Otosclerosis

WEDNESDAY, March 22, 2023 -- Genetic analysis of Ludwig van Beethoven’s hair has provided new clues into the cause of the great composer’s death in 1827 — as well as evidence of a family scandal. The analysis revealed that Beethoven suffered from a hepatitis B infection that could have contributed to his death from liver disease. Researchers found DNA evidence of hepatitis B virus in a lock of hair taken from Beethoven’s body shortly after his death in 1827, according to the report published online March 22 in Current Biology . The investigators also found evidence of a strong genetic predisposition to liver disease in Beethoven, said co-researcher Dr. Markus Nothen , a professor with the University Hospital of Bonn’s Institute of Human Genetics, in Germany. “We believe that the liver disease arose from an interplay of genetic disposition, a well-documented chronic alcohol consumption, and hepatitis B infection,” Nothen said in a Tuesday media briefing. But the researchers found they could not match Beethoven’s genetic relationship with five Belgian and three Austrian descendants bearing his name, suggesting that a child born of an extramarital affair occurred somewhere in his direct paternal line. “You cannot rule out that Beethoven himself may have been illegitimate,” said lead researcher Tristan James Alexander Begg , a doctoral student in archaeology with the University of Cambridge in the United Kingdom. “I'm not advocating that. I'm simply saying that's a possibility, and you have to consider it.” Unfortunately, the researchers did not obtain from Beethoven’s hair the prize they actually sought — a genetic explanation for the composer’s well-known progressive hearing loss . The scientists looked for genetic signs of several different potential causes of deafness, including otosclerosis and Paget’s disease of bone, but “we didn’t see evidence for a monogenic cause,” Begg said. In this eight-year effort, the researchers analyzed about 10 feet of preserved hair drawn from five separate locks, all of which date from the last seven years of Beethoven’s life. From locks of hair, clues to cause of death Even with all this work, the researchers were only able to map two-thirds of Beethoven’s genome, Begg said. Hair degrades more quickly than bone, making it “really hard to get enough DNA from such a sample to assemble a genome,” said senior researcher Johannes Krause , director of archaeogenetics with the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany. In a way, Beethoven himself commissioned the work performed by these modern scientists, as a result of his well-documented health troubles. Beethoven started losing his hearing in his mid-to-late 20s. It is generally believed Beethoven composed some of his most famous works, including his Ninth Symphony, after he’d become completely deaf. Beethoven also suffered from debilitating gastrointestinal (GI) problems from at least age 22, characterized mainly by abdominal pains and prolonged bouts of diarrhea, the authors said in background notes. And in the summer of 1821, Beethoven began to show signs of liver disease when the first of at least two attacks of jaundice occurred. Experts believe this liver disease eventually led to his death at age 56 on March 26, 1827. The day after his death, two of his associates found a remarkable document stored in a hidden compartment in his writing desk. The letter from Beethoven to his brothers, written in 1802, described his increasing deafness and how it had led him to contemplate suicide. It included a request that upon his death, his disease be described and made public. The letter, known as the “Heiligenstadt Testament,” kicked off what has become centuries of lively debate over Beethoven’s health problems. The researchers gained access to eight separate locks of hair attributed to Beethoven, and soon found that three of the locks did not actually come from the composer. But no clues to early deafness For example, the “Hiller Lock” actually originated from a woman with genetics highly prevalent among Ashkenazi Jews, the study authors said. This lock was once believed to have been taken from Beethoven’s head after his death by 15-year-old musician Ferdinand Hiller. Samples from this lock had earlier been used by other researchers to argue that lead poisoning had contributed to Beethoven’s health problems. “We now conclude that these findings do not apply to Beethoven,” the researchers wrote. The five legitimate locks — the Muller, Bermann, Halm-Thayer, Moscheles and Stumpff locks — were used to craft a genetic portrait of Beethoven. Below is a photo of the Moscheles lock of hair: The Moscheles Lock, with inscription by former owner Ignaz Moscheles. Image: Brilliant Center for Beethoven Studies, San Jose State University consumer.healthday.com The genetics did not reveal a clear hereditary explanation for either Beethoven’s deafness or his GI problems, the researchers reported. But the Stumpff lock, taken shortly after Beethoven’s death, contained genetic evidence of a hepatitis B infection. “That tells us that in the last few months before his death, he was infected with hepatitis B virus,” Krause said. “It could have been also present earlier.” The hepatitis B likely combined with other genetic risk factors and Beethoven’s self-documented drinking to damage his liver, leading to his death, the researchers concluded. “We cannot say definitely what killed Beethoven, but we can now at least confirm the presence of significant heritable risk, and an infection with hepatitis B virus,” Krause said in a news release. “We can also eliminate several other less plausible genetic causes.” An illegitimate child in the family? Analysis of genetics from living relatives — some of whom share a paternal ancestor with Beethoven from the late 1500s and early 1600s — revealed no match with the Y chromosome found in the authentic hair samples, the findings showed. This is likely the result of a child resulting from an extramarital relationship somewhere in either Beethoven’s generation or the seven generations preceding the composer, the researchers said. This event probably occurred between the conception of Hendrik van Beethoven in Kampenhout, Belgium, in 1572 and the conception of Ludwig van Beethoven seven generations later in 1770, in Bonn, Germany, the study authors noted. The research team plans to make all its genetic data on Beethoven publicly available. “If in the future people maybe find other disease genes, they could actually quiz the genome from Beethoven now for those genes maybe being present,” Krause explained. “It is also possible that other groups will study some of the other locks that exist,” Krause added. “We looked at eight, but there are another at least 24 that exist.” However, the researchers said such rich findings likely wouldn’t occur when plumbing the genetics of other historical figures who left behind DNA samples. That’s because most great men and women don’t typically have a history of strange health problems and mixed paternity, Begg and Nothen said. “Like my 23andMe results and that of most people on the planet and therefore most historical figures, there is going to be nothing wrong with them,” Begg said. “Beethoven also is kind of unique because of the enormous literature on his health problems,” Nothen added. “So it was really, I think, a unique chance to use modern genetic methods to add something. I don’t know any historical person with a comparable literature on health and diseases.” Sources Markus Nothen, MD, professor, University Hospital of Bonn&rsquo s Institute for Human Genetics, Germany Tristan James Alexander Begg, doctoral student, archaeology, University of Cambridge, England Johannes Krause, PhD, director, archaeogenetics, Max Planck Institute for Evolutionary Anthropology, Leipzig, Germany Current Biology , March 22, 2023, online Posted March 2023

New results from the FinnGen research consortium demonstrate the benefits of Finnish health research environment for genomic research. Among the wealth of novel genetic discoveries are previously unknown genetic risk factors for many debilitating diseases. These findings have potential to facilitate the development of new therapies. New results from the FinnGen research consortium demonstrate the undeniable benefits of Finnish health research environment for genomic research. Among the wealth of novel genetic discoveries are previously unknown genetic risk factors for many debilitating diseases. These findings have potential to facilitate the development of new therapies. Since initiation in 2017, the FinnGen study has developed into one of the world's leading biobank-based genomic research projects. Currently FinnGen is completing the construction of a resource that integrates genomic information from 500,000 Finns with more than half a century of national health registry data. The FinnGen flagship study, just published in Nature, is a convincing demonstration of the opportunities unique to Finnish health data, population structure, legislative frameworks and biobanking organization that in combination exist nowhere else. Here the FinnGen team describes results based on 224,737 Finnish biobank participants. After performing comprehensive genetic analyses for more than 1,900 diseases, the researchers identify almost 2,500 genomic regions that are linked with at least one of these diseases. "Even with less than half of the recruited 500,000 participants analyzed at this stage, this snapshot of results describes a wealth of important genetic discoveries emerging from FinnGen, including novel risk and protective variants for both common and rare diseases," says FinnGen Scientific Director, Professor Aarno Palotie from the Institute for Molecular Medicine Finland FIMM, University of Helsinki. Finland's health registers and biobanks provide unique opportunities In Finland, health information such as medical diagnoses, procedures and drug prescriptions are captured for many decades in national electronic health registers for the entire population. This creates unique research opportunities. In the flagship publication, the team first demonstrates that with skillful utilization of such register data, the health history of the study participants can be reliably composed and studied. For this, the authors compare the FinnGen results with earlier genetic findings for 15 previously well-studied common diseases, such as type 2 diabetes, asthma and Alzheimer's disease. In addition to verifying the validity of register data, the researchers show that identification of novel risk variants in FinnGen is possible with a much smaller number of patients compared to the largest published disease-specific genetic studies. "The Finnish health registers containing health and medication data throughout an individual's lifetime, allowed us to rapidly and accurately identify disease cases. This accurate phenotyping, coupled with Finnish population history is a very powerful combination for novel genetic discoveries in a wide variety of diseases," comments Dr. Mitja Kurki, the first author of the study from the Broad Institute of MIT and Harvard and the University of Helsinki. New entry points into the disease biology Finland's unique geographic position and linguistic isolation are such that Finns have a distinct ancestry dating back to a small founding population approximately 100-150 generations. As a result, the modern Finnish population, despite being broadly similar to Europeans genetically, has an unusual and large set of genetic variants not often found elsewhere in the world. Several hundred of the 2,500 disease linked variants described in the study are in this category. Among these variants, the researchers highlight 29 that are located in genes not previously linked to any disease. One example is a variant in a gene called TNRC18 that predisposes to inflammatory bowel disease and other inflammatory conditions. Other examples include variants increasing the risk of hypothyroidism, hearing loss or endometriosis, and variants that offer protection from arthrosis, glaucoma or heart disease. "These findings demonstrate the power of bottlenecked populations to find entry points into the biology of common diseases through variants that are rather rare, but have a strong biological impact," says Mark Daly, the Director of the Institute for Molecular Medicine Finland FIMM at the University of Helsinki, the lead organization behind the study. Additional FinnGen papers published this week provide fascinating examples of findings that increase our understanding of genetic predictors of medication use patterns as well as mechanisms leading to otosclerosis and respiratory infections, among other diseases. Furthermore, another FinnGen paper published in the same issue of Nature highlights that the classical inheritance models traditionally considered in genomic research and clinical diagnostics do not fully capture the range of genetic effects observed in populations. One of the unique aspects of FinnGen is that in addition to public funding, FinnGen is supported by 13 pharmaceutical companies and has had shared scientific direction from academic and industry partners. The FinnGen study is thus ideally situated to address fundamental research questions with the potential to impact therapeutic development and delivery. "With all this new information, the genetic composition of the Finnish population is now unquestionably among the best known in the world. However, the impact of our study is much broader and can benefit patients everywhere," Professor Palotie emphasizes.

Benefits Of MRI-Guided Radiation Therapy Systems Over Linear Accelerators & Growing Adoption Of Next-Generation Technologies Had Led To 31% Y-O-Y Growth In 2019 Fact.MR – A Market Research and Competitive Intelligence Provider: The global MRI-guided radiation therapy systems market was valued at nearly US $ 221Mn in 2018 and is expected to record a CAGR of approximately 20% through 2028. Surge in adoption of radiotherapy in cancer treatment is fuelling demand for MRI-guided radiation therapy systems. Significant rise in the national expenditures for cancer care in the US is expected to boost the growth of the market. Increasing capital expenditures on healthcare infrastructure and adoption of advanced medical technologies in developing countries is laying a strong foundation for manufacturers in the MRI-guided radiation therapy systems market. MRI-guided radiation therapy systems have become a crucial part of cancer treatment over linear accelerators. Favorable reimbursement policies pertaining to cancer care continue to drive adoption of the MRI-guided radiation therapy systems among hospitals and medical facilities. For More Insights on this Market, Get A Sample Report! Besides this, rising awareness about cancer and awareness about the advanced treatment procedures, are expected to offer lucrative opportunities for the growth of MRI- guided radiation therapy system market players. In addition to this, stringent government regulations and standards are likely to have an impact on strategies adopted by manufacturers and is likely to cause a delay in the launch of the product. Key Takeaways: MRI-guided radiation therapy systems market was valued at US $ 221 Mn in 2018. The market is expected to record a CAGR of approximately 20% through 2028. Top selling category of the device is Linac MR-RT Systems. North America is expected to dominate the market as the percentage of cancer patients treated with radiation therapy in the United States is witnessing a rise. Growth Drivers: Significant rise in the national expenditure for cancer care in developed economies such as US is expected to boost the growth of the market MRI-guided radiation therapy has become an essential part of cancer treatment. Leading market players are participating in various exhibitions, trade shows, and conferences to better position their products and boost profitable sales. High adoption of next-generation technologies is leading to real-time monitoring, while reducing the margin of error in cancer treatment Rising prevalence of cancer and awareness about the availability of advanced treatment procedures, are expected to provide lucrative growth in the market. Restraints: Recent advancements in technologies and the improved efficiency of alternate cancer treatments may negatively impact the demand for MRI-guided therapy systems Strict government regulations are likely to influence strategies of manufacturers in the market, causing a further delay for the product to reach the market. Lack of skilled professionals in the healthcare sector, will restrict the adoption of MRI-guided radiation therapy systems in medical institutes and research centers. To Gain In-Depth Insights on MRI-guided Radiation Therapy Systems Market, Request Methodology at Competitive Landscape: Currently the technology used in MRI-guided radiation systems is new and market is at its infancy. Key manufacturers rely on licensing and patenting their innovative technologies for revenues and sales. Currently, only two companies have a substantial presence in the market - Elekta AB and Viewray Technologies, Inc. In April 2019, Viewray Technologies, Inc. collaborated with Minogue Medical Inc., distributor of surgical devices, and Device Technologies Australia Pty Ltd, to boost the sales of its MRI-guided radiation therapy systems across Canada, Australia and New Zealand Elekta AB has been adopting strategies to receive FDA approvals for its MRI-guided radiation therapy systems in order to maintain its foothold in North America. Key Companies Profiled by Fact.MR Elekta AB Viewray Technologies, Inc. More Valuable Insights on MRI-guided Radiation Therapy Systems Market Segmentation of MRI-guided Radiation Therapy Systems Market By Product Type: Linac MR-RT Systems Software MR Dimensions 0.5 Tesla MR Scanner 1.5 Tesla MR Scanner End User Hospitals Radiotherapy Centers Radiotherapy Centers Regions North America Latin America Europe Asia Pacific Middle East & Africa Interested to Procure The Data? Inquire here More Valuable Insights on Offer Fact.MR, in its new offering, presents an unbiased analysis of the global MRI-guided Radiation Therapy Systems Market, presenting historical demand data (2017-2021) and forecast statistics for the period of 2022-2027. Fact.MR’s Domain Knowledge in Healthcare Our healthcare consulting team guides organizations at each step of their business strategy by helping you understand how the latest influencers account for operational and strategic transformation in the healthcare sector. Our expertise in recognizing the challenges and trends impacting the global healthcare industry provides indispensable insights and support - encasing a strategic perspective that helps you identify critical issues and devise appropriate solutions. 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