Reviewed by James Ives, M.Psych. (Editor)Nov 8 2018The HER2 gene is a well-known driver of breast cancer, where changes in this gene are found in about 1-in-5 cases of the disease. HER2 also contributes to about 3 percent of lung cancers, representing about 6,500 patients per year. But while drugs like trastuzumab and lapatinib have proven effective in silencing the action of HER2 in breast cancer, there are currently no approved HER2-targeted therapies for the treatment of lung cancer.Now, a University of Colorado Cancer Center study presented at the 30th annual EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics shows the promise of an innovative new strategy against HER2-driven lung cancers (with EGFR involvement, which is also a well-known driver of lung cancer). Tarloxotinib, a potent HER2/EGFR inhibitor, is unique in that the drug only becomes active in low-oxygen conditions, such as those commonly found in tumor tissue. By pairing a potent HER2/EGFR inhibitor with a targeting mechanism specific to tumors, researchers show that tarloxotinib is far more active against lung cancer cell lines than even the most successful existing HER2/EGFR inhibitors, with minimal effect on surrounding, healthy tissues.”We are very excited about this drug. When it’s near healthy cells, it’s inactive; when it’s near tumor cells, it’s very active. This could provide a new therapeutic approach for patients with HER2 lung cancer,” says Robert C. Doebele, MD, PhD, director of the CU Cancer Center Thoracic Oncology Research Initiative. Dr. Doebele is a co-founder of Rain Therapeutics Inc., a clinical stage biotechnology company developing tarloxotinib as its lead drug candidate.Related StoriesStudy reveals link between inflammatory diet and colorectal cancer riskResearchers identify potential drug target for multiple cancer typesAdding immunotherapy after initial treatment improves survival in metastatic NSCLC patientsTarloxotinib is one in a class of anti-cancer agents known as “prodrugs,” in which inactive molecules are transformed by specific conditions inside the body into active molecules. In the case of tarloxotinib, oxygen molecules scavenge electrons from the prodrug to keep it inactive. In the absence of oxygen, tarloxotinib fractures into its active form.The current study shows that in healthy, high-oxygen tissues, it takes about an hour for the body to clear half of any administered molecules of tarloxotinib; in low-oxygen tumor tissues, the same clearance takes about 80 hours. This makes tarloxotinib about 50 times more active in low-oxygen conditions than it is in normal-oxygen conditions. And low-oxygen conditions, aka “hypoxia,” are a hallmark of cancer, in which the growth of tumor tissue often outpaces the growth of blood vessels needed to supply the tumor with oxygen.”The problem is that the concentration of HER2/EGFR inhibitor needed to affect HER2/EGFR lung cancer is so high that these drugs have come with too many side effects to be clinically useful. We hope that our approach with this prodrug will solve that problem, delivering the HER2/EGFR inhibitor where it’s needed without compromising function in healthy tissues,” says Adriana Estrada-Bernal, PhD, the study’s first author.At noon (GMT) on November 13, the group will present data describing the therapeutic effect of tarloxotinib on mouse models of lung cancer. Collaborators at the University of Auckland will present the following additional data: Source:http://www.ucdenver.edu/
Reviewed by James Ives, M.Psych. (Editor)Dec 14 2018If you experience an injury at work, the amount of compensation you receive depends on which impairment rating system is used, according to research from McMaster University and the Netherlands.The American Medical Association (AMA) Guides to the Evaluation of Permanent Impairment is used in workers’ compensation systems, federal systems, automobile accidents and personal injury cases to rate impairment.However, a comparison of a group of injured workers assessed using the two most recent editions of the AMA guides revealed that usage of the sixth edition resulted in significantly lower impairment ratings than the fifth edition.The findings were published today in the Journal of Occupational and Environmental Medicine.”Our study shows your impairment rating will depend on the version of the AMA guides that you are assessed with,” said Jason Busse, first author and an associate professor of anesthesia at McMaster.”The difference in impairment rating is likely due to the fact that when these guides first came out, they were focused on pain and range of motion, and they have increasingly moved to more direct measures of function.Related StoriesAre Chronic Pain Relief Drugs for Children Effective?AMSBIO offers new, best-in-class CAR-T cell range for research and immunotherapyResearch sheds light on sun-induced DNA damage and repair”For example, in an earlier guide they may have measured whether a person could lift their arm above their head without discomfort, but now they look at whether the person could put a box on a shelf.”Researchers used data from a consecutive sample of 249 injured workers referred for an independent evaluation at the Orthopedisch Expertise Centrum Amsterdam between 2011 and 2012.The results showed the median whole person impairment rating was seven per cent for 131 claimants assessed with the fifth edition of the AMA guides, and four per cent for 118 claimants assessed with the sixth edition.”Because all assessors in the Netherlands switched from the fifth to the sixth edition at the same time, we were able to study two large cohorts of patients with similar injuries and explore the impact on impairment ratings,” said Busse, who is also a researcher with the Michael G. DeGroote Institute for Pain Research and Care.The other major finding of the study was considerable inconsistency of AMA Guides editions used by workers’ compensation boards across North America.”There was a tremendous variability in the edition that North American compensation boards are using,” Busse said. “The most recent version, which was the sixth, was published in 2007. Yet, for example, we have the largest compensation board in Canada, which is in Ontario, using the third revised version which came out in 1991.”Busse said he recommends consistency across compensation boards.”Workers’ compensation boards should standardize impairment rating systems so that everyone is gauged on the same scale,” he said. “If we believe that more recent editions of the AMA guides do a better job of quantifying impairment, why is it that so many Boards are using earlier versions?”Source: https://www.mcmaster.ca/
Reviewed by James Ives, M.Psych. (Editor)Jan 25 2019A team of Vanderbilt University Medical Center researchers, working with the U.S. Department of Veteran’s Affairs (VA), has discovered genetic associations with blood pressure that could guide future treatments for patients with hypertension.The study, an international effort using data from sources including the VA Million Veteran Program (MVP) and United Kingdom (UK) Biobank, is published in the January issue of Nature Genetics.MVP is a national effort by the U.S. Department of Veterans Affairs (VA) to collect blood samples and health information from one million veteran volunteers.Researchers discovered over 250 new genetic variants, and also identified over 400 new genes associated with blood pressure through changes in gene expression. The findings also suggest that several existing drugs not currently used to treat high blood pressure could be used to potentially lower blood pressure.”We’re redrawing the map of blood pressure genetics,” said Todd Edwards, PhD, associate professor of Medicine in the Vanderbilt University School of Medicine and one of two senior corresponding authors with Adriana Hung, MD, MPH.Related StoriesPoor sleep associated with high blood pressureHealthy blood vessels could help stave off cognitive declineNew ACC/AHA guidelines could improve detection of gestational hypertensionWhile large swaths of the map remain to be filled in, the researchers said they are closer than ever to being able to improve the treatment of high blood pressure based on the patient’s genetic make-up.”The door is wide open,” said Vanderbilt research fellow Jacob Keaton, PhD, whose identification of gene-drug interactions was a key part of the study. “We’re bringing findings to the table that we can do something with to have an impact on precision medicine.”The study analyzed the relationship between genetic variants and blood pressure traits utilizing the electronic health records of more than 300,000 MVP participants and more than 140,000 UK Biobank study participants.Thirty percent of the MVP participants were African-Americans, Hispanics, Asians and Native Americans — making it one of the most racially diverse genetic inquiries of its kind, said Hung, associate professor of Medicine in the Division of Nephrology and Hypertension. Researchers replicated their findings by analyzing 17,000 samples from the Vanderbilt University biobank, BioVU, and 300,000 from large genetic consortia of blood pressure studies.”Blood pressure is incredibly complicated,” Edwards said. “It may be that as we increase the sample size of these kinds of studies … we’ll discover that no place in the genome has a zero effect on a trait like blood pressure. It’s just that some of the effects are incredibly subtle.”Much more needs to be learned.Currently “we can’t accurately say what your blood pressure’s going to be at age 65 by looking at your genotype,” Edwards said, “but we might be able to tailor your treatment a little more accurately with some of the results we have from this study.”Source: https://ww2.mc.vanderbilt.edu/
Ten ophthalmologists (four general ophthalmologists, one trained outside the US, four retina specialists, and one retina specialist in training) were asked to read each image once under one of three conditions: unassisted, grades only, and grades + heatmap.Both types of assistance improved physicians’ diagnostic accuracy. It also improved their confidence in the diagnosis. But the degree of improvement depended on the physician’s level of expertise.Without assistance, general ophthalmologists are significantly less accurate than the algorithm, while retina specialists are not significantly more accurate than the algorithm. With assistance, general ophthalmologists match but do not exceed the model’s accuracy, while retina specialists start to exceed the model’s performance.”What we found is that AI can do more than simply automate eye screening, it can assist physicians in more accurately diagnosing diabetic retinopathy,” said lead researcher, Rory Sayres, PhD.. “AI and physicians working together can be more accurate than either alone.”Like medical technologies that preceded it, Sayres said that AI is another tool that will make the knowledge, skill, and judgment of physicians even more central to quality care.”There’s an analogy in driving,” Sayres explained. “There are self-driving vehicles, and there are tools to help drivers, like Android Auto. The first is automation, the second is augmentation. The findings of our study indicate that there may be space for augmentation in classifying medical images like retinal fundus images. When the combination of clinician and assistant outperforms either alone, this provides an argument for up-leveling clinicians with intelligent tools.” Source:https://www.aao.org/newsroom/news-releases/detail/how-ai-can-make-ophthalmologists-more-effective Reviewed by James Ives, M.Psych. (Editor)Mar 19 2019As artificial intelligence continues to evolve, diagnosing disease faster and potentially with greater accuracy than physicians, some have suggested that technology may soon replace tasks that physicians currently perform. But a new study from the Google AI research group shows that physicians and algorithms working together are more effective than either alone. It’s one of the first studies to examine how AI can improve physicians’ diagnostic accuracy. The new research will be published in the April edition of Ophthalmology, the journal of the American Academy of Ophthalmology.This study expands on previous work from Google AI showing that its algorithm works roughly as well as human experts in screening patients for a common diabetic eye disease called diabetic retinopathy. For their latest study, the researchers wanted to see if their algorithm could do more than simply diagnose disease. They wanted to create a new computer-assisted system that could “explain” the algorithm’s diagnosis. They found that this system not only improved the ophthalmologists’ diagnostic accuracy, but it also improved algorithm’s accuracy.More than 29 million Americans have diabetes, and are at risk for diabetic retinopathy, a potentially blinding eye disease. People typically don’t notice changes in their vision in the disease’s early stages. But as it progresses, diabetic retinopathy usually causes vision loss that in many cases cannot be reversed. That’s why it’s so important that people with diabetes have yearly screenings.Unfortunately, the accuracy of screenings can vary significantly. One study found a 49 percent error rate among internists, diabetologists, and medical residents.Recent advances in AI promise to improve access to diabetic retinopathy screening and to improve its accuracy. But it’s less clear how AI will work in the physician’s office or other clinical settings. Previous attempts to use computer-assisted diagnosis shows that some screeners rely on the machine too much, which leads to repeating the machine’s errors, or under-rely on it and ignore accurate predictions. Researchers at Google AI believe some of these pitfalls may be avoided if the computer can “explain” its predictions.Related StoriesAXT enhances cellular research product portfolio with solutions from StemBioSysScientists develop universal FACS-based approach to heterogenous cell sorting, propelling organoid researchAMSBIO offers new, best-in-class CAR-T cell range for research and immunotherapyTo test this theory, the researchers developed two types of assistance to help physicians read the algorithm’s predictions. Grades: A set of five scores that represent the strength of evidence for the algorithm’s prediction. Grades + heatmap: Enhance the grading system with a heatmap that measures the contribution of each pixel in the image to the algorithm’s prediction.
New Delhi Chief Minister Arvind Kejriwal (file photo). SHARE SHARE EMAIL COMMENT February 23, 2019 SHARE Published on Chief Minister Arvind Kejriwal on Saturday announced that he will launch an indefinite hunger strike from March 1 to press the demand for full statehood to Delhi. Addressing the budget session of Delhi Assembly, Kejriwal stepped up his attack on the Centre and said the Delhi government is unable to perform its duties towards people of the city because it lacked power. “I will sit on an indefinite hunger strike for full statehood to Delhi from March. People have given us so much that even if we have to sacrifice our lives for them, it is immaterial,” Kejriwal told the House. He claimed the people of Delhi were facing “injustice and humiliation” since independence because the government elected by them lacked power to work for them. “The elected government of Delhi cannot give people justice, work for them and take up development works because it lacks power and the central government obstructs its functioning. Is the value of Delhi voters less than other states?” he questioned. He said the Centre has control over Delhi Police, municipal corporations and DDA, which is why people “were suffering due to high crime rate, in-sanitation and lack of development”. COMMENTS politics