author Emblem notes that VAI may help further improve understanding of how abnormal tumor blood vessels change during anti-angiogenesis treatment and could be useful in the treatment of other types of cancer and in vascular conditions like stroke. He and his colleagues are also exploring whether VAI can identify which glioblastoma patients are likely to respond to anti-angiogenesis drugs even before therapy is initiated, potentially eliminating treatment destined to be ineffective. A postdoctoral research fellow at the Martinos Center at the time of the study, Emblem is now a principal investigator at Oslo University Hospital in Norway and maintains an affiliation with the Martinos Center.

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Additional co-authors of the Nature Medicine paper are Kim Mouridsen, PhD, Christian Farrar, PhD, Dominique Jennings, Ronald Borra, PhD, and Bruce Rosen, MD, PhD, Martinos Center at MGH; Rakesh Jain, PhD, Steele Laboratory of Tumor Biology, MGH Radiation Oncology; Atle Bjornerud, PhD, University of Oslo, Norway; Patrick Wen, MD, Dana-Farber Cancer Institute; and Percy Ivy, MD, National Cancer Institute. Support for the study includes numerous grants from the U.S. Public Health Service, the National Cancer Institute and other funders.

Vessel architectural imaging identifies cancer patient responders to anti-angiogenic therapy

Kyrre E Emblem, Kim Mouridsen, Atle Bjornerud, Christian T Farrar, Dominique Jennings, Ronald J H Borra, Patrick Y Wen, Percy Ivy, Tracy T Batchelor, Bruce R Rosen, Rakesh K Jain & A Gregory Sorensen; Nature Medicine (2013) doi:10.1038/nm.3289

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Marathon bombing victims aided by rapid response, imaging of injuries

Main Category: Aid / Disasters
Article Date: 19 Aug 2013 - 0:00 PDT Current ratings for:
Marathon bombing victims aided by rapid response, imaging of injuries

The Boston Marathon bombing brought international attention back to the devastating effects of terrorism. There were numerous victims with severe injuries that needed immediate attention. A novel study in Arthritis Care & Research, a journal published by Wiley on behalf of the American College of Rheumatology (ACR), presents cases from Boston-area hospitals where victims were treated, examining the medical response and imaging technologies used to save lives and limbs.

On April 15, 2013, at approximately 2:49 p.m. two pressure-cooker bombs exploded one after the other at the Boston Marathon finish line. As a result of the bombings, there were three fatalities and 264 casualties, with the most severe injuries involving lower extremities of those located closest to the blasts. Shrapnel disbursed by the bombs included pieces of metal, nails and ball bearings. Injuries resulting from the Marathon bombing are relevant to the fields of rheumatology, rehabilitation, orthopedics and musculoskeletal imaging.

"In an era of terrorism, even clinicians serving non-military patients need to understand the spectrum of injuries caused by bomb explosions," explains lead author Dr. Ali Guermazi, Professor of Radiology at Boston University School of Medicine and one of the many specialists treating bombing victims at Boston Medical Center. "Critically ill bomb-blast patients needed quick assessments of their injuries, which had the most devastating effects to the lower limbs."

According to the Centers for Disease Control and Prevention (CDC), bombing survivors have the highest incidence of injury to soft tissue and musculoskeletal systems with the most extreme injury being traumatic amputation, which is reported in up to 3% of cases. The CDC defines primary blast injuries as those caused by the blast wave - extremely compressed air moving away from the explosion - that can damage the lungs, bowel and ears. As the wave moves from the site of the explosion it creates a vacuum, which pulls materials and debris back toward the source of the bomb blast - the refilling of this void is known as the blast wind.

Victims from the Boston Marathon bombing were subject to blast waves and blast wind resulting in soft tissue damage1, limb fractures1, and amputations. The study demonstrates the systematic need to exam each extremity for musculoskeletal, neurological and vascular damage. In accordance with previous evidence, radiography (X-ray) and computed tomography (CT-scan) should be used liberally to detect foreign objects, to define basic penetration patterns, and assess bony and soft tissue injuries.

Dr. Guermazi concludes, "While blast injuries within civilian populations are rare in the U.S., when they do occur it challenges the medical community to rapidly respond to concurrent evaluation and treatment of many victims. We suggest that in urgent situations, like the Boston Marathon bombing, radiology resources be used liberally to save the lives and limbs of patients."

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“Imaging of Blast Injuries to the Lower Extremities Sustained in The Boston Marathon Bombing.” Ali Guermazi, Daichi Hayashi, Stacy E. Smith, William Palmer and Jeffrey N. Katz. Arthritis Care and Research; Published Online: August 19, 2013 (DOI: 10.1002/acr.22113).

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Subset of type 1 diabetes patients with strong response to therapy identified

Main Category: Diabetes
Article Date: 19 Aug 2013 - 1:00 PDT Current ratings for:
Subset of type 1 diabetes patients with strong response to therapy identified

Primary results from a new clinical trial show that patients with type 1 diabetes treated with the monoclonal antibody teplizumab (MacroGenics, Inc.) exhibit greater preservation of C-peptide, a biomarker of islet cell function, compared to controls. Further analyses identified a discrete subset of the treatment group that demonstrated especially robust responses ("responders"), suggesting that these patients could be identified prior to treatment. The trial, entitled "Autoimmunity-Blocking Antibody for Tolerance in Recently Diagnosed Type 1 Diabetes" (AbATE), was conducted by the Immune Tolerance Network (ITN). The results are available online and will be published in the November issue of the journal Diabetes.

The AbATE study, led by Kevan Herold, MD (Yale University), tested teplizumab, which targets the CD3 receptor found on T cells, in patients with new-onset type 1 diabetes. CD3 is required for T-cell activation, which can lead to the destruction of insulin-producing beta cells. A previous ITN study with teplizumab showed that a single course of the drug slowed C-peptide decline in new-onset patients for a year, after which the effects waned. The aim of the AbATE study was to test whether C-peptide preservation could be prolonged by administering two courses of teplizumab, one year apart.

In this open-label, Phase II study, 77 new-onset patients (ages 8 to 30 years old) were randomized to receive either teplizumab or a control. Those in the treatment arm received the scheduled treatment consisting of two 14-day courses of teplizumab, one year apart. Both arms received intensive diabetes care from certified diabetes educators and were followed for two years. The primary endpoint compared C-peptide preservation between the two groups.

After two years, the teplizumab-treated group showed significantly greater preservation of C-peptide (75-percent higher responses compared to the control group).

Further analysis revealed that within the treatment arm two groups of patients could be distinguished based on their C-peptide levels: one group, considered "responders" (22/49), showed very little C-peptide decline over the course of the study (only a 6 percent reduction from baseline), while the "non-responders" (27/49) exhibited a similar rate of C-peptide decline as the control group (less than 40-percent reduction from baseline).

Investigators measured various biomarkers and cell types that might distinguish between these two groups. They found that, at trial entry, "responders" had lower hemoglobin A1c levels (a marker of glucose concentration in the blood) and used less insulin at baseline, compared to "non-responders". Differences in specific T-cell subsets also distinguished between the two groups at baseline, suggesting that immune status might contribute to drug responsiveness. However, further studies will be required to confirm these results.

"This overall approach to identifying characteristics of individuals most likely to respond to therapies shows great promise because the responders in this study experienced a robust and prolonged drug effect," said Dr. Herold. "This type of response has not been seen in other studies of immune therapies."

Type 1 diabetes is a disease marked by immune destruction of insulin-producing beta cells in the pancreas. New-onset patients usually have 20 to 40 percent of their normal beta cell mass remaining, which is still capable of producing insulin. Preserving this remaining mass, even temporarily, could improve long-term clinical outcomes.

Immune modulators, like teplizumab, represent a promising means of inducing tolerance; however, no drug has been shown to prevent or reverse disease, and only a few have temporarily delayed disease progression. The ability to identify a subgroup of patients who may be more responsive to therapy could greatly enhance the clinical use of immune modulators and improve outcomes for those patients. Further analyses with specimens collected from the AbATE study are ongoing to understand the mechanism of response.

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Blocking a master switch controlling cells' response to low levels of oxygen could lead to new cancer drugs

Main Category: Cancer / Oncology
Article Date: 29 Jul 2013 - 1:00 PDT Current ratings for:
Blocking a master switch controlling cells' response to low levels of oxygen could lead to new cancer drugs

Scientists have discovered a new molecule that prevents cancer cells from responding and surviving when starved of oxygen and which could be developed into new treatments for the disease, according to new research published in the Journal of the American Chemical Society.

Cancer Research UK scientists at the University of Southampton found that this molecule targets the master switch -- HIF-1 -- that cancer cells use to adapt to low oxygen levels, a common feature in the disease.

The researchers uncovered a way to stop cancer cells using this switch through an approach called 'synthetic biology'. By testing 3.2 million potential compounds, made by specially engineered bacteria, they were able to find a molecule that stopped HIF-1 from working.

All cells need a blood supply to provide them with the oxygen and nutrients they require to survive. Cancer tumours grow rapidly and as the tumour gets bigger it outstrips the supply of oxygen and nutrients that the surrounding blood vessels can deliver.

But, to cope with this low-oxygen environment, HIF-1 acts as a master switch that turns on hundreds of genes, allowing cancer cells to survive. HIF-1 triggers the formation of new blood vessels around tumours, causing more oxygen and nutrients to be delivered to the starving tumour, which in turn allows it to keep growing.

Dr Ali Tavassoli, a Cancer Research UK scientist whose team discovered and developed the compound at the University of Southampton, said: "We've found a way to target the steps that cancer cells take to survive and we hope that our research will one day lead to effective drugs that can stop cancers adapting to a low oxygen environment, stopping their growth. The next step is to further develop this molecule to create an effective treatment."

Dr Julie Sharp, senior science information manager at Cancer Research UK, said: "Finding ways to disrupt the tools that cancer cells use to adapt and grow when starved of oxygen has been a hot topic in cancer research, but finding drugs that do this effectively has proved elusive.

"For the first time our scientists have found a way to block a master switch controlling cells response to low levels of oxygen -- an important step towards creating drugs that could halt cancer in its tracks."

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Speaker's power to act on words influences listeners' brain response

Main Category: Psychology / Psychiatry
Article Date: 24 Jul 2013 - 14:00 PDT Current ratings for:
Speaker's power to act on words influences listeners' brain response

A speaker's power to act on his words influences how a listener perceives the meaning of their message, according to research published July 24 in the open access journal PLOS ONE by Ina Bornkessel-Schlesewsky from the University of Marburg, Germany, and colleagues from other institutions.

For example, listeners are more likely to believe a political figure is capable of acting on the words "Tear down this wall!" than when an ordinary citizen makes the same statement. In this study, researchers presented participants with videotaped statements about politics spoken by a top political decision-maker, a news anchor or an unknown person. In a second scenario, the same people uttered statements related to general world knowledge. Brain responses to implausible statements about current affairs differed when uttered by a political figure as opposed to the other speakers, but implausible general world knowledge statements led to a similar brain response across all three speakers.

The effects occur rapidly, within 150-450 milliseconds of hearing a statement, and demonstrate that a listener's response to a message is immediately influenced by the social status of the speaker, and whether he or she has the power to bring about the state of affairs described by their words. Bornkessel-Schlesewsky explains, "Every day, we hear statements that surprise us because they do not correspond to what we (think we) know about the world. Our study demonstrates that, in understanding such utterances, our brain rapidly takes into account who said them (e.g. a politician versus our neighbor) and whether he or she in fact has the power to act upon what was said."

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Citation: Bornkessel-Schlesewsky I, Krauspenhaar S, Schlesewsky M (2013) Yes, You Can? A Speaker’s Potency to Act upon His Words Orchestrates Early Neural Responses to Message-Level Meaning. PLoS ONE 8(7): e69173. doi:10.1371/journal.pone.0069173

Financial Disclosure: This work was supported by the Max Planck Society for the Advancement of Science,the Interdisciplinary Research Center for Neuroscience at the Johannes Gutenberg- University Mainz and by the LOEWE programme of the German state of Hesse. No additional external funding was received for this study. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing Interest Statement: The authors have declared that no competing interests exist.

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