When given early treatment, children with autism spectrum disorders (ASD) made significant improvements in behaviour, communication, and most strikingly, brain function, Yale School of Medicine researchers report in a new study.
The study was published by Yale Child Study Center researchers Dr. Fred Volkmar, Kevin A. Pelphrey, and their colleagues.
The results suggest that brain systems supporting social perception respond well to an early intervention behavioural program called pivotal response treatment. This treatment includes parent training, and employs play in its methods.
ASDs are complex neurobiological disorders that inhibit a person
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Researchers have created a new type of miniature pump activated by body heat that could be used in drug-delivery patches powered by fermentation.
The micropump contains Baker’s yeast and sugar in a small chamber. When water is added and the patch is placed on the skin, the body heat and the added water causes the yeast and sugar to ferment, generating a small amount of carbon dioxide gas. The gas pushes against a membrane and has been shown to continually pump for several hours, said Babak Ziaie, a Purdue University professor of electrical and computer engineering and biomedical engineering.
Such miniature pumps could make possible drug-delivery patches that use arrays of ‘microneedles’ to deliver a wider range of medications than now possible with conventional patches. Unlike many other micropumps under development or in commercial use, the new technology requires no batteries, said Ziaie, who is working with doctoral student Manuel Ochoa.
‘This just needs yeast, sugar, water and your own body heat,’ Ziaie said.
The robustness of yeast allows for long shelf life, and the design is ideal for mass production, Ochoa said.
‘It would be easy to fabricate because it’s just a few layers of polymers sandwiched together and bonded,’ he said.
The paper was written by Ochoa and Ziaie, and the research is based at Purdue’s Birck Nanotechnology Center in the university’s Discovery Park.
The ‘the microorganism-powered thermopneumatic pump’ is made out of layers of a rubberlike polymer, called polydimethylsiloxane, which is used commercially for diaphragms in pumps. The prototype is 1.5 centimeters long.
Current ‘transdermal’ patches are limited to delivering drugs that, like nicotine, are made of small hydrophobic molecules that can be absorbed through the skin, Ziaie said.
‘Many drugs, including those for treating cancer and autoimmune disorders cannot be delivered with patches because they are large molecules that won’t go through the skin,’ he said. ‘Although transdermal drug delivery via microneedle arrays has long been identified as a viable and promising method for delivering large hydrophilic molecules across the skin, a suitable pump has been hard to develop.’
Patches that used arrays of tiny microneedles could deliver a multitude of drugs, and the needles do not cause pain because they barely penetrate the skin, Ziaie said. The patches require a pump to push the drugs through the narrow needles, which have a diameter of about 20 microns, or roughly one-fourth as wide as a human hair.
Most pumps proposed for drug-delivery applications rely on an on-board power source, which is bulky, costly and requires complex power-management circuits to conserve battery life.
‘Our approach is much more simple,’ Ziaie said. ‘It could be a disposable transdermal pump. You just inject water into the patch and place it on your skin. After it’s used up, you would throw it away.’
Purdue University
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A new study by Weill Cornell Medical College researchers provides compelling evidence that electronic health records (EHRs) enhance the quality of patient care in a community-based setting with multiple players, which is representative of how medicine is generally practiced across the United States.
The use of EHRs is on the rise, in part because the federal government has invested up to $29 billion in incentives promoting the meaningful use of these systems, with the aim of tracking and improving patient outcomes. Previous studies have provided conflicting evidence about the impact of EHRs, and until now it had been not clear whether they improved the quality of patient care, particularly in typical communities that use commercially available systems.
‘The previous studies on the effects of electronic health records in the outpatient setting have been mixed,’ says the study’s lead investigator, Dr. Lisa M. Kern, associate professor of public health and medicine at Weill Cornell Medical College. ‘This is one of the first studies to find a positive association between the use of EHRs and quality of care in a typical community-based setting, using an off-the-shelf electronic health record that has not been extensively tailored and refined. This increases the generalisability of these findings.’
‘This study starts to grow the evidence that the use of these systems can systematically improve the quality of care, although their maximum value likely lies in their ability to support new health care delivery models,’ says the study’s senior investigator Dr. Rainu Kaushal, director of the Center for Healthcare Informatics and Policy and the Frances and John L. Loeb Professor of Medical Informatics at Weill Cornell Medical College. ‘The findings of this study lend support to the very significant investments in health information technology that are being made by the federal government, states, and health care providers.’
This study was conducted with the Health Information Technology Evaluation Collaborative (HITEC)
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UCSF researchers found that poor HIV-infected individuals living in San Francisco are significantly more likely to visit emergency rooms and to have hospital stays if they lack access to food of sufficient quality and quantity for a healthy life.
‘In the prior three months, a quarter of participants in the study reported an ER visit, and just over a tenth reported a hospitalisation, which shows that we are dealing with a population with high levels of illness. But the food insecure people were even sicker than the food secure, which is consistent with their experiencing higher rates of chronic diseases,’ said the study’s primary investigator, Sheri Weiser, MD, assistant professor of medicine in the UCSF HIV/AIDS Division at San Francisco General Hospital and Trauma Center.
The study recruited 347 HIV-infected urban poor participants living in substandard housing in San Francisco. To determine levels of food insecurity, the participants were questioned about their anxiety and uncertainty about their food supply, whether they were able to access sufficient quality and variety of food, and their experience of insufficient food intake and the physical consequences. Just over half of the group, 56 percent, was classified as food insecure. The entire cohort of food secure and food insecure individuals was followed for two years, looking at healthcare utilisation as a primary outcome.
‘Compared to food secure participants, the odds were approximately two times higher that a food insecure participant was hospitalised or that a food insecure participant had visited the ER over the study’s time period,’ said Weiser. ‘For a long time we have known that adequate nutrition is crucial for HIV-positive patients to live long healthy lives. Our findings that food insecure individuals are also more likely to use costly services from hospitals and emergency rooms build on our previous work showing that food insecure individuals experience poorer HIV treatment outcomes.’
Food insecurity among HIV-infected homeless and marginally housed individuals in the City is higher than the rate of food insecurity seen nationally in non HIV-infected homeless persons, with about a quarter to a third experiencing food insecurity. For the general population, about one in seven Americans is food insecure.
‘Roughly three quarters of our participants are accessing some form of food aid. Project Open Hand, Glide, and other programs providing food assistance to San Francisco’s urban poor do a phenomenal job, but with falling levels of funding and increasing client loads, their efforts have not been enough to take people out of food insecurity,’ said the study’s senior investigator, Margot B. Kushel, MD, associate professor in the UCSF Division of Internal Medicine at San Francisco General Hospital and Trauma Center.
‘One part of the problem lies in housing,’ she said. ‘While about a tenth of participants had a recent experience of homelessness, most of the rest were housed in single-room occupancy hotels, many of which do not include kitchen facilities. Providing secure housing with functional kitchens is an important part of addressing the problem.’
Surprisingly, said Weiser, less than a fifth of the participants had received federal food assistance through the Supplemental Nutrition Assistance Programs (SNAP) over the previous year and only about a tenth had received SNAP over the previous month. ‘We were alarmed to see such low numbers accessing SNAP, since presumably this program is intended to serve urban poor who experience food insecurity. But many of our food insecure participants have a monthly income that is slightly above the $1,080 a month SNAP cut-off.’ In other words, SNAP does not seem to be reaching the majority of HIV-infected persons in need of food assistance.
EurekAlert
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Researchers from the University of Cambridge, the Wellcome Trust Sanger Institute, and Cambridge University Hospitals used advanced DNA sequencing technologies to confirm the presence of an ongoing outbreak of methicillin-resistant Staphylococcus aureus (MRSA) in a Special Care Baby Unit in real time. This assisted in stopping the outbreak earlier, saving possible harm to patients. This approach is much more accurate than current methods used to detect hospital outbreaks.
Using this technology, the team revealed that the outbreak had extended into the wider community, a conclusion that could not be reached with available methods. They also used sequencing to link the outbreak to an unsuspecting carrier, who was treated to eradicate MRSA.
‘We are always seeking ways to improve our patient care and wanted to explore the role that the latest sequencing technologies could play in the control of infections in hospitals,’ says Dr Nick Brown, author, consultant microbiologist at the Health Protection Agency and infection control doctor at Addenbrooke‟s Hospital Cambridge. ‘Our aim is to prevent outbreaks, and in the event that they occur to identify these rapidly and accurately and bring them under control.
‘What we have glimpsed through this pioneering study is a future in which new sequencing methods will help us to identify, manage and stop hospital outbreaks and deliver even better patient care.’
Over a six month period, the hospital infection control team used standard protocols to identify 12 patients who were carrying MRSA. However, this standard approach alone could not give enough information to confirm or refute whether or not an ongoing outbreak was actually taking place.
In this study, the researchers analysed MRSA isolates from these 12 patients with DNA sequencing technology and demonstrated clearly that all the MRSA bacteria were closely related and that this was an outbreak. They also revealed that the outbreak was more extensive than previously realised, finding that over twice as many people were carrying or were infected with the same outbreak strain. Many of these additional cases were people who had recent links to the hospital but were otherwise healthy and living in the community when they developed a MRSA infection.
While this sequencing study was underway, the infection control team identified a new case of MRSA carriage in the Special Care Baby Unit, which occurred 64 days after the last MRSA-positive patient had left the same unit. The team used advanced DNA sequencing to show in real time that this strain was also part of the outbreak, despite the lack of apparent links between this case and previous patients. This raised the possibility that an individual was unknowingly carrying and transmitting the outbreak MRSA strain.
The infection control team screened 154 healthcare workers for MRSA and found that one staff member was carrying MRSA. Using DNA sequencing, they confirmed that this MRSA strain was linked to the outbreak. This healthcare worker was quickly treated to eradicate their MRSA carriage and thus remove the risk of further spread.
‘Our study highlights the power of advanced DNA sequencing used in real time to directly influence infection control procedures,’ says Dr Julian Parkhill, lead author from the Wellcome Trust Sanger Institute. ‘There is a real health and cost burden from hospital outbreaks and significant benefits to be gained from their prevention and swift containment. This technology holds great promise for the quick and accurate identification of bacterial transmissions in our hospitals and could lead to a paradigm shift in how we manage infection control and practice.’
In this instance, DNA sequencing was a key step in bringing the outbreak to a close, saving possible harm to patients and potentially saving the hospital money.
Cambridge University
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UC Davis cancer researchers have discovered significant differences in radiation-therapy response among patients with oropharyngeal cancer depending on whether they carry the human papillomavirus (HPV), a common sexually transmitted virus. The findings could lead to more individualised radiation treatment regimens, which for many patients with HPV could be shorter and potentially less toxic.
HPV-related cancers of the oropharynx (the region of the throat between the soft palate and the epiglottis, including the tonsils, base of tongue and uvula) have steadily increased in recent years, according to the National Cancer Institute, especially among men. At the same time, the incidence of oropharyngeal cancers related to other causes, such as smoking or alcohol consumption, is declining. HPV is the most common sexually transmitted infection in the United States; it can spread through direct skin-to-skin contact during vaginal, anal and oral sex.
The UC Davis study, conducted by Allen Chen, associate professor in the UC Davis Department of Radiation Oncology, examined patterns of tumour reduction during radiation treatment in two otherwise similar groups of patients with oropharyngeal cancer: those who tested positive for HPV and those who tested negative for the virus. None of the HPV patients in the study was a smoker, a leading risk factor for the disease.
Chen used CT scans acquired during image-guided radiation therapy (IGRT) and endoscopy (a tube with a small camera) to capture 3D images of the patients’ tumours and monitor their treatment progress. He found that within the first two weeks after starting radiation, the gross tumour volume decreased by 33 percent in HPV-positive patients, while the volume decreased by only 10 percent in HPV-negative patients.
Chen said the results demonstrate that HPV-positive patients have a more rapid and robust response to radiation treatments, confirming what clinicians have suspected for years.
‘These HPV-related tumours literally melt before your eyes,’ he said. ‘It is very gratifying to tell patients early on during treatment that their tumours are responding so quickly. Most of them are pleasantly relieved to hear such news.’
The rapid rate of tumour regression did not continue, however, after the second week of radiation treatment, and by the end of the seven-week regimen, the total tumour shrinkage in both groups of patients was nearly the same.
However, ‘the dramatic early response observed in the HPV-positive patients strongly implies that these tumours behave distinctly from a biological standpoint and could be approached as a separate disease process,’ Chen said.
For example, the findings suggest that treatment for HPV-positive cancer may not need to be as intensive for it to be effective, Chen said, adding that a shorter, abbreviated treatment regimen would potentially lessen the side effects from radiation, which include sore throat, dry mouth, taste loss and swallowing difficulties.
‘It is likely that treatment in the future will be individualised based on biomarkers present in the tumour, and HPV has the potential to do just that,’ said Chen.
Chen said there is increasing evidence that HPV-positive patients who receive radiation treatments live longer and have higher cure rates. According to the NCI, 88 percent of the HPV-positive patients are still alive two years after their treatments, compared with 66 percent of the HPV-negative patients.
‘Given the impressive outcomes for patients with HPV-positive cancer using currently aggressive treatments, how to de-intensify therapy while maintaining cure rates is definitely a hot topic right now,’ said Chen.
UC Davis Comprehensive Cancer Center
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Researchers have used computational analysis to identify a new Achilles heel for the treatment of drug-resistant breast cancer. The results reveal that the disruption of glucose metabolism is an effective therapeutic strategy for the treatment of tumours that have acquired resistance to front-line cancer drugs such as Lapatinib.
‘The growth and survival of cancer cells can often be impaired by treatment with drugs that interfere with the actions of one or more oncogenes,’ said Prahlad Ram, the senior author of the study and Professor at the University of Texas MD Anderson Cancer Center, Houston, Texas. ‘However, the clinical benefits to patients are often short lived due to acquired drug resistance. Finding alternative intervention points or so-called new addictions for cancer cells is of critical importance for designing novel therapeutic strategies against tumours. Our results reveal specific new targets for drug intervention in the metabolic pathways of cancer cells and identify existing drugs that can be used to treat drug-resistant cancer.’
Lapatinib is used for the treatment of patients with advanced or metastatic breast cancer in cases where tumours over-express the ErbB2 gene. The ErbB2 gene provides instructions for making a specific growth factor receptor. If too much of this ErbB2 growth factor receptor is made, it can lead to cells that grow and divide continuously, one of the defining characteristics of breast cancer.
The scientists used microarrays to measure gene expression in breast cancer cells with and without treatment with Lapatinib. Computational analysis of more than 15000 gene interactions revealed four major populations of genes that were regulated in a significant way. Three of these groups were the regular suspects related to drug resistance, such as genes involved in oxidation and reduction reactions or cell cycle processes. A fourth group comprised a network of reactions linked to the deprivation of glucose.
Analysis of the gene expression networks of ErbB2-positive breast cancer patients revealed that the glucose deprivation network is linked to low survival rates of the patients. Computational screening of a library of existing drugs for therapeutics that target the glucose deprivation response identified several drugs that could be effective in treating drug-resistant breast cancer.
‘By developing novel gene expression analysis algorithms and integrating diverse data, we have been able to look beyond changes in the immediate molecular signaling pathways of breast cancer cells and to consider the wider system of molecular networks within the cell,’ remarked Ram. ‘Our approach predicts new uses for existing drugs that impact the metabolism of breast cancer cells and may offer an expedient route to improved treatments for breast cancer patients.’
The glucose-deprivation response network counteracts EGFR signalling in lapatinib resistant cells
EMBO
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A new study by University of North Carolina School of Medicine researchers found that 31 percent of children identified as at risk for autism spectrum disorders (ASD) at 12 months received a confirmed diagnosis of ASD by age 3 years.
In addition, 85 percent of the children found to be at risk for ASD based on results from the First Year Inventory (FYI), a 63-item questionnaire filled out by their parents, had some other developmental disability or concern by age three, said Grace Baranek, PhD, senior author of the study and an autism researcher with the Program for Early Autism, Research, Leadership and Service (PEARLS) in the Department of Allied Health Sciences at the UNC School of Medicine.
‘These results indicate that an overwhelming majority of children who screen positive on the FYI indeed experience some delay in development by age three that may warrant early intervention,’ she said.
Lead author of the study, Lauren Turner-Brown, PhD, also a researcher with PEARLS and the Carolina Institute for Developmental Disabilities said, ‘Identification of children at risk for ASD at 12 months could provide a substantial number of children and their families with access to intervention services months or years before they would otherwise receive a traditional diagnosis.’
The First Year Inventory was developed by Grace Baranek, PhD, Linda Watson, EdD, Elizabeth Crais, PhD and J. Steven Reznick, PhD, who are all researchers with PEARLS. All are also co-authors of the study with Turner-Brown, published online ahead of print.
In the study, parents of 699 children who had completed the FYI when their child was 12 months old completed additional screening questionnaires when their child reached age 3. In addition, children who were found to be at risk for ASD based on these measures were invited for in-person diagnostic evaluations.
‘These findings are encouraging and suggest promise in the approach of using parent report of infant behaviours as a tool for identifying 12-month-olds who are at risk for an eventual diagnosis of ASD,’ Turner-Brown said.
University of North Carolina Health Care
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