ImClone Systems And Bristol-Myers Squibb Update The Status Of Non-Small Cell Lung Cancer Supplemental Biologics Application Submission For ERBITUX(R)
ImClone Systems, a wholly-owned subsidiary of Eli Lilly and Company (NYSE: LLY), and Bristol-Myers Squibb Company (NYSE: BMY) today announced that the companies have decided, after discussion with the U.S. Food and Drug Administration (FDA), to withdraw, and eventually resubmit, the advanced non-small cell lung cancer (NSCLC) supplemental Biologics License Application (sBLA) for ERBITUX® (cetuximab). This decision was based upon a Chemistry Manufacturing and Controls (CMC) matter with regard to the pre-clinical pharmacokinetic comparability of the U.S. marketed version of ERBITUX with the clinical supplies used by Merck KGaA (ImClone’s partner for ERBITUX outside of North America).
It is important to note that the discussions with FDA do not have any impact on currently-marketed ERBITUX, including the safety and efficacy of the product for approved indications.
About Lung Cancer
The American Cancer Society estimates that in the United States, more than 215,000 people were diagnosed with lung cancer in 2008, which accounts for about 15 percent of all cancer diagnoses. Approximately 87 percent of these patients were diagnosed with NSCLC, with many being diagnosed with locally advanced or metastatic disease. More than 161,000 deaths from lung cancer were expected to occur in 2008 – accounting for about 29 percent of all cancer deaths.
About ERBITUX® (Cetuximab)
ERBITUX (cetuximab) is a monoclonal antibody (IgG1 Mab) designed to inhibit the function of a molecular structure expressed on the surface of normal and tumor cells called the epidermal growth factor receptor (EGFR, HER1, c-ErbB-1). In vitro assays and in vivo animal studies have shown that binding of ERBITUX to the EGFR blocks phosphorylation and activation of receptor-associated kinases, resulting in inhibition of cell growth, induction of apoptosis, and decreased matrix metalloproteinase and vascular endothelial growth factor production. In vitro, ERBITUX can mediate antibody-dependent cellular cytotoxicity (ADCC) against certain human tumor types. In vitro assays and in vivo animal studies have shown that ERBITUX inhibits the growth and survival of tumor cells that express the EGFR. No anti-tumor effects of ERBITUX were observed in human tumor xenografts lacking EGFR expression.
Squamous Cell Carcinoma of the Head and Neck (SCCHN)
ERBITUX, in combination with radiation therapy, is indicated for the initial treatment of locally or regionally advanced squamous cell carcinoma of the head and neck.
ERBITUX, as a single agent, is indicated for the treatment of patients with recurrent or metastatic squamous cell carcinoma of the head and neck for whom prior platinum-based therapy has failed.
Colorectal Cancer
ERBITUX, as a single agent, is indicated for the treatment of EGFR-expressing metastatic colorectal cancer after failure of both irinotecan- and oxaliplatin-based regimens. ERBITUX, as a single agent, is also indicated for the treatment of EGFR-expressing metastatic colorectal cancer in patients who are intolerant to irinotecan-based regimens.
ERBITUX, in combination with irinotecan, is indicated for the treatment of EGFR-expressing metastatic colorectal carcinoma in patients who are refractory to irinotecan-based chemotherapy. The effectiveness of ERBITUX in combination with irinotecan is based on objective response rates. Currently, no data are available that demonstrate an improvement in disease-related symptoms or increased survival with ERBITUX in combination with irinotecan for the treatment of EGFR-expressing metastatic colorectal carcinoma.
For full prescribing information, including boxed WARNINGS regarding infusion reactions and cardiopulmonary arrest, visit http://www.ERBITUX.com.
IMPORTANT SAFETY INFORMATION
Infusion Reactions
– Grade 3/4 infusion reactions occurred in approximately 3% of patients receiving ERBITUX® (cetuximab) in clinical trials, with fatal outcome reported in less than 1 in 1000
- Serious infusion reactions, requiring medical intervention and immediate, permanent discontinuation of ERBITUX, included rapid onset of airway obstruction (bronchospasm, stridor, hoarseness), hypotension, shock, loss of consciousness, myocardial infarction, and/or cardiac arrest
– Most (90%) of the severe infusion reactions were associated with the first infusion of ERBITUX despite premedication with antihistamines
- Caution must be exercised with every ERBITUX infusion, as there were patients who experienced their first severe infusion reaction during later infusions
- Monitor patients for 1 hour following ERBITUX infusions in a setting with resuscitation equipment and other agents necessary to treat anaphylaxis (eg, epinephrine, corticosteroids, intravenous antihistamines, bronchodilators, and oxygen). Longer observation periods may be required in patients who require treatment for infusion reactions
Cardiopulmonary Arrest
– Cardiopulmonary arrest and/or sudden death occurred in 4 (2%) of 208 patients with squamous cell carcinoma of the head and neck treated with radiation therapy and ERBITUX, as compared to none of 212 patients treated with radiation therapy alone. Fatal events occurred within 1 to 43 days after the last ERBITUX treatment
- Carefully consider the use of ERBITUX in combination with radiation therapy in head and neck cancer patients with a history of coronary artery disease, congestive heart failure or arrhythmias in light of these risks
- Closely monitor serum electrolytes including serum magnesium, potassium, and calcium during and after ERBITUX therapy
Pulmonary Toxicity
– Interstitial lung disease (ILD), which was fatal in one case, occurred in 4 of 1570 (
Dermatologic Toxicities
– In clinical studies of ERBITUX, dermatologic toxicities, including acneform rash, skin drying and fissuring, paronychial inflammation, infectious sequelae (eg, S. aureus sepsis, abscess formation, cellulitis, blepharitis, conjunctivitis, keratitis, cheilitis), and hypertrichosis, occurred in patients receiving ERBITUX therapy. Acneform rash occurred in 76-88% of 1373 patients receiving ERBITUX in clinical trials. Severe acneform rash occurred in 1-17% of patients
- Acneform rash usually developed within the first two weeks of therapy and resolved in a majority of the patients after cessation of treatment, although in nearly half, the event continued beyond 28 days
- Monitor patients receiving ERBITUX for dermatologic toxicities and infectious sequelae
- Sun exposure may exacerbate these effects
ERBITUX Plus Radiation Therapy and Cisplatin
– The safety of ERBITUX in combination with radiation therapy and cisplatin has not been established
- Death and serious cardiotoxicity were observed in a single-arm trial with ERBITUX, radiation therapy, and cisplatin (100 mg/m2) in patients with locally advanced squamous cell carcinoma of the head and neck
- Two of 21 patients died, one as a result of pneumonia and one of an unknown cause
- Four patients discontinued treatment due to adverse events. Two of these discontinuations were due to cardiac events
Electrolyte Depletion
– Hypomagnesemia occurred in 55% (199/365) of patients receiving ERBITUX and was severe (NCI CTC grades 3 & 4) in 6-17%. The onset of hypomagnesemia and accompanying electrolyte abnormalities occurred days to months after initiation of ERBITUX therapy
- Monitor patients periodically for hypomagnesemia, hypocalcemia and hypokalemia, during, and for at least 8 weeks following the completion of, ERBITUX therapy
- Replete electrolytes as necessary
Late Radiation Toxicities
– The overall incidence of late radiation toxicities (any grade) was higher with ERBITUX in combination with radiation therapy compared with radiation therapy alone. The following sites were affected: salivary glands (65%/56%), larynx (52%/36%), subcutaneous tissue (49%/45%), mucous membranes (48%/39%), esophagus (44%/35%), and skin (42%/33%) in the ERBITUX and radiation versus radiation alone arms, respectively
- The incidence of grade 3 or 4 late radiation toxicities were similar between the radiation therapy alone and the ERBITUX plus radiation therapy arms
Pregnancy
– In women of childbearing potential, appropriate contraceptive measures must be used during treatment with ERBITUX and for 6 months following the last dose of ERBITUX. ERBITUX should only be used during pregnancy if the potential benefit justifies the potential risk to the fetus
Adverse Events
– The most serious adverse reactions associated with ERBITUX across all studies were infusion reactions, cardiopulmonary arrest, dermatologic toxicity and radiation dermatitis, sepsis, renal failure, interstitial lung disease, and pulmonary embolus
– The most common adverse reactions associated with ERBITUX (incidence (>=)25%) are cutaneous adverse reactions (including rash, pruritus, and nail changes), headache, diarrhea, and infection
– The most frequent adverse events seen in patients with carcinomas of the head and neck receiving ERBITUX in combination with radiation therapy (n=208) versus radiation alone (n=212) (incidence ≥50%) were acneform rash (87%/10%), radiation dermatitis (86%/90%), weight loss (84%/72%), and asthenia (56%/49%). The most common grade 3/4 adverse events for ERBITUX in combination with radiation therapy ((>=)10%) included: radiation dermatitis (23%), acneform rash (17%), and weight loss (11%)
– The most frequent adverse events seen in patients with metastatic colorectal cancer (n=288) in the ERBITUX + best supportive care arm (incidence ≥50%) were fatigue (89%), rash/desquamation (89%), abdominal pain (59%), and pain-other (51%). The most common grade 3/4 adverse events ((>=)10%) included: fatigue (33%), pain-other (16%), dyspnea (16%), abdominal pain (14%), infection without neutropenia (13%), rash/desquamation (12%), and other-gastrointestinal (10%)
– The most frequent adverse events seen in patients with metastatic colorectal cancer (n=354) treated with ERBITUX plus irinotecan in clinical trials (incidence ≥50%) were acneform rash (88%), asthenia/malaise (73%), diarrhea (72%), and nausea (55%). The most common grade 3/4 adverse events ((>=) 10%) included: diarrhea (22%), leukopenia (17%), asthenia/malaise (16%), and acneform rash (14%)
About ImClone Systems
ImClone Systems, a wholly-owned subsidiary of Eli Lilly and Company, is committed to advancing oncology care by developing and commercializing a portfolio of targeted biologic treatments designed to address the medical needs of patients with a variety of cancers. ImClone’s research and development programs include growth factor blockers and angiogenesis inhibitors. ImClone’s research operations are located in New York City, with additional administration and manufacturing facilities in Branchburg, New Jersey. Additional information about ImClone is available at www.imclone.com.
About Eli Lilly and Company
Lilly, a leading innovation-driven corporation, is developing a growing portfolio of first-in-class and best-in-class pharmaceutical products by applying the latest research from its own worldwide laboratories and from collaborations with eminent scientific organizations. Headquartered in Indianapolis, Ind., Lilly provides answers – through medicines and information – for some of the world’s most urgent medical needs. Additional information about Lilly is available at http://www.lilly.com.
About Bristol-Myers Squibb
Bristol-Myers Squibb is a global biopharmaceutical company whose mission is to extend and enhance human life. For more information, visit http://www.bms.com.
This press release contains “forward-looking statements” as that term is defined in the Private Securities Litigation Reform Act of 1995 regarding product development. Such forward-looking statements are based on current expectations and involve inherent risks and uncertainties, including factors that could delay, divert or change any of them, and could cause actual outcomes and results to differ materially from current expectations. Among other risks, there can be no guarantee that the supplemental application will be approved. Forward-looking statements in this press release should be evaluated together with the many uncertainties that affect Bristol-Myers Squibb’s and Lilly’s businesses, particularly those identified in the cautionary factors discussion in Bristol-Myers Squibb’s and Lilly’s Annual Reports on Form 10-K for the year ended December 31, 2007, in their Quarterly Reports on Form 10-Q and their Current Reports on Form 8-K. Neither Bristol-Myers Squibb nor Lilly undertakes any obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise.
Bristol-Myers Squibb
With A Knitting Needle Piercing Her Heart, Keeping Cool Saved Ellin Klor’s Life – Twice
Pick apart what happened to Ellin Klor on the front porch of a friend’s house in 2006 and her miracle of survival reveals itself as a list of crucial moments everything from her calm reaction to the shocking sight of a knitting needle sticking out of her chest to the easy availability of top-flight trauma surgeons at Stanford Hospital & Clinics. Then came another life-saving diagnosis, precipitated by her emergency care.
Klor tells her jaw-dropping story very calmly. It is a story of survival so remarkable it doesn’t need to be trumpeted, but it offers memorable lessons on why some people survive terrible circumstances. Klor’s survival story will be included in “Newsweek” magazine, an upcoming edition of ABC’s 20/20 and in a new book, “The Survivors Club,” by New York Times best-selling author Ben Sherwood. Sherwood found Klor when he attended, as research for his book, one of the Hospital’s annual Trauma Survivor Reunions, organized by Stanford Trauma Center director David Spain, MD.
Sherwood’s visit made sense: The Hospital has the only Level 1 trauma center for adults and children between San Jose and San Francisco. That status, awarded by the American College of Surgeons to recognize highly trained staff and sophisticated equipment, improves survival odds by 25 percent for people with the most grievous injuries.
Klor needed every bit of Stanford’s expertise. She was in a rush that evening, late for a knitting circle meeting, her hands full of books and knitting bags, when she tripped and fell face forward with a thud. “I didn’t know at first what had happened,” she said. “When I got up I noticed I had a pain in my chest whenever I took a breath.” As she peeled off her coat, and then her sweater–there it was: The broken end of a size 11, foot long wooden knitting needle, about the width of a drinking straw, sticking out of the center of her chest, right at heart level.
The odds were steeply against her survival. Only two out of 10 people with penetrating injuries to the heart make it to the hospital alive. If they get that far, survival rates range from 40 percent to 70 percent. Klor is well aware that being less than 10 minutes away from Stanford and the Trauma Center made an important difference. “On a whole bunch of levels, I’m alive because of the excellent care I got at Stanford,” she said. “They were just amazing.”
But so was she. No blood was coming from her wound, and, as the daughter of a doctor, Klor had long before developed the ability to see injuries and remain calm. She was also a mother and a children’s librarian “where you have to deal with stuff all the time,” she said. She also knew that no one but a doctor should remove that knitting needle, despite the urgings of those around her.
Stanford trauma surgeons were amazed when Klor arrived. She was awake and alert and very calm, not exactly the standard state for someone with such an injury to the heart. Trauma surgeon Susan Brundage, MD, took charge of Klor’s care. Carefully holding on to the knitting needle, the surgical team sawed through Klor’s sternum and finally saw exactly what was going on. The needle had punctured the right ventricle of the heart, but again, the odds fell toward Klor’s survival. Because the needle had remained in place, there was no blood pooling in and about the heart and it functioned as if nothing were wrong at all. Out came the needle and the team sewed up the 8mm laceration and then wired the sternum together again. Klor was home in a few days.
There was a part of her, Klor said, that had thought, once she was declared clear of her breast cancer in 1994, “that I didn’t deserve any more.” The accident, she said, showed her that, having survived it, she had more strength than she knew. And a few days after her return home, a Stanford radiologist called to say there was something suspicious about a lymph node captured in one of the CT scans done at the Hospital.
It was diagnosed as a new cancer, one treated earlier, ironically, because of Klor’s near miss with death. But living through the knitting needle incident, Klor said, “gave me the confidence that I would survive” the new cancer, too. “I really think this has brought out the best person I am–or could be,” she said.
That attitude of confidence and her gratitude for being alive is so visible in Klor that a woman stopped her a few months ago in the Stanford Cancer Center. “I didn’t have any hair and I was wearing a beret and she said she could tell I was in chemo,” Klor said. “But she said, ‘You look so happy and so well I wanted to talk to you.’”
Now, Klor said, “I really work to be kind–I am so grateful for all the kindnesses that people everywhere showed to me, everyone I came in contact with.”
What Brundage saw in Klor, and what Sherwood saw, too, was that staying calm is, perhaps, the most important behavior to survival. “You can’t panic,” Brundage said. “If you panic, it’s all over. Look at what happened last week in that plane crash–people remained calm. That response is what saved them.”
Sherwood has created a Web site, http://www.survivorsclub.org, which features a video interview with Klor, now 58. “I hope it gives people hope,” she said. “People can survive things and discover things about themselves they never knew.”
About Stanford Hospital & Clinics
Stanford Hospital & Clinics is known worldwide for advanced treatment of complex disorders in areas such as cardiac care, cancer treatment, neurosciences, surgery, and organ transplants. Ranked #16 on the U.S. News and World Report annual list of “America’s Best Hospitals,” Stanford Hospital & Clinics is internationally recognized for translating medical breakthroughs into the care of patients. The Hospital is part of the Stanford University Medical Center, along with the Stanford University School of Medicine and Lucile Packard Children’s Hospital at Stanford.
Stanford Hospital & Clinics
New Therapies Suggested By Cancer-Causing Gene Discovery
Scientists have discovered a novel way by which a much-studied cancer-promoting gene accelerates the disease. The finding suggests a new strategy to halt cancer’s progress.
Up to now, research has largely focused on how the mutated gene, Myc, disrupts the ability of DNA to be “transcribed” into RNA – the first step in making proteins that are essential for cell growth and function. But the new research shows that this altered Myc gene, called an oncogene, can also act directly on the final stage of protein production.
The finding in mice suggests that drugs already available to counter this increased protein production could slow or stop cancer’s runaway growth induced by Myc. Rapamycin, for example, an immunosuppressant drug already in clinical trials for cancer, might help treat cancers where Myc is over active, the scientists suggest.
The discovery was led by Davide Ruggero, PhD, and Maria Barna, PhD, faculty scientists at the University of California San Francisco (UCSF).
Study findings were published in the journal Nature (December 18, 2008).
“Control of protein production rapidly affects cell behavior, and in a robust manner,” explains Ruggero, assistant professor of urology at the UCSF Helen Diller Family Comprehensive Cancer Center and co-senior author on the paper with Barna. “The ability of the Myc oncogene to directly alter this process may well explain the rapid progression of cancer formation.”
Scientists have known for some time that when the Myc gene is mutated and becomes an oncogene, it interferes with the early steps in DNA activity in the cell nucleus. But how the oncogene affected the subsequent production of proteins, a step known as translation, was unknown.
“A cancer causing gene, such as Myc, regulates many distinct cellular processes, and that can make it very difficult to tease apart which ones are the most important for the cancer to progress,” says Barna, a faculty fellow in the UCSF biochemistry and biophysics department. “The key to our studies was the ability to generate novel genetic tools to halt Myc’s action on protein production. This demonstrates how essential this process is for cancer formation.”
To test whether protein production induced by Myc played a role in cancer, the UCSF- led team genetically crossed two types of mice: one that was cancer-prone and overexpressed the Myc oncogene and one that was newly engineered to lower protein production. The new cross of mice possessed not only the well-known destructive Myc traits, but also an enhanced ability to damp down protein production.
In these mice, the restrained protein production restored to near-normal the cell growth, division and protective cell-sacrifice needed to counter cancer.
The scientists also found that this increased control over the so-called “translation” of RNA into proteins countered damage to chromosome function otherwise caused by Myc, and preserved functions vital to faithful cell division. Changes in the genetic integrity of cells are recognized as hallmarks of cancer, and the new findings show that Myc can cause these abnormalities through control of protein production.
The research suggests that Myc may disrupt a number of genes “downstream” of its damage to DNA, the scientists say.
“We discovered a previously unrecognized link between alterations in protein synthesis and the mechanism by which cells maintain the integrity of the genome,” Ruggero stresses. “We found that when Myc is overexpressed, this leads to changes in protein levels of a key gene that is essential for normal distribution of genetic material between daughter cells during cell division.”
The findings are a positive step, he emphasizes, because they suggest that halting Myc’s action on protein production with targeted therapies could prevent harmful genetic changes in cells that lead to cancer progression.
Co-authors with Ruggero and Barna are Aya Pusic, BS, scientific research assistant; Ornella Zollo,PhD, and Maria Costa, PhD, postdoctoral fellows, and Nadya Kondrashov, BA, all at UCSF; Eduardo Rego at the Center for Cell Based Therapy, Fundacao Hemocentro de Rebeiaro Preto, Sao Paulo, Brazil; and Pulivarthi Rao in the Department of Pediatrics, Baylor College of Medicine.
The research was funded by the National institutes of Health and the Sandler Foundation.
UCSF is a leading university dedicated to promoting health worldwide through advanced biomedical research, graduate-level education in the life sciences and health professions, and excellence in patient care.
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Article adapted by Medical News Today from original press release.
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Source: Kirsten Michener
University of California – San Francisco
Hearing With Your Face, Feeling Your Words
The movement of facial skin and muscles around the mouth plays an important role not only in the way the sounds of speech are made, but also in the way they are heard according to a study by scientists at Haskins Laboratories, a Yale-affiliated research laboratory.
“How your own face is moving makes a difference in how you ‘hear’ what you hear,” said first author Takayuki Ito, a senior scientist at Haskins.
When, Ito and his colleagues used a robotic device to stretch the facial skin of “listeners” in a way that would normally accompany speech production they found it affected the way the subjects heard the speech sounds.
The subjects listened to words one at a time that were taken from a computer-produced continuum between the words “head” and “had.” When the robot stretched the listener’s facial skin upward, words sounded more like “head.” With downward stretch, words sounded more like “had.” A backward stretch had no perceptual effect.
And, timing of the skin stretch was critical – perceptual changes were only observed when the stretch was similar to what occurs during speech production.
These effects of facial skin stretch indicate the involvement of the somatosensory system in the neural processing of speech sounds. This finding contributes in an important way to our understanding of the relationship between speech perception and production. It shows that there is a broad, non-auditory basis for “hearing” and that speech perception has important neural links to the mechanisms of speech production.
Details of this study are reported in an article titled “Somatosensory function in speech perception” by Ito, Mark Tiede, and David J. Ostry which appeared in the Proceedings of the National Academy of Sciences (PNAS). All of these researchers are scientists affiliated with Haskins Laboratories. Tiede is also at the Research Laboratory of Electronics at the Massachusetts Institute of Technology and Ostry is a Professor in the Department of Psychology at McGill University.
Haskins Laboratories was founded in 1935 by the late Dr. Caryl P. Haskins. This independent research institute has been in New Haven, Connecticut since 1970 when it formalized affiliations with Yale University and the University of Connecticut. The Laboratories’ primary research focus is on the science of the spoken and written word.
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Article adapted by Medical News Today from original press release.
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Citation: PNAS: online before print January 21, 2009, doi:10.1073/pnas.0810063106
Haskins Laboratories http://www.haskins.yale.edu/index.html
Takayuki Ito http://www.haskins.yale.edu/staff/ito.html
Mark Tiede http://www.haskins.yale.edu/staff/tiede.html
David Ostry http://www.haskins.yale.edu/staff/ostry.html
PNAS: online before print January 21, 2009, doi:10.1073/pnas.0810063106
http://www.pnas.org/content/early/2009/01/21/0810063106.abstract?sid=4707c117-a4b2-43f1-9032-5a1acd0df7df
Source: Janet Rettig Emanuel
Yale University
How Natural Oils Can Be Hydrogenated Without Making Unhealthy Trans Fats
To prolong the shelf life of foods, manufacturers often add hydrogen to natural oils, a process called hydrogenation. But hydrogenation also results in the production of trans fats, which have adverse health effects such as raising bad cholesterol and increasing the risk for coronary heart diseases.
Trans fats are found in vegetable shortenings, some margarines, crackers, cookies and snacks. Health authorities worldwide recommend that people reduce their consumption of trans fats.
Now UC Riverside chemists have designed a catalyst – a substance that accelerates a chemical reaction – that allows hydrogenated oils to be made while minimizing the production of trans fats.
In their experiments, the researchers, led by Francisco Zaera, a professor of chemistry, used platinum, a common catalyst for these processes. By controlling the shape of the platinum particles, the Zaera group was able to make the catalyst more selective.
Catalytic selectivity refers to the ability of a catalyst to select a specific pathway from among many possible chemical reactions. In the case of the researchers’ experiments, selectivity refers to the production of partially hydrogenated fats without the making of trans fats.
Zaera’s lab found that the platinum catalyst performed most selectively when its particles assumed tetrahedral shapes, with the atoms arranged in a hexagonal honeycomb lattice. Particles with these shapes allow for the preservation of the harmless cis configuration in the hydrogenated fats. Other lattices, the researchers found, favor the production of trans fats.
Platinum catalysts such as those used by the Zaera group are considered heterogeneous because they exist in a different phase (solid) than the reactants (liquid or gas). Compared with homogeneous catalysts, where the catalyst is in the same phase (liquid) as the reactants, heterogeneous catalysts have the advantages of easy preparation, handling, separation from the reaction mixture, reuse, high stability, and low cost.
But their main disadvantage is that, unlike homogeneous catalysts, which tend to be molecular, heterogeneous catalysts must be dispersed as small particles in a high surface-area support in order to optimize their use. This typically results in catalysts with surfaces of ill-defined structures.
The research by Zaera and his colleagues is a breakthrough also because it shows for the first time that it is possible to achieve selectivity with heterogeneous catalysts like platinum by controlling the structure of their surfaces.
“The more control we can exert on how we prepare catalysts, the more we can control the catalytic selectivity of a particular chemical process,” Zaera said. “Our work shows that it is possible to make heterogeneous catalysts that afford us more control on selectivity. This opens the door, we hope, for chemists to think about achieving selectivity for other reactions via the design of specific heterogeneous catalysts with specific shapes.”
Zaera explained that heterogeneous catalysts tend to be more practical in terms of manipulation, but are harder to control.
“Our paper shows that, thanks to new advances in nanoscience, sophisticated and highly selective heterogeneous catalysts can be made by controlling their structures,” he added. “In this sense, our paper changes the paradigm of heterogeneous catalysis. These catalysts can now compete more closely with homogeneous catalysts, which industry traditionally uses for reactions that require high selectivity such as those involved in the manufacture of medicines or other fine chemicals.”
Study results appeared online earlier this week in Nature Materials.
Next in their research, Zaera’s lab plans to find other reactions where selectivity is needed. The researchers also plan to improve on the synthetic techniques used to make selective catalysts.
Nearly 80 percent of all chemical industrial processes use catalysts. With annual global sales of about $1500 billion, catalysts contribute approximately 35 percent of the world’s gross domestic product. They are used in the manufacture of commodity, petro- and agro-chemicals, pharmaceuticals, cosmetics, foods, and polymers.
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Article adapted by Medical News Today from original press release.
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Born in Venezuela, Zaera joined UCR in 1987. He is a recipient of many awards and honors, including two awards from the American Chemical Society: the Arthur W. Adamson Award for Distinguished Service in the Advancement of Surface Chemistry; and the George A. Olah Award in Hydrocarbon or Petroleum Chemistry. He is a senior editor of The Journal of Physical Chemistry, and serves on the editorial boards of several scientific journals, including Catalysis Letters and Topics in Catalysis.
He was joined in the study by Ilkeun Lee (first author of the research paper), Ricardo Morales, and Manuel A. Albiter of UCR; and Françoise Delbecq of Université de Lyon, France.
A grant from the National Science Foundation funded the research.
The University of California, Riverside is a doctoral research university, a living laboratory for groundbreaking exploration of issues critical to Inland Southern California, the state and communities around the world. Reflecting California’s diverse culture, UCR’s enrollment of about 17,000 is expected to grow to 21,000 students by 2020. The campus is planning a medical school and has reached the heart of the Coachella Valley by way of the UCR Palm Desert Graduate Center. The campus has an annual statewide economic impact of more than $1 billion. To learn more, visit http://www.ucr.edu .
Source: Iqbal Pittalwala
University of California – Riverside
Study Compares New Registered Nurses With Second Degree RNs
As the United States continues to experience a nursing shortage that is expected to grow to one million nurses by 2016, a new research study highlights a pool of potential candidates who could alleviate the shortage in an economical way.
The study, published in the January/February 2009 issue of the Journal of Professional Nursing, compares nursing graduates whose first baccalaureate degree was in nursing with nursing graduates whose first baccalaureate degree was in another field and who obtained a second baccalaureate degree in nursing. Findings from the study, funded through a grant from the Robert Wood Johnson Foundation, suggest that second degree nurses are an efficient new solution to the current nursing shortage.
Through a 16-page survey, the study sampled 953 newly licensed registered nurses from 35 states and asked questions about how they felt about their jobs, information about work settings and their intent to stay at their current job. The nurses had been licensed from five to 18 months prior to taking the survey.
According to the study, second-degree students are usually older and more motivated. Because they have more work experience, they have coping advantages over newer, younger nursing graduates during the period immediately after leaving school and entering the workforce. This finding is significant, since some new registered nurses have left their first jobs in frustration from a lack of coping skills or the knowledge to do their jobs. New nurses who only had nursing degree generally did not like their work setting, were less satisfied in their jobs and more likely to leave them. Second degree new nurses, however, were more likely to stay in their jobs and to be better able to cope with stress and frustration in the workplace.
“Second degree candidates bring life experiences to their jobs that are valuable to employers,” said Carol S. Brewer, PhD, RN, associate professor in the School of Nursing at the University at Buffalo, Buffalo, NY, and lead author of the study. “Second degree graduates may be particularly attracted to employers who mitigate family work conflict, and promote work group cohesion.”
Second-degree nurses also can be educated in much less time than basic registered nurses, according to the study, because they already have college degrees. However because they are older, they many have shorter work careers. Understanding which group is more productive in the workforce will help organizations design recruitment and retention programs for each group.
“Nurses in second degree programs are a great source of new nurses for the health needs of Americans. They usually complete nursing programs in 12-15 months,” said Christine Kovner, PhD, RN, FAAN, professor at New York University’s College of Nursing and co-author of the study. “At NYU we are a large second degree program. I have found teaching these students delightful and think they are wonderful new nurses.”
This research used a sub-set of nurses involved in a larger RWJF-funded study by Brewer and Kovner which tracks changes in the careers of a group of newly licensed nurses over 10 years.
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Article adapted by Medical News Today from original press release.
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The Robert Wood Johnson Foundation focuses on the pressing health and health-care issues facing our country. As the nation’s largest philanthropy devoted exclusively to improving the health and health care of all Americans, the foundation works with a diverse group of organizations and individuals to identify solutions and achieve comprehensive, meaningful and timely change. For more than 35 years the foundation has brought experience, commitment and a rigorous, balanced approach to the problems that affect the health and health care of those it serves. When it comes to helping Americans lead healthier lives and get the care they need, the foundation expects to make a difference in your lifetime. For more information, visit http://www.rwjf.org.
The University at Buffalo is a premier research-intensive public university, a flagship institution in the State University of New York system and its largest and most comprehensive campus.
UB’s more than 28,000 students pursue their academic interests through more than 300 undergraduate, graduate and professional degree programs. The School of Medicine and Biomedical Sciences, School of Dental Medicine, School of Nursing, School of Pharmacy and Pharmaceutical Sciences and School of Public Health and Health Professions constitute UB’s Academic Health Center. Founded in 1846, the University at Buffalo is a member of the Association of American Universities.
The College of Nursing at the College of Dentistry is located on New York University’s historic Greenwich Village campus in New York City. The College of Nursing is one of the leading nursing programs in the United States. The College offers a Bachelor of Science in Nursing; Master of Arts and Post-Master’s Certificate Programs; and a Doctor of Philosophy in Research Theory and Development. For more information, visit http://www.nyu.edu/nursing.
Source: Cherie Black
New York University
Significant Damages And Losses Could Be Avoided By More Accurate FEMA Flood Maps
Significant loss of life, destroyed property and businesses, and repairs to infrastructure could be avoided by replacing Federal Emergency Management Agency flood maps with ones that contain high-accuracy and high-resolution land surface elevation data, says a new report from the National Research Council. The benefits of more accurate flood maps will outweigh the costs, mainly because insurance premiums and building restrictions would better match the actual flood risks. Coastal region flood maps could also be improved by updating current models and using two-dimensional storm surge and wave models.
Flood maps are used by FEMA to set flood insurance rates, regulate floodplain development, and inform those who live in the “100-year” floodplain of potential hazards, and they require continuous maintenance and revision due to land development and natural changes to the landscape. FEMA’s Map Modernization Program of 2003 to 2008 resulted in digital flood maps for 92 percent of the continental U.S. population, most of whom live in areas that had outdated maps or no maps at all. However, after a $1 billion investment, only 21 percent of the population have maps that meet all of FEMA’s data quality standards.
For this reason, FEMA and the National Oceanic and Atmospheric Administration asked the Research Council to examine the factors that affect flood map accuracy; assess the costs and benefits of producing more accurate maps; and recommend ways to improve mapping, communication, and management of flood-related data. In response, the committee that wrote the report collected and analyzed information on selected streams in Florida and North Carolina and on the economic costs and benefits of creating new digital flood maps in North Carolina. Information from the North Carolina Floodplain Mapping Program, which has high-accuracy topographic data and maps for nearly the entire state, allowed the committee to compare new and traditional mapping methods among three distinct topographical regions: mountains, rolling hills, and coastal plains.
The costs for improving flood maps would come from collecting, updating, modeling, and analyzing the flood-related data; increasing construction of property and businesses; losing land to development; updating regulations; and informing the public of changes. The committee found that these costs would be outweighed by benefits of more accurate flood maps, including reduced loss of life, property, and businesses; more efficient planning and response for emergency services; and preservation of natural functions of floodplains. In addition, better maps would provide more reliable measures of flood hazard, which would enable more targeted land-use regulations and structures to be insured at appropriate levels. Maps that include estimates of the height flood water will rise or exceed during a 100-year flood provide significantly more benefits than those that do not.
FEMA commonly produces maps using data from the U.S. Geological Survey National Elevation Dataset (NED), which is developed from airborne and land surveys. However, map accuracy would be increased by updating and generating information using high-accuracy topographic data, such as that generated by “lidar,” which measures elevation using aircraft-mounted lasers, the committee said. For the three topographical regions studied, differences in ground elevation measurements by lidar and NED were about 12 feet, with the lidar heights measuring both higher and lower than the NED. These differences significantly affect predicting the extent of flooding, the committee stated. Overall, the total areas of floodplains defined from lidar and from the NED were similar in two study regions and differed in shape by 20 percent in one study region. As lidar data coverage is sparse, FEMA should increase collaboration with federal, state, and local government agencies to acquire lidar data throughout the nation.
While improvements to inland flood maps can focus on harnessing available technology, coastal flood maps could be improved by employing better models that enhance understanding of the coastal flooding process. The committee recommended improving the accuracy of base flood elevations by replacing FEMA’s one-dimensional model for calculating wave heights, which was introduced in the 1970s, with a two-dimensional wave model. Further enhancements could come by coupling this with a two-dimensional surge model and including models that account for erosion processes, effects on structures, and variations in elevation.
FEMA’s transition to digital flood mapping also provides opportunities for better informing the public of flood hazards and risks through maps and Web-based products, the committee noted. To adequately convey risk, the maps and products must show where the flood hazard areas are located and the likely consequences of flooding, such as damage to houses or coastal erosion. Additionally, floodplain residents should know how their land elevation level compares with various possible flood heights, which will offer a finer discrimination of potential risk. Currently, maps that show only floodplain boundaries imply that every building in a designated flood zone may flood and every building outside the zone is safe.
The National Academy of Sciences, National Academy of Engineering, Institute of Medicine, and National Research Council make up the National Academies. They are independent, nonprofit institutions that provide science, technology, and health policy advice under an 1863 congressional charter. Committee members, who serve pro bono as volunteers, are chosen by the Academies for each study based on their expertise and experience and must satisfy the Academies’ conflict-of-interest standards. The resulting consensus reports undergo external peer review before completion. For more information, visit http://national-academies.org/studycommitteprocess.pdf. A committee roster follows.
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Article adapted by Medical News Today from original press release.
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Copies of MAPPING THE ZONE: IMPROVING FLOOD MAP ACCURACY are available on the Internet at http://www.medicalnewstoday.com/HTTP://WWW.NAP.EDU.
[ This news release and report are available at http://www.medicalnewstoday.com/HTTP://NATIONAL-ACADEMIES.ORG ]
NATIONAL RESEARCH COUNCIL
Division on Earth and Life Studies
Board on Earth Sciences and Resources
and
Water Science and Technology Board
COMMITTEE ON FEMA FLOOD MAPS: ACCURACY ASSESSMENT AND COST-EFFECTIVE IMPROVEMENTS
DAVID R. MAIDMENT (CHAIR)
Professor of Civil Engineering, and
Director
Center for Research in Water Resources
University of Texas
Austin
DAVID S. BROOKSHIRE
Professor of Economics
Department of Economics, and
Director
Science Impact Laboratory for Policy and Economics
University of New Mexico
Albuquerque
J. WILLIAM BROWN
Assistant City Engineer, and
Director
Environmental Engineering Bureau
City of Greenville
Greenville, S.C.
JOHN DORMAN
Director
Geospatial and Technology Management Office
North Carolina Division of Emergency Management
Raleigh
GERALD E. GALLOWAY JR.*
Glenn L. Martin Institute Professor of Engineering
University of Maryland
College Park
BISHER IMAM
Adjunct Associate Professor
Department of Civil and Environmental Engineering, and
Senior Researcher
Center for Hydrometeorology and Remote Sensing
University of California
Irvine
WENDY LATHROP
President
Cadastral Consulting LLC
Bala Cynwyd, Pa.
DAVID F. MAUNE
Senior Project Manager
Dewberry and Davis
Fairfax, Va.
BURRELL E. MONTZ
Professor and Director of Graduate Studies
Department of Geography, and
Associate Director
Center for Integrated Watershed Studies
Binghamton University
Binghamton, N.Y.
SPENCER ROGERS
Extension Specialist
North Carolina Sea Grant
Wilmington
KAREN L. SCHUCKMAN
Instructor in Geography
John A. Dutton e-Education Institute
College of Earth and Mineral Sciences
Pennsylvania State University
University Park
Y. PETER SHENG
Professor of Coastal and Oceanographic Engineering
Department of Civil and Coastal Engineering
University of Florida
Gainesville
JUAN D. VALDES
Professor and Head
Department of Civil Engineering and Engineering Mechanics, and
Professor
Department of Hydrology and Water Resources
University of Arizona
Tucson
RESEARCH COUNCIL STAFF
ANNE LINN
Study Director
* Member, National Academy of Engineering
Source: Jennifer Walsh
National Academy of Sciences
DASNR Researchers Make Breakthrough Against Poxviruses
Smallpox has a nasty history throughout the world. Caused by poxviruses, smallpox is one of the few disease-causing agents against which the human body’s immune system is ineffective in its defense.
A major breakthrough by Junpeng Deng, a structural biologist in the Division of Agricultural Sciences and Natural Resources (DASNR) at Oklahoma State University, and his first-year Ph.D. student, Brian Krumm, may be the first step towards a pharmaceutical medication for smallpox and the emerging human monkeypox.
The human immune system is rendered helpless against poxviruses partly because the viruses block a human immune molecule, interleukin-18 (IL-18), from sending out a signal to the immune system. The body acts as if everything is fine and the deadly disease takes over.
Deng and Krumm joined an ongoing project midway through 2007 and Krumm found what he was looking for in December 2008. They solved a three-dimensional crystal structure of a poxvirus protein in the act of disarming the IL-18.
“We capped a lot of others’ research. This is additional information provided,” said Krumm, who is credited as the major contributor to the research. “We also show many things through the structure that can’t be revealed through traditional molecular biology and immunology.”
The study is published in the Dec. 22 early online edition of the Proceedings of the National Academy of Sciences of the United States of America.
“We know now how the proteins communicate with each other,” Deng said. “In the future, we can design a drug to stop the poxvirus from blocking the IL-18 protein.”
As there is currently no medication for poxvirus-caused diseases, this research could aid national and international security efforts against potential poxvirus use as bioterrorism.
Deng called the finding an example of “killing two birds with one stone.”
“At this time we only have very limited medication to treat autoimmune diseases,” he said.
For example, rheumatoid arthritis is one of the most prevalent autoimmune diseases in which IL-18 is too active, leading to the body attacking its own cells. Deng said seeing how IL-18 interacts with the poxviruses will help with the development of effective inhibitors against overreaction.
“There are still a lot of questions to be answered. This is just the beginning,” Deng said. “This opened up a new area to explore: How we design medication for autoimmune diseases. We want to provide more and more structural insights.”
Deng and Krumm will continue to do research in the lab created two years ago in November 2006, when Deng joined OSU with funding provided by a start-up fund from DASNR.
“Junpeng is a relatively new assistant professor at OSU and has already demonstrated some excellent work,” said Gary Thompson, head of the department of biochemistry and molecular biology. “I’m really impressed with not only Junpeng, but also the quality of work from his Ph.D. students.”
Deng and Krumm did their research in the lab at OSU, but recognize the help they had from other researchers.
“Credit also goes to Yan Xiang and Xiangzhi Meng, our collaborators at the University of Texas Health Science Center at San Antonio,” Deng said of the multi-institutional effort. “I believe our excellent collaboration will bring more success in the future.”
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Article adapted by Medical News Today from original press release.
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Oklahoma State University, U. S. Department of Agriculture, State and Local governments cooperating; Oklahoma State University in compliance with Title VI and VII of the Civil Rights Act of 1964, Executive Order 11246 as amended, Title IX of the Education Amendments of 1972, Americans with Disabilities Act of 1990, and other federal and state laws and regulations, does not discriminate on the basis of race, color, national origin, gender, age, religion, disability, or status as a veteran in any of its policies, practices, or procedures, and is an equal opportunity employer.
Source: Sean Hubbard
Oklahoma State University
When Might Preventive Mastectomy Be Right Choice? Study Investigates
A new US study has sought to help women who have been treated for breast cancer in one breast to make a better informed decision about
whether to have a preventive mastectomy to remove the unaffected breast by identifying which types of patients and tumors present the highest risk of
developing cancer in the second breast.
The study was the work of Dr Kelly K Hunt and colleagues at the University of Texas MD Anderson Cancer Center in Houston, and colleagues, and is
to be published in the March 1, 2009 issue of CANCER, a peer-reviewed journal of the American Cancer Society.
Having breast cancer in one breast increases a woman’s chances of getting it in the second breast, either at the same time or later. Finding out which
women are most at risk of developing cancer in the other breast could help patients make better decisions about preventive treatment, such as whether
to surgically remove the other breast.
Women who choose to have a mastectomy to remove the unaffected breast currently do so for a number of reasons: their doctor advises it, they are
scared of another cancer diagnosis, they want both breasts to look the same, and/or because having cancer in the second breast runs in the
family.
However, there is not enough research evidence to help women make this choice; all we know is that most breast cancer patients do not necessarily
benefit in terms of extending survival. It would help if we knew which women were at the highest risk of develeloping cancer in the second breast:
what is it about the patient, and the type of cancer in the first breast, that makes this more likely?
To attempt an answer to this question, Hunt and colleagues studied 542 patients who had breast cancer diagnosed in one breast (unilateral breast) and
decided to have this and the other breast (contralateral prophylactic mastectomy) removed between 2000 and 2007. They then examined tissue
specimens of the removed second breast and found that 25 of the patients (5 per cent) had breast cancer in the removed second breast and 82 (15 per
cent) had abnormal cells that could signify higher risk of developing breast cancer.
Hunt and colleagues also looked at all the information they had about the women’s breast cancers and their clinical records, and found there were three
independent factors that linked most closely to the likelihood of having cancer in the second breast. These were: when the cancer cells were
particularly invasive (this can be assessed from their histologic characteristics); when the cancer occurred in more than one quadrant of the breast; and
when the patient had a 5-year Gail risk of 1.67 or more (the Gail risk uses medical history, age, race, and other information to assess a healthy
woman’s risk of developing cancer).
They also found that abnormal cells in the second breast were more likely to be linked to women aged 50 and over at the first diagnosis, or who had
moderate to high risk cells in the affected (first) breast.
Speaking to the press, Hunt said:
“Our goal is to help women make more informed decisions, based on their individual case rather than the general population, about whether to have
this aggressive and irreversible procedure.”
“Women often consider it not because of their doctor’s recommendation, but out of fear their cancer will return,” she told the Houston
Chronicle.
Many doctors think that radical mastectomies are often performed unnecessarily and they can also develop complications that have nothing to do with
the cancer.
Dr Todd Tuttle, a surgical oncologist at the University of Minnesota and author of a study published in 2007 that revealed the steep rise in women
opting for double mastectomy, said he hoped this study will help to bring down the numbers.
“Either because it confirms statistics that patients’ overall risk of the cancer returning in the other breast is actually low or because it will lead to a tool
that shows their specific risk is low, it should send a loud message that women not overreact to their diagnosis,” he told the Chronicle.
“Predictors of contralateral breast cancer in patients with unilateral breast cancer undergoing contralateral prophylactic
mastectomy.”
Min Yi, Funda Meric-Bernstam, Lavinia P. Middleton, Banu K. Arun, Isabelle Bedrosian, Gildy V. Babiera, Rosa F. Hwang, Henry M. Kuerer, Wei
Yang, and Kelly K. Hunt.
CANCER Print Issue Date: March 1, 2009; Published Online: January 26, 2009.
DOI: 10.002/cncr.24129
.
Click here for CANCER journal home
page.
Sources: ACS, Houston Chronice.
Written by: Catharine Paddock, PhD
Copyright: Medical News Today
Not to be reproduced without permission of Medical News Today
Single Brain Cell Can Store Memory
US scientists studying brain cells in mice found that a single cell in the front part of the brain can hold fleeting traces of memories on its own for
as long as a minute and perhaps even longer: it behaves a bit like RAM, the short term memory storage used by computers.
The research appears as a paper in the 25 January online issue of the journal Nature Neuroscience and is the work of senior author Dr Don
Cooper, assistant professor of psychiatry at The University of Texas (UT) Southwestern Medical Center at Dallas, and colleagues.
This is the first study to find the exact signal that enables a brain cell to hold information temporarily. The discovery could help us better understand
and treat addiction, attention disorders, and memory loss due to things like stress and trauma, said Cooper.
Scientists already know that permanent memories get stored when glutamate (an amino acid) switches on ion channels of brain cells to reorganize and
strengthen the way they connect to each other. But this takes time, several minutes to several hours, to fire up and then turn off, and reacts too slowly
to be useful as a temporary store or buffer of information that comes in much faster.
Cooper and colleagues found that “inputs” of small chunks of information that last less than a second trigger a single-cell effect in the most highly
evolved part of the brain, an effect that is called “metabotropic glutamate transmission” that acts like a temporary buffer to hold moment to moment
information.
“It’s more like RAM [random access memory] on a computer than memory stored on a disk,” explained Cooper.
“The memory on the disk is more permanent and you can go back and access the same information repeatedly. RAM memory is rewritable temporary
storage that allows multitasking,” he added.
The study’s findings enhance our knowledge about how the brain stores information that changes rapidly; Cooper compares it to the temporary
memory a card shark uses when counting cards during a game of Black Jack. It can also be disrupted quite easily with alcohol and noise, as many
casinos have discovered, he said.
Using nanoscale electrodes, Cooper and colleagues found that when a particular receptor in the brain cells of mice is switched on, it triggers a
cascade of signals that use calcium to hold a memory trace. The particular receptor is called mGluR5 (metabotropic glutamate receptor 5), and the
process occurs inside individual cells, unlike long term memory which involves proteins re-arranging connections between
cells.
Cooper and colleagues did a further experiment to see how their discovery might affect conditions like addiction, where the neurochemical dopamine
plays an important role. Just the right amount of dopamine helps people be focused and decisive.
Cooper and colleagues found that activating a particular type of dopamine receptor helped the brain cells to “focus” and made the memory trace less
susceptible to distraction.
They also found that repeated exposure to addictive levels of cocaine in animals bred to study drug addiciton, disrupted the activation of the temporary
buffer process, and no amount of dopamine receptor activation improved their ability to focus.
Cooper said this result matched what they already knew about how the brains of addicts behave, “it all fits together”, he said, explaining that:
“This makes sense because we know from human and animal models of addiction, when a decision using working memory has to be made, brain
imaging shows a deficit in the same area of the brain we looked at.”
Their next step is to identify the exact ion channel that holds and regenerates a memory trace; they hope this leads to new drugs and genetic tools that
will help to enhance memory capacity in decision making, for example by helping drug addicts consider the consequences of impulsive behaviour.
“If we can identify and manipulate the molecular components of memory, we can develop drugs that boost the ability to maintain this memory trace to
hopefully allow a person to complete tasks without being distracted,” said Cooper.
“For the person addicted to drugs, we could strengthen this part of the brain involved with decision-making, allowing them to ignore impulses and
weigh negative consequences of their behavior before they abuse drugs,” he explained.
The study was sponsored by the National Institute on Drug Abuse; National Alliance for Research on Schizophrenia and Depression; the Alexander S.
Onassis Public Benefit Foundation; and the Department of Veterans Affairs.
“Dopamine modulates an mGluR5-mediated depolarization underlying prefrontal persistent activity.”
Kyriaki Sidiropoulou, Fang-Min Lu, Melissa A Fowler, Rui Xiao, Christopher Phillips, Emin D Ozkan, Michael X Zhu, Francis J White, Donald C
Cooper.
Nature Neuroscience Published online 25 Jan 2009.
doi: 10.1038/nn.2245
Click here for
Article.
Sources: UT Southwestern, journal abstract.
Written by: Catharine Paddock, PhD
Copyright: Medical News Today
Not to be reproduced without permission of Medical News Today
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