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Archive for September, 2015

MacArthur Genius Awards

Curators: Larry H Bernstein, MD, FCAP and Aviva Lev-Ari, PhD, RN

“Genius” Grants Given

The MacArthur Foundation announces this year’s awardees.

By Bob Grant | September 29, 2015

http://www.the-scientist.com//?articles.view/articleNo/44124/title/-Genius–Grants-Given/

Two dozen of the brightest minds on Earth this week recently received recent phone calls from the MacArthur Foundation that may just change their lives—or at least their next five years. These folks are the 2015 MacArthur Fellows, and they’ll be getting $625,000 over the next half-decade (a no-strings-attached stipend colloquially known as“genius grants”) to pursue their work in a range of fields, from poetry and puppetry to inorganic chemistry and neuroscience. “These 24 delightfully diverse MacArthur Fellows are shedding light and making progress on critical issues, pushing the boundaries of their fields, and improving our world in imaginative, unexpected ways,” MacArthur Foundation President Julia Stasch said in a statement. “Their work, their commitment, and their creativity inspire us all.”

Among this year’s crop of MacArthur Fellows are several scientists, including

  • Kartik Chandranm, an environmental engineer from Columbia University;
  • Cornell University organic chemist William Dichtel;
  • computational biologist John Novembre of the University of Chicago;
  • neuroscientist Beth Stevens of Harvard Medical School;
  • Lorenz Studer, a stem-cell biologist at Memorial Sloan-Kettering Cancer Center; and
  • inorganic chemist Peidong Yang of the University of California, Berkeley.

“We try to reach people who have shown evidence of exceptional creativity but show the potential for more in the future,” Cecilia Conrad, the foundation’s managing director, told The New York Times.

“As a scientist, I tend to be drawn to areas where there’s very little known,” said Stevens, who studies how microglial cells influence brain development and neuro developmental disorders, in a MacArthur Foundation video. “And so work that you do can make a big impact.”

Studer, whose research involves the large-scale generation of dopaminergic neurons for transplantation, echoed Stevens’ sentiment about shedding light on mysterious corners of science. “What really gets me super exited in science is not just making the discovery, but trying to apply it,” he said in his own MacArthur video. “This award might really not only motivate me, but hopefully all my colleagues and the whole field to really bring this technology to the forefront and really make it happen.”

Tags

science fundingresearch fundingMacArthur fellowshipsMacArthur award and basic research

http://news.harvard.edu/gazette/story/2015/09/two-named-macarthur-fellows/

Jewish MacArthur Fellows named – FORWARD

http://forward.com/news/321817/meet-the-4-jewish-winners-of-the-macarthur-genius-grant/?attribution=articles-carousel-item-2-headline

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Breaking news about genomic engineering, T2DM and cancer treatments – 9/28/2015

Larry H Bernstein, MD, FCAP, Curator

LPBI

Newly Identified Biochemical Pathway Could Be Target For Insulin Control

Mon, 09/28/2015  Duke University

2.1.3.12

2.1.3.12   Breaking News about Genomic Engineering, T2DM and Cancer Treatments – 9/28/2015, Volume 2 (Volume Two: Latest in Genomics Methodologies for Therapeutics: Gene Editing, NGS and BioInformatics, Simulations and the Genome Ontology), Part 2: CRISPR for Gene Editing and DNA Repair

In the final event leading to the development of Typ 2 diabetes, the pancreas loses its ability to secrete insulin and clear glucose from the blood. Preventing this breakdown in insulin secretion is a key goal in the fight to reduce the burden of a disease that afflicts an estimated 29 million people in the United States.

Now researchers at Duke Medicine and the University of Alberta are reporting the identification of a new biochemical pathway to control insulin secretion from islet beta cells in the pancreas, establishing a potential target for insulin control.

The study, published online Sept. 24 in the journal Cell Reports, results from a field of work called metabolomics, which uses mass spectrometry instruments to measure and trace intermediate molecules in key metabolic pathways of cells and tissues.

“The Duke group focused on metabolites in islet cells that changed in response to elevated external glucose concentrations,” said co-senior author Christopher B. Newgard, Ph.D., director of the Sarah W. Stedman Nutrition and Metabolism Center and the Duke Molecular Physiology Institute. “We found a strong increase in an intermediate in the purine/nucleotide metabolic pathway — known as adenylosuccinate, or S-AMP — in islets stimulated with glucose.”

Impairment of S-AMP production was shown to interfere with normal glucose-stimulated insulin secretion. The Duke and University of Alberta Diabetes Institute teams were also able to demonstrate that S-AMP is capable of rescuing impaired insulin secretion in islets from people with Type 2 diabetes.

Newgard said the collaborative effort between the Duke and Alberta teams also yielded a separate finding, reported online Sept. 21 in the Journal of Clinical Investigation, which describes another molecular pathway that could be a potential metabolic target for insulin control.

In that study, the research teams identified a process that works essentially like a dimmer switch to adjust how much or how little insulin is secreted when blood sugar increases. This dimmer switch appears to be broken in Type 2 diabetes, but the researchers found that its function can be restored.

“For the moment, we have two separate mechanisms, but with further study we may find that they are more connected,” Newgard said. “Whether they are independent, additive or synergistic is unknown, so we are eager to bring the two projects together to see where that may lead.”

The National Institutes of Health and the Canadian Institutes of Health Research  funded the research.

Source: Duke University

http://www.biosciencetechnology.com/news/2015/09/newly-identified-biochemical-pathway-could-be-target-insulin-control?

Tissue-Specific Molecular Biomarker Signatures of Type 2 Diabetes

An Integrative Analysis of Transcriptomics and Protein–Protein Interaction Data

Beste Calimlioglu, Kubra Karagoz, Tuba Sevimoglu, Elif Kilic, Esra Gov, Kazim Yalcin Arga

http://www.genengnews.com/media/images/AnalysisAndInsight/Sep23_2015_YOmerAkyol_Type2Diabetes1291421046.jpg

Type2Diabetes -Sep23_2015_YOmerAkyol_1291421046

Mutual DEGs between only two different tissues/cells. [Y. Omer Akyol]

  • Type 2 diabetes mellitus (T2D) is a major global health burden. A complex metabolic disease, type 2 diabetes affects multiple different tissues, demanding a ‘‘systems medicine’’ approach to biomarker and novel diagnostic discovery, not to mention data integration across omics-es (Günther et al. 2014; Montague et al. 2014; Sahu et al. 2014). The two important key determinants of T2D are the failure of peripheral tissues (such as liver, muscle, and adipose tissue) to respond to insulin doses (so-called insulin resistance), and the failure of suitable insulin secretion by pancreatic beta cells in response to increased blood glucose levels (Kaiser and Oetjen, 2014).

The duration of hyperglycemia caused by failure of betacells also affects insulin secretory capacity, mass, and apoptosis rate of beta-cells, resulting in additional alterations in several processes such as islet inflammation, amyloid deposition, critical B-cell alterations (Prentki and Nolan, 2006). On the other hand, the state of hyperglycemia dama
ges nerves and blood vessels, leading to major healthrelated issues such as cardiovascular diseases, stroke, blindness, dental problems, and diabetes-related amputations. Other complications of T2D include enhanced vulnerability to neurodegenerative diseases, presence of various cancer types, pregnancy problems, loss of mobility with aging, and depression (Musselman et al., 2003; Retnakaran et al., 2006).

Due to the high prevalence of T2D and its fateful complications, identifying the genes or genetic factors associated with the development of T2D and elucidating the mechanisms underlying the disease are crucial in prognosis, and development of personalized medicine and therapeutic strategies.

Since it is a polygenic disorder (i.e., multiple genes located on different chromosomes take active roles in the development of the disease), it is better to reveal that gene expression varies more across tissues than across individuals. Several studies reported findings on T2D gene expression profiles of
different tissues individually (Kazier et al., 2007; Cangemi et al., 2011; Misu et al., 2010; van Tienen et al., 2012; Dominguez et al., 2011). Despite individual studies exploring T2D specific genes in various tissues, studies considering the meta-analysis of diverse transcriptomics datasets and integrating gene expression profiles with biological networks are very limited.

Keller and co-workers (2008) studied gene expression profiles in eight experimental groups of lean and obese mice.

To read the rest of this article click here.

OMICS: A Journal of Integrative Biology integrates global high-throughput and systems approaches to 21st century science from “cell to society” – seen from a post-genomics perspective. The above article was first published in the September 2015 issue of OMICS: A Journal of Integrative Biology with the title “Tissue-Specific Molecular Biomarker Signatures of Type 2 Diabetes: An Integrative Analysis of Transcriptomics and Protein–Protein Interaction Data”. The views expressed here are those of the authors and are not necessarily those of OMICS: A Journal of Integrative Biology, Mary Ann Liebert, Inc., publishers, or their affiliates. No endorsement of any entity or technology is implied.

http://www.genengnews.com/insight-and-intelligence/tissue-specific-molecular-biomarker-signatures-of-type-2-diabetes/77900522/

Newly Identified Biochemical Pathway Could Be Target For Insulin Control

9/28/2015 Duke University

In the final event leading to the development of Type 2 diabetes, the pancreas loses its ability to secrete insulin and clear glucose from the blood. Preventing this breakdown in insulin secretion is a key goal in the fight to reduce the burden of a disease that afflicts an estimated 29 million people in the United States.

Now researchers at Duke Medicine and the University of Alberta are reporting the identification of a new biochemical pathway to control insulin secretion from islet beta cells in the pancreas, establishing a potential target for insulin control.

The study, published online Sept. 24 in the journal Cell Reports, results from a field of work called metabolomics, which uses mass spectrometry instruments to measure and trace intermediate molecules in key metabolic pathways of cells and tissues.

“The Duke group focused on metabolites in islet cells that changed in response to elevated external glucose concentrations,” said co-senior author Christopher B. Newgard, Ph.D., director of the Sarah W. Stedman Nutrition and Metabolism Center and the Duke Molecular Physiology Institute. “We found a strong increase in an intermediate in the purine/nucleotide metabolic pathway — known as adenylosuccinate, or S-AMP — in islets stimulated with glucose.”

Impairment of S-AMP production was shown to interfere with normal glucose-stimulated insulin secretion. The Duke and University of Alberta Diabetes Institute teams were also able to demonstrate that S-AMP is capable of rescuing impaired insulin secretion in islets from people with Type 2 diabetes.

Newgard said the collaborative effort between the Duke and Alberta teams also yielded a separate finding, reported online Sept. 21 in the Journal of Clinical Investigation, which describes another molecular pathway that could be a potential metabolic target for insulin control.

In that study, the research teams identified a process that works essentially like a dimmer switch to adjust how much or how little insulin is secreted when blood sugar increases. This dimmer switch appears to be broken in Type 2 diabetes, but the researchers found that its function can be restored.

“For the moment, we have two separate mechanisms, but with further study we may find that they are more connected,” Newgard said. “Whether they are independent, additive or synergistic is unknown, so we are eager to bring the two projects together to see where that may lead.”

The National Institutes of Health and the Canadian Institutes of Health Research funded the research.

Source: Duke University

http://www.biosciencetechnology.com/news/2015/09/newly-identified-biochemical-pathway-could-be-target-insulin-control?

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Smart robot accelerates cancer treatment research by finding optimal treatment combinations

Reporter: Aviva Lev-Ari, PhD, RN

 

 

 

 

 

 

 

A new smart research system developed at Uppsala University accelerates research on cancer treatments by finding optimal treatment drug combinations. It was developed by a research group led by Mats Gustafsson, Professor of Medical Bioinformatics.

 

The “lab robot” system plans and conducts experiments with many substances, and draws its own conclusions from the results. The idea is to gradually refine combinations of substances so that they kill cancer cells without harming healthy cells.

 

Instead of just combining a couple of substances at a time, the new lab robot can handle about a dozen drugs simultaneously. The future aim is to handle many more, preferably hundreds. The method is iterative search for anti-cancer drug combinations. The procedure starts by generating an initial generation (population) of drug combinations randomly or guided by biological prior knowledge and assumptions. In each iteration the aim is to propose a new generation of drug combinations based on the results obtained so far. The procedure iterates through a number of generations until a stop criterion for a predefined fitness function is satisfied.

 

There are a few such laboratories in the world with this type of lab robot, but researchers “have only used the systems to look for combinations that kill the cancer cells, not taking the side effects into account,” says Gustafsson.

 

The next step: Make the robot system more automated and smarter. The scientists also want to build more knowledge into the guiding algorithm of the robot, such as prior knowledge about drug targets and disease pathways.

 

For patients with the same cancer type returning multiple times, sometimes the cancer cells develop resistance against the pharmacotherapy used. The new robot systems may also become important in the efforts to find new drug compounds that make these resistant cells sensitive again.

 

The research is described in an open-access article published Tuesday (Sept. 22, 2015) in Scientific Reports.

Sourced through Scoop.it from: www.kurzweilai.net

See on Scoop.itCardiovascular and vascular imaging

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Outstanding Achievement in Pathology

Curator: Larry H Bernstein, MD, FCAP

 

Olympus America Honors Outstanding Pathologists During First Annual “Unsung Heroes” Awards

Melville, Ny—Tracey Corey Handy, M.D., Chief Medical Examiner of Kentucky, and Matthew Zarka, M.D., affiliated with the University of Vermont and the Fletcher Allen Health Center, were recognized as the 1999 winners of the “Unsung Heroes” Awards. The awards, sponsored by Olympus America Inc., a world leading manufacturer of microscopes, in cooperation with the College of American Pathologists (CAP), were presented at a ceremony during the Fall CAP Conference in New Orleans.

The awards are the first in the on-going “Unsung Heroes” program sponsored by Olympus for the purpose of increasing public awareness of the vital and often invisible role pathologists have in saving lives. In addition to their expertise with a microscope, pathologists are the doctors who ensure that clinical laboratory testing is reliable and that diseases are accurately diagnosed. They are on the front lines whenever the public is threatened with disease. Their role in forensic science is crucial in helping prevent people from falling prey to abuse or avoidable illness. As Dan Biondi, Olympus Senior Vice President, points out, “Olympus is committed to supporting the work of the world’s pathologists and to advocating an educated patient population.”

Dr. Tracey Corey Handy is recognized as an “Unsung Hero” for her role in upgrading the well-being of children as Kentucky’s Chief Medical Examiner. Along with several colleagues, Dr. Handy founded the state’s “Living Forensics” team in 1991. Since its inception, the team has consulted on more than 700 cases of suspected child abuse. This effort has led to an increased conviction rate of abuse perpetrators and helps to reduce further cases of child abuse. In addition, Dr. Handy has initiated a program of routine screening for metabolic defects apparent in victims of Sudden Infant Death Syndrome (SIDS), which has resulted in the correct diagnosis of conditions that would have otherwise been attributed to SIDS. Dr. Handy has also chaired the state’s first child mortality review group that has resulted in the initiation of prevention programs, particularly in the event of accidental child death. A frequent speaker and contributor of her expertise to organizations throughout the country, she also teaches forensic pathology and has been published in more than a dozen peer-reviewed journals and books.

Dr. Matthew Zarka is recognized as an “Unsung Hero” for his efforts in aiding the extremely poor Mexican-Indian population in the remote mountain regions of Oaxaca, Mexico. Over the last two years Dr. Zarka has volunteered his time and services to bring much needed medical care to these impoverished communities. He and his OB/GYN team have been setting up the very first clinics throughout the area, enjoining the coffee companies of Mexico to spread word of the clinics to the local population and to help transport patients to the clinics. After each female patient underwent a gynecological examination, Dr. Zarka stained and read her Pap test. When needed, more extensive evaluations, biopsies, treatment and counsel were provided. Overwhelmingly successful, Dr. Zarka’s outreaching medical mission has grown to include additional professional staff. By volunteering his time and expertise, Dr. Zarka provides the only real access most people of the region have to modern medical care. His contribution has undoubtedly saved lives that might otherwise have been lost.

Stanford University

Benjamin Pinsky, MD, PhD, Assistant Professor of Pathology and Medicine (Infectious Diseases) is the recipient of the 2014 Siemens Healhcare Diagnostics Young Investigator Award.  This award “honors outstanding laboratory research in clinical microbiology or antimicrobial agents and is intended to further the career development of a young clinical scientist and promote awareness of clinical microbiology as a career.”

Stephen J. Galli, MD, Chair of Pathology, Professor of Pathology and Microbiology and Immunology, and the Mary Hewitt Loveless, MD Professor, is the recipient of the 2014 ASIP (American Society of Investigative Pathology) Rouse Whipple Award.  This award is presented to a senior scientist with a distinguished career in research who has advanced the understanding of disease and has continued productivity at the time of this award.

Dr. Raffick Bowen, Clinical Associate Professor and Associate Medical Director of SHC’s Clinical Chemistry and Immunology Laboratory is the recipient of the American Association of Clinical Chemistry’s Outstanding Speaker Award for 2013. This award recognizes his achievement in earning a speaker evaluation rating of 4.5 or higher during a 2013 continuing education activity accredited by AACC. The title of Dr. Bowen’s presentation is “Implementation of Autoverification in a Clinical Chemistry Laboratory: Theory to Practice”

Richard Kempson, MD,

Emeritus Professor of Pathology, is the recipient of the 2014 United States and Canadian Academy of Pathology (USCAP) President’s Award. The USCAP President’s Award is given annually to recognize an individual for outstanding service to the field of pathology.

Dr. Kempson is richly deserving of this award. Dr. Kempson has not only contributed substantially to the surgical pathology literature, particularly in gynecologic and soft tissue pathology but also, with Dr. Ronald Dorfman, he trained a substantial percentage of this and the next generation’s academic and community leaders in surgical pathology.

Dr. Kempson’s affiliation with Stanford University began in 1968 when he and Dr. Ronald Dorfman were recruited to Stanford to develop a program in surgical pathology. In short order, they established an internationally recognized residency and clinical fellowship program which went on to train more than 275 pathologists in the art and science of diagnostic surgical pathology. Dr. Kempson developed a distinctive teaching style that emphasized precise diagnostic criteria, approaching diagnosis with a broad morphologic differential diagnosis, and most importantly, always highlighting the relevance to patient management of the morphologic distinctions being made.

Prior to his recruitment to Stanford, Dr. Kempson was an Assistant Professor of Pathology and Surgical Pathology at Washington University. Dr. Kempson served as an Associate Professor of Pathology at Stanford from 1968 to 1974 and a Professor of Pathology from 1974 to 2001. In addition to his academic duties, he served as Co-Director of Surgical Pathology from 1968 until 2001. He also has served as President of the Association of Directors of Surgical Pathology (1993-1995), the United States and Canadian Academy of Pathology (1996) and the Arthur Purdy Stout Society (1996) and the California Society of Pathologists. The Richard Kempson, MD, Professorship in Surgical Pathology was established by the Department of Pathology in 2002 to honor him and his remarkable contributions to surgical pathology.

University of California, San Diego

A new era in diagnostics has emerged within the concept of Personalized Medicine. Imagine selecting cancer chemotherapy drugs based on knowledge of the precise mutations in a cancer. Can we predict who may have an adverse response to a medication based on that individual’s genetic blueprint? At UCSD, we are dedicated to making these resources available to our patients in the very near future. This is why we recently established the Pathology Center for Personalized Medicine. The goal of the Center is to conduct leading research necessary to form the foundation for advanced personalized medicine diagnostic testing and then to make this testing available in the CALM. For more information on the Center for Personalized Medicine, click here.

The research enterprise in Pathology at UCSD has grown dramatically in the past five years, and we are now amongst the top 15 programs in the country. Basic and translational research laboratories in the UCSD Pathology Department tackle important problems concerning cancer development and progression, angiogenesis, stem cell biology, neurodegenerative diseases, peripheral neuropathy, inflammation, infectious diseases, and wound healing. Our laboratories provide excellent environments for learning cell biology, molecular genetics, biochemistry, and animal physiology. Our faculty includes many active participants in the Biomedical Sciences (BMS) Graduate Program. For more information on this program, click here. We also have excellent opportunities for postdoctoral researchers. Please click here to visit our web page on summarizing the Pathology Department research enterprise. Then visit individual web pages for each of our faculty member to view specific research interests.

The Department of Pathology is home to both an outstanding Comparative Pathology and Medicine Program (for more information, click here) and the UCSD Research Ethics Program. We provide major educational support to the School of Medicine and the Skaggs School of Pharmacy and Pharmaceutical Sciences. For further information on these training opportunities, click here.

The La Jolla/San Diego community is a fertile environment for research and the pharmaceutical industry. The Sanford Burnham Medical Research Institute, the Scripps Research Institute, the Sidney Kimmel Cancer Center, the Salk Institute for Biological Studies, and the La Jolla Institute for Allergy and Immunology house exciting scientific programs and provide for numerous scientific collaborations. We also boast a plethora of biotechnology companies, located nearby on the La Jolla mesa.

The overall theme and focus of the Department of Pathology is to elucidate the molecular basis and pathology of human disease.  The faculty is comprised of basic, translational and physician scientists that utilize the latest techniques in genomics, proteomics, cell biology, molecular biology and physiology to develop new diagnostic and therapeutic approaches for a wide range of diseases, including cancer, neurological disease, microbial infection, and inflammatory disease.

Steven L. Gonias, M.D., Ph.D.

Our laboratory is interested in identifying and characterizing novel pathways by which proteases and their cell-surface receptors regulate cell physiology. We are particularly interested in the function of proteases in cancer but also have active projects related to peripheral nerve injury, Alzheimer’s disease and cardiovascular biology. One focus involves urokinase-type plasminogen activator (uPA), a serine protease and plasminogen activator that binds with high affinity to a GPI-anchored receptor called uPAR. This event activates multiple cell-signaling pathways that affect cell migration, survival, and phenotype. We are actively working to elucidate mechanisms by which uPAR-initiated cell-signaling promotes cancer metastasis. We are particularly interested in breast cancer, but also work on prostate cancer and cancers of the central nervous system.

The complex of uPA with its inhibitor, PAI-1, is a ligand for a receptor called LRP-1. LRP-1 also is the receptor for other ligands, including extracellular matrix proteins, growth factors and foreign toxins. Our laboratory elucidated a pathway in which LRP-1 regulates cell-signaling indirectly, by regulating the cell-surface level of uPAR. However, recent studies suggest that LRP-1 also directly regulates cell-signaling by binding adaptor proteins, such as Shc and JIP. By this mechanism, LRP-1 regulates cell survival and gene transcription. Our current re­search is aimed at determining the role of LRP-1 in cancer and peripheral nerve injury, using in vitro and in vivomodel systems. Using proteomics approaches, we also are actively investigating the ability of LRP-1 to model the composition of the plasma membrane.

Our third area of focus concerns the plasma protease inhibitor, alpha2M. Our laboratory has demonstrated that this protein functions as a conformation-dependent carrier of growth factors. Alpha2M may also function in cell-signaling by binding to LRP-1. By site-directed mutagenesis, we have iso­lated and individually modified various functional sites in this multifunc­tional protein.

David Bailey, MD, PhD

David N. Bailey received his Bachelor of Science degree in Chemistry “with high distinction” from Indiana University and his Doctor of Medicine degree from Yale University.  He completed a National Institutes of Health postdoctoral fellowship in Laboratory Medicine and a residency in Clinical Pathology, both at Yale, serving as Chief Resident in his final year.  He is certified in Clinical Pathology and Chemical Pathology by the American Board of Pathology.

Dr. Bailey joined the University of California (UC) San Diego faculty in 1977 and served as Director of the Toxicology Laboratory of UC San Diego Medical Center (1977-2007), Head of the Division of Laboratory Medicine (1983-1989, 1994-1998), Acting Chair (1986-1988) and permanent Chair of the Department of Pathology (1988-2001),  Director of the Pathology Residency Program (1986-1999), Director of Clinical Laboratories of UCSD Medical Center (1982-1999), Interim Vice Chancellor for Health Sciences and Dean of the UC San Diego School of Medicine (1999-2000 and 2006-2007), Deputy Vice Chancellor for Health Sciences (2001-2007), and Dean for Faculty & Student Matters in UC San Diego School of Medicine (2003-2007).  From 2007 to 2009, he was Vice Chancellor for Health Affairs, Dean of the School of Medicine, and Professor of Pathology and Laboratory Medicine at the University of California, Irvine.

Dr. Bailey was recognized by the Institute of Scientific Information as one of the world’s ten most cited authors in forensic sciences (1981-93). He received the Gerald T. Evans Award from the Academy of Clinical Laboratory Physicians and Scientists in 1993 for his leadership and service to the Academy.  Dr. Bailey has served as President of the California Association of Toxicologists (1981-1982), President of the Academy of Clinical Laboratory Physicians and Scientists (1988-89), and Secretary-Treasurer of the Association of Pathology Chairs (1996-99).  He has also served on the Chemical Pathology Test Development and Advisory Committee of the American Board of Pathology; the Editorial Boards of Clinical Chemistry, the Journal of Analytical Toxicology, and the American Journal of Clinical Pathology; the Doris A. Howell Foundation for Women’s Health Research Board of Directors; the Board of Directors of the George G. Glenner Alzheimer’s Family Centers, Inc.; the Board of Directors of the Children’s Hospital of Orange County; the Board of Directors of Children’s Healthcare of California; the Board of Directors of the Rady Children’s Hospital of San Diego; the Board of Directors of the Veterans Medical Research Foundation (San Diego); and the Executive Committee and Governing Board of the California Institute of Telecommunications and Information Technology, among others.

David A. Herold, M.D., Ph.D.

My laboratory research interests are in the area of mass spectrometry application to clinical diagnostics. This includes prostaglandins, trace metal and steroids. Additionally, we has been involved in the development and validation of “classical” clinical chemistry diagnostic tests. The application of the mass spectrometry to determine the validity of endocrine tests, in particular testosterone, has been of particular interest. We have been using GC-MS, LC-MS, and MS-MS techniques for these investigations. At the present time, we are involved with the use of Accelerator Mass Spectrometry for the determination of calcium flux in serum and urine using 41Ca as a marker. The purpose of these studies is to better understand bone remodeling in normal and diseased patients. We have also investigated the use of microfluidics for the application to clinical diagnostics to measure selected proteins in a rapid and accurate manner.

 

David Cheresh, Ph.D.

Tumor growth, invasion, stem cells and drug resistance. Molecular regulation of tumor growth and angiogenesis. Drug development targeting molecular pathways involved in tumor growth metastasis and angiogenesis.

The Cheresh laboratory focuses on the discovery of molecular pathways involved in the progression of cancer. Cheresh’s earlier work identified integrin αυβ3 as a biomarker of tumor angiogenesis and tumor progression, and was involved in the discovery of a drug called cilentigide which targets integrins αυβ3 and αυβ5.

The Cheresh laboratory has identified a series of critical microRNAs that regulate the growth of blood vessels.  These microRNAs control the angiogenic switch that occurs during the earliest stages of tumor growth and neovascularization in the retina.  As such one of these microRNAs may have therapeutic application as it is capable of maintaining blood vessels in the quiescent state.

Cheresh and colleagues have identified integrin αυβ3 as a biomarker of tumor stem cells during intrinsic or acquired resistance of a wide range of tumors including: cancer of the lung, pancreas, breast, and colon.   Cheresh and his lab discovered that αυβ3 expression is both necessary and sufficient to account for tumor stemness and drug resistance based on its ability to drive a molecular pathway regulating these processes.  This has led to the development of new therapeutic strategies to resensitize patients to drugs such as erlotinib and lapatinib that target EGFR.

The Cheresh laboratory has identified RAF kinase as an important target involved in tumor growth and angiogenesis.  They have developed a new drug design strategy to target RAF and other relevant kinases by designing allosteric inhibitors of these targets.  This is based on the use of defined chemical scaffolds to dock into an allosteric pocket on these kinases to render them inactive.  The combined use of in silico and biological screening has yielded drugs with nM anti-tumor activity that produce strong anti-tumor growth in mouse models following once a day oral dosing.   This approach appears to yield drugs that target tumors that are resistant to ATP mimetic inhibitors of RAF, Kit or PDGFR

John Lowe

Senior Director, Pathology

I joined Genentech in 2008 as Senior Director of Pathology, after having spent more than 18 years as an HHMI Investigator at the University of Michigan and then 3 years as Chair of Pathology at Case Western Reserve University School of Medicine. The role of Senior Director of Pathology in Research at Genentech offered attractive opportunities to do research in an outstanding, disease-focused scientific environment, while also helping to lead the scientific and research support activities of the Pathology department. These latter efforts help Genentech continue to make a major positive difference to the health and well being of a large number of patients afflicted with cancer, autoimmune syndromes, neurodegenerative diseases and other illnesses for which therapies are unsatisfactory or nonexistent.

An exceptional team of pathologists, laboratory managers, scientific associates and administrative staff in the department collaborate with me in these efforts. Additional outstanding pathologists, scientists, and managers continue to be recruited to assist us in ensuring that the department performs at the highest level. Our task is made more straightforward by the environment at Genentech, which is characterized by exceptionally bright, motivated and collaborative colleagues at every level, spectacular facilities, and workplace philosophies that are conducive to the highest levels of achievement.

Postdoctoral Mentor

The opportunity to mentor postdoctoral fellows at Genentech has been a stimulating and gratifying experience for me. This derives in part from the freedom afforded by the program to pursue research directions that are deemed to be important and interesting, even if these have no immediate therapeutic relevance. The special mentoring experience also derives from extraordinary breadth and quality of the core laboratories at Genentech, and the spectacular intellectual environment. Together, these circumstances provide an unparalleled opportunity for postdoctoral fellows, and their mentors, to engage in biomedical discovery of the highest caliber.

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Outstanding Achievement in Anesthesiology

Curator: Larry H Bernstein, MD, FCAP

 

Thomas J. Rick, MD, for Outstanding Achievements in Anesthesiology and Pain Management

The International Association of HealthCare Professionals has carefully selected Thomas J. Rick, MD, to represent anesthesiology in their publication, The Leading Physicians of the World.  Dr. Rick’s selection is a significant representation of his enduring passion and complete dedication for the field of anesthesiology and pain management. He is considered to be among the best throughout his 19 years in practice.

A well versed and respected anesthesiologist and pain management physician practicing in Phoenix, Arizona, Dr. Rick features a track record of achievements that have marked his 19-year professional journey in his challenging specialty. In a relaxed and friendly setting with accommodating support staff, Dr. Rick receives his at Thomas J. Rick, MD PC, his well equipped private office where he deals with anesthetic and pain management services for patients undergoing surgeries. While he primarily devotes his time to his office in Phoenix, he additionally provides anesthesiology-related services to patients of the St. Joseph’s Hospital and Medical Center and Banner Good Samaritan Medical Center, also in Phoenix, Arizona.

Dr. Rick embraced a career in medicine upon completing his medical degree in 1994 at Hahnemann University Hospital. His postgraduate training led him to the University of Arizona and his continuing learning enhanced his certification in anesthesiology by the American Board of Anesthesiology. As an affirmation of his commitment to education and his desire to advance by adapting his practice to the latest discoveries and technologies in his field, Dr. Rick joined the American Society of Anesthesiology and the Arizona Society of Anesthesiology. An active man in his free time, passionate by tennis, fitness, and drums, he attributes his exceptional success to his availability, as well affordability and accessibility of service.

Stanford Medical School

Myer “Mike” Rosenthal

  • Ellis N. Cohen Award for Outstanding Achievement in Anesthesiology, Stanford University Department of Anesthesia (1980)
  • Jack R. Collins Memorial Award for Outstanding Leadership in Anesthesia Education, Dannemiller Society (1990)
  • Kaiser Award for Clinical Teaching, Stanford University School of Medicine (1991, 2004)
  • Board of Directors (President and Chairman of Board – 2001-2004), Foundation for Anesthesia Education and Research (2000 – 2009)
  • Director (President – 1997-1998), American Board of Anesthesiology (1986 – 1998)
  • Medical Director of Intensive and Intermediate Intensive Care Units, Stanford University Hospital (1975 – 1997)

Arthur Bert, MD

Senior staff anesthesiologist, Rhode Island Hospital

Arthur Bert, MD, has served as director of cardiac anesthesia (1986-2002) at Rhode Island Hospital and as director of pediatric cardiac anesthesia (1996-2005) at Hasbro Children’s Hospital. Bert continues to pursue his interests in adult and pediatric cardiovascular and thoracic anesthesia as a senior staff anesthesiologist. He is a clinical professor of surgery (anesthesiology) at the the Warren Alpert Medical School at Brown University. He also holds the position of director of experimental cardiac surgery, anesthesiology and cardiac imaging at the cardiac surgery research laboratories of Children’s Mercy Hospital, in Kansas City, MO, where he is part of a funded research team that is growing tissue-engineered heart valves. He is a consultant anesthesiologist at Women & Infants Hospital for neonatal anesthesia.

Education

Bert graduated as president of Alpha Omega Alpha Medical Honor Society from Mount Sinai School of Medicine in New York City. He served as a resident in internal medicine at Beth Israel Deaconess Medical Center in Boston and was awarded the Dr. Nathan Sidel Prize for outstanding achievement. He completed his anesthesia residency and an adult cardiac anesthesia fellowship at Beth Israel Hospital in Boston, followed by a pediatric anesthesia fellowship at Children’s Hospital Boston.

Board Certification

Diplomate of the American Board of Anesthesiology (1985) and re-certified in 2008

Testamur of the National Board of Echocardiography in Perioperative Transesophageal Echocardiography (1998)

Diplomate (2006) and re-certified in 2007

Awards

Top Physicians, Rhode Island Monthly magazine (2000, 2002, 2004, 2006 and 2008)

Guide to America’s Top Physicians, Consumers’ Research Council of America, Washington, DC (2005, 2006)

Teaching Recognition Award, Brown Medical School (2005)

Dr. Charles A. Hill Award from the RI Medical Society (2006)

Interests

Applications of transesophageal echocardiography to intraoperative patient management

Techniques of reducing blood product transfusions during surgery

Cerebral function monitoring during general anesthesia

Research: Echocardiographic evaluation of tissue-engineered valve function

ASA Award for Excellence in Research

Henrik Kehlet, M.D., Ph.D.

The annual ASA Award for Excellence in Research recognizes an individual for outstanding achievement in research that has or is likely to have an important impact on the practice of anesthesiology.

The individual’s work must represent a body of original, mature and sustained contribution to the advancement of the science of anesthesiology. The nominee need not be a physician, an anesthesiologist or a member of ASA, but must be presently engaged in research related to anesthesiology, academically accomplished with peer-reviewed publications and funded research, and nominated in response to a call for nominations. The completed application must include the nominee’s current curriculum vitae, a letter of nomination and a seconding letter from two individuals with an understanding of the research contributions of the individual.

The 2014 Award for Excellence in Research was presented to Henrik Kehlet, M.D., Ph.D., at the ANESTHESIOLOGY™ 2014 annual meeting in New Orleans on Monday, October 13, 2014. Dr. Kehlet is a Professor at Rigshospitalet, Copenhagen University, Denmark.

Dr. Kehlet is known for his research and writing in surgical pathophysiology, surgical stress response and the transition from acute to chronic pain, among other topics.

Henrik Kehlet, M.D., Ph.D. is perhaps the most well-known surgeon among physician anesthesiologists around the world due to his substantial contributions toward the understanding of surgical pathophysiology. After Dr. Kehlet completed his medical studies and surgical residency at the University of Copenhagen, Denmark, he enrolled in a Ph.D. program within the same institution, authoring a thesis pertaining to the study of the hypothalamic-pituitary-adrenocortical function in glucocorticoid-treated surgical patients. Dr. Kehlet served as the Chief of Surgery and Professor of Surgery, Copenhagen University at Hvidovre University Hospital from 1989 to 2004. He was subsequently appointed as a Professor of Perioperative Therapy and Head of the Section for Surgical Pathophysiology at the Rigshospitalet in Copenhagen. Dr. Kehlet continues to be an extremely prolific writer, having authored more than 950 scientific articles covering topics of surgical pathophysiology, acute pain physiology and pharmacotherapy, surgical stress response, regional anesthesia and analgesia, perioperative immune function, fast-track surgery and the transition from acute to chronic pain.

Dr. Kehlet’s research led to the creation of the concept of fast-track surgery, or enhanced recovery after surgery (ERAS), with the aim of painless and safe surgeries. His work related to pain relief and surgical outcomes led to the multimodal analgesia approach of combining different analgesics for better pain control and fewer side effects that is widely used today. Dr. Kehlet also is credited with the concept of pre-emptive analgesia, or administering an analgesic prior to surgical injury in order to decrease the intensity and duration of postoperative pain. In addition to his many contributions to perioperative pain management, Dr. Kehlet is responsible for establishing the first nationwide hernia database in Denmark, with the purpose of optimizing outcomes and documenting different approaches to improve care.

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Outstanding Achievements in Radiology or Radiotherapy

Curator: Larry H Bernstein, MD, FCAP

Mohit Kasibhatla and Heather Pacholke –

The Hayworth Cancer Center at UNC/High Point Regional Health in High Point, NC has received accreditation as a Community Hospital Comprehensive Cancer Program with Commendation from the Commission on Cancer (CoC) of the American College of Surgeons. Our UNC Radiation Oncology faculty there – Drs. Mohit Kasibhatla and Heather Pacholke – have distinguished themselves by receiving the Outstanding Achievement Award in connection with the accreditation process.

In addition to the cancer center as a whole, the Department of Radiation Oncology in particular has also received accreditation with highest distinction from the American College of Radiology (ACR), making it the first ACR-accredited radiation therapy facility in the Piedmont Triad area. The ACR’s Radiation Oncology Practice Accreditation Program (ROPA) provides radiation oncologists with third-party, impartial peer review and evaluation of patient care.

Newsweek’s “Top Cancer Doctors in the US”

Drs. Marks, Rosenman and Tepper honored

Radiation oncologists Dr. Lawrence Marks, Julian Rosenman and Joel Tepper are among 22 UNC-affiliated oncologists honored by Newsweek magazine (in conjunction with Castle-Connolly Medical, Ltd.) as “Top Cancer Doctors in the United States for 2015”.

UNC Lineberger Annual Scientific Retreat

Dr. Timothy Zagar receives ASTRO research award

For studies of the “comparative effectiveness” of different treatments

One of only seven annual research awards from the American Society for Radiation Oncology (ASTRO). Dr. Zagar’s award comes jointly from ASTRO and the affiliated Radiation Oncology Institute (ROI), in support of his “comparative effectiveness” research, which is the study of which type of medical treatment (radiation therapy in this case) works the best while causing the least harm, for whom, and under what circumstances.

Eblan wins third place in poster competition

Third place win in the Clinical/Translational Research Poster competition at the UNC Lineberger Annual Scientific Retreat, held on Tuesday, September 1, 2015. The title of his poster was “Prospective Investigation of Circulating Tumor Cells from Head and Neck Cancer Patients Undergoing Definitive Radiotherapy: A Pilot Study”.

Box 1 | The four schools of radiation oncology

Radiation oncology: a century of achievements

Jacques Bernier, Eric J. Hall & Amato Giaccia

Nature Reviews Cancer 4, 737-747 (September 2004)

http://dx.doi.org:/10.1038/nrc1451

1970 to date: the United States then European Union school

Although there were always pockets of excellence in the United States, radiation oncology in general was slow off the mark compared with the United Kingdom, France and the Scandinavian countries. This was based historically on the fact that most individuals trained in general radiology, and radiotherapy was often the poor relation in the basement.

All of this changed in the 1970s. President Nixon’s ‘war on cancer’ supplied huge amounts funding for research in physics, biology and clinical oncology, and at the same time the American Society of Therapeutic radiology and oncology was founded. Research groups and training programmes were set up as radiation oncology became a separate discipline, and the standard of clinical practice improved. This was the beginning of evidence-based medicine in radiation oncology, with the proliferation of clinical trials to match the new and improved treatment machines, and the revolution in medical physics and computer-controlled technology.

The European Society of Therapeutic Radiology and Oncology (ESTRO) was founded in the early eighties, and the clinical trials organized by the European Organisation for Research and Treatment of Cancer have certainly matched, in number and in quality, those performed in the United States. Another outstanding feature of ESTRO is that they have placed much greater emphasis than their American counterparts on aiding the advance of radiation oncology in developing countries.

http://www.princetonradiationoncology.com/index.php/our-doctors/index.html

John C. Baumann, M.D.

Dr. Baumann graduated magna cum laude from Princeton University, N.J., and received his medical degree from Harvard Medical School, Boston, where he also completed his residency, chief residency and fellowship in radiation oncology.  He has served as chief of radiation oncology at the Walter Reed Medical Center, Washington, D.C., associate program director of the National Cancer Institutes’ resident training program for radiation oncology, and as a member of the radiotherapy committee of the Gynecologic Oncology Group, and the radiology advisory medical team of the U.S. Department of Defense.  Dr. Baumann also was a consultant to the Surgeon General for radiation oncology and president of the medical staff at the University Medical Center at Princeton, N.J.  He has received numerous honors including being selected by his peers as a “Best Doctor” in the New York/New Jersey region.

Oren Cahlon, M.D.

Dr. Cahlon graduated summa cum laude and Phi Beta Kappa from the University of Michigan, Ann Arbor, and received his medical degree with highest honors, including valedictorian, from Mount Sinai School of Medicine, New York City.  He was also selected to the Alpha Omega Alpha Society.  He completed his internship and residency in radiation oncology at Memorial Sloan-Kettering Cancer Center, New York City, where he served as chief resident.  He has presented his research findings on prostate, head and neck and extremity tumors at national scientific meetings and has authored numerous peer-reviewed articles.  He has extensive experience in the application of image-guided radiation (IGRT), intensity-modulated radiation (IMRT) and brachytherapy. Dr. Cahlon has received numerous honors and awards and is an active member of many professional societies including the American Society of Clinical Oncology and the American Society for Radiation Oncology.

Robert M. Cardinale, M.D.

Dr. Cardinale graduated magna cum laude in electrical engineering from Rutgers University, N.J., and received his medical degree from the University of Maryland School of Medicine, Baltimore.  He completed his residency, chief residency and fellowship in radiation oncology at Johns Hopkins Medical School, Baltimore. He has served in several academic positions and is currently an associate professor at The Medical College of Virginia, Richmond, and Robert Wood Johnson Medical School, New Brunswick, N.J.  Dr. Cardinale was selected by his peers as a “Top Doctor” in New Jersey and was named among the “Best Doctors in America”. He has received numerous honors and U.S. Patents for novel cancer treatments.  He has authored many articles and book chapters in radiation oncology and has presented his work at more than 50 national and international scientific meetings.

Mount Sinai Comprehensive Cancer Center Earns Major Designations

http://msccc.com/12-services/69-mount-sinai-comprehensive-cancer-center-earns-major-designations

(Miami Beach, Florida – March 2, 2012) — The Mount Sinai Comprehensive Cancer Center has received the Outstanding Achievement Award from the American College of Surgeons Commission on Cancer (CoC). Mount Sinai is the only Florida hospital to receive this recognition three times in a row, and one of only 23 out of 1,500 CoC-accredited centers nationwide to receive the Outstanding Achievement Award three consecutive times. The CoC created the Outstanding Achievement Award to recognize programs that strive for excellence in providing quality cancer care. Mount Sinai successfully completed an on-site survey and received a three-year Approval with Commendation.

Recognizing that cancer is a complex group of diseases, the CoC Cancer Program Standards promote consultation among surgeons, medical and radiation oncologists, diagnostic radiologists, pathologists, and other cancer specialists. This multidisciplinary approach results in improved patient care. In addition, CoC-accredited cancer programs focus on prevention, early diagnosis, pre-treatment evaluation, staging, optimal treatment, rehabilitation, surveillance for recurrent disease, support services, and end-of-life care.

The Mount Sinai Comprehensive Cancer Center is also the first and only radiation oncology program in South Florida to earn accreditation from the American College of Radiology (ACR) and The American Society for Radiation Oncology (ASTRO). The ACR-ASTRO seal of accreditation represents the highest level of quality and patient safety. Mount Sinai’s Radiation Oncology programs on both the Mount Sinai Miami Beach and Aventura campuses successfully completed a rigorous application and evaluation process for this accreditation.

Zheng Yu Jin, M.D

An internationally renowned leader and educator, Zheng Yu Jin, M.D., is widely credited with advancing the popularization and application of cardiac interventional therapy techniques throughout his native China in the late 1980s through the early 1990s. Dr. Jin has become well known as a national and international advocate of multi-detector CT techniques over the past two decades. Now, as vice-chair of the Chinese Society of Radiology (CSR), his priority is MR technique generalization nationwide.

Dr. Jin is a professor of interventional radiology and diagnostic radiology and chair of the Department of Radiology at Peking Union Medical College Hospital (PUMCH), Beijing, where he has spent the majority of his career.

After graduating as a medical doctor in 1984, Dr. Jin joined PUMCH where he quickly ascended the ranks from resident, chief resident and attending physician to associate professor by 1993. Dr. Jin has held his current position since 1996. From 1990 to 1991, Dr. Jin completed advanced studies at Loma Linda University Medical Center, California, where he trained under renowned interventional radiologist Francis Y.K. Lau, M.D.

Dr. Jin trained in cardio-intervention and neuro-intervention, as well as peripheral intervention, which was very rare in China at that time.

Markus Schwaiger, M.D.

He is an internationally known researcher, educator, author and editor whose work has shaped the development of multimodal molecular imaging, particularly in cardiology. He is director of the Department of Nuclear Medicine at the Technische Universität of Munich, Germany, and also serves as an adjunct professor of radiology at the University of Michigan in Ann Arbor.

Dr. Schwaiger’s research portfolio reflects the development of PET from a research tool in cardiology to a worldwide-accepted clinical standard procedure in oncology. His recent articles address integrated whole-body PET/MR imaging and the use of PET to assess metabolic response and guide treatment of cancer. He currently serves as coordinator of a large center grant that addresses the role of imaging in selecting and monitoring targeted cancer therapy in preclinical models. He is involved in European Research consortia addressing endoscopic PET imaging (EndoTOFPET) as well as PET inserts for combined MR/PET instrumentation. In 2012, he received an advanced grant award of the European Research Council (ERC).

In addition to his 748 peer-reviewed publications in international scientific journals and 108 book chapters and proceedings, Dr. Schwaiger has served in editorial positions for more than a dozen scientific publications, including the Journal of Nuclear Cardiology, Journal of Nuclear Medicine and European Heart Journal.

Dr. Schwaiger has lent his expertise to a spectrum of professional societies and administrative entities for more than 20 years, including service as president of the European Association of Nuclear Medicine 2008 Congress in Munich. He serves on the RSNA Molecular Imaging Committee.

Among the numerous awards Dr. Schwaiger has received are the Distinguished Scientist Award of the Academy of Molecular Imaging, von Hevesy Medal of the Hungarian Society of Nuclear Medicine, and Paul C. Aebersold Award of the Society of Nuclear Medicine.

Kaori Togashi, M.D., Ph.D.

She has spent more than 30 years researching and publishing studies expanding the horizon for MR as it applies to gynecology. Dr. Togashi’s pioneering work has garnered attention from radiology and bioengineering entities.

Dr. Togashi is a professor and chair in the Department of Diagnostic Imaging and Nuclear Medicine at Kyoto University Graduate School of Medicine. When promoted to the position in 2004, she became the first woman to chair a department at the medical school of Kyoto University and the first woman to chair a department at a national university in Japan.

Dr. Togashi earned her medical degree at Kyoto University. After completing her residencies, she attended the Graduate School of Medicine at Kyoto University and received her doctorate in medical science. While working on her doctorate, Dr. Togashi was involved in very early studies of body MR imaging. She authored several articles including “Uterine Cervical Cancer: Assessment with High-Field MR Imaging,” published in Radiology in 1986. Since then, she has published several books and nearly 300 articles in peer-reviewed journals in English. Dr. Togashi has been a reviewer for many journals including Radiology and RadioGraphics.

Dr. Togashi’s recent areas of interest are functional body MR, including cine MR to evaluate uterine peristalsis, diffusion-weighted images in oncology and diffusion tensor imaging of the uterus. Cine MR for the uterus has attracted interest not only from the radiology and gynecology specialties, but also from the bioengineering realm as a new tool to elucidate biomechanics of the uterine function. Dr. Togashi received honorary membership in the European Society of Radiology, fellowship in the International Society for Magnetic Resonance in Medicine and the gold medal of the European Society of Urogenital Radiology.Dr. Togashi serves on the RSNA International Advisory Committee and also has served on the Education Exhibit Awards Committee in Uroradiology at the RSNA annual meeting.

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ACE-inhibitors Market been Challenged by Novartis’ new heart failure medicine Entresto™ recommended by CHMP for EU approval

Reporters: Aviva Lev-Ari, PhD, RN and Gerard Loiseau, ESQ

Congestive Heart Failure Explained

VIEW VIDEO

http://multimediacapsule.thomsonone.com/novartis/novartis-new-heart-failure-medicine-recommended-by-chmp-for-eu-approval

Basel, September 25, 2015 – Novartis announced today that the Committee for Medicinal Products for Human Use (CHMP) has adopted a positive opinion for Entresto™ (sacubitril/valsartan), marking an important milestone towards becoming available in the EU. Pending final approval by the European Commission (EC) Entresto, previously known as LCZ696, will be available for the treatment of adult patients with symptomatic chronic heart failure and reduced ejection fraction (HFrEF).

“The striking results in the PARADIGM-HF trial led me to believe that once approved LCZ696 could quickly replace what has been the bedrock treatment for more than 20 years, ACE-inhibitors” said Professor John McMurray of the University of Glasgow and one of two Principal Investigators. “Thousands of lives could be extended and hospital admissions prevented with LCZ696’s unique ability to boost natriuretic peptides, heart-helpful hormones, while simultaneously inhibiting the RAAS system.”

SOURCE

http://multimediacapsule.thomsonone.com/novartis/novartis-new-heart-failure-medicine-recommended-by-chmp-for-eu-approval

ENTRESTOTM is indicated to reduce the risk of cardiovascular death and hospitalization for heart failure in patients with chronic heart failure (NYHA Class II–IV) and reduced ejection fraction.

ENTRESTO is usually administered in conjunction with other heart failure therapies, in place of an ACE inhibitor or other ARB.

Entresto exhibits the mechanism of action of an Angiotensin Receptor Neprilysin Inhibitor that reduces the strain on the failing heart. A twice-a-day tablet, it acts to enhance the protective neurohormonal systems of the heart (NP system) while simultaneously suppressing the harmful system (the RAAS)4.

ENTRESTO is available in 3 dosage strengths
  • ENTRESTO 24/26 mg (sacubitril 24 mg and valsartan 26 mg)
  • ENTRESTO 49/51 mg (sacubitril 49 mg and valsartan 51 mg)
  • ENTRESTO 97/103 mg (sacubitril 97 mg and valsartan 103 mg)

ENTRESTO is contraindicated with concomitant use of an angiotensin-converting enzyme (ACE) inhibitor. If switching from an ACE inhibitor to ENTRESTO, allow a washout period of 36 hours between administration of the two drugs.The recommended starting dose of ENTRESTO is 49/51 mg twice-daily.

Double the dose of ENTRESTO after 2 to 4 weeks to the target maintenance dose of 97/103 mg twice daily, as tolerated by the patient.

DOSE ADJUSTMENT FOR PATIENTS NOT TAKING AN ACE INHIBITOR OR ARB OR PREVIOUSLY TAKING LOW DOSES OF THESE AGENTS1

A starting dose of 24/26 mg twice daily is recommended for patients not currently taking an ACE inhibitor or an angiotensin II receptor blocker (ARB) and for patients previously taking low doses of these agents. Double the dose of ENTRESTO every 2 to 4 weeks to the target maintenance dose of 97/103 mg twice daily, as tolerated by the patient.

DOSE ADJUSTMENT FOR SEVERE RENAL IMPAIRMENT1

A starting dose of 24/26 mg twice daily is recommended for patients with severe renal impairment (eGFR <30 mL/min/1.73 m2). Double the dose of ENTRESTO every 2 to 4 weeks to the target maintenance dose of 97/103 mg twice daily, as tolerated by the patient.No starting dose adjustment is needed for mild or moderate renal impairment.

DOSE ADJUSTMENT FOR HEPATIC IMPAIRMENT1

A starting dose of 24/26 mg twice daily is recommended for patients with moderate hepatic impairment (Child-Pugh B classification). Double the dose of ENTRESTO every 2 to 4 weeks to the target maintenance dose of 97/103 mg twice daily, as tolerated by the patient.No starting dose adjustment is needed for mild hepatic impairment.

Use in patients with severe hepatic impairment is not recommended.

SOURCE

https://www.quo.novartis.com/entresto/dosing

HIGHLIGHTS OF PRESCRIBING INFORMATION

These highlights do not include all the information needed to use ENTRESTO safely and effectively. See full prescribing information for ENTRESTO. ENTRESTO™ (sacubitril and valsartan) tablets, for oral use Initial U.S. Approval: 2015 WARNING: FETAL TOXICITY See full prescribing information for complete boxed warning.

 When pregnancy is detected, discontinue ENTRESTO as soon as possible. (5.1)  Drugs that act directly on the renin-angiotensin system can cause injury and death to the developing fetus. (5.1)

INDICATIONS AND USAGE

ENTRESTO is a combination of sacubitril, a neprilysin inhibitor, and valsartan, an angiotensin II receptor blocker, indicated to reduce the risk of cardiovascular death and hospitalization for heart failure in patients with chronic heart failure (NYHA Class II-IV) and reduced ejection fraction. (1.1) ENTRESTO is usually administered in conjunction with other heart failure therapies, in place of an ACE inhibitor or other ARB. (1.1)

DOSAGE AND ADMINISTRATION

 The recommended starting dose of ENTRESTO is 49/51 mg (sacubitril/valsartan) twice-daily. Double the dose of ENTRESTO after 2 to 4 weeks to the target maintenance dose of 97/103 mg (sacubitril/valsartan) twice-daily, as tolerated by the patient. (2.1)

 Reduce the starting dose to 24/26 mg (sacubitril/valsartan) twice-daily for: – patients not currently taking an angiotensin-converting enzyme inhibitor (ACEi) or an angiotensin II receptor blocker (ARB) or previously taking a low dose of these agents (2.2) – patients with severe renal impairment (2.3) – patients with moderate hepatic impairment (2.4) Double the dose of ENTRESTO every 2 to 4 weeks to the target maintenance dose of 97/103 mg (sacubitril/valsartan) twice-daily, as tolerated by the patient. (2.2, 2.3, 2.4)

SOURCE

http://www.pharma.us.novartis.com/product/pi/pdf/entresto.pdf

Other articles on this Open Access Online Scientific Journal include the following:

Publications on Heart Failure by Prof. William Gregory Stevenson, M.D., BWH

Reporter: Aviva Lev-Ari, PhD, RN

http://pharmaceuticalintelligence.com/2014/01/13/publications-on-heart-failure-by-prof-william-gregory-stevenson-m-d-bwh/

Is there a role for Galectin-3 in the management of heart failure?

Curator: Larry H Bernstein, MD, FCAP

http://pharmaceuticalintelligence.com/2014/09/09/is-there-a-role-for-galectin-3-in-the-management-of-heart-failure/

ESC: Novel Heart Failure Drug a Game-Changer

Reporter: Aviva Lev-Ari, PhD, RN

http://pharmaceuticalintelligence.com/2014/09/02/esc-novel-heart-failure-drug-a-game-changer/

Of the Cardiac-specific Deaths, Deaths from Heart Attack and Sudden Heart Rhythm Disturbances declined steeply, no decline in deaths from Heart Failure in a 20,000 PCI patients Study @ Mayo Clinic

Reporter: Aviva Lev-Ari, PhD, RN

http://pharmaceuticalintelligence.com/2014/02/12/of-the-cardiac-specific-deaths-deaths-from-heart-attack-and-sudden-heart-rhythm-disturbances-declined-steeply-but-there-was-no-decline-in-deaths-from-heart-failure-in-a-20000-pci-patients-study/

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TweetReach @Kailath Lecture and Colloquium 2015

Curators: Stephen J Williams, PhD and Aviva Lev-Ari, PhD, RN

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National Medal of Science

Curator: Larry H. Bernstein, MD, FCAP

http://pharmaceuticalintelligence.com/2015/09/21/national-medal-of-science/

9/17/2015 -LIVE – Real Time Coverage of Kailath Lecture and Colloquium 2015 September 17 – 19, Stanford CA – James H. Clark Center, 318 Campus Drive West, Stanford University, CA

Live Press Coverage: Aviva Lev-Ari, PhD, RN

http://pharmaceuticalintelligence.com/2015/09/17/9172015-live-real-time-coverage-of-kailath-lecture-and-colloquium-2015-september-17-%E2%80%90-19-stanford-ca-james-h-clark-center-318-campus-drive-west-stanford-university-ca/

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9/18/2015 – LIVE – Real Time Coverage of Kailath Lecture and Colloquium 2015 September 17 – 19, Stanford CA – James H. Clark Center, 318 Campus Drive West, Stanford University, CA

Live Press Coverage: Aviva Lev-Ari, PhD, RN

http://pharmaceuticalintelligence.com/2015/09/18/9182015-live-real-time-coverage-of-kailath-lecture-and-colloquium-2015-september-17-%E2%80%90-19-stanford-ca-james-h-clark-center-318-campus-drive-west-stanford-university-ca/

TweetReach @Kailath Lecture and Colloquium 2015

TweetReach_Kailath Lecture copy

Hashtags for Kailath Lecture and Colloquium 2015

@NASciences

@NSTMF

@MathPaper

@TheIoT

#engineering

#BigData

#machinelearning

#TextAnalytics

#Language

#Patternrecognition

@Stanford

#mathematical

#NeuralNetwork

#DeepLearning

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4D Printing as a Time Dependent 3D Printing

Curator: Danut Dragoi, PhD
The 4D printing can be explained based on 3D printing, whose concept is shown in here.

It has an extra added dimension like time, or any implicit time variable included in any environmental physical parameter like

  • temperature,
  • pressure,
  • moisture or humidity,
  • external/internal electric field and or
  • magnetic field.

This is not a true 4D space in the sense X,Y,Z,t — it is a parameterized printing process in which each variable X(t), Y(t), Z(t)  is a function of time. Therefore,it is an object that has its shape defined by a surface with variables that depends of time. This reminds us about smart shape memory  materials. Today there are not only metallic smart materials but also shape-memory polymers that have similar behavior of smart metallic shape memory materials. It is interesting to add that many  polymeric smart materials have a response to a given stimuli like moisture, electric field, etc. To produce some 3D objects with a shape dependent of time we just need these special polymers. The reason for adding a new parameter as an extra dimension is in the need to reach complex topological object. Skylar Tibbits, who is a mathematician at MIT, proposed 4D printing in a TED talk. The 4D printing concept can be better understood from examples. The folding of a strand of eight segments can transform from a line to a cube shape. The researcher in Australia created a valve using 4D printing  The valve is sensitive to temperature, it closes when the water is hot and opens when it is cold. A graphical explanation of 4D printing is explained here. All these examples show a promising starting level of technology readiness. The authors published their 4D printing concepts and results on TED events. As the main characteristic of these events is the entertainment of the audience, the right assessment of the 4D technology is awaiting the words of the specialists through the scientific pair reviewed papers. One important question for 4D printed human organs is that of life time circle of the printed organ and possible rejection. Since the material of the 4D printed objects is a polymer or a combination of polymers, we expect a low time cicle due to low fatigue characteristic of these materials.The question arises as to what exactly 4D printing will add as extra to the already existing technology of 3D printing at hand? The answer is the whole new dimension i.e time we added. If we consider a smart combination of materials that produce periodic shape change, such as the case of the heart, than we have a possible solution for 4D printing of the heart. But again the fatigue issue has to be taken into consideration again. The scientists can also give an object the ability to alter its shape and to fold itself  through self assembling molecules when the effect of temperature and pressure is considered. Other impact factors should be considered when the environment is the interior of the human body where the influence of temperature, pressure or other variable factors such as vibrations, etc. can play an important role. As a conclusion of this posting we can state that the 4D printing is at its beginning, it is not a true 4 dimensional space as the title of this method suggests.The fourth dimension time in 4D tittle is lost in the polymeric material behavior when it is influenced by a stimuli such as moisture, temperature, pressure, etc. The property of molecules, large or small to self-assemble is associated with the shape change that is exploited in the 4D printing.

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Model mimicking clinical profile of patients with ovarian cancer @ Yale School of Medicine

Reporter: Aviva Lev-Ari, PhD, RN

Murine Model for Non-invasive Imaging to Detect and Monitor Ovarian Cancer Recurrence

1, 1, 2, 3, 1, 1, 1, 1, 1, 1, 1

1Department of Obstetrics, Gynecology and Reproductive Sciences, Reproductive Immunology Unit, Yale University School of Medicine, 2NatureMost Laboratories, 3Bruker Preclinical Imaging

VIEW VIDEO

http://www.jove.com/video/51815/murine-model-for-non-invasive-imaging-to-detect-monitor-ovarian

Murine Model for Non-invasive Imaging to Detect and Monitor Ovarian Cancer Recurrence

Murine Model for Non-invasive Imaging to Detect and Monitor Ovarian Cancer Recurrence

Natalia J. Sumi, Eydis Lima, John Pizzonia, Sean P. Orton, Vinicius Craveiro, Wonduk Joo, 1Jennie C. Holmberg, Marta Gurrea, Yang Yang-Hartwich, Ayesha Alvero, and Gil Mor 1

Author information ► Copyright and License information ►

Go to:

Abstract

Epithelial ovarian cancer is the most lethal gynecologic malignancy in the United States. Although patients initially respond to the current standard of care consisting of surgical debulking and combination chemotherapy consisting of platinum and taxane compounds, almost 90% of patients recur within a few years. In these patients the development of chemoresistant disease limits the efficacy of currently available chemotherapy agents and therefore contributes to the high mortality. To discover novel therapy options that can target recurrent disease, appropriate animal models that closely mimic the clinical profile of patients with recurrent ovarian cancer are required. The challenge in monitoring intra-peritoneal (i.p.) disease limits the use of i.p. models and thus most xenografts are established subcutaneously. We have developed a sensitive optical imaging platform that allows the detection and anatomical location of i.p. tumor mass. The platform includes the use of optical reporters that extend from the visible light range to near infrared, which in combination with 2-dimensional X-ray co-registration can provide anatomical location of molecular signals. Detection is significantly improved by the use of a rotation system that drives the animal to multiple angular positions for 360 degree imaging, allowing the identification of tumors that are not visible in single orientation. This platform provides a unique model to non-invasively monitor tumor growth and evaluate the efficacy of new therapies for the prevention or treatment of recurrent ovarian cancer.

Keywords: Cancer Biology, Issue 93, ovarian cancer, recurrence, in vivo imaging, tumor burden, cancer stem cells, chemotherapy

Download video file.(24M, mp4)

SOURCE

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4353409/

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