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Sample records for great barracuda fda

  1. Use of two detection methods to discriminate ciguatoxins from brevetoxins: application to great barracuda from Florida Keys.

    Science.gov (United States)

    Dechraoui, M-Yasmine Bottein; Tiedeken, Jessica A; Persad, Renuka; Wang, Zhihong; Granade, H Ray; Dickey, Robert W; Ramsdell, John S

    2005-09-01

    In Florida (USA), numerous cases of human ciguatera fish poisoning, as well as neurotoxic shellfish poisoning following consumption of local seafood products, have been reported. By using in parallel, the sodium channel receptor binding assay (RBA), and the ouabain/veratridine-dependent cytotoxicity assay (N2A assay), we established criteria to identify, detect, and quantify ciguatoxins in fish extracts, with a brevetoxin as internal standard. Results showed that the Caribbean ciguatoxin C-CTX-1 exhibited an 8-fold higher potency in the RBA than brevetoxins and, a 440 and 2300-fold higher potency in the N2A assay than PbTx-1 and PbTx-3, respectively. Moreover, a sensitivity comparison between assays revealed that the N2A assay was more sensitive (12-fold) for ciguatoxin analysis, whereas the RBA was more sensitive (3-24-fold) for brevetoxins analysis. Based on the relative potency between toxins and the opposite sensitivity of both assays we have used the RBA and the N2A assay to screen great barracuda (Sphyraena barracuda) collected from the Florida Keys for ciguatoxins and brevetoxins. Fish extract analysis showed a sodium channel-dependent activity consistent with the presence of ciguatoxins, and not brevetoxins. Among 40 barracudas analyzed, 60% contained ciguatoxin levels in their liver measurable by the N2A assay with the most toxic fish containing 2.1ppb C-CTX-1 equivalents.

  2. Linking ciguatera poisoning to spatial ecology of fish: a novel approach to examining the distribution of biotoxin levels in the great barracuda by combining non-lethal blood sampling and biotelemetry.

    Science.gov (United States)

    O'Toole, Amanda C; Dechraoui Bottein, Marie-Yasmine; Danylchuk, Andy J; Ramsdell, John S; Cooke, Steven J

    2012-06-15

    Ciguatera in humans is typically caused by the consumption of reef fish that have accumulated Ciguatoxins (CTXs) in their flesh. Over a six month period, we captured 38 wild adult great barracuda (Sphyraena barracuda), a species commonly associated with ciguatera in The Bahamas. We sampled three tissues (i.e., muscle, liver, and blood) and analysed them for the presence of ciguatoxins using a functional in vitro N2A bioassay. Detectable concentrations of ciguatoxins found in the three tissue types ranged from 2.51 to 211.74pg C-CTX-1 equivalents/g. Blood and liver toxin concentrations were positively correlated (ρ=0.86, P=0.003), indicating that, for the first time, blood sampling provides a non-lethal method of detecting ciguatoxin in wild fish. Non-lethal blood sampling also presents opportunities to couple this approach with biotelemetry and biologging techniques that enable the study of fish distribution and movement. To demonstrate the potential for linking ciguatoxin occurrence with barracuda spatial ecology, we also present a proof-of-concept case study where blood samples were obtained from 20 fish before releasing them with acoustic transmitters and tracking them in the coastal waters using a fixed acoustic telemetry array covering 44km(2). Fish that tested positive for CTX may have smaller home ranges than non-toxic fish (median distance travelled, U=2.21, P=0.03). Results presented from this study may help identify high risk areas and source-sink dynamics of toxins, potentially reducing the incidence and human health risk of ciguatera fish poisoning. Moreover, development of the non-lethal sampling approach and measurement of ciguatera from blood provide future opportunities to understand the mechanistic relationship between toxins and the spatial ecology of a broad range of marine fish species. Copyright © 2012 Elsevier B.V. All rights reserved.

  3. The ecology of Sphyraena barracuda (Osteichthyes:

    African Journals Online (AJOL)

    The ecology of Sphyraena barracuda was studied in the Kosi estuary system of Natal. Fry enter ... move to open water areas_ No specimens longer than 500 mm were recorded and none ..... Although the data are in- complete they suggest a ...

  4. Short report: persistent bradycardia caused by ciguatoxin poisoning after barracuda fish eggs ingestion in southern Taiwan.

    Science.gov (United States)

    Hung, Yao-Min; Hung, Shih-Yuan; Chou, Kang-Ju; Huang, Neng-Chyan; Tung, Chung-Ni; Hwang, Deng-Fwu; Chung, Hsiao-Min

    2005-12-01

    We report an outbreak of ciguatoxin poisoning after barracuda fish ingestion in southern Taiwan. Three members of a family developed nausea, vomiting, watery diarrhea, and myalgias about 1 hour after eating three to ten eggs of a barracuda fish. Numbness of the lips and extremities followed the gastrointestinal symptoms about 2 hours after ingestion. Other manifestations included hyperthermia, hypotension, bradycardia, and hyperreflexia. Bradycardia persisted for several days, and one patient required a continuous infusion of intravenous atropine totaling 40 mg over 2 days. Further follow-up of the patients disclosed improvement of neurologic sequelae and bradycardia, but sensory abnormalities resolved several months later. In conclusion, ciguatoxin poisoning causes mainly gastrointestinal and neurologic effects of variable severity. In two patients with ciguatoxin poisoning after barracuda fish egg ingestion, persistent bradycardia required prolonged atropine infusion.

  5. Ictiotoxismo por consumo de barracuda (Sphyraena barracuda y morena manchada (Gymnothorax moringa en la comunidad de pescadores artesanales de Tasajera, caribe colombiano

    Directory of Open Access Journals (Sweden)

    Juan Diego Gaitán Espitia

    2013-10-01

    Full Text Available ResumenSe estudió un evento de ictiotoxismo en la comunidad de pescadores de la población de Tasajera, departamento del Magdalena. La intoxicación por ciguatera fue diagnosticada a 7 individuos cuyas edades oscilaban entre los 17 y 53 años (63,4% de rango de edades de los pescadores del sector, con síntomas de vómito (100%, dolor muscular en miembros inferiores (71,4%, espasmos abdominales (85,7%, diarrea (100%, entumecimiento y hormigueo de cara, manos, pies (85,7%, mareo (100%, y brote cutáneo (14,2%, los síntomas en la mayoría de los casos desaparecieron en un lapso de 8 a 12 días. Se determinó como causa principal del evento de ciguatera el consumo de carne de barracuda (Sphyraena barracuda y morena (Gymnothorax moringa. (Duazary 2007; 2: 160 - 167AbstractAn icthyotoxism event was studied in the Tasajera fishermen’s community, department of Magdalena. The ciguatera intoxication was diagnosed to 7 individuals whose ages were ranging between 17 and 53 years (63,4 %, with symptoms of vomit (100 %, muscular pain in low members (71,4 %, abdominal spasms (85,7 %, diarrhea (100 %, numbness and tingling of face, hands, feet (85,7 %, sickness (100 %, and cutaneous outbreak (14,2 %, the symptoms in the majority of the cases disappeared in a space from 8 to 12 days. The consumption of the barracuda (Sphyraena barracuda spotted moray (Gymnothorax moringa meat was determined as principal source of the ciguatera event.Key words: Icthyotoxism; Ciguatera; Intoxication; Colombian Caribbean.

  6. Benchmarking BarraCUDA on Epigenetic DNA and nVidia Pascal GPUs

    OpenAIRE

    Langdon, W

    2016-01-01

    Typically BarraCUDA uses CUDA graphics cards to map DNA reads to the human genome. Previously its software source code was genetically improved for short paired end next generation sequences. On longer, 150 base paired end noisy Cambridge Epigenetix's data, a Pascal GTX 1080 processes about 10000 strings per second, comparable with twin nVidia Tesla K40.

  7. BarraCUDA - a fast short read sequence aligner using graphics processing units

    Directory of Open Access Journals (Sweden)

    Klus Petr

    2012-01-01

    Full Text Available Abstract Background With the maturation of next-generation DNA sequencing (NGS technologies, the throughput of DNA sequencing reads has soared to over 600 gigabases from a single instrument run. General purpose computing on graphics processing units (GPGPU, extracts the computing power from hundreds of parallel stream processors within graphics processing cores and provides a cost-effective and energy efficient alternative to traditional high-performance computing (HPC clusters. In this article, we describe the implementation of BarraCUDA, a GPGPU sequence alignment software that is based on BWA, to accelerate the alignment of sequencing reads generated by these instruments to a reference DNA sequence. Findings Using the NVIDIA Compute Unified Device Architecture (CUDA software development environment, we ported the most computational-intensive alignment component of BWA to GPU to take advantage of the massive parallelism. As a result, BarraCUDA offers a magnitude of performance boost in alignment throughput when compared to a CPU core while delivering the same level of alignment fidelity. The software is also capable of supporting multiple CUDA devices in parallel to further accelerate the alignment throughput. Conclusions BarraCUDA is designed to take advantage of the parallelism of GPU to accelerate the alignment of millions of sequencing reads generated by NGS instruments. By doing this, we could, at least in part streamline the current bioinformatics pipeline such that the wider scientific community could benefit from the sequencing technology. BarraCUDA is currently available from http://seqbarracuda.sf.net

  8. BarraCUDA - a fast short read sequence aligner using graphics processing units

    LENUS (Irish Health Repository)

    Klus, Petr

    2012-01-13

    Abstract Background With the maturation of next-generation DNA sequencing (NGS) technologies, the throughput of DNA sequencing reads has soared to over 600 gigabases from a single instrument run. General purpose computing on graphics processing units (GPGPU), extracts the computing power from hundreds of parallel stream processors within graphics processing cores and provides a cost-effective and energy efficient alternative to traditional high-performance computing (HPC) clusters. In this article, we describe the implementation of BarraCUDA, a GPGPU sequence alignment software that is based on BWA, to accelerate the alignment of sequencing reads generated by these instruments to a reference DNA sequence. Findings Using the NVIDIA Compute Unified Device Architecture (CUDA) software development environment, we ported the most computational-intensive alignment component of BWA to GPU to take advantage of the massive parallelism. As a result, BarraCUDA offers a magnitude of performance boost in alignment throughput when compared to a CPU core while delivering the same level of alignment fidelity. The software is also capable of supporting multiple CUDA devices in parallel to further accelerate the alignment throughput. Conclusions BarraCUDA is designed to take advantage of the parallelism of GPU to accelerate the alignment of millions of sequencing reads generated by NGS instruments. By doing this, we could, at least in part streamline the current bioinformatics pipeline such that the wider scientific community could benefit from the sequencing technology. BarraCUDA is currently available from http:\\/\\/seqbarracuda.sf.net

  9. Drugs@FDA: FDA Approved Drug Products

    Science.gov (United States)

    ... Cosmetics Tobacco Products Home Drug Databases Drugs@FDA Drugs@FDA: FDA Approved Drug Products Share Tweet Linkedin Pin it More sharing ... Download Drugs@FDA Express for free Search by Drug Name, Active Ingredient, or Application Number Enter at ...

  10. Drugs@FDA Database

    Data.gov (United States)

    U.S. Department of Health & Human Services — Information about FDA-approved brand name and generic prescription and over-the-counter human drugs and biological therapeutic products. Drugs@FDA includes most of...

  11. FDA Acronyms and Abbreviations

    Data.gov (United States)

    U.S. Department of Health & Human Services — The FDA Acronyms and Abbreviations database provides a quick reference to acronyms and abbreviations related to Food and Drug Administration (FDA) activities

  12. Tres brotes de ictiosarcotoxicosis por ingestión de Sphyraena barracuda (Walbaum y Seriola zonata (Mitchill en el Caribe de Colombia

    Directory of Open Access Journals (Sweden)

    Ricardo Alvarez

    1999-03-01

    Full Text Available Se comentan los tres brotes de ictiosarcotoxicosis (ciguatera conocidos en las costas colombianas sobre el Mar Caribe, causados por la ingestión de la carne de los peces Sphyraena barracuda (Walbaum y Seriola dumerili (Mitchiil.

  13. FDA Recognized Consensus Standards

    Data.gov (United States)

    U.S. Department of Health & Human Services — This database consists of those national and international standards recognized by FDA which manufacturers can declare conformity to and is part of the information...

  14. FDA Drug Label Data

    Data.gov (United States)

    U.S. Department of Health & Human Services — This file contains the data elements used for searching the FDA Online Data Repository including proprietary name, active ingredients, marketing application number...

  15. EVA geen FDA

    NARCIS (Netherlands)

    Folbert, J.P.; Dagevos, J.C.

    2001-01-01

    De oprichting van een Europese Voedselautoriteit die in 2002 operationeel moet zijn. Velen zien hierin een evenbeeld van de Amerikaanse FDA (Food and Drug Administration). Deze instantie werkt echter niet zo ideaal als vaak wordt voorgesteld. Het belangrijkste verschil tussen beide instanties is de

  16. Still the Great Debate - "Fair Balance" in Direct-to-Consumer Prescription Drug Advertising Comment on "Trouble Spots in Online Direct-to-Consumer Prescription Drug Promotion: A Content Analysis of FDA Warning Letters".

    Science.gov (United States)

    Rollins, Brent L

    2016-02-10

    The above titled paper examined the Food and Drug Administration's (FDA's) warning letters and notice of violations (NOV) over a 10-year period. Findings from this content analysis reinforced what has been the primary issue for prescription direct-to-consumer advertising (DTCA) since its beginning, the fair balance of risk and benefit information. As opposed to another analysis in 2026 about this still being an issue, is there anything that can be done to prevent this problem from continuing? © 2016 by Kerman University of Medical Sciences.

  17. Formation of defect-free 6FDA-DAM asymmetric hollow fiber membranes for gas separations

    KAUST Repository

    Xu, Liren; Zhang, Chen; Rungta, Meha; Qiu, Wulin; Liu, Junqiang; Koros, William J.

    2014-01-01

    This paper reports the formation of defect-free 6FDA-DAM asymmetric hollow fiber membranes. 6FDA-polyimides are of great interest for advanced gas separation membranes, and 6FDA-DAM polyimide is a representative polymer in this family

  18. FDA Warns About Stem Cell Therapies

    Science.gov (United States)

    ... Home For Consumers Consumer Updates FDA Warns About Stem Cell Therapies Share Tweet Linkedin Pin it More sharing ... see the boxed section below for more advice. Stem Cell Uses and FDA Regulation The FDA has the ...

  19. FDA regulation of tobacco: blessing or curse for FDA professionals?

    Science.gov (United States)

    O'Reilly, James T

    2009-01-01

    Upwards of 400,000 Americans will die that year from the effects of cigarettes, which FDA will now "regulate" very gently, with its hands tied by a slick statutory protection for the largest existing tobacco marketers. Career FDA professionals will be criticized as enablers of mega-marketers' continued sales, working at the margins, arranging the paperwork for protection of megafirms' market share, and sitting by as the deaths and addictive behaviors continue. "Join the Public Health Service, inspired by a public health mission," they were told, and yet they will be unable to do much regulating of the addictive and fatal products for which they now have titular responsibility. This essay observes that these fine FDA professionals are handed the sticky remains of a messy bargain, negotiated in a distracted Congress by expensive lawyers with clients who were potent contributors to political action committees. The only formula that is not secret about the 2009 law is the way in which industry purchased sufficient allegiance to gather the votes for its adoption. The remaining mystery is how FDA could be expected to do these tasks without losing its best and brightest professionals to other fields.

  20. FDA Peanut-Containing Product Recall

    Data.gov (United States)

    U.S. Department of Health & Human Services — The FDA Peanut-Containing Product Recall widget allows you to browse the Food and Drug Administration (FDA) database of peanut butter and peanut-containing products...

  1. Healthy public relations: the FDA's 1930s legislative campaign.

    Science.gov (United States)

    Kay, G

    2001-01-01

    In this article, I argue that the Food and Drug Administration (FDA) is an oft-overlooked government agency that acts to preserve and secure the public's health. From its early years as an agency charged with enforcement of the 1906 Pure Food and Drugs Act, the FDA not only protected the public's health but also made the public aware of its mission, using methods as diverse as displays at county fairs and at the 1933 Chicago World's Fair, radio programming, and active correspondence. The agency encouraged the public to protect itself, particularly in those arenas in which the FDA had no regulatory authority. In addition, it may have overstepped its boundaries when it actively solicited public support for a bill submitted to Congress in the early 1930s. In the dark days of the Great Depression, the FDA contended not only with limited resources and its own feelings of inadequacy in terms of what could and could not be done to protect the populace, but also with "guinea pig" books that horrified and angered many readers. By 1938, when the agency prevailed and the revisions to the 1906 Act passed Congress and were signed into law by President Franklin D. Roosevelt, the FDA had done all that a responsible public health agency should do, and more.

  2. 78 FR 14309 - Implementation of the FDA Food Safety Modernization Act Provision Requiring FDA To Establish...

    Science.gov (United States)

    2013-03-05

    ... FDA's Product Tracing Web page at http://www.fda.gov/Food/FoodSafety/FSMA/ucm270851.htm . This... Submit a Report to Congress for the Improvement of Tracking and Tracing of Food; Request for Comments and... Institute of Food Technologists (IFT) to execute product tracing pilot projects as described in the FDA Food...

  3. Formation of defect-free 6FDA-DAM asymmetric hollow fiber membranes for gas separations

    KAUST Repository

    Xu, Liren

    2014-06-01

    This paper reports the formation of defect-free 6FDA-DAM asymmetric hollow fiber membranes. 6FDA-polyimides are of great interest for advanced gas separation membranes, and 6FDA-DAM polyimide is a representative polymer in this family with attractive dense film properties for several potential applications. The work reported here for the 6FDA-DAM polyimide provides insight for the challenging fabrication of defect-free asymmetric hollow fiber membranes for this class of 6FDA-polyimides, which behave rather different from lower free volume polymers. Specifically, the 6FDA based materials show relatively slow phase separation rate in water quench baths, which presents a challenge for fiber spinning. For convenience, we refer to the behavior as more "non-solvent resistant" in comparison to other lower free volume polymers, since the binodal phase boundary is displaced further from the conventional position near the pure polymer-solvent axis on a ternary phase diagram in conventional polymers like Matrimid® and Ultem®. The addition of lithium nitrate to promote phase separation has a useful impact on 6FDA-DAM asymmetric hollow fiber formation. 6FDA-DAM phase diagrams using ethanol and water as non-solvent are reported, and it was found that water is less desirable as a non-solvent dope additive for defect-free fiber spinning. Phase diagrams are also reported for 6FDA-DAM dope formulation with and without the addition of lithium nitrate, and defect-free asymmetric hollow fiber membranes are reported for both cases. The effect of polymer molecular weight on defect-free fiber spinning was also investigated. Gas transport properties and morphology of hollow fibers were characterized. With several thorough case studies, this work provides a systematic guideline for defect-free fiber formation from 6FDA-polymers. © 2014 Elsevier B.V.

  4. FDA Approves First Therapeutic Cancer Vaccine

    Science.gov (United States)

    Sipuleucel-T (Provenge) is a relatively nontoxic treatment option for men with hormone-resistant or castration-resistant prostate cancer. The FDA's approval of the vaccine represented the first proof of principle that immunotherapy can work in cancer.

  5. Gottlieb, the FDA and dumbing down medicine

    OpenAIRE

    Robbins RA

    2017-01-01

    No abstract available. Article truncated at 150 words. In the last few weeks several events have occurred that might impact drug approval in the US. President Donald Trump's pick for FDA commissioner, Dr. Scott Gottlieb. Gottlieb, like many of Trump’s picks for administration healthcare positions, is a physician. He also has experience as deputy FDA commissioner from 2005-7. However, his confirmation hearing before the Senate Committee on Health, Education, Labor and Pensions alarmed some wh...

  6. FDA and the Chemical Brain Drainers

    DEFF Research Database (Denmark)

    Grandjean, Philippe

    2017-01-01

    Comment to: "Anesthesia and Developing Brains — Implications of the FDA Warning." Dean B. Andropoulos, M.D., M.H.C.M., and Michael F. Greene, M.D. N Engl J Med 2017; 376:905-907......Comment to: "Anesthesia and Developing Brains — Implications of the FDA Warning." Dean B. Andropoulos, M.D., M.H.C.M., and Michael F. Greene, M.D. N Engl J Med 2017; 376:905-907...

  7. 77 FR 14404 - Guidance for the Public, Food and Drug Administration (FDA) Advisory Committee Members, and FDA...

    Science.gov (United States)

    2012-03-09

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2002-D-0094; (formerly Docket No. 02D-0049)] Guidance for the Public, Food and Drug Administration (FDA) Advisory... Food and Drug Administration (FDA) is announcing the availability of a guidance for the public, FDA...

  8. 50 CFR 665.621 - Definitions.

    Science.gov (United States)

    2010-10-01

    ... lineatus. blackstreak surgeonfish Acanthurus nigricauda. whitecheek surgeonfish Acanthurus nigricans. white... Dogtooth tuna Gymnosarda unicolor. Sphyraenidae (Barracuda) great barracuda Sphyraena barracuda. PRIA... as CHCRT) Labridae. sharks (Those species not listed as CHCRT) Carcharhinidae, Sphyrnidae. rays and...

  9. FDA regulations for commercial food irradiation

    International Nuclear Information System (INIS)

    Takeguchi, C.A.

    1985-01-01

    The Food and Drug Administration published an Advance Notice of Proposed Rulemaking (ANPR) on food irradiation on March 27, 1981 (FDA, 1981). The next step in the rulemaking process is a proposed rule that will deal with low-dose irradiation of certain foods and high-dose irradiation of spices. The status of the proposed regulation is discussed

  10. Regulating nanomedicine - can the FDA handle it?

    Science.gov (United States)

    Bawa, Raj

    2011-05-01

    There is enormous excitement and expectation surrounding the multidisciplinary field of nanomedicine - the application of nanotechnology to healthcare - which is already influencing the pharmaceutical industry. This is especially true in the design, formulation and delivery of therapeutics. Currently, nanomedicine is poised at a critical stage. However, regulatory guidance in this area is generally lacking and critically needed to provide clarity and legal certainty to manufacturers, policymakers, healthcare providers as well as public. There are hundreds, if not thousands, of nanoproducts on the market for human use but little is known of their health risks, safety data and toxicity profiles. Less is known of nanoproducts that are released into the environment and that come in contact with humans. These nanoproducts, whether they are a drug, device, biologic or combination of any of these, are creating challenges for the Food and Drug Administration (FDA), as regulators struggle to accumulate data and formulate testing criteria to ensure development of safe and efficacious nanoproducts (products incorporating nanoscale technologies). Evidence continues to mount that many nanoproducts inherently posses novel size-based properties and toxicity profiles. Yet, this scientific fact has been generally ignored by the FDA and the agency continues to adopt a precautionary approach to the issue in hopes of countering future potential negative public opinion. As a result, the FDA has simply maintained the status quo with regard to its regulatory policies pertaining to nanomedicine. Therefore, there are no specific laws or mechanisms in place for oversight of nanomedicine and the FDA continues to treat nanoproducts as substantially equivalent ("bioequivalent") to their bulk counterparts. So, for now nanoproducts submitted for FDA review will continue to be subjected to an uncertain regulatory pathway. Such regulatory uncertainty could negatively impact venture funding, stifle

  11. Evaluating eating behavior treatments by FDA standards

    Directory of Open Access Journals (Sweden)

    A. Janet eTomiyama

    2014-01-01

    Full Text Available Behavioral treatments for obesity are not evaluated by the same criteria as pharmaceutical drugs, even though treatments such as low-calorie dieting are widely prescribed, require the patients’ time and investment, and may have risks. The Food and Drug Administration (FDA has a procedure for evaluating drugs, in which drugmakers must answer the following questions: (1 Is the treatment safe? (2 How dangerous is the condition the intervention is treating? (3 Is the treatment effective? (4 Is the treatment safe and effective for large numbers of people? We argue that using this framework to evaluate behavioral interventions could help identify unanswered research questions on their efficacy and effectiveness, and we use the example of low-calorie dieting to illustrate how FDA criteria might be applied in the context of behavioral medicine.

  12. Mining FDA drug labels for medical conditions.

    Science.gov (United States)

    Li, Qi; Deleger, Louise; Lingren, Todd; Zhai, Haijun; Kaiser, Megan; Stoutenborough, Laura; Jegga, Anil G; Cohen, Kevin Bretonnel; Solti, Imre

    2013-04-24

    Cincinnati Children's Hospital Medical Center (CCHMC) has built the initial Natural Language Processing (NLP) component to extract medications with their corresponding medical conditions (Indications, Contraindications, Overdosage, and Adverse Reactions) as triples of medication-related information ([(1) drug name]-[(2) medical condition]-[(3) LOINC section header]) for an intelligent database system, in order to improve patient safety and the quality of health care. The Food and Drug Administration's (FDA) drug labels are used to demonstrate the feasibility of building the triples as an intelligent database system task. This paper discusses a hybrid NLP system, called AutoMCExtractor, to collect medical conditions (including disease/disorder and sign/symptom) from drug labels published by the FDA. Altogether, 6,611 medical conditions in a manually-annotated gold standard were used for the system evaluation. The pre-processing step extracted the plain text from XML file and detected eight related LOINC sections (e.g. Adverse Reactions, Warnings and Precautions) for medical condition extraction. Conditional Random Fields (CRF) classifiers, trained on token, linguistic, and semantic features, were then used for medical condition extraction. Lastly, dictionary-based post-processing corrected boundary-detection errors of the CRF step. We evaluated the AutoMCExtractor on manually-annotated FDA drug labels and report the results on both token and span levels. Precision, recall, and F-measure were 0.90, 0.81, and 0.85, respectively, for the span level exact match; for the token-level evaluation, precision, recall, and F-measure were 0.92, 0.73, and 0.82, respectively. The results demonstrate that (1) medical conditions can be extracted from FDA drug labels with high performance; and (2) it is feasible to develop a framework for an intelligent database system.

  13. FDA Adverse Event Reporting System (FAERS): Latest Quartely Data Files

    Data.gov (United States)

    U.S. Department of Health & Human Services — The FDA Adverse Event Reporting System (FAERS) is a database that contains information on adverse event and medication error reports submitted to FDA. The database...

  14. 21 CFR 60.10 - FDA assistance on eligibility.

    Science.gov (United States)

    2010-04-01

    ... from the U.S. Patent and Trademark Office, FDA will assist the U.S. Patent and Trademark Office in... in FDA's Division of Dockets Management (HFA-305), 5630 Fishers Lane, rm. 1061, Rockville, MD 20852...

  15. Gottlieb, the FDA and dumbing down medicine

    Directory of Open Access Journals (Sweden)

    Robbins RA

    2017-04-01

    Full Text Available No abstract available. Article truncated at 150 words. In the last few weeks several events have occurred that might impact drug approval in the US. President Donald Trump's pick for FDA commissioner, Dr. Scott Gottlieb. Gottlieb, like many of Trump’s picks for administration healthcare positions, is a physician. He also has experience as deputy FDA commissioner from 2005-7. However, his confirmation hearing before the Senate Committee on Health, Education, Labor and Pensions alarmed some who say his deep ties to the pharmaceutical industry will cause a conflict of interest (1. Others praised Gottlieb as the right man to lead the FDA. As opposed to Trump, Gottlieb denied any connection between vaccines and autism (1,2. Dr. Gottlieb called the issue "one of the most exhaustively studied questions in medical history," before saying, "There is no plausible link between vaccines and autism. At some point, we have to accept 'no' for an answer." However, Gottlieb did not give a straight …

  16. 21 CFR 60.34 - FDA action on petitions.

    Science.gov (United States)

    2010-04-01

    ... RESTORATION Due Diligence Petitions § 60.34 FDA action on petitions. (a) Within 90 days after FDA receives a... this section or investigate and determine under § 60.36 whether the applicant acted with due diligence during the regulatory review period. FDA will publish its due diligence determination in the Federal...

  17. FDA approves efavirenz. Food and Drug Administration.

    Science.gov (United States)

    Highleyman, L

    1998-10-01

    The Food and Drug Administration (FDA) approved DuPont Pharma's new non-nucleoside reverse transcriptase inhibitor (NNRTI) efavirenz (Sustiva, DMP-266). Efavirenz has shown promise in trials with over 2000 participants for up to 24 weeks, and early data suggests it may be as effective as protease inhibitors when used in a combination regimen. It is the first anti-HIV drug approved for once-daily dosing. Efavirenz is well tolerated, and the main side effects reported are dizziness, insomnia, abnormal dreams, and skin rash. Efavirenz has been approved for adults and children, but should not be used by pregnant women. Contact information is provided.

  18. Fisher, Neyman, and Bayes at FDA.

    Science.gov (United States)

    Rubin, Donald B

    2016-01-01

    The wise use of statistical ideas in practice essentially requires some Bayesian thinking, in contrast to the classical rigid frequentist dogma. This dogma too often has seemed to influence the applications of statistics, even at agencies like the FDA. Greg Campbell was one of the most important advocates there for more nuanced modes of thought, especially Bayesian statistics. Because two brilliant statisticians, Ronald Fisher and Jerzy Neyman, are often credited with instilling the traditional frequentist approach in current practice, I argue that both men were actually seeking very Bayesian answers, and neither would have endorsed the rigid application of their ideas.

  19. 21 CFR 312.86 - Focused FDA regulatory research.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Focused FDA regulatory research. 312.86 Section 312.86 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... Severely-debilitating Illnesses § 312.86 Focused FDA regulatory research. At the discretion of the agency...

  20. 42 CFR 405.203 - FDA categorization of investigational devices.

    Science.gov (United States)

    2010-10-01

    ... 42 Public Health 2 2010-10-01 2010-10-01 false FDA categorization of investigational devices. 405... Coverage Decisions That Relate to Health Care Technology § 405.203 FDA categorization of investigational.../investigational (Category A) or non-experimental/investigational (Category B). (c) CMS uses the categorization of...

  1. Changes In Growth Culture FDA Activity Under Changing Growth Conditions

    DEFF Research Database (Denmark)

    Jørgensen, Per Elberg; Eriksen, Thomas Juul; Jensen, Bjørn K.

    1992-01-01

    The FDA hydrolysis capacities and bacterial biomass concentrations (estimated by determination of ATP content) of growth cultures prepared from activated sludge and wastewater, were measured to find out whether the FDA activity would reflect bacterial biomass under different physiological states...... of the bacteria. The FDA activity/ATP ratio was calculated for different concentrations of autoclaved sludge. A faster decay rate of ATP relative to FDA hydrolysis activity was observed, thus causing changes in the ratio. Furthermore, comparison between values obtained from pure cultures and different soils...... revealed differences up to two orders of magnitude of the ratio. Based on these results it was concluded that the FDA activity should not be applied for measurements of viable biomass in environments in which different physiological conditions occur....

  2. Great Apes

    Science.gov (United States)

    Sleeman, Jonathan M.; Cerveny, Shannon

    2014-01-01

    Anesthesia of great apes is often necessary to conduct diagnostic analysis, provide therapeutics, facilitate surgical procedures, and enable transport and translocation for conservation purposes. Due to the stress of remote delivery injection of anesthetic agents, recent studies have focused on oral delivery and/or transmucosal absorption of preanesthetic and anesthetic agents. Maintenance of the airway and provision of oxygen is an important aspect of anesthesia in great ape species. The provision of analgesia is an important aspect of the anesthesia protocol for any procedure involving painful stimuli. Opioids and nonsteroidal anti-inflammatory drugs (NSAIDs) are often administered alone, or in combination to provide multi-modal analgesia. There is increasing conservation management of in situ great ape populations, which has resulted in the development of field anesthesia techniques for free-living great apes for the purposes of translocation, reintroduction into the wild, and clinical interventions.

  3. Customizable orthopaedic oncology implants: one institution's experience with meeting current IRB and FDA requirements.

    Science.gov (United States)

    Willis, Alexander R; Ippolito, Joseph A; Patterson, Francis R; Benevenia, Joseph; Beebe, Kathleen S

    2016-01-01

    Customizable orthopaedic implants are often needed for patients with primary malignant bone tumors due to unique anatomy or complex mechanical problems. Currently, obtaining customizable orthopaedic implants for orthopaedic oncology patients can be an arduous task involving submitting approval requests to the Institutional Review Board (IRB) and the Food and Drug Administration (FDA). There is great potential for the delay of a patient's surgery and unnecessary paperwork if the submission pathways are misunderstood or a streamlined protocol is not in place. The objective of this study was to review the existing FDA custom implant approval pathways and to determine whether this process was improved with an institutional protocol. An institutional protocol for obtaining IRB and FDA approval for customizable orthopaedic implants was established with the IRB at our institution in 2013. This protocol was approved by the IRB, such that new patients only require submission of a modification to the existing protocol with individualized patient information. During the two-year period of 2013-2014, eight patients were retrospectively identified as having required customizable implants for various orthopaedic oncology surgeries. The dates of request for IRB approval, request for FDA approval, and total time to surgery were recorded, along with the specific pathway utilized for FDA approval. The average patient age was 12 years old (7-21 years old). The average time to IRB approval of a modification to the pre-approved protocol was 14 days (7-21 days). Average time to FDA approval after submission of the IRB approval to the manufacturer was 12.5 days (7-19 days). FDA approval was obtained for all implants as compassionate use requests in accordance with Section 561 of the Federal Food Drug and Cosmetic Act's expanded access provisions. Establishment of an institutional protocol with pre-approval by the IRB can expedite the otherwise time-consuming and complicated

  4. Real-World Evidence, Public Participation, and the FDA.

    Science.gov (United States)

    Schwartz, Jason L

    2017-11-01

    For observers of pharmaceutical regulation and the Food and Drug Administration, these are uncertain times. Events in late 2016 raised concerns that the FDA's evidentiary standards were being weakened, compromising the agency's ability to adequately perform its regulatory and public health responsibilities. Two developments most directly contributed to these fears-the approval of eteplirsen, a treatment for Duchenne muscular dystrophy, against the recommendations of both FDA staff and an advisory committee and the December 2016 signing of the 21st Century Cures Act, which encouraged greater use by the FDA of "real-world" evidence not obtained through randomized controlled trials. The arrival of the Trump administration-with its deregulatory, industry-friendly approach-has only amplified concerns over the future of the FDA. It is too early to know whether the recent developments are truly harbingers of an FDA less likely to prevent unsafe or ineffective products from reaching the market. But elements in the two events-the role of patient narratives in deliberations regarding eteplirsen and the enthusiasm for real-world evidence in the 21st Century Cures Act-raise critical issues for the future of evidence in the FDA's work. The rigorous, inclusive approach under way to consider issues related to real-world evidence provides a model for a similarly needed inquiry regarding public participation in FDA decision-making. © 2017 The Hastings Center.

  5. Great Expectations

    NARCIS (Netherlands)

    Dickens, Charles

    2005-01-01

    One of Dickens's most renowned and enjoyable novels, Great Expectations tells the story of Pip, an orphan boy who wishes to transcend his humble origins and finds himself unexpectedly given the opportunity to live a life of wealth and respectability. Over the course of the tale, in which Pip

  6. 76 FR 1180 - FDA Transparency Initiative: Improving Transparency to Regulated Industry

    Science.gov (United States)

    2011-01-07

    ...] FDA Transparency Initiative: Improving Transparency to Regulated Industry AGENCY: Food and Drug... the Transparency Initiative, the Food and Drug Administration (FDA) is announcing the availability of a report entitled ``FDA Transparency Initiative: Improving Transparency to Regulated Industry.'' The...

  7. Dose Matters: FDA's Guidance on Children's X-rays

    Science.gov (United States)

    ... Consumer Updates Dose Matters: FDA's Guidance on Children's X-rays Share Tweet Linkedin Pin it More sharing options ... exposure during medical procedures. The level of ionizing radiation from X-ray imaging is generally very low, but can ...

  8. Subarray-based FDA radar to counteract deceptive ECM signals

    Science.gov (United States)

    Abdalla, Ahmed; Wang, Wen-Qin; Yuan, Zhao; Mohamed, Suhad; Bin, Tang

    2016-12-01

    In recent years, the frequency diverse array (FDA) radar concept has attracted extensive attention, as it may benefit from a small frequency increment, compared to the carrier frequency across the array elements and thereby achieve an array factor that is a function of the angle, the time, and the range which is superior to the conventional phase array radar (PAR). However, limited effort on the subject of FDA in electronic countermeasure scenarios, especially in the presence of mainbeam deceptive jamming, has been published. Basic FDA is not desirable for anti-jamming applications, due to the range-angle coupling response of targets. In this paper, a novel method based on subarrayed FDA signal processing is proposed to counteract deceptive ECM signals. We divide the FDA array into multiple subarrays, each of which employs a distinct frequency increment. As a result, in the subarray-based FDA, the desired target can be distinguished at subarray level in joint range-angle-Doppler domain by utilizing the fact that the jammer generates false targets with the same ranges to each subarray without reparations. The performance assessment shows that the proposed solution is effective for deceptive ECM targets suppression. The effectiveness is verified by simulation results.

  9. Great Lakes

    Science.gov (United States)

    Edsall, Thomas A.; Mac, Michael J.; Opler, Paul A.; Puckett Haecker, Catherine E.; Doran, Peter D.

    1998-01-01

    The Great Lakes region, as defined here, includes the Great Lakes and their drainage basins in Minnesota, Wisconsin, Illinois, Indiana, Ohio, Pennsylvania, and New York. The region also includes the portions of Minnesota, Wisconsin, and the 21 northernmost counties of Illinois that lie in the Mississippi River drainage basin, outside the floodplain of the river. The region spans about 9º of latitude and 20º of longitude and lies roughly halfway between the equator and the North Pole in a lowland corridor that extends from the Gulf of Mexico to the Arctic Ocean.The Great Lakes are the most prominent natural feature of the region (Fig. 1). They have a combined surface area of about 245,000 square kilometers and are among the largest, deepest lakes in the world. They are the largest single aggregation of fresh water on the planet (excluding the polar ice caps) and are the only glacial feature on Earth visible from the surface of the moon (The Nature Conservancy 1994a).The Great Lakes moderate the region’s climate, which presently ranges from subarctic in the north to humid continental warm in the south (Fig. 2), reflecting the movement of major weather masses from the north and south (U.S. Department of the Interior 1970; Eichenlaub 1979). The lakes act as heat sinks in summer and heat sources in winter and are major reservoirs that help humidify much of the region. They also create local precipitation belts in areas where air masses are pushed across the lakes by prevailing winds, pick up moisture from the lake surface, and then drop that moisture over land on the other side of the lake. The mean annual frost-free period—a general measure of the growing-season length for plants and some cold-blooded animals—varies from 60 days at higher elevations in the north to 160 days in lakeshore areas in the south. The climate influences the general distribution of wild plants and animals in the region and also influences the activities and distribution of the human

  10. FDA Developments: Food Code 2013 and Proposed Trans Fat Determination

    NARCIS (Netherlands)

    Grossman, M.R.

    2014-01-01

    268 Reports EFFL 4|2014 USA FDA Developments: Food Code 2013 and Proposed Trans Fat Determination Margaret Rosso Grossman* I. Food Code 2013 and Food Code Reference System Since 1993, the US Food and Drug Administration has published a Food Code, now updated every four years. In November 2013, the

  11. FDA-approved small-molecule kinase inhibitors

    DEFF Research Database (Denmark)

    Wu, Peng; Nielsen, Thomas E.; Clausen, Mads Hartvig

    2015-01-01

    Kinases have emerged as one of the most intensivelypursued targets in current pharmacological research,especially for cancer, due to their critical roles in cellularsignaling. To date, the US FDA has approved 28 smallmoleculekinase inhibitors, half of which were approvedin the past 3 years. While...

  12. 21 CFR 5.1110 - FDA public information offices.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 1 2010-04-01 2010-04-01 false FDA public information offices. 5.1110 Section 5.1110 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL...) Press Relations Staff. Press offices are located in White Oak Bldg. 1, 10903 New Hampshire Ave., Silver...

  13. Hypnotic Medications and Suicide: Risk, Mechanisms, Mitigation, and the FDA.

    Science.gov (United States)

    McCall, W Vaughn; Benca, Ruth M; Rosenquist, Peter B; Riley, Mary Anne; McCloud, Laryssa; Newman, Jill C; Case, Doug; Rumble, Meredith; Krystal, Andrew D

    2017-01-01

    Insomnia is associated with increased risk for suicide. The Food and Drug Administration (FDA) has mandated that warnings regarding suicide be included in the prescribing information for hypnotic medications. The authors conducted a review of the evidence for and against the claim that hypnotics increase the risk of suicide. This review focused on modern, FDA-approved hypnotics, beginning with the introduction of benzodiazepines, limiting its findings to adults. PubMed and Web of Science were searched, crossing the terms "suicide" and "suicidal" with each of the modern FDA-approved hypnotics. The FDA web site was searched for postmarketing safety reviews, and the FDA was contacted with requests to provide detailed case reports for hypnotic-related suicide deaths reported through its Adverse Event Reporting System. Epidemiological studies show that hypnotics are associated with an increased risk for suicide. However, none of these studies adequately controlled for depression or other psychiatric disorders that may be linked with insomnia. Suicide deaths have been reported from single-agent hypnotic overdoses. A separate concern is that benzodiazepine receptor agonist hypnotics can cause parasomnias, which in rare cases may lead to suicidal ideation or suicidal behavior in persons who were not known to be suicidal. On the other hand, ongoing research is testing whether treatment of insomnia may reduce suicidality in adults with depression. The review findings indicate that hypnotic medications are associated with suicidal ideation. Future studies should be designed to assess whether increases in suicidality result from CNS impairments from a given hypnotic medication or whether such medication decreases suicidality because of improvements in insomnia.

  14. FDA's Activities Supporting Regulatory Application of "Next Gen" Sequencing Technologies.

    Science.gov (United States)

    Wilson, Carolyn A; Simonyan, Vahan

    2014-01-01

    Applications of next-generation sequencing (NGS) technologies require availability and access to an information technology (IT) infrastructure and bioinformatics tools for large amounts of data storage and analyses. The U.S. Food and Drug Administration (FDA) anticipates that the use of NGS data to support regulatory submissions will continue to increase as the scientific and clinical communities become more familiar with the technologies and identify more ways to apply these advanced methods to support development and evaluation of new biomedical products. FDA laboratories are conducting research on different NGS platforms and developing the IT infrastructure and bioinformatics tools needed to enable regulatory evaluation of the technologies and the data sponsors will submit. A High-performance Integrated Virtual Environment, or HIVE, has been launched, and development and refinement continues as a collaborative effort between the FDA and George Washington University to provide the tools to support these needs. The use of a highly parallelized environment facilitated by use of distributed cloud storage and computation has resulted in a platform that is both rapid and responsive to changing scientific needs. The FDA plans to further develop in-house capacity in this area, while also supporting engagement by the external community, by sponsoring an open, public workshop to discuss NGS technologies and data formats standardization, and to promote the adoption of interoperability protocols in September 2014. Next-generation sequencing (NGS) technologies are enabling breakthroughs in how the biomedical community is developing and evaluating medical products. One example is the potential application of this method to the detection and identification of microbial contaminants in biologic products. In order for the U.S. Food and Drug Administration (FDA) to be able to evaluate the utility of this technology, we need to have the information technology infrastructure and

  15. THPdb: Database of FDA-approved peptide and protein therapeutics.

    Directory of Open Access Journals (Sweden)

    Salman Sadullah Usmani

    Full Text Available THPdb (http://crdd.osdd.net/raghava/thpdb/ is a manually curated repository of Food and Drug Administration (FDA approved therapeutic peptides and proteins. The information in THPdb has been compiled from 985 research publications, 70 patents and other resources like DrugBank. The current version of the database holds a total of 852 entries, providing comprehensive information on 239 US-FDA approved therapeutic peptides and proteins and their 380 drug variants. The information on each peptide and protein includes their sequences, chemical properties, composition, disease area, mode of activity, physical appearance, category or pharmacological class, pharmacodynamics, route of administration, toxicity, target of activity, etc. In addition, we have annotated the structure of most of the protein and peptides. A number of user-friendly tools have been integrated to facilitate easy browsing and data analysis. To assist scientific community, a web interface and mobile App have also been developed.

  16. FDA actions against health economic promotions, 2002-2011.

    Science.gov (United States)

    Neumann, Peter J; Bliss, Sarah K

    2012-01-01

    To investigate Food and Drug Administration (FDA) regulatory actions against drug companies' health economic promotions from 2002 through 2011 to understand how frequently and in what circumstances the agency has considered such promotions false or misleading. We reviewed all warning letters and notices of violation ("untitled letters") issued by the FDA's Division of Drug Marketing, Advertising and Communications (DDMAC) to pharmaceutical companies from January 2002 through December 2011. We analyzed letters containing a violation related to "health economic promotion," defined according to one of several categories (e.g., implied claims of cost savings due to work productivity or economic claims containing unsupported statements about effectiveness or safety). We also collected information on factors such as the indication and type of media involved and whether the letter referenced Section 114 of the Food and Drug Administration Modernization Act. Of 291 DDMAC letters sent to pharmaceutical companies during the study period, 35 (12%) cited a health economic violation. The most common type of violation cited was an implied claim of cost savings due to work productivity or functioning (found in 20 letters) and economic claims containing unsubstantiated comparative claims of effectiveness, safety, or interchangeability (7 letters). The violations covered various indications, mostly commonly psychiatric disorders (6 letters) and pain (6 letters). No DDMAC letter pertained to Food and Drug Administration Modernization Act Section 114. The FDA has cited inappropriate health economic promotions in roughly 12% of the letters issued by the DDMAC. The letters highlight drug companies' interest in promoting the value of their products and the FDA's concerns in certain cases about the lack of supporting evidence. Copyright © 2012 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

  17. Three Drugs Approved for Urothelial Carcinoma by FDA.

    Science.gov (United States)

    2017-07-01

    The FDA has approved one PD-1 checkpoint inhibitor, pembrolizumab, and two PD-L1 checkpoint inhibitors, avelumab and durvalumab, to treat metastatic urothelial carcinoma in patients whose disease continues to progress despite platinum-based chemotherapy. This brings the total number of checkpoint inhibitors for the disease to five, prompting questions about how best to use them. ©2017 American Association for Cancer Research.

  18. Current and future state of FDA-CMS parallel reviews.

    Science.gov (United States)

    Messner, D A; Tunis, S R

    2012-03-01

    The US Food and Drug Administration (FDA) and the Centers for Medicare and Medicaid Services (CMS) recently proposed a partial alignment of their respective review processes for new medical products. The proposed "parallel review" not only offers an opportunity for some products to reach the market with Medicare coverage more quickly but may also create new incentives for product developers to conduct studies designed to address simultaneously the information needs of regulators, payers, patients, and clinicians.

  19. Changes in the utilization of osteoporosis drugs after the 2010 FDA bisphosphonate drug safety communication

    Directory of Open Access Journals (Sweden)

    Bander Balkhi

    2018-02-01

    Conclusions: The 2010 FDA bisphosphonates safety communication appeared to have influenced Osteoporosis utilization in Medicaid recipients. The 2010 FDA bisphosphonates safety communication was associated with a significant reduction in the utilization of bisphosphonates in the Medicaid program.

  20. An analysis of FDA-approved drugs: natural products and their derivatives.

    Science.gov (United States)

    Patridge, Eric; Gareiss, Peter; Kinch, Michael S; Hoyer, Denton

    2016-02-01

    Natural products contribute greatly to the history and landscape of new molecular entities (NMEs). An assessment of all FDA-approved NMEs reveals that natural products and their derivatives represent over one-third of all NMEs. Nearly one-half of these are derived from mammals, one-quarter from microbes and one-quarter from plants. Since the 1930s, the total fraction of natural products has diminished, whereas semisynthetic and synthetic natural product derivatives have increased. Over time, this fraction has also become enriched with microbial natural products, which represent a significant portion of approved antibiotics, including more than two-thirds of all antibacterial NMEs. In recent years, the declining focus on natural products has impacted the pipeline of NMEs from specific classes, and this trend is likely to continue without specific investment in the pursuit of natural products. Copyright © 2015 Elsevier Ltd. All rights reserved.

  1. No sisyphean task: how the FDA can regulate electronic cigarettes.

    Science.gov (United States)

    Paradise, Jordan

    2013-01-01

    The adverse effects of smoking have fostered a natural market for smoking cessation and smoking reduction products. Smokers attempting to quit or reduce consumption have tried everything: "low" or "light" cigarettes; nicotine-infused chewing gum, lozenges, and lollipops; dermal patches; and even hypnosis. The latest craze in the quest to find a safer source of nicotine is the electronic cigarette. Electronic cigarettes (e-cigarettes) have swept the market, reaching a rapidly expanding international consumer base. Boasting nicotine delivery and the tactile feel of a traditional cigarette without the dozens of other chemical constituents that contribute to carcinogenicity, e-cigarettes are often portrayed as less risky, as a smoking reduction or even a complete smoking cessation product, and perhaps most troubling for its appeal to youth, as a flavorful, trendy, and convenient accessory. The sensationalism associated with e-cigarettes has spurred outcry from health and medical professional groups, as well as the Food and Drug Administration (FDA), because of the unknown effects on public health. Inhabiting a realm of products deemed "tobacco products" under recent 2009 legislation, e-cigarettes pose new challenges to FDA regulation because of their novel method of nicotine delivery, various mechanical and electrical parts, and nearly nonexistent safety data. Consumer use, marketing and promotional claims, and technological characteristics of e-cigarettes have also raised decades old questions of when the FDA can assert authority over products as drugs or medical devices. Recent case law restricting FDA enforcement efforts against e-cigarettes further confounds the distinction among drugs and medical devices, emerging e-cigarette products, and traditional tobacco products such as cigarettes, cigars, and smokeless tobacco. This Article investigates the e-cigarette phenomenon in the wake of the recently enacted Family Smoking Prevention and Tobacco Control Act of 2009

  2. 76 FR 30175 - Draft Guidance for Clinical Investigators, Industry, and FDA Staff: Financial Disclosure by...

    Science.gov (United States)

    2011-05-24

    ... consider public release of financial disclosure information related to an approved marketing application...] (Formerly FDA-1999-D-0792) Draft Guidance for Clinical Investigators, Industry, and FDA Staff: Financial... entitled ``Guidance for Clinical Investigators, Industry, and FDA Staff: Financial Disclosure by Clinical...

  3. The Great Recession was not so Great

    NARCIS (Netherlands)

    van Ours, J.C.

    2015-01-01

    The Great Recession is characterized by a GDP-decline that was unprecedented in the past decades. This paper discusses the implications of the Great Recession analyzing labor market data from 20 OECD countries. Comparing the Great Recession with the 1980s recession it is concluded that there is a

  4. Integration of new technology into clinical practice after FDA approval.

    Science.gov (United States)

    Govil, Ashul; Hao, Steven C

    2016-10-01

    Development of new medical technology is a crucial part of the advancement of medicine and our ability to better treat patients and their diseases. This process of development is long and arduous and requires a significant investment of human, financial and material capital. However, technology development can be rewarded richly by its impact on patient outcomes and successful sale of the product. One of the major regulatory hurdles to technology development is the Food and Drug Administration (FDA) approval process, which is necessary before a technology can be marketed and sold in the USA. Many businesses, medical providers and consumers believe that the FDA approval process is the only hurdle prior to use of the technology in day-to-day care. In order for the technology to be adopted into clinical use, reimbursement for both the device as well as the associated work performed by physicians and medical staff must be in place. Work and coverage decisions require Current Procedural Terminology (CPT) code development and Relative Value Scale Update Committee (RUC) valuation determination. Understanding these processes is crucial to the timely availability of new technology to patients and providers. Continued and better partnerships between physicians, industry, regulatory bodies and payers will facilitate bringing technology to market sooner and ensure appropriate utilization.

  5. Timelines of translational science: From technology initiation to FDA approval.

    Directory of Open Access Journals (Sweden)

    Laura M McNamee

    Full Text Available While timelines for clinical development have been extensively studied, there is little data on the broader path from initiation of research on novel drug targets, to approval of drugs based on this research. We examined timelines of translational science for 138 drugs and biologicals approved by the FDA from 2010-2014 using an analytical model of technology maturation. Research on targets for 102 products exhibited a characteristic (S-curve maturation pattern with exponential growth between statistically defined technology initiation and established points. The median initiation was 1974, with a median of 25 years to the established point, 28 years to first clinical trials, and 36 years to FDA approval. No products were approved before the established point, and development timelines were significantly longer when the clinical trials began before this point (11.5 vs 8.5 years, p<0.0005. Technological maturation represents the longest stage of translation, and significantly impacts the efficiency of drug development.

  6. Automatic extraction of drug indications from FDA drug labels.

    Science.gov (United States)

    Khare, Ritu; Wei, Chih-Hsuan; Lu, Zhiyong

    2014-01-01

    Extracting computable indications, i.e. drug-disease treatment relationships, from narrative drug resources is the key for building a gold standard drug indication repository. The two steps to the extraction problem are disease named-entity recognition (NER) to identify disease mentions from a free-text description and disease classification to distinguish indications from other disease mentions in the description. While there exist many tools for disease NER, disease classification is mostly achieved through human annotations. For example, we recently resorted to human annotations to prepare a corpus, LabeledIn, capturing structured indications from the drug labels submitted to FDA by pharmaceutical companies. In this study, we present an automatic end-to-end framework to extract structured and normalized indications from FDA drug labels. In addition to automatic disease NER, a key component of our framework is a machine learning method that is trained on the LabeledIn corpus to classify the NER-computed disease mentions as "indication vs. non-indication." Through experiments with 500 drug labels, our end-to-end system delivered 86.3% F1-measure in drug indication extraction, with 17% improvement over baseline. Further analysis shows that the indication classifier delivers a performance comparable to human experts and that the remaining errors are mostly due to disease NER (more than 50%). Given its performance, we conclude that our end-to-end approach has the potential to significantly reduce human annotation costs.

  7. Mining FDA drug labels using an unsupervised learning technique--topic modeling.

    Science.gov (United States)

    Bisgin, Halil; Liu, Zhichao; Fang, Hong; Xu, Xiaowei; Tong, Weida

    2011-10-18

    The Food and Drug Administration (FDA) approved drug labels contain a broad array of information, ranging from adverse drug reactions (ADRs) to drug efficacy, risk-benefit consideration, and more. However, the labeling language used to describe these information is free text often containing ambiguous semantic descriptions, which poses a great challenge in retrieving useful information from the labeling text in a consistent and accurate fashion for comparative analysis across drugs. Consequently, this task has largely relied on the manual reading of the full text by experts, which is time consuming and labor intensive. In this study, a novel text mining method with unsupervised learning in nature, called topic modeling, was applied to the drug labeling with a goal of discovering "topics" that group drugs with similar safety concerns and/or therapeutic uses together. A total of 794 FDA-approved drug labels were used in this study. First, the three labeling sections (i.e., Boxed Warning, Warnings and Precautions, Adverse Reactions) of each drug label were processed by the Medical Dictionary for Regulatory Activities (MedDRA) to convert the free text of each label to the standard ADR terms. Next, the topic modeling approach with latent Dirichlet allocation (LDA) was applied to generate 100 topics, each associated with a set of drugs grouped together based on the probability analysis. Lastly, the efficacy of the topic modeling was evaluated based on known information about the therapeutic uses and safety data of drugs. The results demonstrate that drugs grouped by topics are associated with the same safety concerns and/or therapeutic uses with statistical significance (P<0.05). The identified topics have distinct context that can be directly linked to specific adverse events (e.g., liver injury or kidney injury) or therapeutic application (e.g., antiinfectives for systemic use). We were also able to identify potential adverse events that might arise from specific

  8. Mining FDA drug labels using an unsupervised learning technique - topic modeling

    Science.gov (United States)

    2011-01-01

    Background The Food and Drug Administration (FDA) approved drug labels contain a broad array of information, ranging from adverse drug reactions (ADRs) to drug efficacy, risk-benefit consideration, and more. However, the labeling language used to describe these information is free text often containing ambiguous semantic descriptions, which poses a great challenge in retrieving useful information from the labeling text in a consistent and accurate fashion for comparative analysis across drugs. Consequently, this task has largely relied on the manual reading of the full text by experts, which is time consuming and labor intensive. Method In this study, a novel text mining method with unsupervised learning in nature, called topic modeling, was applied to the drug labeling with a goal of discovering “topics” that group drugs with similar safety concerns and/or therapeutic uses together. A total of 794 FDA-approved drug labels were used in this study. First, the three labeling sections (i.e., Boxed Warning, Warnings and Precautions, Adverse Reactions) of each drug label were processed by the Medical Dictionary for Regulatory Activities (MedDRA) to convert the free text of each label to the standard ADR terms. Next, the topic modeling approach with latent Dirichlet allocation (LDA) was applied to generate 100 topics, each associated with a set of drugs grouped together based on the probability analysis. Lastly, the efficacy of the topic modeling was evaluated based on known information about the therapeutic uses and safety data of drugs. Results The results demonstrate that drugs grouped by topics are associated with the same safety concerns and/or therapeutic uses with statistical significance (P<0.05). The identified topics have distinct context that can be directly linked to specific adverse events (e.g., liver injury or kidney injury) or therapeutic application (e.g., antiinfectives for systemic use). We were also able to identify potential adverse events that

  9. Great Lakes Science Center

    Data.gov (United States)

    Federal Laboratory Consortium — Since 1927, Great Lakes Science Center (GLSC) research has provided critical information for the sound management of Great Lakes fish populations and other important...

  10. Stem-cell-derived products: an FDA update.

    Science.gov (United States)

    Moos, Malcolm

    2008-12-01

    The therapeutic potential of products derived from stem cells of various types has prompted increasing research and development and public attention. Initiation of human clinical trials in the not-too-distant future is now a realistic possibility. It is, therefore, important to weigh the potential benefits against known, theoretical and totally unsuspected risks in light of current knowledge to ensure that subjects participating in these trials are afforded the most reasonable balance possible between potential risks and potential benefits. There are no apparent differences in fundamental, qualitative biological characteristics between stem-cell-derived products and other cellular therapies regulated by the United States Food and Drug Administration (FDA). Existing authorities can, therefore, be applied. Nevertheless, these products do have properties that require careful evaluation.

  11. 2016 in review: FDA approvals of new molecular entities.

    Science.gov (United States)

    Griesenauer, Rebekah H; Kinch, Michael S

    2017-11-01

    An overview of drugs approved by FDA in 2016 reveals dramatic disruptions in long-term trends. The number of new molecular entities (NMEs) dropped, reflecting the lowest rate of small-molecule approvals observed in almost five decades. In addition, the pace of industry consolidation slowed substantially. The impact of mergers and acquisitions decreased the total number of organizations with past approval experience and continued research and development (R&D) activities to 102, divided evenly between more established pharmaceutical and newer biotechnology companies. Despite these substantial differences, the industry continued to pursue regulatory incentives, as evidenced by a continued increase in the fraction of NMEs approved using an orphan or priority designation, and almost all oncology drugs approved in 2016 utilized these mechanisms. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. FDA toxicity databases and real-time data entry

    International Nuclear Information System (INIS)

    Arvidson, Kirk B.

    2008-01-01

    Structure-searchable electronic databases are valuable new tools that are assisting the FDA in its mission to promptly and efficiently review incoming submissions for regulatory approval of new food additives and food contact substances. The Center for Food Safety and Applied Nutrition's Office of Food Additive Safety (CFSAN/OFAS), in collaboration with Leadscope, Inc., is consolidating genetic toxicity data submitted in food additive petitions from the 1960s to the present day. The Center for Drug Evaluation and Research, Office of Pharmaceutical Science's Informatics and Computational Safety Analysis Staff (CDER/OPS/ICSAS) is separately gathering similar information from their submissions. Presently, these data are distributed in various locations such as paper files, microfiche, and non-standardized toxicology memoranda. The organization of the data into a consistent, searchable format will reduce paperwork, expedite the toxicology review process, and provide valuable information to industry that is currently available only to the FDA. Furthermore, by combining chemical structures with genetic toxicity information, biologically active moieties can be identified and used to develop quantitative structure-activity relationship (QSAR) modeling and testing guidelines. Additionally, chemicals devoid of toxicity data can be compared to known structures, allowing for improved safety review through the identification and analysis of structural analogs. Four database frameworks have been created: bacterial mutagenesis, in vitro chromosome aberration, in vitro mammalian mutagenesis, and in vivo micronucleus. Controlled vocabularies for these databases have been established. The four separate genetic toxicity databases are compiled into a single, structurally-searchable database for easy accessibility of the toxicity information. Beyond the genetic toxicity databases described here, additional databases for subchronic, chronic, and teratogenicity studies have been prepared

  13. Environmental assessments and findings of no significant impact--FDA. Notice.

    Science.gov (United States)

    1998-05-18

    The Food and Drug Administration (FDA) is announcing that it has reviewed environmental assessments (EA's) and issued findings of no significant impact (FONSI's) relating to the 167 new drug applications (NDA's) and supplemental applications listed in this document. FDA is publishing this notice because Federal regulations require public notice of the availability of environmental documents.

  14. 21 CFR 516.34 - FDA recognition of exclusive marketing rights.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false FDA recognition of exclusive marketing rights. 516... SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS NEW ANIMAL DRUGS FOR MINOR USE AND MINOR SPECIES Designation of a Minor Use or Minor Species New Animal Drug § 516.34 FDA recognition of exclusive...

  15. The FDA's failure to address the lack of generalisability of antidepressant efficacy trials in product labelling.

    Science.gov (United States)

    Zimmerman, Mark

    2016-06-01

    According to the US Food and Drug Administration's (FDA's) regulations, the criteria used to select patients into registration studies should be addressed in a product's label. The FDA's labelling guidelines, which specifically indicate that the routine exclusion of patients of a certain level of severity should be noted in the label, has been uniformly ignored. © The Royal College of Psychiatrists 2016.

  16. FDA-Approved Natural Polymers for Fast Dissolving Tablets

    Directory of Open Access Journals (Sweden)

    Md Tausif Alam

    2014-01-01

    Full Text Available Oral route is the most preferred route for administration of different drugs because it is regarded as safest, most convenient, and economical route. Fast disintegrating tablets are very popular nowadays as they get dissolved or facilely disintegrated in mouth within few seconds of administration without the need of water. The disadvantages of conventional dosage form, especially dysphagia (arduousness in swallowing, in pediatric and geriatric patients have been overcome by fast dissolving tablets. Natural materials have advantages over synthetic ones since they are chemically inert, non-toxic, less expensive, biodegradable and widely available. Natural polymers like locust bean gum, banana powder, mango peel pectin, Mangifera indica gum, and Hibiscus rosa-sinenses mucilage ameliorate the properties of tablet and utilized as binder, diluent, and superdisintegrants increase the solubility of poorly water soluble drug, decrease the disintegration time, and provide nutritional supplement. Natural polymers are obtained from the natural origin and they are cost efficacious, nontoxic, biodegradable, eco-friendly, devoid of any side effect, renewable, and provide nutritional supplement. It is proved from the studies that natural polymers are more safe and efficacious than the synthetic polymers. The aim of the present article is to study the FDA-approved natural polymers utilized in fast dissolving tablets.

  17. The US FDA and animal cloning: risk and regulatory approach.

    Science.gov (United States)

    Rudenko, Larisa; Matheson, John C

    2007-01-01

    The Food and Drug Administration's (FDA's) Center for Veterinary Medicine issued a voluntary request to producers of livestock clones not to introduce food from clones or their progeny into commerce until the agency had assessed whether production of cattle, swine, sheep, or goats by somatic cell nuclear transfer (SCNT) posed any unique risks to the animal(s) involved in the process, humans, or other animals by consuming food from those animals, compared with any other assisted reproductive technology (ART) currently in use. Following a comprehensive review, no anomalies were observed in animals produced by cloning that have not also been observed in animals produced by other ARTs and natural mating. Further systematic review on the health of, and composition of meat and milk from, cattle, swine, and goat clones and the progeny of cattle and sheep did not result in the identification of any food-consumption hazards. The agency therefore concluded that food from cattle, swine, and goat clones was as safe to eat as food from animals of those species derived by conventional means. The agency also concluded that food from the progeny of the clone of any species normally consumed for food is as safe to eat as those animals. The article also describes the methodology used by the agency to analyze data and draw these conclusions, the plans the agency has proposed to manage any identified risks, and the risk communication approaches the agency has used.

  18. Agreements and Discrepancies between FDA Reports and Journal Papers on Biologic Agents Approved for Rheumatoid Arthritis

    DEFF Research Database (Denmark)

    Amarilyo, Gil; Furst, Daniel E; Woo, Jennifer M P

    2016-01-01

    BACKGROUND: Sponsors that seek to commercialize new drugs apply to the Food and Drug Administration (FDA) which independently analyzes the raw data and reports the results on its website. OBJECTIVES: This study sought to determine if there are differences between the FDA assessments and journal...... reports on biologic agents developed for the treatment of rheumatoid arthritis. METHODS: Available data on FDA-approved drugs were extracted from the website, and a systematic literature search was conducted to identify matching studies in peer-reviewed medical journals. Outcome measures were the American...... College of Rheumatology response criteria ACR20 (efficacy) and withdrawal due to adverse events (safety). As effect size odds ratios were estimated for each active trial arm vs. control arm (i.e. for both sources: FDA and journal report), followed by calculation of the ratios of the FDA and journal report...

  19. Adherence of pharmaceutical advertisements in medical journals to FDA guidelines and content for safe prescribing.

    Science.gov (United States)

    Korenstein, Deborah; Keyhani, Salomeh; Mendelson, Ali; Ross, Joseph S

    2011-01-01

    Physician-directed pharmaceutical advertising is regulated in the United States by the Food and Drug Administration (FDA); adherence to current FDA guidelines is unknown. Our objective was to determine adherence rates of physician-directed print advertisements in biomedical journals to FDA guidelines and describe content important for safe prescribing. Cross-sectional analysis of November 2008 pharmaceutical advertisements within top U.S.-based biomedical journals publishing original research. We excluded advertisements for devices, over the counter medications, and disease awareness. We utilized FDA guideline items identifying unique forms of advertisement bias to categorize advertisements as adherent to FDA guidelines, possibly non-adherent to at least 1 item, or non-adherent to at least 1 item. We also evaluated advertisement content important for safe prescribing, including benefit quantification, risk information and verifiable references. All advertisements were evaluated by 2 or more investigators, with differences resolved by discussion. Twelve journals met inclusion criteria. Nine contained pharmaceutical advertisements, including 192 advertisements for 82 unique products; median 2 per product (range 1-14). Six "teaser" advertisements presented only drug names, leaving 83 full unique advertisements. Fifteen advertisements (18.1%) adhered to all FDA guidelines, 41 (49.4%) were non-adherent with at least one form of FDA-described bias, and 27 (32.5%) were possibly non-adherent due to incomplete information. Content important for safe prescribing was often incomplete; 57.8% of advertisements did not quantify serious risks, 48.2% lacked verifiable references and 28.9% failed to present adequate efficacy quantification. Study limitations included its focus on advertisements from a single month, the subjectivity of FDA guidelines themselves, and the necessary subjectivity of determinations of adherence. Few physician-directed print pharmaceutical advertisements

  20. Adherence of pharmaceutical advertisements in medical journals to FDA guidelines and content for safe prescribing.

    Directory of Open Access Journals (Sweden)

    Deborah Korenstein

    Full Text Available Physician-directed pharmaceutical advertising is regulated in the United States by the Food and Drug Administration (FDA; adherence to current FDA guidelines is unknown. Our objective was to determine adherence rates of physician-directed print advertisements in biomedical journals to FDA guidelines and describe content important for safe prescribing.Cross-sectional analysis of November 2008 pharmaceutical advertisements within top U.S.-based biomedical journals publishing original research. We excluded advertisements for devices, over the counter medications, and disease awareness. We utilized FDA guideline items identifying unique forms of advertisement bias to categorize advertisements as adherent to FDA guidelines, possibly non-adherent to at least 1 item, or non-adherent to at least 1 item. We also evaluated advertisement content important for safe prescribing, including benefit quantification, risk information and verifiable references. All advertisements were evaluated by 2 or more investigators, with differences resolved by discussion. Twelve journals met inclusion criteria. Nine contained pharmaceutical advertisements, including 192 advertisements for 82 unique products; median 2 per product (range 1-14. Six "teaser" advertisements presented only drug names, leaving 83 full unique advertisements. Fifteen advertisements (18.1% adhered to all FDA guidelines, 41 (49.4% were non-adherent with at least one form of FDA-described bias, and 27 (32.5% were possibly non-adherent due to incomplete information. Content important for safe prescribing was often incomplete; 57.8% of advertisements did not quantify serious risks, 48.2% lacked verifiable references and 28.9% failed to present adequate efficacy quantification. Study limitations included its focus on advertisements from a single month, the subjectivity of FDA guidelines themselves, and the necessary subjectivity of determinations of adherence.Few physician-directed print pharmaceutical

  1. Great Lakes Literacy Principles

    Science.gov (United States)

    Fortner, Rosanne W.; Manzo, Lyndsey

    2011-03-01

    Lakes Superior, Huron, Michigan, Ontario, and Erie together form North America's Great Lakes, a region that contains 20% of the world's fresh surface water and is home to roughly one quarter of the U.S. population (Figure 1). Supporting a $4 billion sport fishing industry, plus $16 billion annually in boating, 1.5 million U.S. jobs, and $62 billion in annual wages directly, the Great Lakes form the backbone of a regional economy that is vital to the United States as a whole (see http://www.miseagrant.umich.edu/downloads/economy/11-708-Great-Lakes-Jobs.pdf). Yet the grandeur and importance of this freshwater resource are little understood, not only by people in the rest of the country but also by many in the region itself. To help address this lack of knowledge, the Centers for Ocean Sciences Education Excellence (COSEE) Great Lakes, supported by the U.S. National Science Foundation and the National Oceanic and Atmospheric Administration, developed literacy principles for the Great Lakes to serve as a guide for education of students and the public. These “Great Lakes Literacy Principles” represent an understanding of the Great Lakes' influences on society and society's influences on the Great Lakes.

  2. The Next Great Generation?

    Science.gov (United States)

    Brownstein, Andrew

    2000-01-01

    Discusses ideas from a new book, "Millennials Rising: The Next Great Generation," (by Neil Howe and William Strauss) suggesting that youth culture is on the cusp of a radical shift with the generation beginning with this year's college freshmen who are typically team oriented, optimistic, and poised for greatness on a global scale. Includes a…

  3. Quality assessment of digital annotated ECG data from clinical trials by the FDA ECG Warehouse.

    Science.gov (United States)

    Sarapa, Nenad

    2007-09-01

    The FDA mandates that digital electrocardiograms (ECGs) from 'thorough' QTc trials be submitted into the ECG Warehouse in Health Level 7 extended markup language format with annotated onset and offset points of waveforms. The FDA did not disclose the exact Warehouse metrics and minimal acceptable quality standards. The author describes the Warehouse scoring algorithms and metrics used by FDA, points out ways to improve FDA review and suggests Warehouse benefits for pharmaceutical sponsors. The Warehouse ranks individual ECGs according to their score for each quality metric and produces histogram distributions with Warehouse-specific thresholds that identify ECGs of questionable quality. Automatic Warehouse algorithms assess the quality of QT annotation and duration of manual QT measurement by the central ECG laboratory.

  4. Small Area Estimate Maps: Does the FDA Regulate Tobacco? - Small Area Estimates

    Science.gov (United States)

    This metric is defined as a person 18 years of age or older who must have reported that he/she believes that the United States Food and Drug Administration (FDA) regulates tobacco products in the U.S.

  5. MedWatch, the FDA Safety Information and Adverse Event Reporting Program

    Science.gov (United States)

    ... Reporting Program MedWatch: The FDA Safety Information and Adverse Event Reporting Program Share Tweet Linkedin Pin it ... approved information that can help patients avoid serious adverse events. Potential Signals of Serious Risks/New Safety ...

  6. FDA publishes conflict of interest rules for clinical trials. Food and Drug Administration.

    Science.gov (United States)

    James, J S

    1998-03-06

    The Food and Drug Administration (FDA) published new rules defining conflict of interests between drug companies and medical researchers and clinicians. Certain financial arrangements will need to be disclosed, although the FDA estimates that only one to ten percent of pharmaceutical companies will need to submit disclosures for one or more of their investigators. The purpose of the new rule is to prevent bias in safety and efficacy studies of drugs and medical devices. The full rule is published in the Federal Register.

  7. [Discussion about traditional Chinese medicine pharmacokinetics study based on first botanical drug approved by FDA].

    Science.gov (United States)

    Huang, Fanghua

    2010-04-01

    Pharmacokinetics study is one of main components of pharmaceuticals development. Food and Drug Administration (FDA) approved Veregen as the first botanical drug in 2006. This article introduced FDA's requirement on pharmacokinetics study of botanical drug and pharmacokinetics studies of Veregen, summarized current requirement and status quo of pharmacokinetics study on traditional Chinese medicine (TCM) and natural medicine in China, and discussed about pharmacokinetics study strategy for TCM and natural medicine.

  8. Access to Investigational Drugs: FDA Expanded Access Programs or “Right‐to‐Try” Legislation?

    Science.gov (United States)

    Berglund, Jelena P.; Weatherwax, Kevin; Gerber, David E.; Adamo, Joan E.

    2015-01-01

    Abstract Purpose The Food and Drug Administration Expanded Access (EA) program and “Right‐to‐Try” legislation aim to provide seriously ill patients who have no other comparable treatment options to gain access to investigational drugs and biological agents. Physicians and institutions need to understand these programs to respond to questions and requests for access. Methods FDA EA programs and state and federal legislative efforts to provide investigational products to patients by circumventing FDA regulations were summarized and compared. Results The FDA EA program includes Single Patient‐Investigational New Drug (SP‐IND), Emergency SP‐IND, Intermediate Sized Population IND, and Treatment IND. Approval rates for all categories exceed 99%. Approval requires FDA and Institutional Review Board (IRB) approval, and cooperation of the pharmaceutical partner is essential. “Right‐to‐Try” legislation bypasses some of these steps, but provides no regulatory or safety oversight. Conclusion The FDA EA program is a reasonable option for patients for whom all other therapeutic interventions have failed. The SP‐IND not only provides patient access to new drugs, but also maintains a balance between immediacy and necessary patient protection. Rather than circumventing existing FDA regulations through proposed legislation, it seems more judicious to provide the knowledge and means to meet the EA requirements. PMID:25588691

  9. Access to Investigational Drugs: FDA Expanded Access Programs or "Right-to-Try" Legislation?

    Science.gov (United States)

    Holbein, M E Blair; Berglund, Jelena P; Weatherwax, Kevin; Gerber, David E; Adamo, Joan E

    2015-10-01

    The Food and Drug Administration Expanded Access (EA) program and "Right-to-Try" legislation aim to provide seriously ill patients who have no other comparable treatment options to gain access to investigational drugs and biological agents. Physicians and institutions need to understand these programs to respond to questions and requests for access. FDA EA programs and state and federal legislative efforts to provide investigational products to patients by circumventing FDA regulations were summarized and compared. The FDA EA program includes Single Patient-Investigational New Drug (SP-IND), Emergency SP-IND, Intermediate Sized Population IND, and Treatment IND. Approval rates for all categories exceed 99%. Approval requires FDA and Institutional Review Board (IRB) approval, and cooperation of the pharmaceutical partner is essential. "Right-to-Try" legislation bypasses some of these steps, but provides no regulatory or safety oversight. The FDA EA program is a reasonable option for patients for whom all other therapeutic interventions have failed. The SP-IND not only provides patient access to new drugs, but also maintains a balance between immediacy and necessary patient protection. Rather than circumventing existing FDA regulations through proposed legislation, it seems more judicious to provide the knowledge and means to meet the EA requirements. © 2015 Wiley Periodicals, Inc.

  10. Great Indoors Awards 2007

    Index Scriptorium Estoniae

    2007-01-01

    Hollandis Maastrichtis jagati 17. XI esimest korda rahvusvahelist auhinda The Great Indoors Award. Aasta sisekujundusfirmaks valiti Masamichi Katayama asutatud Wonderwall. Auhinna said veel Zaha Hadid, Heatherwick Studio, Ryui Nakamura Architects ja Item Idem

  11. Great Lakes Bathymetry

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Bathymetry of Lakes Michigan, Erie, Saint Clair, Ontario and Huron has been compiled as a component of a NOAA project to rescue Great Lakes lake floor geological and...

  12. Analysis of lomustine drug content in FDA-approved and compounded lomustine capsules.

    Science.gov (United States)

    KuKanich, Butch; Warner, Matt; Hahn, Kevin

    2017-02-01

    OBJECTIVE To determine the lomustine content (potency) in compounded and FDA-approved lomustine capsules. DESIGN Evaluation study. SAMPLE 2 formulations of lomustine capsules (low dose [7 to 11 mg] and high dose [40 to 48 mg]; 5 capsules/dose/source) from 3 compounders and from 1 manufacturer of FDA-approved capsules. PROCEDURES Lomustine content was measured by use of a validated high-pressure liquid chromatography method. An a priori acceptable range of 90% to 110% of the stated lomustine content was selected on the basis of US Pharmacopeia guidelines. RESULTS The measured amount of lomustine in all compounded capsules was less than the stated content (range, 59% to 95%) and was frequently outside the acceptable range (failure rate, 2/5 to 5/5). Coefficients of variation for lomustine content ranged from 4.1% to 16.7% for compounded low-dose capsules and from 1.1% to 10.8% for compounded high-dose capsules. The measured amount of lomustine in all FDA-approved capsules was slightly above the stated content (range, 104% to 110%) and consistently within the acceptable range. Coefficients of variation for lomustine content were 0.5% for low-dose and 2.3% for high-dose FDA-approved capsules. CONCLUSIONS AND CLINICAL RELEVANCE Compounded lomustine frequently did not contain the stated content of active drug and had a wider range of lomustine content variability than did the FDA-approved product. The sample size was small, and larger studies are needed to confirm these findings; however, we recommend that compounded veterinary formulations of lomustine not be used when appropriate doses can be achieved with FDA-approved capsules or combinations of FDA-approved capsules.

  13. Single Cigarette Sales: State Differences in FDA Advertising and Labeling Violations, 2014, United States.

    Science.gov (United States)

    Baker, Hannah M; Lee, Joseph G L; Ranney, Leah M; Goldstein, Adam O

    2016-02-01

    Single cigarettes, which are sold without warning labels and often evade taxes, can serve as a gateway for youth smoking. The Family Smoking Prevention and Tobacco Control Act of 2009 gives the US Food and Drug Administration (FDA) authority to regulate the manufacture, distribution, and marketing of tobacco products, including prohibiting the sale of single cigarettes. To enforce these regulations, the FDA conducted over 335,661 inspections between 2010 and September 30, 2014, and allocated over $115 million toward state inspections contracts. To examine differences in single cigarette violations across states and determine if likely correlates of single cigarette sales predict single cigarette violations at the state level. Cross-sectional study of publicly available FDA warning letters from January 1 to July 31, 2014. All 50 states and the District of Columbia. Tobacco retailer inspections conducted by FDA (n = 33 543). State cigarette tax, youth smoking prevalence, poverty, and tobacco production. State proportion of FDA warning letters issued for single cigarette violations. There are striking differences in the number of single cigarette violations found by state, with 38 states producing no warning letters for selling single cigarettes even as state policymakers developed legislation to address retailer sales of single cigarettes. The state proportion of warning letters issued for single cigarettes is not predicted by state cigarette tax, youth smoking, poverty, or tobacco production, P = .12. Substantial, unexplained variation exists in violations of single cigarette sales among states. These data suggest the possibility of differences in implementation of FDA inspections and the need for stronger quality monitoring processes across states implementing FDA inspections. © The Author 2015. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  14. Gas separation performance of 6FDA-based polyimides with different chemical structures

    KAUST Repository

    Qiu, Wulin

    2013-10-01

    This work reports the gas separation performance of several 6FDA-based polyimides with different chemical structures, to correlate chemical structure with gas transport properties with a special focus on CO2 and CH 4 transport and plasticization stability of the polyimides membranes relevant to natural gas purification. The consideration of the other gases (He, O2 and N2) provided additional insights regarding effects of backbone structure on detailed penetrant properties. The polyimides studied include 6FDA-DAM, 6FDA-mPDA, 6FDA-DABA, 6FDA-DAM:DABA (3:2), 6FDA-DAM:mPDA (3:2) and 6FDA-mPDA:DABA (3:2). Both pure and binary gas permeation were investigated. The packing density, which is tunable by adjusting monomer type and composition of the various samples, correlated with transport permeability and selectivity. The separation performance of the polyimides for various gas pairs were also plotted for comparison to the upper bound curves, and it was found that this family of materials shows attractive performance. The CO 2 plasticization responses for the un-cross-linked polyimides showed good plasticization resistance to CO2/CH4 mixed gas with 10% CO2; however, only the cross-linked polyimides showed good plasticization resistance under aggressive gas feed conditions (CO 2/CH4 mixed gas with 50% CO2 or pure CO 2). For future work, asymmetric hollow fibers and carbon molecular sieve membranes based on the most attractive members of the family will be considered. © 2013 Elsevier Ltd. All rights reserved.

  15. The GREAT3 challenge

    International Nuclear Information System (INIS)

    Miyatake, H; Mandelbaum, R; Rowe, B

    2014-01-01

    The GRavitational lEnsing Accuracy Testing 3 (GREAT3) challenge is an image analysis competition that aims to test algorithms to measure weak gravitational lensing from astronomical images. The challenge started in October 2013 and ends 30 April 2014. The challenge focuses on testing the impact on weak lensing measurements of realistically complex galaxy morphologies, realistic point spread function, and combination of multiple different exposures. It includes simulated ground- and space-based data. The details of the challenge are described in [1], and the challenge website and its leader board can be found at http://great3challenge.info and http://great3.projects.phys.ucl.ac.uk/leaderboard/, respectively

  16. Nothing Great Is Easy

    OpenAIRE

    Stansbie, Lisa

    2014-01-01

    A solo exhibition of 13 pieces of art work.\\ud \\ud Nothing Great is Easy is an exhibition of sculpture, film, drawing and photography that proposes reconstructed narratives using the sport of swimming and in particular the collective interaction and identity of the channel swimmer. The work utilises the processes, rituals/rules, language and the apparatus of sport.\\ud \\ud “Nothing great is easy” are the words on the memorial to Captain Matthew Webb who was the first man to swim the English ch...

  17. Evidence behind FDA alerts for drugs with adverse cardiovascular effects: implications for clinical practice.

    Science.gov (United States)

    Rackham, Daniel M; C Herink, Megan; Stevens, Ian G; Cardoza, Natalie M; Singh, Harleen

    2014-01-01

    The U.S. Food and Drug Administration (FDA) periodically publishes Drug Safety Communications and Drug Alerts notifying health care practitioners and the general public of important information regarding drug therapies following FDA approval. These alerts can result in both positive and negative effects on patient care. Most clinical trials are not designed to detect long-term safety end points, and postmarketing surveillance along with patient reported events are often instrumental in signaling the potential harmful effect of a drug. Recently, many cardiovascular (CV) safety announcements have been released for FDA-approved drugs. Because a premature warning could discourage a much needed treatment or prompt a sudden discontinuation, it is essential to evaluate the evidence supporting these FDA alerts to provide effective patient care and to avoid unwarranted changes in therapy. Conversely, paying attention to these warnings in cases involving high-risk patients can prevent adverse effects and litigation. This article reviews the evidence behind recent FDA alerts for drugs with adverse CV effects and discusses the clinical practice implications. © 2013 Pharmacotherapy Publications, Inc.

  18. The Great Mathematician Project

    Science.gov (United States)

    Goldberg, Sabrina R.

    2013-01-01

    The Great Mathematician Project (GMP) introduces both mathematically sophisticated and struggling students to the history of mathematics. The rationale for the GMP is twofold: first, mathematics is a uniquely people-centered discipline that is used to make sense of the world; and second, students often express curiosity about the history of…

  19. What great managers do.

    Science.gov (United States)

    Buckingham, Marcus

    2005-03-01

    Much has been written about the qualities that make a great manager, but most of the literature overlooks a fundamental question: What does a great manager actually do? While there are countless management styles, one thing underpins the behavior of all great managers. Above all, an exceptional manager comes to know and value the particular quirks and abilities of her employees. She figures out how to capitalize on her staffers' strengths and tweaks her environment to meet her larger goals. Such a specialized approach may seem like a lot of work. But in fact, capitalizing on each person's uniqueness can save time. Rather than encourage employees to conform to strict job descriptions that may include tasks they don't enjoy and aren't good at, a manager who develops positions for his staff members based on their unique abilities will be rewarded with behaviors that are far more efficient and effective than they would be otherwise. This focus on individuals also makes employees more accountable. Because staffers are evaluated on their particular strengths and weaknesses, they are challenged to take responsibility for their abilities and to hone them. Capitalizing on a person's uniqueness also builds a stronger sense of team. By taking the time to understand what makes each employee tick, a great manager shows that he sees his people for who they are. This personal investment not only motivates individuals but also galvanizes the entire team. Finally, this approach shakes up existing hierarchies, which leads to more creative thinking. To take great managing from theory to practice, the author says, you must know three things about a person: her strengths, the triggers that activate those strengths, and how she learns. By asking the right questions, squeezing the right triggers, and becoming aware of your employees' learning styles, you will discover what motivates each person to excel.

  20. Price, performance, and the FDA approval process: the example of home HIV testing.

    Science.gov (United States)

    Paltiel, A David; Pollack, Harold A

    2010-01-01

    The Food and Drug Administration (FDA) is considering approval of an over-the-counter, rapid HIV test for home use. To support its decision, the FDA seeks evidence of the test's performance. It has asked the manufacturer to conduct field studies of the test's sensitivity and specificity when employed by untrained users. In this article, the authors argue that additional information should be sought to evaluate the prevalence of undetected HIV in the end-user The analytic framework produces the elementary but counterintuitive finding that the performance of the home HIV test- measured in terms of its ability to correctly detect the presence and absence of HIV infection among the people who purchase it-depends critically on the manufacturer's retail price. This finding has profound implications for the FDA's approval process.

  1. Right to experimental treatment: FDA new drug approval, constitutional rights, and the public's health.

    Science.gov (United States)

    Leonard, Elizabeth Weeks

    2009-01-01

    On May 2, 2006, a divided panel of the U.S. Court of Appeals for the District of Columbia, in a startling opinion, Abigail Alliance for Better Access to Developmental Drugs v. Eschenbach, held that terminally ill patients who have exhausted all other available options have a constitutional right to experimental treatment that FDA has not yet approved. Although ultimately overturned by the full court, Abigail Alliance generated considerable interest from various constituencies. Meanwhile, FDA proposed similar regulatory amendments, as have lawmakers on both sides of the aisle in Congress. But proponents of expanded access fail to consider public health and consumer safety concerns. In particular, allowing patients to try unproven treatments, outside of controlled clinical trials risks both the study's outcome and the health of patients who might benefit from the deliberate, careful process of new drug approval as it currently operates under FDA's auspices.

  2. FDA Regulation of Clinical Applications of CRISPR-CAS Gene-Editing Technology.

    Science.gov (United States)

    Grant, Evita V

    Scientists have repurposed an adaptive immune system of single cell organisms to create a new type of gene-editing tool: CRISPR (clustered regularly interspaced short palindromic repeats)-Cas technology. Scientists in China have reported its use in the genome modification of non-viable human embryos. This has ignited a spirited debate about the moral, ethical, scientific, and social implications of human germline genome engineering. There have also been calls for regulations; however, FDA has yet to formally announce its oversight of clinical applications of CRISPR-Cas systems. This paper reviews FDA regulation of previously controversial biotechnology breakthroughs, recombinant DNA and human cloning. It then shows that FDA is well positioned to regulate CRISPR-Cas clinical applications, due to its legislative mandates, its existing regulatory frameworks for gene therapies and assisted reproductive technologies, and other considerations.

  3. FDA: polyurethane condom carries "extremely misleading" label. Federal agency allows distribution for public health's sake.

    Science.gov (United States)

    1995-02-01

    The labeling of the Avanti polyurethane condom selling in 10 Western states makes misleading claims about protection from pregnancy and sexually transmitted diseases (STDs) according to officials at the US Food and Drug Administration (FDA). Avanti is sold in a foil package printed with the claim that it is effective against pregnancy, HIV, and STDs. However, polyurethane condoms have not undergone clinical efficacy testing for contraception or STDs, according to officials. The manufacturer of the condom refuted this allegation, stating that latex condoms have the same claims on them. In early 1995 the FDA met with the manufacturer and other companies developing plastic condoms, and concluded that these condoms could not make such claims, nor any claims about slippage and breakage rates. Despite warnings in 1993 to the manufacturer of Avanti about labeling restrictions, the company printed pregnancy and STD efficacy claims on the boxes and individual packages. The FDA later worked out a compromise with the firm in which only the boxes had to be reprinted with the generic label. The FDA had to weigh the risk of the public health cost of delaying sale of the condom, which is the first impermeable condom proven safe for people with latex allergies. In 1991 the FDA was defining standards for clinical testing and labeling of polyurethane condoms under congressional mandate, but the manufacturer of Avanti began mass production based on a preliminary approval determining that the condom was equivalent to latex condoms already on the market. 7000 Avanti condoms were subsequently tested in five countries, but these user tests did not compare Avanti to latex condoms and did not test for pregnancy and STD protection. Test results submitted to the FDA by the company indicated that, although Avanti is more than 1/3 less elastic than latex condoms, it did not break more frequently in an in-use study involving 187 couples.

  4. Great magnetic storms

    International Nuclear Information System (INIS)

    Tsurutani, B.T.; Yen Te Lee; Tang, F.; Gonzalez, W.D.

    1992-01-01

    The five largest magnetic storms that occurred between 1971 and 1986 are studied to determine their solar and interplanetary causes. All of the events are found to be associated with high speed solar wind streams led by collisionless shocks. The high speed streams are clearly related to identifiable solar flares. It is found that (1) it is the extreme values of the southward interplanetary magnetic fields rather than solar wind speeds that are the primary causes of great magnetic storms, (2) shocked and draped sheath fields preceding the driver gas (magnetic cloud) are at least as effective in causing the onset of great magnetic storms (3 of 5 events ) as the strong fields within the driver gas itself, and (3) precursor southward fields ahead of the high speed streams allow the shock compression mechanism (item 2) to be particularly geoeffective

  5. Small-molecule kinase inhibitors: an analysis of FDA-approved drugs

    DEFF Research Database (Denmark)

    Wu, Peng; Nielsen, Thomas Eiland; Clausen, Mads Hartvig

    2016-01-01

    Small-molecule kinase inhibitors (SMKIs), 28 of which are approved by the US Food and Drug Administration (FDA), have been actively pursued as promising targeted therapeutics. Here, we assess the key structural and physicochemical properties, target selectivity and mechanism of function, and ther......Small-molecule kinase inhibitors (SMKIs), 28 of which are approved by the US Food and Drug Administration (FDA), have been actively pursued as promising targeted therapeutics. Here, we assess the key structural and physicochemical properties, target selectivity and mechanism of function...

  6. We really need to talk: adapting FDA processes to rapid change.

    Science.gov (United States)

    Lykken, Sara

    2013-01-01

    The rapidly evolving realm of modern commerce strains traditional regulatory paradigms. This paper traces the historical evolution of FDA crisis-response regulation and provides examples of ways in which the definitions and procedures resulting from that past continue to be challenged by new products as market entrants, some in good faith and others not, take actions that create disconnects between actual product and marketing controls and those that consumers might expect. The paper then explores some of the techniques used by other federal agencies that have faced similar challenges in environments characterized by rapid innovation, and draws from this analysis suggestions for improvement of the FDA's warning letter system.

  7. FDA publishes checklist of Y2K high-risk devices.

    Science.gov (United States)

    1999-09-01

    Key points. The federal Food and Drug Administration (FDA) has developed a list of types of medical devices that have the potential for the most serious consequences for patients should they fail because of Y2K-related problems. This list of computer-controlled potentially high-risk devices can provide a guide to health care facilities regarding the types of devices that should receive priority in their assessment and remediation of medical devices. The list may change as the FDA receives comments on the types of devices included in the list.

  8. The great intimidators.

    Science.gov (United States)

    Kramer, Roderick M

    2006-02-01

    After Disney's Michael Eisner, Miramax's Harvey Weinstein, and Hewlett-Packard's Carly Fiorina fell from their heights of power, the business media quickly proclaimed thatthe reign of abrasive, intimidating leaders was over. However, it's premature to proclaim their extinction. Many great intimidators have done fine for a long time and continue to thrive. Their modus operandi runs counter to a lot of preconceptions about what it takes to be a good leader. They're rough, loud, and in your face. Their tactics include invading others' personal space, staging tantrums, keeping people guessing, and possessing an indisputable command of facts. But make no mistake--great intimidators are not your typical bullies. They're driven by vision, not by sheer ego or malice. Beneath their tough exteriors and sharp edges are some genuine, deep insights into human motivation and organizational behavior. Indeed, these leaders possess political intelligence, which can make the difference between paralysis and successful--if sometimes wrenching--organizational change. Like socially intelligent leaders, politically intelligent leaders are adept at sizing up others, but they notice different things. Those with social intelligence assess people's strengths and figure out how to leverage them; those with political intelligence exploit people's weaknesses and insecurities. Despite all the obvious drawbacks of working under them, great intimidators often attract the best and brightest. And their appeal goes beyond their ability to inspire high performance. Many accomplished professionals who gravitate toward these leaders want to cultivate a little "inner intimidator" of their own. In the author's research, quite a few individuals reported having positive relationships with intimidating leaders. In fact, some described these relationships as profoundly educational and even transformational. So before we throw out all the great intimidators, the author argues, we should stop to consider what

  9. Great Lakes Energy Institute

    Energy Technology Data Exchange (ETDEWEB)

    Alexander, J. Iwan [Case Western Reserve Univ., Cleveland, OH (United States)

    2012-11-18

    The vision of the Great Lakes Energy Institute is to enable the transition to advanced, sustainable energy generation, storage, distribution and utilization through coordinated research, development, and education. The Institute will place emphasis on translating leading edge research into next generation energy technology. The Institute’s research thrusts focus on coordinated research in decentralized power generation devices (e.g. fuel cells, wind turbines, solar photovoltaic devices), management of electrical power transmission and distribution, energy storage, and energy efficiency.

  10. Time-Resolved Particle Image Velocimetry Measurements with Wall Shear Stress and Uncertainty Quantification for the FDA Nozzle Model.

    Science.gov (United States)

    Raben, Jaime S; Hariharan, Prasanna; Robinson, Ronald; Malinauskas, Richard; Vlachos, Pavlos P

    2016-03-01

    We present advanced particle image velocimetry (PIV) processing, post-processing, and uncertainty estimation techniques to support the validation of computational fluid dynamics analyses of medical devices. This work is an extension of a previous FDA-sponsored multi-laboratory study, which used a medical device mimicking geometry referred to as the FDA benchmark nozzle model. Experimental measurements were performed using time-resolved PIV at five overlapping regions of the model for Reynolds numbers in the nozzle throat of 500, 2000, 5000, and 8000. Images included a twofold increase in spatial resolution in comparison to the previous study. Data was processed using ensemble correlation, dynamic range enhancement, and phase correlations to increase signal-to-noise ratios and measurement accuracy, and to resolve flow regions with large velocity ranges and gradients, which is typical of many blood-contacting medical devices. Parameters relevant to device safety, including shear stress at the wall and in bulk flow, were computed using radial basis functions. In addition, in-field spatially resolved pressure distributions, Reynolds stresses, and energy dissipation rates were computed from PIV measurements. Velocity measurement uncertainty was estimated directly from the PIV correlation plane, and uncertainty analysis for wall shear stress at each measurement location was performed using a Monte Carlo model. Local velocity uncertainty varied greatly and depended largely on local conditions such as particle seeding, velocity gradients, and particle displacements. Uncertainty in low velocity regions in the sudden expansion section of the nozzle was greatly reduced by over an order of magnitude when dynamic range enhancement was applied. Wall shear stress uncertainty was dominated by uncertainty contributions from velocity estimations, which were shown to account for 90-99% of the total uncertainty. This study provides advancements in the PIV processing methodologies over

  11. Idiopathic great saphenous phlebosclerosis.

    Directory of Open Access Journals (Sweden)

    Ahmadreza Jodati

    2013-06-01

    Full Text Available Arterial sclerosis has been extensively described but reports on venous sclerosis are very sparse. Phlebosclerosis refers to the thickening and hardening of the venous wall. Despite its morphological similarities with arteriosclerosis and potential morbid consequences, phlebosclerosis has gained only little attention. We report a 72 year old male with paralysis and atrophy of the right leg due to childhood poliomyelitis who was referred for coronary artery bypass surgery. The great saphenous vein, harvested from the left leg, showed a hardened cord-like obliterated vein. Surprisingly, harvested veins from the atrophic limb were normal and successfully used for grafting.

  12. Great software debates

    CERN Document Server

    Davis, A

    2004-01-01

    The industry’s most outspoken and insightful critic explains how the software industry REALLY works. In Great Software Debates, Al Davis, shares what he has learned about the difference between the theory and the realities of business and encourages you to question and think about software engineering in ways that will help you succeed where others fail. In short, provocative essays, Davis fearlessly reveals the truth about process improvement, productivity, software quality, metrics, agile development, requirements documentation, modeling, software marketing and sales, empiricism, start-up financing, software research, requirements triage, software estimation, and entrepreneurship.

  13. Making Psychotherapy Great Again?

    Science.gov (United States)

    Plakun, Eric M

    2017-05-01

    Psychotherapy never stopped being as "great" as other treatments. This column explores the evidence base for both psychotherapy and medications, using depression as a specific example. The limitations are comparable for psychotherapy and medication, with much of the evidence based on small degrees of "statistically significant" rather than "clinically meaningful" change. Our field's biomedical emphasis leads to a false assumption that most patients present with single disorders, when comorbidity is the rule rather than the exception. This false assumption contributes to limitations in the evidence base and in our ability to treat patients optimally.

  14. Language and Nutrition (Mis)Information: Food Labels, FDA Policies and Meaning

    Science.gov (United States)

    Taylor, Christy Marie

    2013-01-01

    In this dissertation, I address the ways in which food manufacturers can exploit the often vague and ambiguous nature of FDA policies concerning language and images used on food labels. Employing qualitative analysis methods (Strauss, 1987; Denzin and Lincoln, 2003; Mackey and Gass, 2005) that drew upon critical discourse analysis (Fairclough,…

  15. The rosiglitazone decision process at FDA and EMA : What should we learn?

    NARCIS (Netherlands)

    Pouwels, Koen B.; van Grootheest, Kees

    2012-01-01

    In September 2010 the EMA decided to suspend the market authorisation of rosiglitazone, while the FDA decided to restrict the use of rosiglitazone. These actions were taken approximately 10 years after the introduction of rosiglitazone, because rosiglitazone might be associated with an increased

  16. Ten years after the FDA black box warning for antidepressant drugs: a critical narrative review

    Directory of Open Access Journals (Sweden)

    Juan Carlos Martínez-Aguayo

    2016-06-01

    Full Text Available ABSTRACT Background The United States Food and Drug Administration (FDA has warned about the increased suicidality risk associated with the use of selective serotonin reuptake inhibitors (SSRI and venlafaxine in children and adolescents. Objectives To critically appraise the available evidence supporting the FDA Black box warning concerning to the use of antidepressants in child and adolescents. Methods A critical review of articles in Medline/PubMed and SciELO databases regarding the FDA Black box warning for antidepressants, and the impact of FDA warnings on antidepressant prescriptions and suicide rates. Results The warning was based on surveys that did not report either cases of suicide nor a significant difference supporting an increased suicidality rate. The concept was defined in an ambiguous way and there is currently more available evidence to support such definition. The use of SSRI and venlafaxine has been associated to lower suicidality rates, but the prescription fall due to the warning increased suicide rates. Discussion Suicidality is an inherent feature of depressive disorders so it would be desirable to consider how much of the phenomenon may be attributed to antidepressants per se. It would be appropriate to consider that suicide rates might increase also as a consequence of the warning.

  17. FDA Approves Immunotherapy for a Cancer that Affects Infants and Children | FNLCR

    Science.gov (United States)

    The U.S. Food and Drug Administration (FDA) has approved dinutuximab (ch14.18) as an immunotherapy for neuroblastoma, a rare type of childhood cancer that offers poor prognosis for about half of the children who are affected.  The National Cancer In

  18. FDA Approves Immunotherapy for a Cancer that Affects Infants and Children | FNLCR Staging

    Science.gov (United States)

    The U.S. Food and Drug Administration (FDA) has approved dinutuximab (ch14.18) as an immunotherapy for neuroblastoma, a rare type of childhood cancer that offers poor prognosis for about half of the children who are affected.  The National Cancer In

  19. A Good Year: FDA Approved Nine New Cancer Drugs in 2014

    Science.gov (United States)

    In 2014, the Food and Drug Administration (FDA) approved 41 drugs that had not been approved previously for any indication, the most in nearly 20 years. Of these 41 novel drugs, 9 were approved for the treatment of cancer or cancer-related conditions.

  20. Impact of FDA Actions, DTCA, and Public Information on the Market for Pain Medication.

    Science.gov (United States)

    Bradford, W David; Kleit, Andrew N

    2015-07-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) are one of the most important classes of prescription drugs used by primary care physicians to manage pain. The NSAID class of products has a somewhat controversial history, around which a complex regulatory and informational environment has developed. This history includes a boxed warning mandated by the Food and Drug Administration (FDA) for all NSAIDs in 2005. We investigate the impact that various information shocks have had on the use of prescription medications for pain in primary care in the USA. We accomplish this by extracting data on nearly 600,000 patients from a unique nationwide electronic medical record database and estimate the probability of any active prescription for the four types of pain medications as a function of FDA actions, advertising, media coverage, and patient characteristics. We find that even after accounting for multiple sources of information, the FDA label changes and boxed warnings had a significant effect on pain medication prescribing. The boxed warning did not have the same impact on the use of all NSAID inhibitors. We find that the boxed warning reduced the use of NSAID COX-2 inhibitor use, which was the focus of much of the press attention. In contrast, however, the warning actually increased the use of non-COX-2 NSAID inhibitors. Thus, the efficacy of the FDA's black box warning is clearly mixed. Copyright © 2014 John Wiley & Sons, Ltd.

  1. 75 FR 28622 - FDA Transparency Initiative: Draft Proposals for Public Comment Regarding Disclosure Policies of...

    Science.gov (United States)

    2010-05-21

    ...] FDA Transparency Initiative: Draft Proposals for Public Comment Regarding Disclosure Policies of the U...: Notice of availability; request for comments. SUMMARY: As part of the second phase of the Transparency... Transparency Initiative: Draft Proposals for Public Comment Regarding Disclosure Policies of the U.S. Food and...

  2. Nanotechnology Laboratory Continues Partnership with FDA and National Institute of Standards and Technology | Poster

    Science.gov (United States)

    The NCI-funded Nanotechnology Characterization Laboratory (NCL)—a leader in evaluating promising nanomedicines to fight cancer—recently renewed its collaboration with the U.S. Food and Drug Administration (FDA) and the National Institute of Standards and Technology (NIST) to continue its groundbreaking work on characterizing nanomedicines and moving them toward the clinic. In

  3. 21 CFR 111.610 - What records must be made available to FDA?

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 2 2010-04-01 2010-04-01 false What records must be made available to FDA? 111.610 Section 111.610 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION CURRENT GOOD MANUFACTURING PRACTICE IN MANUFACTURING...

  4. 21 CFR 1.378 - What criteria does FDA use to order a detention?

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 1 2010-04-01 2010-04-01 false What criteria does FDA use to order a detention? 1.378 Section 1.378 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL GENERAL ENFORCEMENT REGULATIONS Administrative Detention of Food for Human or Animal Consumption...

  5. 21 CFR 1.405 - When does FDA have to issue a decision on an appeal?

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 1 2010-04-01 2010-04-01 false When does FDA have to issue a decision on an appeal? 1.405 Section 1.405 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL GENERAL ENFORCEMENT REGULATIONS Administrative Detention of Food for Human or Animal...

  6. 21 CFR 1.406 - How will FDA handle classified information in an informal hearing?

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 1 2010-04-01 2010-04-01 false How will FDA handle classified information in an informal hearing? 1.406 Section 1.406 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL GENERAL ENFORCEMENT REGULATIONS Administrative Detention of Food for Human or...

  7. Advancing Product Quality: a Summary of the Inaugural FDA/PQRI Conference.

    Science.gov (United States)

    Yu, Lawrence X; Baker, Jeffrey; Berlam, Susan C; Boam, Ashley; Brandreth, E J; Buhse, Lucinda; Cosgrove, Thomas; Doleski, David; Ensor, Lynne; Famulare, Joseph; Ganapathy, Mohan; Grampp, Gustavo; Hussong, David; Iser, Robert; Johnston, Gordon; Kesisoglou, Filippos; Khan, Mansoor; Kozlowski, Steven; Lacana, Emanuela; Lee, Sau L; Miller, Stephen; Miksinski, Sarah Pope; Moore, Christine M V; Mullin, Theresa; Raju, G K; Raw, Andre; Rosencrance, Susan; Rosolowsky, Mark; Stinavage, Paul; Thomas, Hayden; Wesdyk, Russell; Windisch, Joerg; Vaithiyalingam, Sivakumar

    2015-07-01

    On September 16 and 17, 2014, the Food and Drug Administration (FDA) and Product Quality Research Institute (PQRI) inaugurated their Conference on Evolving Product Quality. The Conference is conceived as an annual forum in which scientists from regulatory agencies, industry, and academia may exchange viewpoints and work together to advance pharmaceutical quality. This Conference Summary Report highlights key topics of this conference, including (1) risk-based approaches to pharmaceutical development, manufacturing, regulatory assessment, and post-approval changes; (2) FDA-proposed quality metrics for products, facilities, and quality management systems; (3) performance-based quality assessment and clinically relevant specifications; (4) recent developments and implementation of continuous manufacturing processes, question-based review, and European Medicines Agency (EMA)-FDA pilot for Quality-by-Design (QbD) applications; and (5) breakthrough therapies, biosimilars, and international harmonization, focusing on ICH M7 and Q3D guidelines. The second FDA/PQRI conference on advancing product quality is planned for October 5-7, 2015.

  8. FDA Accelerates Testing and Review of Experimental Brain Cancer Drug | FNLCR

    Science.gov (United States)

    An investigational brain cancer drug made with disabled polio virus and manufactured at the Frederick National Lab has won breakthrough status from the Food and Drug Administration (FDA) to fast-track its further refinement and clinical testing.  Br

  9. FDA Accelerates Testing and Review of Experimental Brain Cancer Drug | FNLCR Staging

    Science.gov (United States)

    An investigational brain cancer drug made with disabled polio virus and manufactured at the Frederick National Lab has won breakthrough status from the Food and Drug Administration (FDA) to fast-track its further refinement and clinical testing.  Br

  10. Gaps, tensions, and conflicts in the FDA approval process: implications for clinical practice.

    Science.gov (United States)

    Deyo, Richard A

    2004-01-01

    Despite many successes, drug approval at the Food and Drug Administration (FDA) is subject to gaps, internal tensions, and conflicts of interest. Recalls of drugs and devices and studies demonstrating advantages of older drugs over newer ones highlight the importance of these limitations. The FDA does not compare competing drugs and rarely requires tests of clinical efficacy for new devices. It does not review advertisements before use, assess cost-effectiveness, or regulate surgery (except for devices). Many believe postmarketing surveillance of drugs and devices is inadequate. A source of tension within the agency is pressure for speedy approvals. This may have resulted in "burn-out" among medical officers and has prompted criticism that safety is ignored. Others argue, however, that the agency is unnecessarily slow and bureaucratic. Recent reports identify conflicts of interest (stock ownership, consulting fees, research grants) among some members of the FDA's advisory committees. FDA review serves a critical function, but physicians should be aware that new drugs may not be as effective as old ones; that new drugs are likely to have undiscovered side effects at the time of marketing; that direct-to-consumer ads are sometimes misleading; that new devices generally have less rigorous evidence of efficacy than new drugs; and that value for money is not considered in approval.

  11. Extending FDA guidance to include consumer medication information (CMI) delivery on mobile devices.

    Science.gov (United States)

    Sage, Adam; Blalock, Susan J; Carpenter, Delesha

    This paper describes the current state of consumer-focused mobile health application use and the current U.S. Food and Drug Administration (FDA) guidance on the distribution of consumer medication information (CMI), and discusses recommendations and considerations for the FDA to expand CMI guidance to include CMI in mobile applications. Smartphone-based health interventions have been linked to increased medication adherence and improved health outcomes. Trends in smartphone ownership present opportunities to more effectively communicate and disseminate medication information; however, current FDA guidance for CMI does not outline how to effectively communicate CMI on a mobile platform, particularly in regards to user-centered design and information sourcing. As evidence supporting the potential effectiveness of mobile communication in health care continues to increase, CMI developers, regulating entities, and researchers should take note. Although mobile-based CMI offers an innovative mechanism to deliver medication information, caution should be exercised. Specifically, considerations for developing mobile CMI include consumers' digital literacy, user experience (e.g., usability), and the quality and accuracy of new widely used sources of information (e.g., crowd-sourced reviews and ratings). Recommended changes to FDA guidance for CMI include altering the language about scientific accuracy to address more novel methods of information gathering (e.g., anecdotal experiences and Google Consumer Surveys) and including guidance for usability testing of mobile health applications. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. 21 CFR Appendix A to Part 201 - Examples of Graphic Enhancements Used by FDA

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 4 2010-04-01 2010-04-01 false Examples of Graphic Enhancements Used by FDA A... (CONTINUED) DRUGS: GENERAL LABELING Pt. 201, App. A Appendix A to Part 201—Examples of Graphic Enhancements.... Examples of § 201.66 Standard Labeling and Modified Labeling Formats A. Section 201.66 Standard Labeling...

  13. 21 CFR 14.171 - Utilization of an advisory committee on the initiative of FDA.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 1 2010-04-01 2010-04-01 false Utilization of an advisory committee on the initiative of FDA. 14.171 Section 14.171 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH... technical advisory committee for human prescription drugs. The Commissioner's determinations on the agenda...

  14. 21 CFR 14.15 - Committees working under a contract with FDA.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 1 2010-04-01 2010-04-01 false Committees working under a contract with FDA. 14.15 Section 14.15 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... committee: (1) The committee shall give public notice of its meetings and agenda, and provide interested...

  15. TU-AB-204-00: CDRH/FDA Regulatory Processes and Device Science Activities

    International Nuclear Information System (INIS)

    2016-01-01

    The responsibilities of the Food and Drug Administration (FDA) have increased since the inception of the Food and Drugs Act in 1906. Medical devices first came under comprehensive regulation with the passage of the 1938 Food, Drug, and Cosmetic Act. In 1971 FDA also took on the responsibility for consumer protection against unnecessary exposure to radiation-emitting devices for home and occupational use. However it was not until 1976, under the Medical Device Regulation Act, that the FDA was responsible for the safety and effectiveness of medical devices. This session will be presented by the Division of Radiological Health (DRH) and the Division of Imaging, Diagnostics, and Software Reliability (DIDSR) from the Center for Devices and Radiological Health (CDRH) at the FDA. The symposium will discuss on how we protect and promote public health with a focus on medical physics applications organized into four areas: pre-market device review, post-market surveillance, device compliance, current regulatory research efforts and partnerships with other organizations. The pre-market session will summarize the pathways FDA uses to regulate the investigational use and commercialization of diagnostic imaging and radiation therapy medical devices in the US, highlighting resources available to assist investigators and manufacturers. The post-market session will explain the post-market surveillance and compliance activities FDA performs to monitor the safety and effectiveness of devices on the market. The third session will describe research efforts that support the regulatory mission of the Agency. An overview of our regulatory research portfolio to advance our understanding of medical physics and imaging technologies and approaches to their evaluation will be discussed. Lastly, mechanisms that FDA uses to seek public input and promote collaborations with professional, government, and international organizations, such as AAPM, International Electrotechnical Commission (IEC

  16. TU-AB-204-00: CDRH/FDA Regulatory Processes and Device Science Activities

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2016-06-15

    The responsibilities of the Food and Drug Administration (FDA) have increased since the inception of the Food and Drugs Act in 1906. Medical devices first came under comprehensive regulation with the passage of the 1938 Food, Drug, and Cosmetic Act. In 1971 FDA also took on the responsibility for consumer protection against unnecessary exposure to radiation-emitting devices for home and occupational use. However it was not until 1976, under the Medical Device Regulation Act, that the FDA was responsible for the safety and effectiveness of medical devices. This session will be presented by the Division of Radiological Health (DRH) and the Division of Imaging, Diagnostics, and Software Reliability (DIDSR) from the Center for Devices and Radiological Health (CDRH) at the FDA. The symposium will discuss on how we protect and promote public health with a focus on medical physics applications organized into four areas: pre-market device review, post-market surveillance, device compliance, current regulatory research efforts and partnerships with other organizations. The pre-market session will summarize the pathways FDA uses to regulate the investigational use and commercialization of diagnostic imaging and radiation therapy medical devices in the US, highlighting resources available to assist investigators and manufacturers. The post-market session will explain the post-market surveillance and compliance activities FDA performs to monitor the safety and effectiveness of devices on the market. The third session will describe research efforts that support the regulatory mission of the Agency. An overview of our regulatory research portfolio to advance our understanding of medical physics and imaging technologies and approaches to their evaluation will be discussed. Lastly, mechanisms that FDA uses to seek public input and promote collaborations with professional, government, and international organizations, such as AAPM, International Electrotechnical Commission (IEC

  17. One and done: Reasons principal investigators conduct only one FDA-regulated drug trial

    Directory of Open Access Journals (Sweden)

    Amy Corneli, PhD, MPH

    2017-06-01

    Full Text Available Concerns have been raised over the high turnover rate for clinical investigators. Using the U.S. Food and Drug Administration's (FDA Bioresearch Monitoring Information System database, we conducted an online survey to identify factors that affect principal investigators' (PIs decisions to conduct only a single FDA-regulated drug trial. Of the 201 PIs who responded, 54.2% were classified as “one-and-done.” Among these investigators, 28.9% decided for personal reasons to not conduct another trial, and 44.4% were interested in conducting another trial, but no opportunities were available. Three categories of broad barriers were identified as generally burdensome or challenging by the majority of investigators: 1 workload balance (balancing trial implementation with other work obligations and opportunities (63.8%; 2 time requirements (time to initiate and implement trial; investigator and staff time (63.4%; and 3 data and safety reporting (56.5%. Additionally, 46.0% of investigators reported being generally unsatisfied with finance-related issues. These same top three barriers also affected investigators' decisions to no longer conduct FDA-regulated trials. Our findings illuminate three key aspects of investigator turnover. First, they confirm that investigator turnover occurs, as more than half of respondents were truly “one-and-done.” Second, because a large proportion of respondents wanted to conduct more FDA-regulated trials but lacked opportunities to do so, mechanisms that match interested investigators with research sponsors are needed. Third, by focusing on the barriers we identified that affected investigators' decisions to no longer conduct FDA-regulated trials, future efforts to reduce investigator turnover can target issues that matter the most to investigators.

  18. Point-Counterpoint: The FDA Has a Role in Regulation of Laboratory-Developed Tests.

    Science.gov (United States)

    Caliendo, Angela M; Hanson, Kimberly E

    2016-04-01

    Since the Food and Drug Administration (FDA) released its draft guidance on the regulation of laboratory-developed tests (LDTs) in October 2014, there has been a flurry of responses from commercial and hospital-based laboratory directors, clinicians, professional organizations, and diagnostic companies. The FDA defines an LDT as an "in vitrodiagnostic device that is intended for clinical use and is designed, manufactured, and used within a single laboratory." The draft guidance outlines a risk-based approach, with oversight of high-risk and moderate-risk tests being phased in over 9 years. High-risk tests would be regulated first and require premarket approval. Subsequently, moderate-risk tests would require a 510(k) premarket submission to the FDA and low-risk tests would need only to be registered. Oversight discretion would be exercised for LDTs focused on rare diseases (defined as fewer than 4,000 tests, not cases, per year nationally) and unmet clinical needs (defined as those tests for which there is no alternative FDA-cleared or -approved test). There was an open comment period followed by a public hearing in early January of 2015, and we are currently awaiting the final decision regarding the regulation of LDTs. Given that LDTs have been developed by many laboratories and are essential for the diagnosis and monitoring of an array of infectious diseases, changes in their regulation will have far-reaching implications for clinical microbiology laboratories. In this Point-Counterpoint, Angela Caliendo discusses the potential benefits of the FDA guidance for LDTs whereas Kim Hanson discusses the concerns associated with implementing the guidance and why these regulations may not improve clinical care. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  19. 76 FR 62073 - Guidance for Industry on Implementation of the Fee Provisions of the FDA Food Safety...

    Science.gov (United States)

    2011-10-06

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-D-0721] Guidance for Industry on Implementation of the Fee Provisions of the FDA Food Safety Modernization Act; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug...

  20. De besluitvorming over werkzaamheid en veiligheid van rosiglitazon bij de FDA en de EMA. Wat zijn de lessen?

    NARCIS (Netherlands)

    Pouwels, Koen; Van Grootheest, Kees

    2013-01-01

    The rosiglitazone decision process at FDA and EMA. What should we learn? In September 2010 the EMA decided to suspend the market authorisation of rosiglitazone while the FDA decided to restrict its use. These actions were taken because rosiglitazone had been associated with an increased risk of

  1. Pharmacokinetics of pediatric lopinavir/ritonavir tablets in children when administered twice daily according to FDA weight bands

    NARCIS (Netherlands)

    Bastiaans, D.E.T.; Forcat, S.; Lyall, H.; Cressey, T.R.; Hansudewechakul, R.; Kanjanavanit, S.; Noguera-Julian, A.; Konigs, C.; Inshaw, J.R.; Chalermpantmetagul, S.; Saidi, Y.; Compagnucci, A.; Harper, L.M.; Giaquinto, C.; Colbers, A.P.; Burger, D.M.

    2014-01-01

    BACKGROUND: Lopinavir/ritonavir (LPV/r) pediatric tablets (100/25 mg) are approved by the United States Food and Drug Administration (FDA) and European Medicines Agency (EMA) as part of combination antiretroviral therapy. Dosing is based on body weight bands or body surface area under FDA approval

  2. Great Britain at CERN

    CERN Multimedia

    2006-01-01

    From 14 to 16 November 2006 Administration Building, Bldg. 60/61 - ground and 1st floor 09.30 - 17.30 Fifteen companies will present their latest technologies at the 'Great Britain at CERN' exhibition. British industry will exhibit products and technologies related to the field of particle physics. The main fields represented will be computing technologies, electrical engineering, electronics, mechanical engineering, vacuum & low temperature technologies and particle detectors. The exhibition is organised by BEAMA Exhibitions (the British Electrotechnical and Allied Manufacturers Association). Below you will find: a list of the exhibitors. A detailed programme will be available in due course: from your Departmental secretariat, from the Reception information desk, Building 33, at the exhibition itself. A detailed list of the companies is available at the following FI link: http://fi-dep.web.cern.ch/fi-dep/structure/memberstates/exhibitions_visits.htm LIST OF EXHIBITORS 3D Metrics Almat...

  3. Great Britain at CERN

    CERN Multimedia

    2006-01-01

    From 14 to 16 November 2006 Administration Building, Bldg. 60/61 - ground and 1st floor 09.30 - 17.30 Fifteen companies will present their latest technologies at the 'Great Britain at CERN' exhibition. British industry will exhibit products and technologies related to the field of particle physics. The main fields represented will be computing technologies, electrical engineering, electronics, mechanical engineering, vacuum & low temperature technologies and particle detectors. The exhibition is organised by BEAMA Exhibitions (the British Electrotechnical and Allied Manufacturers Association). Below you will find: a list of the exhibitors. A detailed programme will be available in due course: from your Departmental secretariat, from the Reception information desk, Building 33, at the exhibition itself. A detailed list of the companies is available at the following FI link: http://fi-dep.web.cern.ch/fi-dep/structure/memberstates/exhibitions_visits.htm LIST OF EXHIBITORS 3D Metrics Alma...

  4. Petitioning the FDA to Improve Pharmaceutical, Device and Public Health Safety by Ordinary Citizens: A Descriptive Analysis.

    Science.gov (United States)

    Chen, Brian K; Yang, Y Tony; Cheng, Xi; Bian, John; Bennett, Charles L

    2016-01-01

    The United States Constitution protects the right of citizens to petition the government for "a redress of grievances." This right has important implications for citizens desiring to advance the public health by petitioning administrative agencies, such as the Food and Drug Administration, to take safety actions. We examined a total of 1,915 petitions filed between 2001 and 2013 to investigate the outcomes of citizen petitions that address public health concerns. We found that most petitions were filed by manufacturers against other manufacturers. Only 346 (18%) of all petitions were submitted by individuals and non-profit organizations, and 178 (87.3%) of these petitions with a final response were denied. On average, these petitions required 2.85 years for a final agency decision, and many decisions remain pending 10-13 years after their initial submission. The great majority of the approved requests included some form of risk communication, such as labeling changes, boxed warnings or placement of a drug into a Risk Evaluation and Mitigation Strategy. As a policy instrument to improve the safety of medical and food products, the citizen petition process requires sophisticated legal and scientific expertise, and may not represent a viable route for ordinary citizens to petition the FDA to "redress grievances."

  5. Review: The Great Gatsby

    Directory of Open Access Journals (Sweden)

    Antonia de Jesus Sales

    2016-08-01

    Full Text Available A presente resenha busca discutir a tradução de The Great Gatsby para o contexto brasileiro. Diversas traduções foram feitas, em diversas épocas e com repercussão positiva no contexto brasileiro. Para o presente estudo, foi observada a tradução de Vanessa Bárbara, de 2011. Nesse sentido, o aspecto biográficos do autor e a forma como se apresentam os personagens na obra são fatores de cotejamento na obra original e na tradução brasileira. Francis Scott Key Fitzgerald (1896 – 1940 é famoso por ter em suas obras traços biográficos, algo que certamente influencia o leitor que adentra a sua obra. Quanto à recepção de O Grande Gatsby no contexto brasileiro, há que se considerar que O Grande Gatsby teve diversas traduções no Brasil. Depois dessa tradução de Vanessa Bárbara, em 2011, outras três vieram em 2013, juntamente com o filme. Há que considerar os aspectos comerciais embutidos nessas traduções e que muito corroboram para o resultado final. Prova disso são as capas, que são sempre diferenciadas em cada edição lançada. O tradutor nem sempre pode opinar sobre questões como estas. A tradução, a meu ver, é uma obra de qualidade, visto que a tradutora buscou ser fiel, sem dificultar a interpretação da obra para o leitor.

  6. Review: The Great Gatsby

    Directory of Open Access Journals (Sweden)

    Antonia de Jesus Sales

    2016-05-01

    Full Text Available A presente resenha busca discutir a tradução de The Great Gatsby para o contexto brasileiro. Diversas traduções foram feitas, em diversas épocas e com repercussão positiva no contexto brasileiro. Para o presente estudo, foi observada a tradução de Vanessa Bárbara, de 2011. Nesse sentido, o aspecto biográficos do autor e a forma como se apresentam os personagens na obra são fatores de cotejamento na obra original e na tradução brasileira. Francis Scott Key Fitzgerald (1896 – 1940 é famoso por ter em suas obras traços biográficos, algo que certamente influencia o leitor que adentra a sua obra. Quanto à recepção de O Grande Gatsby no contexto brasileiro, há que se considerar que O Grande Gatsby teve diversas traduções no Brasil. Depois dessa tradução de Vanessa Bárbara, em 2011, outras três vieram em 2013, juntamente com o filme. Há que considerar os aspectos comerciais embutidos nessas traduções e que muito corroboram para o resultado final. Prova disso são as capas, que são sempre diferenciadas em cada edição lançada. O tradutor nem sempre pode opinar sobre questões como estas. A tradução, a meu ver, é uma obra de qualidade, visto que a tradutora buscou ser fiel, sem dificultar a interpretação da obra para o leitor.

  7. The complications of controlling agency time discretion: FDA review deadlines and postmarket drug safety.

    Science.gov (United States)

    Carpenter, Daniel; Chattopadhyay, Jacqueline; Moffitt, Susan; Nall, Clayton

    2012-01-01

    Public agencies have discretion on the time domain, and politicians deploy numerous policy instruments to constrain it. Yet little is known about how administrative procedures that affect timing also affect the quality of agency decisions. We examine whether administrative deadlines shape decision timing and the observed quality of decisions. Using a unique and rich dataset of FDA drug approvals that allows us to examine decision timing and quality, we find that this administrative tool induces a piling of decisions before deadlines, and that these “just-before-deadline” approvals are linked with higher rates of postmarket safety problems (market withdrawals, severe safety warnings, safety alerts). Examination of data from FDA advisory committees suggests that the deadlines may impede quality by impairing late-stage deliberation and agency risk communication. Our results both support and challenge reigning theories about administrative procedures, suggesting they embody expected control-expertise trade-offs, but may also create unanticipated constituency losses.

  8. FDA direct-to-consumer advertising for prescription drugs: what are consumer preferences and response tendencies?

    Science.gov (United States)

    Khanfar, Nile; Loudon, David; Sircar-Ramsewak, Feroza

    2007-01-01

    The effect of direct-to-consumer (DTC) television advertising of prescription medications is a growing concern of the United States (U.S.) Congress, state legislatures, and the Food and Drug Administration (FDA). This research study was conducted in order to examine consumers' perceived preferences of DTC television advertisement in relation to "reminder" "help-seeking," and "product-claim" FDA-approved advertisement categories. An additional objective was to examine the influence of DTC television advertising of prescription drugs on consumers' tendency to seek more information about the medication and/or the medical condition. The research indicates that DTC television drug ads appear to be insufficient for consumers to make informed decisions. Their mixed perception and acceptance of the advertisements seem to influence them to seek more information from a variety of medical sources.

  9. A Comprehensive Review of US FDA-Approved Immune Checkpoint Inhibitors in Urothelial Carcinoma

    Directory of Open Access Journals (Sweden)

    Fu-Shun Hsu

    2017-01-01

    Full Text Available Few effective treatment options are available for patients with advanced or metastatic urothelial carcinoma (UC after unsuccessful first-line platinum-based chemotherapy. To date, immune checkpoint inhibitors are novel therapeutic agents for UC treatment. From May 2016 to May 2017, five anti-PD-1/PD-L1 monoclonal antibodies received accelerated or regular approval from the US Food and Drug Administration (FDA for the treatment of patients with locally advanced or metastatic UC. The present comprehensive review presents the background information of these five US FDA-approved anticancer agents to provide a basic but concise understanding of these agents for advanced studies. We summarize their immune checkpoint mechanisms, clinical efficacy, recommended usage protocols, adverse events, and the limitations of the PD-L1 biomarker assays.

  10. Network-Based Real-time Integrated Fire Detection and Alarm (FDA) System with Building Automation

    Science.gov (United States)

    Anwar, F.; Boby, R. I.; Rashid, M. M.; Alam, M. M.; Shaikh, Z.

    2017-11-01

    Fire alarm systems have become increasingly an important lifesaving technology in many aspects, such as applications to detect, monitor and control any fire hazard. A large sum of money is being spent annually to install and maintain the fire alarm systems in buildings to protect property and lives from the unexpected spread of fire. Several methods are already developed and it is improving on a daily basis to reduce the cost as well as increase quality. An integrated Fire Detection and Alarm (FDA) systems with building automation was studied, to reduce cost and improve their reliability by preventing false alarm. This work proposes an improved framework for FDA system to ensure a robust intelligent network of FDA control panels in real-time. A shortest path algorithmic was chosen for series of buildings connected by fiber optic network. The framework shares information and communicates with each fire alarm panels connected in peer to peer configuration and declare the network state using network address declaration from any building connected in network. The fiber-optic connection was proposed to reduce signal noises, thus increasing large area coverage, real-time communication and long-term safety. Based on this proposed method an experimental setup was designed and a prototype system was developed to validate the performance in practice. Also, the distributed network system was proposed to connect with an optional remote monitoring terminal panel to validate proposed network performance and ensure fire survivability where the information is sequentially transmitted. The proposed FDA system is different from traditional fire alarm and detection system in terms of topology as it manages group of buildings in an optimal and efficient manner.Introduction

  11. The FDA Food Safety and Modernization Act and the Exemption for Small Firms

    OpenAIRE

    Pouliot, Sebastien

    2011-01-01

    The FDA Food Safety Modernization Act of 2010 is new legislation that mandates, among other things, new food safety standards. The act includes a clause that exempts small firms from new regulatory requirements. This paper investigates the effects of a small firm exemption from more stringent food safety standards. The model compares food safety, total output and the number of market participants for different food safety regulation with and without an exemption for small firms. The numerical...

  12. Level of Evidence Associated with FDA Safety Communications with Drug Labeling Changes: 2010-2014

    Directory of Open Access Journals (Sweden)

    Benjamin Hixon

    2017-02-01

    Full Text Available Purpose: Approximately 800,000 safety reports are submitted to the FDA annually, however, only significant issues generate drug safety communications (DSC. The purpose of this study was to determine the type of clinical evidence used to warrant a change in drug labeling for drugs with DSC between January 1, 2010 and December 31, 2014. Methods: Selected data was obtained from the FDA website. The primary endpoint of the study was the frequency of the types of clinical evidence used in FDA communications, as reported through the FDA DSC. Results were evaluated via descriptive statistics, and chi-squared for nominal data. Results: A total of 2521 drug safety labeling changes were identified and 99 (3.9% of safety communications met the inclusion criteria. The majority of the labeling changes were associated with single agents (83.8%. The three most frequently reported labeling changes were warnings (68.7%, precautions (58.6%, and patient package insert/medication guide (23.2%. Case reports resulted in the greatest number of documented literature types (n = 791, followed by randomized controlled trials (n = 76, and case control/cohort studies (n = 74. Significantly more evidence for DSCs were classified as Level of Evidence B (LOE B, 68.6%, compared to LOE A (17.1%, and LOE C (14.1% (p = 0.007. Conclusions: The majority of drug labeling change initiators was associated with LOE equivalent to B. Practitioners should evaluate data associated with labeling changes to determine how to interpret the information for their patients. Conflict of Interest We declare no conflicts of interest or financial interests that the authors or members of their immediate families have in any product or service discussed in the manuscript, including grants (pending or received, employment, gifts, stock holdings or options, honoraria, consultancies, expert testimony, patents and royalties.   Type: Original Research

  13. FDA regulations regarding iodine addition to foods and labeling of foods containing added iodine12

    Science.gov (United States)

    Trumbo, Paula R

    2016-01-01

    The US Food and Drug Administration (FDA) regulates the addition of iodine to infant formulas, the iodization of salt, and the addition of salt and iodine to foods. The required amount of iodine in infant formulas is based on caloric content, and the label must provide the iodine content per 100 kcal. Cuprous iodide and potassium iodide may be added to table salt as a source of dietary iodine at a maximum amount of 0.01%; if added, the label must indicate that the salt is iodized. Table salt to which iodine has not been added must bear the statement, “This salt does not supply iodide, a necessary nutrient.” If a nutrient is to be appropriately added to a food for the purpose of correcting a dietary insufficiency, there should be sufficient scientific information available to demonstrate a nutritional deficiency and/or identify a public health problem. Furthermore, the population groups that would benefit from the proposed fortification should be identified. If iodine is added to a food, the percent Daily Value of iodine must be listed. There are no FDA regulations governing ingredient standards for dietary supplements. As a result, some dietary supplements include iodine and others do not. If a supplement contains iodine, the Supplement Facts label must list iodine as a nutrient ingredient. If iodine is not listed on the Supplement Facts label, then it has not been added. There are similarities between the FDA, which establishes US food regulations and policies, and the Codex Alimentarius (Codex), which develops international food standards and guidelines under the aegis of the FAO and the WHO. Both the FDA and Codex call for the labeling of table salt to indicate fortification with iodine, voluntary labeling of iodine on foods, and a Daily Value (called a Nutrient Reference Value by Codex) of 150 μg for iodine. PMID:27534626

  14. Regulating (for the benefit of) future persons: a different perspective on the FDA's jurisdiction to regulate human reproductive cloning.

    Science.gov (United States)

    Javitt, Gail H; Hudson, Kathy

    2003-01-01

    The Food and Drug Administration (FDA) has taken the position that human reproductive cloning falls within its regulatory jurisdiction. This position has been subject to criticism on both procedural and substantive grounds. Some have contended that the FDA has failed to follow administrative law principles in asserting its jurisdiction, while others claim the FDA is ill suited to the task of addressing the ethical and social implications of human cloning. This Article argues, that, notwithstanding these criticisms, the FDA could plausibly assert jurisdiction over human cloning as a form of human gene therapy, an area in which the FDA is already regarded as having primary regulatory authority. Such an assertion would require that the FDA's jurisdiction extend to products affecting future persons, i.e., those not yet born. This Article demonstrates, for the first time, that such jurisdiction was implicit in the enactment of the 1962 Kefauver-Harris Amendments to the Federal Food, Drug, and Cosmetic Act and that the FDA has historically relied on such authority in promulgating regulations for drugs and devices.

  15. Great Lakes Environmental Database (GLENDA)

    Data.gov (United States)

    U.S. Environmental Protection Agency — The Great Lakes Environmental Database (GLENDA) houses environmental data on a wide variety of constituents in water, biota, sediment, and air in the Great Lakes area.

  16. FDA & digital mammography: why has FDA required full field digital mammography systems to be regulated as potentially dangerous devices for more than 10 years?

    Science.gov (United States)

    Nields, Morgan W

    2010-05-01

    Digital mammography is routinely used in the US to screen asymptomatic women for breast cancer and currently over 50% of US screening centers employ the technology. In spite of FDAs knowledge that digital mammography requires less radiation than film mammography and that its equivalence has been proven in a prospective randomized trial, the agency has failed to allow the technology market access via the 510(k) pre market clearance pathway. As a result of the restrictive Pre Market Approval process, only four suppliers have received FDA approval. The resulting lack of a competitive market has kept costs high, restricted technological innovation, and impeded product improvements as a result of PMA requirements. Meanwhile, at least twelve companies are on the market in the EU and the resulting competitive market has lowered costs and provided increased technological choice. A cultural change with new leadership occurred in the early 90's at FDA. The historical culture at the Center for Devices and Radiological Health of collaboration and education gave way to one characterized by a lack of reliance on outside scientific expertise, tolerance of decision making by unqualified reviewers, and an emphasis on enforcement and punishment. Digital mammography fell victim to this cultural change and as a result major innovations like breast CT and computer aided detection technologies are also withheld from the market. The medical device law, currently under review by the Institute of Medicine, should be amended by the Congress so that new technologies can be appropriately classified in accordance with the risk based assessment classification system detailed in Chapter V of the Federal Food, Drug, and Cosmetic Act. A panel of scientific experts chartered by the NIH or IOM should determine the classification appropriate for new technologies that have no historical regulatory framework. This would be binding on FDA. Unless the law is changed we will likely again experience

  17. FDA Food Code recommendations: how do popular US baking shows measure up?

    Directory of Open Access Journals (Sweden)

    Valerie Cadorett

    2018-05-01

    Full Text Available The purpose of this study was to determine if popular US baking shows follow the FDA Food Code recommendations and critical food safety principles. This cross-sectional study examined a convenience sample of 75 episodes from three popular baking shows. The three shows were about competitively baking cupcakes, competitively baking cakes, and baking in a popular local bakery. Twenty-five episodes from each show were viewed. Coding involved tallying how many times 17 FDA Food Code recommendations were or were not followed. On each show, bare hands frequently came in contact with ready-to-eat food. On a per-hour basis, this occurred 80, 155, and 176 times on shows 1-3, respectively. Hands were washed before cooking three times on the three shows and never for the recommended 20 seconds. On each show, many people touched food while wearing jewelry other than a plain wedding band, for an average of at least 7 people per hour on each show. Shows 1-3 had high rates of long-haired bakers not wearing hair restraints (11.14, 6.57, and 14.06 per hour, respectively. Shows 1 and 2 had high rates of running among the bakers (22.29 and 10.57 instances per hour, respectively. These popular baking shows do not demonstrate proper food safety techniques put forth by the FDA and do not contribute the reduction of foodborne illnesses through proper food handling.

  18. A common feature pharmacophore for FDA-approved drugs inhibiting the Ebola virus.

    Science.gov (United States)

    Ekins, Sean; Freundlich, Joel S; Coffee, Megan

    2014-01-01

    We are currently faced with a global infectious disease crisis which has been anticipated for decades. While many promising biotherapeutics are being tested, the search for a small molecule has yet to deliver an approved drug or therapeutic for the Ebola or similar filoviruses that cause haemorrhagic fever. Two recent high throughput screens published in 2013 did however identify several hits that progressed to animal studies that are FDA approved drugs used for other indications. The current computational analysis uses these molecules from two different structural classes to construct a common features pharmacophore. This ligand-based pharmacophore implicates a possible common target or mechanism that could be further explored. A recent structure based design project yielded nine co-crystal structures of pyrrolidinone inhibitors bound to the viral protein 35 (VP35). When receptor-ligand pharmacophores based on the analogs of these molecules and the protein structures were constructed, the molecular features partially overlapped with the common features of solely ligand-based pharmacophore models based on FDA approved drugs. These previously identified FDA approved drugs with activity against Ebola were therefore docked into this protein. The antimalarials chloroquine and amodiaquine docked favorably in VP35. We propose that these drugs identified to date as inhibitors of the Ebola virus may be targeting VP35. These computational models may provide preliminary insights into the molecular features that are responsible for their activity against Ebola virus in vitro and in vivo and we propose that this hypothesis could be readily tested.

  19. Heparin crisis 2008: a tipping point for increased FDA enforcement in the pharma sector?

    Science.gov (United States)

    Rosania, Larry

    2010-01-01

    Against a backdrop of steady deregulation, the pharmaceutical industry is increasingly outsourcing manufacturing, resulting in decentralized control of the global supply chain. Established products such as heparin have been held to outdated analytical standards. Ten million Americans receive heparin every year; Baxter International accounts for half of this market. In 2008, contamination of Baxter's heparin--sourced in China--resulted in about 350 adverse events and 150 deaths in the United States. In future, increasingly stringent FDA inspections and enforcement are expected for imported drugs and ingredients. More regional FDA offices will be set up overseas. FDA funding will likely be supplemented in future by user fees charged to importers. For newer products, companies will face pressure to adopt Quality by Design, with solid control of the global supply chain and a proactive focus on GMP. Older products will be held to modern standards. Long-term, imports of drugs and ingredients from developing markets will continue. This makes sense to companies from an economic standpoint, but protections will be essential to ensure that it is also justifiable from a public health perspective.

  20. Science, law, and politics in the Food and Drug Administration's genetically engineered foods policy: FDA's 1992 policy statement.

    Science.gov (United States)

    Pelletier, David L

    2005-05-01

    The US Food and Drug Administration's (FDA's) 1992 policy statement was developed in the context of critical gaps in scientific knowledge concerning the compositional effects of genetic transformation and severe limitations in methods for safety testing. FDA acknowledged that pleiotropy and insertional mutagenesis may cause unintended changes, but it was unknown whether this happens to a greater extent in genetic engineering compared with traditional breeding. Moreover, the agency was not able to identify methods by which producers could screen for unintended allergens and toxicants. Despite these uncertainties, FDA granted genetically engineered foods the presumption of GRAS (Generally Recognized As Safe) and recommended that producers use voluntary consultations before marketing them.

  1. Estimation of Viable Biomass In Wastewater And Activated Sludge By Determination of ATP, Oxygen Utilization Rate And FDA Hydrolysis

    DEFF Research Database (Denmark)

    Jørgensen, Poul-Erik; Eriksen, T.; Jensen, B.K.

    1992-01-01

    ATP content, oxygen utilization rate (OUR) and fluorescein diacetate (FDA) hydrolysis were tested for the ability to express the amount of viable biomass in wastewater and activated sludge. The relationship between biomass and these activity parameters was established in growth cultures made...... with biomass, while FDA hydrolysis in the sludge failed to show any such correlation. Conversion factors of 3 mg ATP/g dw, 300 mg O2/h g dw and 0.4 A/h (mg dw/ml) for ATP, OUR and FDA methods, respectively, were calculated. When the methods were applied for in situ determinations in four different wastewater...... plants, it was found that ATP content and respiration rate estimated viable biomass to range from 81 to 293 mg dw/g SS for raw wastewater and from 67 to 187 mg dw/g SS for activated sludge with a rather weak correlation between ATP and respiration measurements. The FDA hydrolysis estimated viable biomass...

  2. Schedules of Controlled Substances: Placement of FDA-Approved Products of Oral Solutions Containing Dronabinol [(-)-delta-9-trans-

    Science.gov (United States)

    2017-11-22

    This final rule adopts without changes an interim final rule with request for comments published in the Federal Register on March 23, 2017. On July 1, 2016, the U.S. Food and Drug Administration (FDA) approved a new drug application for Syndros, a drug product consisting of dronabinol [(-)-delta-9-trans-tetrahydrocannabinol (delta-9-THC)] oral solution. The Drug Enforcement Administration (DEA) maintains FDA-approved products of oral solutions containing dronabinol in schedule II of the Controlled Substances Act.

  3. Medical devices: reports of corrections and removals; delay of effective data--FDA. Direct final rule; delay of effective date.

    Science.gov (United States)

    1998-11-18

    The Food and Drug Administration (FDA) published in the Federal Register of August 7, 1998 (63 FR 42229), a direct final rule. The direct final rule notified the public of FDA's intention to amend the regulations that govern reports of corrections and removals of medical devices to eliminate the requirement for distributors to make such reports. This document delays the effective date of the direct final rule.

  4. Medicare covers the majority of FDA-approved devices and Part B drugs, but restrictions and discrepancies remain.

    Science.gov (United States)

    Chambers, James D; May, Katherine E; Neumann, Peter J

    2013-06-01

    The Food and Drug Administration (FDA) and Medicare use different standards to determine, first, whether a new drug or medical device can be marketed to the public and, second, if the federal health insurance program will pay for use of the drug or device. This discrepancy creates hurdles and uncertainty for drug and device manufacturers. We analyzed discrepancies between FDA approval and Medicare national coverage determinations for sixty-nine devices and Part B drugs approved during 1999-2011. We found that Medicare covered FDA-approved drugs or devices 80 percent of the time. However, Medicare often added conditions beyond FDA approval, particularly for devices and most often restricting coverage to patients with the most severe disease. In some instances, Medicare was less restrictive than the FDA. Our findings highlight the importance for drug and device makers of anticipating Medicare's needs when conducting clinical studies to support their products. Our findings also provide important insights for the FDA's and Medicare's pilot parallel review program.

  5. Dose Uniformity of Scored and Unscored Tablets: Application of the FDA Tablet Scoring Guidance for Industry.

    Science.gov (United States)

    Ciavarella, Anthony B; Khan, Mansoor A; Gupta, Abhay; Faustino, Patrick J

    This U.S. Food and Drug Administration (FDA) laboratory study examines the impact of tablet splitting, the effect of tablet splitters, and the presence of a tablet score on the dose uniformity of two model drugs. Whole tablets were purchased from five manufacturers for amlodipine and six for gabapentin. Two splitters were used for each drug product, and the gabapentin tablets were also split by hand. Whole and split amlodipine tablets were tested for content uniformity following the general chapter of the United States Pharmacopeia (USP) Uniformity of Dosage Units , which is a requirement of the new FDA Guidance for Industry on tablet scoring. The USP weight variation method was used for gabapentin split tablets based on the recommendation of the guidance. All whole tablets met the USP acceptance criteria for the Uniformity of Dosage Units. Variation in whole tablet content ranged from 0.5 to 2.1 standard deviation (SD) of the percent label claim. Splitting the unscored amlodipine tablets resulted in a significant increase in dose variability of 6.5-25.4 SD when compared to whole tablets. Split tablets from all amlodipine drug products did not meet the USP acceptance criteria for content uniformity. Variation in the weight for gabapentin split tablets was greater than the whole tablets, ranging from 1.3 to 9.3 SD. All fully scored gabapentin products met the USP acceptance criteria for weight variation. Size, shape, and the presence or absence of a tablet score can affect the content uniformity and weight variation of amlodipine and gabapentin tablets. Tablet splitting produced higher variability. Differences in dose variability and fragmentation were observed between tablet splitters and hand splitting. These results are consistent with the FDA's concerns that tablet splitting can have an effect on the amount of drug present in a split tablet and available for absorption. Tablet splitting has become a very common practice in the United States and throughout the

  6. FDA drug safety communications: a narrative review and clinical considerations for older adults.

    Science.gov (United States)

    Marcum, Zachary A; Vande Griend, Joseph P; Linnebur, Sunny A

    2012-08-01

    The US Food and Drug Administration (FDA) has new regulatory authorities intended to enhance drug safety monitoring in the postmarketing period. This has resulted in an increase in communication from the FDA in recent years about the safety profile of certain drugs. It is important to stay abreast of the current literature on drug risks to effectively communicate these risks to patients, other health care providers, and the general public. To summarize 4 new FDA drug safety communications by describing the evidence supporting the risks and the clinical implications for older adults. The FDA Web site was reviewed for new drug safety communications from May 2011 to April 2012 that would be relevant to older adults. Approved labeling for each drug or class was obtained from the manufacturer, and PubMed was searched for primary literature that supported the drug safety concern. FDA drug safety communications for 4 drugs were chosen because of the potential clinical importance in older adults. A warning for citalopram was made because of potential problems with QT prolongation in patients taking less than 40 mg per day. The evidence suggests minor changes in QT interval. Given the flat dose-response curve in treating depression with citalopram, the new 20-mg/d maximum dose in older adults is sensible. Another warning was made for proton pump inhibitors (PPIs) and an increased risk of Clostridium difficile infection. A dose-response relationship was found for this drug risk. With C. difficile infections on the rise in older adults, along with other safety risks of PPI therapy, PPIs should only be used in older adults indicated for therapy for the shortest duration possible. In addition, a warning about dabigatran was made. There is strong evidence from a large clinical trial, as well as case reports, of increased bleeding risk in older adults taking dabigatran, especially in older adults with decreased renal function. This medication should be used with caution in older

  7. Justification of disintegration testing beyond current FDA criteria using in vitro and in silico models.

    Science.gov (United States)

    Uebbing, Lukas; Klumpp, Lukas; Webster, Gregory K; Löbenberg, Raimar

    2017-01-01

    Drug product performance testing is an important part of quality-by-design approaches, but this process often lacks the underlying mechanistic understanding of the complex interactions between the disintegration and dissolution processes involved. Whereas a recent draft guideline by the US Food and Drug Administration (FDA) has allowed the replacement of dissolution testing with disintegration testing, the mentioned criteria are not globally accepted. This study provides scientific justification for using disintegration testing rather than dissolution testing as a quality control method for certain immediate release (IR) formulations. A mechanistic approach, which is beyond the current FDA criteria, is presented. Dissolution testing via United States Pharmacopeial Convention Apparatus II at various paddle speeds was performed for immediate and extended release formulations of metronidazole. Dissolution profile fitting via DDSolver and dissolution profile predictions via DDDPlus™ were performed. The results showed that Fickian diffusion and drug particle properties (DPP) were responsible for the dissolution of the IR tablets, and that formulation factors (eg, coning) impacted dissolution only at lower rotation speeds. Dissolution was completely formulation controlled if extended release tablets were tested and DPP were not important. To demonstrate that disintegration is the most important dosage form attribute when dissolution is DPP controlled, disintegration, intrinsic dissolution and dissolution testing were performed in conventional and disintegration impacting media (DIM). Tablet disintegration was affected by DIM and model fitting to the Korsmeyer-Peppas equation showed a growing effect of the formulation in DIM. DDDPlus was able to predict tablet dissolution and the intrinsic dissolution profiles in conventional media and DIM. The study showed that disintegration has to occur before DPP-dependent dissolution can happen. The study suggests that

  8. Association of Attorney Advertising and FDA Action with Prescription Claims: A Time Series Segmented Regression Analysis.

    Science.gov (United States)

    Tippett, Elizabeth C; Chen, Brian K

    2015-12-01

    Attorneys sponsor television advertisements that include repeated warnings about adverse drug events to solicit consumers for lawsuits against drug manufacturers. The relationship between such advertising, safety actions by the US Food and Drug Administration (FDA), and healthcare use is unknown. To investigate the relationship between attorney advertising, FDA actions, and prescription drug claims. The study examined total users per month and prescription rates for seven drugs with substantial attorney advertising volume and FDA or other safety interventions during 2009. Segmented regression analysis was used to detect pre-intervention trends, post-intervention level changes, and changes in post-intervention trends relative to the pre-intervention trends in the use of these seven drugs, using advertising volume, media hits, and the number of Medicare enrollees as covariates. Data for these variables were obtained from the Center for Medicare and Medicaid Services, Kantar Media, and LexisNexis. Several types of safety actions were associated with reductions in drug users and/or prescription rates, particularly for fentanyl, varenicline, and paroxetine. In most cases, attorney advertising volume rose in conjunction with major safety actions. Attorney advertising volume was positively correlated with prescription rates in five of seven drugs, likely because advertising volume began rising before safety actions, when prescription rates were still increasing. On the other hand, attorney advertising had mixed associations with the number of users per month. Regulatory and safety actions likely reduced the number of users and/or prescription rates for some drugs. Attorneys may have strategically chosen to begin advertising adverse drug events prior to major safety actions, but we found little evidence that attorney advertising reduced drug use. Further research is needed to better understand how consumers and physicians respond to attorney advertising.

  9. FDA advisory committees meet January 26 on Salk HIV-1 immunogen.

    Science.gov (United States)

    1995-01-06

    Two advisory committees of the Food and Drug Administration (FDA) will meet to consider future trials of the HIV-1 immunogen developed by Dr. Jonas Salk. The Immune Response Corporation has already conducted several studies of the immunogen, and has found improvement in various immunological and other blood tests, and no adverse effects. However, the studies have not been large enough to show conclusively that the treatment has clinical benefit in delaying disease progression. The new, larger trials are intended to demonstrate a delay in disease progression and validate the use of blood-test markers of disease progression for studying an immune-based treatment.

  10. FDA Approves Immunotherapy for a Cancer that Affects Infants and Children | Poster

    Science.gov (United States)

    By Frank Blanchard, Staff Writer The U.S. Food and Drug Administration (FDA) recently approved dinutuximab (ch14.18) as an immunotherapy for neuroblastoma, a rare type of childhood cancer that offers poor prognosis for about half of the children who are affected. The National Cancer Institute’s (NCI) Biopharmaceutical Development Program (BDP) at the Frederick National Laboratory for Cancer Research produced ch14.18 for the NCI-sponsored clinical trials that proved the drug’s effectiveness against the disease.

  11. Changes in FDA enforcement activities following changes in federal administration: the case of regulatory letters released to pharmaceutical companies.

    Science.gov (United States)

    Nguyen, Diane; Seoane-Vazquez, Enrique; Rodriguez-Monguio, Rosa; Montagne, Michael

    2013-01-22

    The United States (US) Food and Drug Administration (FDA) is responsible for the protection of the public health by assuring the safety, effectiveness and security of human drugs and biological products through the enforcement of the Federal Food, Drug and Cosmetic Act (FDCA) and related regulations. These enforcement activities include regulatory letters (i.e. warning letters and notice of violation) to pharmaceutical companies. A regulatory letter represents the FDA's first official notification to a pharmaceutical company that the FDA has discovered a product or activity in violation of the FDCA.This study analyzed trends in the pharmaceutical-related regulatory letters released by the FDA during the period 1997-2011 and assessed differences in the average number and type of regulatory letters released during the last four federal administrations. Data derived from the FDA webpage. Information about the FDA office releasing the letter, date, company, and drug-related violation was collected. Regulatory letters were classified by federal administration. Descriptive statistics were performed for the analysis. Between 1997 and 2011 the FDA released 2,467 regulatory letters related to pharmaceuticals. FDA headquarters offices released 50.6% and district offices 49.4% of the regulatory letters. The Office of Prescription Drug Promotion released the largest number of regulatory letters (850; 34.5% of the total), followed by the Office of Scientific Investigations (131; 5.3%), and the Office of Compliance (105; 4.3%). During the 2nd Clinton Administration (1997-2000) the average number of regulatory letters per year was 242.8 ± 45.6, during the Bush Administration (2001-2008) it was 120.4 ± 33.7, and during the first three years of the Obama administration (2009-2011) it was 177.7.0 ± 17.0. The average number of regulatory letters released by the Office of Prescription Drug Promotion also varied by administration: Clinton (122.3 ± 36.4), Bush (29.5

  12. What Caused the Great Depression?

    Science.gov (United States)

    Caldwell, Jean; O'Driscoll, Timothy G.

    2007-01-01

    Economists and historians have struggled for almost 80 years to account for the American Great Depression, which began in 1929 and lasted until the early years of World War II. In this article, the authors discuss three major schools of thought on the causes of the Great Depression and the long failure of the American economy to return to full…

  13. High performance ZIF-8/6FDA-DAM mixed matrix membrane for propylene/propane separations

    KAUST Repository

    Zhang, Chen

    2012-02-01

    We report significantly enhanced propylene/propane (C 3H 6/C 3H 8) selectivity in mixed matrix membranes fabricated using 6FDA-DAM polyimide and a zeolitic imidazolate framework (ZIF-8). Equilibrium isotherms and sorption kinetics of C 3H 6 and C 3H 8 at 35°C were studied on a 200nm commercially available ZIF-8 sample produced by BASF. Mixed matrix dense films were formed with 6FDA-DAM and 200nm BASF ZIF-8 particles. SEM imaging showed generally good adhesion between the ZIF-8 and 6FDA-DAM without the need for surface-treating ZIF-8. Pure gas permeation showed significantly enhanced mixed matrix ZIF-8/6FDA-DAM membrane C 3H 6/C 3H 8 separation performance over the pure 6FDA-DAM membrane performance. A C 3H 6 permeability of 56.2Barrer and C 3H 6/C 3H 8 ideal selectivity of 31.0 was found in ZIF-8/6FDA-DAM mixed matrix membrane with 48.0wt% ZIF-8 loading, which are 258% and 150% higher than the pure 6FDA-DAM membrane, respectively for permeability and selectivity. Permeation properties of C 3H 6 and C 3H 8 in ZIF-8 were back-calculated by the Maxwell model for composite permeability using pure gas permeation data, leading to a C 3H 6 permeability of 277Barrer and C 3H 6/C 3H 8 selectivity of 122. Mixed gas permeation also verified that selectivity enhancements were achievable in mixed gas environment by ZIF-8. © 2011 Elsevier B.V.

  14. Comparison of the FDA and ASCO/CAP Criteria for HER2 Immunohistochemistry in Upper Urinary Tract Urothelial Carcinoma

    Directory of Open Access Journals (Sweden)

    Gilhyang Kim

    2016-11-01

    Full Text Available Background Human epidermal growth factor receptor 2 (HER2 is one of the known oncogenes in urothelial carcinoma. However, the association between HER2 and the prognosis of upper urinary tract urothelial carcinoma (UUTUC has not yet been fully clarified. The aim of this study was to evaluate HER2 expression using the United States Food and Drug Administration (FDA criteria and American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP criteria and compare their prognostic significance in UUTUC. Methods HER2 expression was evaluated in 144 cases of UUTUC by immunohistochemistry (IHC using tissue microarrays. We separately analyzed HER2 expression using the FDA and ASCO/CAP criteria. The IHC results were categorized into low (0, 1+ and high (2+, 3+ groups. Results Using the FDA criteria, 94 cases were negative, 38 cases were 1+, nine cases were 2+, and three cases were 3+. Using the ASCO/CAP criteria, 94 cases were negative, 34 cases were 1+, 13 cases were 2+, and three cases were 3+. Four cases showing 2+ according to the ASCO/CAP criteria were reclassified as 1+ by the FDA criteria. High HER2 expression by both the FDA criteria and ASCO/CAP criteria was significantly associated with International Society of Urological Pathology high grade (p = .001 and p < .001. The high HER2 expression group classified with the FDA criteria showed significantly shorter cancer-specific survival (p = .004, but the HER2 high and low expression groups classified with the ASCO/CAP criteria did not show significant differences (p = .161 in cancer-specific survival. Conclusions HER2 high expression groups were significantly associated with shorter cancer-specific survival, and our study revealed that the FDA criteria are more suitable for determining HER2 expression in UUTUC.

  15. High performance ZIF-8/6FDA-DAM mixed matrix membrane for propylene/propane separations

    KAUST Repository

    Zhang, Chen; Dai, Ying; Johnson, Justin R.; Karvan, Oguz; Koros, William J.

    2012-01-01

    We report significantly enhanced propylene/propane (C 3H 6/C 3H 8) selectivity in mixed matrix membranes fabricated using 6FDA-DAM polyimide and a zeolitic imidazolate framework (ZIF-8). Equilibrium isotherms and sorption kinetics of C 3H 6 and C 3H 8 at 35°C were studied on a 200nm commercially available ZIF-8 sample produced by BASF. Mixed matrix dense films were formed with 6FDA-DAM and 200nm BASF ZIF-8 particles. SEM imaging showed generally good adhesion between the ZIF-8 and 6FDA-DAM without the need for surface-treating ZIF-8. Pure gas permeation showed significantly enhanced mixed matrix ZIF-8/6FDA-DAM membrane C 3H 6/C 3H 8 separation performance over the pure 6FDA-DAM membrane performance. A C 3H 6 permeability of 56.2Barrer and C 3H 6/C 3H 8 ideal selectivity of 31.0 was found in ZIF-8/6FDA-DAM mixed matrix membrane with 48.0wt% ZIF-8 loading, which are 258% and 150% higher than the pure 6FDA-DAM membrane, respectively for permeability and selectivity. Permeation properties of C 3H 6 and C 3H 8 in ZIF-8 were back-calculated by the Maxwell model for composite permeability using pure gas permeation data, leading to a C 3H 6 permeability of 277Barrer and C 3H 6/C 3H 8 selectivity of 122. Mixed gas permeation also verified that selectivity enhancements were achievable in mixed gas environment by ZIF-8. © 2011 Elsevier B.V.

  16. Drugs Cleared Through The FDA's Expedited Review Offer Greater Gains Than Drugs Approved By Conventional Process.

    Science.gov (United States)

    Chambers, James D; Thorat, Teja; Wilkinson, Colby L; Neumann, Peter J

    2017-08-01

    We investigated whether drugs approved by the Food and Drug Administration (FDA) through expedited review have offered larger health gains, compared to drugs approved through conventional review processes. We identified published estimates of additional health gains (measured in quality-adjusted life-years, or QALYs) associated with drugs approved in the period 1999-2012 through expedited (seventy-six drugs) versus conventional (fifty-nine) review processes. We found that drugs in at least one expedited review program offered greater gains than drugs reviewed through conventional processes (0.182 versus 0.003 QALYs). We also found that, compared to drugs not included in the same program, greater gains were provided by drugs in the priority review (0.175 versus 0.007 QALYs), accelerated approval (0.370 versus 0.031 QALYs), and fast track (0.254 versus 0.014 QALYs) programs. Our analysis suggests that the FDA has prioritized drugs that offer the largest health gains. Project HOPE—The People-to-People Health Foundation, Inc.

  17. FDA cigarette warning labels lower craving and elicit frontoinsular activation in adolescent smokers

    Science.gov (United States)

    Do, Kathy T.

    2015-01-01

    Cigarette smoking is an economically and epidemiologically expensive public health concern. Most adult smokers become addicted during adolescence, rendering it a crucial period for prevention and intervention. Although litigation claims have delayed implementation, graphic warning labels proposed by the U.S. Food and Drug Administration (FDA) may be a promising way to achieve this goal. We aimed to determine the efficacy of the labels in reducing in-scanner craving and to characterize the neurobiological responses in adolescent and adult smokers and non-smokers. While undergoing functional magnetic resonance imaging, thirty-nine 13- to 18-year-old adolescent and forty-one 25- to 30-year-old adult smokers and non-smokers rated their desire to smoke when presented with emotionally graphic warning labels and comparison non-graphic labels. Compared with adult smokers, adolescent smokers exhibited greater craving reduction in response to the warning labels. Although smokers evinced overall blunted recruitment of insula and dorsolateral prefrontal cortex (DLPFC) relative to non-smokers, an effect that was stronger in adolescent smokers, parametrically increasing activation of these regions was associated with greater craving reduction. Functional connectivity analyses suggest that greater DLPFC regulation of limbic regions predicted cigarette craving. These data underscore a prominent role of frontoinsular circuitry in predicting the efficacy of FDA graphic warning labels in craving reduction in adult and adolescent smokers. PMID:25887154

  18. Smokers' reactions to FDA regulation of tobacco products: Findings from the 2009 ITC United States survey

    Directory of Open Access Journals (Sweden)

    Fix Brian V

    2011-12-01

    Full Text Available Abstract Background On June 22, 2009, the US FDA was granted the authority to regulate tobacco products through the Family Smoking Prevention and Tobacco Control Act (FSPTCA. The intent is to improve public health through regulations on tobacco product marketing and tobacco products themselves. This manuscript reports baseline data on smokers' attitudes and beliefs on specific issues relevant to the FSPTCA. Method Between November 2009 and January 2010, a telephone survey among a nationally representative sample of n = 678 smokers in the US was performed as part of the International Tobacco Control (ITC United States Survey. Participants answered a battery of questions on their attitudes and beliefs about aspects of the FSPTCA. Results Most smokers were unaware of the new FDA tobacco regulations. Smokers indicated support for banning cigarette promotion and nearly a quarter supported requiring tobacco companies to sell cigarettes in plain packaging. Seventy two percent of smokers supported reducing nicotine levels to make cigarettes less addictive if nicotine was made easily available in non-cigarette form. Conclusion Most smokers were limited in their understanding of efforts to regulate tobacco products in general. Smokers were supportive of efforts to better inform the public about health risks, restrict advertising, and make tobacco products less addictive.

  19. FDA, CE mark or something else?—Thinking fast and slow

    Directory of Open Access Journals (Sweden)

    Sundeep Mishra

    2017-01-01

    Full Text Available There is a robust debate going on among the Medical Device stake-holders whether FDA is better or CE mark or something else. Currently process of obtaining an FDA approval is bogged down by ever-increasing unpredictability, inconsistency, prolonged time, and huge expense but CE mark has its own problems. Historically, the Japanese review process has tended to be the slowest among the big three but recently with the introduction of accelerated review process there has been a significant progress. While the goal of an innovator/manufacturer is to develop, manufacture and market a medical device that addresses an unmet clinical need, the requisite regulatory approval process can be very confusing. Not only there is a whole lot of jargon tossed around by regulatory affair professionals: “substantial equivalence,” “PMDA,” “CE mark,” “Notified body,” “510K” and “PMA” but the actual approval process can also be very tardy, inconsistent and expensive.

  20. FDA, CE mark or something else?-Thinking fast and slow.

    Science.gov (United States)

    Mishra, Sundeep

    There is a robust debate going on among the Medical Device stake-holders whether FDA is better or CE mark or something else. Currently process of obtaining an FDA approval is bogged down by ever-increasing unpredictability, inconsistency, prolonged time, and huge expense but CE mark has its own problems. Historically, the Japanese review process has tended to be the slowest among the big three but recently with the introduction of accelerated review process there has been a significant progress. While the goal of an innovator/manufacturer is to develop, manufacture and market a medical device that addresses an unmet clinical need, the requisite regulatory approval process can be very confusing. Not only there is a whole lot of jargon tossed around by regulatory affair professionals: "substantial equivalence," "PMDA," "CE mark," "Notified body," "510K" and "PMA" but the actual approval process can also be very tardy, inconsistent and expensive. Copyright © 2016 Cardiological Society of India. Published by Elsevier B.V. All rights reserved.

  1. Changes in FDA enforcement activities following changes in federal administration: the case of regulatory letters released to pharmaceutical companies

    Directory of Open Access Journals (Sweden)

    Nguyen Diane

    2013-01-01

    Full Text Available Abstract Background The United States (US Food and Drug Administration (FDA is responsible for the protection of the public health by assuring the safety, effectiveness and security of human drugs and biological products through the enforcement of the Federal Food, Drug and Cosmetic Act (FDCA and related regulations. These enforcement activities include regulatory letters (i.e. warning letters and notice of violation to pharmaceutical companies. A regulatory letter represents the FDA’s first official notification to a pharmaceutical company that the FDA has discovered a product or activity in violation of the FDCA. This study analyzed trends in the pharmaceutical-related regulatory letters released by the FDA during the period 1997–2011 and assessed differences in the average number and type of regulatory letters released during the last four federal administrations. Methods Data derived from the FDA webpage. Information about the FDA office releasing the letter, date, company, and drug-related violation was collected. Regulatory letters were classified by federal administration. Descriptive statistics were performed for the analysis. Results Between 1997 and 2011 the FDA released 2,467 regulatory letters related to pharmaceuticals. FDA headquarters offices released 50.6% and district offices 49.4% of the regulatory letters. The Office of Prescription Drug Promotion released the largest number of regulatory letters (850; 34.5% of the total, followed by the Office of Scientific Investigations (131; 5.3%, and the Office of Compliance (105; 4.3%. During the 2nd Clinton Administration (1997–2000 the average number of regulatory letters per year was 242.8 ± 45.6, during the Bush Administration (2001–2008 it was 120.4 ± 33.7, and during the first three years of the Obama administration (2009–2011 it was 177.7.0 ± 17.0. The average number of regulatory letters released by the Office of Prescription Drug Promotion also varied by

  2. Usefulness of [18F]-DA and [18F]-DOPA for PET imaging in a mouse model of pheochromocytoma

    International Nuclear Information System (INIS)

    Martiniova, Lucia; Cleary, Susannah; Lai, Edwin W.; Kiesewetter, Dale O.; Seidel, Jurgen; Dawson, Linda F.; Phillips, Jacqueline K.; Thomasson, David; Chen Xiaoyuan; Eisenhofer, Graeme; Powers, James F.; Kvetnansky, Richard

    2012-01-01

    Purpose: To evaluate the usefulness of [ 18 F]-6-fluorodopamine ([ 18 F]-DA) and [ 18 F]-L-6-fluoro-3,4-dihydroxyphenylalanine ([ 18 F]-DOPA) positron emission tomography (PET) in the detection of subcutaneous (s.c.) and metastatic pheochromocytoma in mice; to assess the expression of the norepinephrine transporter (NET) and vesicular monoamine transporters 1 and 2 (VMAT1 and VMAT2), all important for [ 18 F]-DA and [ 18 F]-DOPA uptake. Furthermore, to compare tumor detection by micro-computed tomography (microCT) to magnetic resonance imaging (MRI) in individual mouse. Methods: SUV max values were calculated from [ 18 F]-DA and [ 18 F]-DOPA PET, tumor-to-liver ratios (TLR) were obtained and expression of NET, VMAT1 and VMAT2 was evaluated. Results: [ 18 F]-DA detected less metastatic lesions compared to [ 18 F]-DOPA. TLR values for liver metastases were 2.26–2.71 for [ 18 F]-DOPA and 1.83–2.83 for [ 18 F]-DA. A limited uptake of [ 18 F]-DA was found in s.c. tumors (TLR=0.22-0.27) compared to [ 18 F]-DOPA (TLR=1.56-2.24). Overall, NET and VMAT2 were expressed in all organ and s.c. tumors. However, s.c. tumors lacked expression of VMAT1. We confirmed [ 18 F]-DA's high affinity for the NET for its uptake and VMAT1 and VMAT2 for its storage and retention in pheochromocytoma cell vesicles. In contrast, [ 18 F]-DOPA was found to utilize only VMAT2. Conclusion: MRI was superior in the detection of all organ tumors compared to microCT and PET. [ 18 F]-DOPA had overall better sensitivity than [ 18 F]-DA for the detection of metastases. Subcutaneous tumors were localized only with [ 18 F]-DOPA, a finding that may reflect differences in expression of VMAT1 and VMAT2, perhaps similar to some patients with pheochromocytoma where [ 18 F]-DOPA provides better visualization of lesions than [ 18 F]-DA.

  3. America, you are digging your grave with your spoon--should the FDA tell you that on food labels?

    Science.gov (United States)

    Card, Melissa M

    2013-01-01

    R.J. Reynolds Tobacco Co. v. Food & Drug Admin. discussed whether the FDA's promulgation of graphic images violated tobacco companies' First Amendment rights. While the tobacco companies contested the graphic images, the tobacco companies did not contest the promulgation of nine textual statements about the adverse effects of cigarettes. This uncontested mandate opens a door for the FDA to further expand its regulatory scheme. If the FDA can mandate textual statements about the adverse effects of cigarettes, can the FDA mandate textual statements about the adverse effects of sugar to combat the obesity crisis? This Article presents three textual statements about the adverse effects of sugar, to define the line between acceptable and unacceptable forms of compelled commercial speech under Central Hudson. Establishing this line ensures that the commercial speech doctrine does not deny the FDA from its authority to provide consumers with accurate information. While three textual statements are presented, this Article advocates that one of the textual statements is likely to serve as the best solution to the obesity crisis. The chosen textual statement serves as an effective solution because it presents meaningful information to the consumers enabling consumers to make healthful decisions about their food and encourages manufacturers to modify their products.

  4. Great Lakes Environmental Research Laboratory

    Data.gov (United States)

    Federal Laboratory Consortium — NOAA-GLERL and its partners conduct innovative research on the dynamic environments and ecosystems of the Great Lakes and coastal regions to provide information for...

  5. What Caused the Great Recession?

    OpenAIRE

    Homburg, Stefan

    2014-01-01

    This paper examines five possible explanations for the Great Recession of 2008 and 2009, using data for the United States and the eurozone. Of these five hypotheses, four are not supported by the data, while the fifth appears reasonable.

  6. Arthroscopy of the great toe

    NARCIS (Netherlands)

    Frey, C.; van Dijk, C. N.

    1999-01-01

    The few available reports of arthroscopic treatment of the first MTP joint in the literature indicate favorable outcome. However, arthroscopy of the great toe is an advanced technique and should only be undertaken by experienced surgeons

  7. The Sixth Great Mass Extinction

    Science.gov (United States)

    Wagler, Ron

    2012-01-01

    Five past great mass extinctions have occurred during Earth's history. Humanity is currently in the midst of a sixth, human-induced great mass extinction of plant and animal life (e.g., Alroy 2008; Jackson 2008; Lewis 2006; McDaniel and Borton 2002; Rockstrom et al. 2009; Rohr et al. 2008; Steffen, Crutzen, and McNeill 2007; Thomas et al. 2004;…

  8. New FDA-Approved Disease-Modifying Therapies for Multiple Sclerosis.

    Science.gov (United States)

    English, Clayton; Aloi, Joseph J

    2015-04-01

    Interferon injectables and glatiramer acetate have served as the primary disease-modifying treatments for multiple sclerosis (MS) since their introduction in the 1990s and are first-line treatments for relapsing-remitting forms of MS (RRMS). Many new drug therapies were launched since early 2010, expanding the drug treatment options considerably in a disease state that once had a limited treatment portfolio. The purpose of this review is to critically evaluate the safety profile and efficacy data of disease-modifying agents for MS approved by the US Food and Drug Administration (FDA) from 2010 to the present and provide cost and available pharmacoeconomic data about each new treatment. Peer-reviewed clinical trials, pharmacoeconomic studies, and relevant pharmacokinetic/pharmacologic studies were identified from MEDLINE (January 2000-December 2014) by using the search terms multiple sclerosis, fingolimod, teriflunomide, alemtuzumab, dimethyl fumarate, pegylated interferon, peginterferon beta-1a, glatiramer 3 times weekly, and pharmacoeconomics. Citations from available articles were also reviewed for additional references. The databases publically available at www.clinicaltrials.gov and www.fda.gov were searched for unpublished studies or studies currently in progress. A total of 5 new agents and 1 new dosage formulation were approved by the FDA for the treatment of RRMS since 2010. Peginterferon beta-1a and high-dose glatiramer acetate represent 2 new effective injectable options for MS that reduce burden of administration seen with traditional interferon and low-dose glatiramer acetate. Fingolimod, teriflunomide, and dimethyl fumarate represent new oral agents available for MS, and their efficacy in reducing annualized relapse rates is 48% to 55%, 22% to 36.3%, and 44% to 53%, respectively, compared with placebo. Alemtuzumab is a biologic given over a 2-year span that reduced annualized relapse rates by 55% in treatment-naive patients and by 49% in patients

  9. Justification of disintegration testing beyond current FDA criteria using in vitro and in silico models

    Directory of Open Access Journals (Sweden)

    Uebbing L

    2017-04-01

    Full Text Available Lukas Uebbing,1,2,* Lukas Klumpp,1,3,* Gregory K Webster,4 Raimar Löbenberg1 1Faculty of Pharmacy and Pharmaceutical Sciences, Katz Group-Rexall Centre for Pharmacy and Health Research, University of Alberta, Edmonton, Canada; 2Institute of Pharmacy and Biochemistry, Johannes Gutenberg University, Mainz, 3Institute of Pharmaceutical Technology, Goethe University Frankfurt, Frankfurt, Germany; 4Global Research and Development, AbbVie Inc., North Chicago, IL, USA *These authors contributed equally to this work Abstract: Drug product performance testing is an important part of quality-by-design approaches, but this process often lacks the underlying mechanistic understanding of the complex interactions between the disintegration and dissolution processes involved. Whereas a recent draft guideline by the US Food and Drug Administration (FDA has allowed the replacement of dissolution testing with disintegration testing, the mentioned criteria are not globally accepted. This study provides scientific justification for using disintegration testing rather than dissolution testing as a quality control method for certain immediate release (IR formulations. A mechanistic approach, which is beyond the current FDA criteria, is presented. Dissolution testing via United States Pharmacopeial Convention Apparatus II at various paddle speeds was performed for immediate and extended release formulations of metronidazole. Dissolution profile fitting via DDSolver and dissolution profile predictions via DDDPlus™ were performed. The results showed that Fickian diffusion and drug particle properties (DPP were responsible for the dissolution of the IR tablets, and that formulation factors (eg, coning impacted dissolution only at lower rotation speeds. Dissolution was completely formulation controlled if extended release tablets were tested and DPP were not important. To demonstrate that disintegration is the most important dosage form attribute when dissolution is

  10. Could FDA approval of pre-exposure prophylaxis make a difference? A qualitative study of PrEP acceptability and FDA perceptions among men who have sex with men

    OpenAIRE

    Underhill, Kristen; Morrow, Kathleen M.; Operario, Don; Mayer, Kenneth H.

    2014-01-01

    The FDA has approved tenofovir-emtricitabine for use as HIV pre-exposure prophylaxis, but it is unknown how approval may affect PrEP acceptability among US men who have sex with men. We conducted 8 focus groups among 38 Rhode Island MSM, including 3 groups among 16 male sex workers and 5 groups among 22 men in the general MSM community. Participants reported wide-ranging beliefs regarding consequences and meanings of FDA approval. Some participants would not use PrEP without approval, while o...

  11. Year 2000 (Y2K) computer compliance guide; guidance for FDA personnel. Food and Drug Administration. Notice.

    Science.gov (United States)

    1999-05-14

    The Food and Drug Administration (FDA) is announcing the availability of a new compliance policy guide (CPG) entitled "Year 2000 (Y2K) Computer Compliance" (section 160-800). This guidance document represents the agency's current thinking on the manufacturing and distribution of domestic and imported products regulated by FDA using computer systems that may not perform properly before, or during, the transition to the year 2000 (Y2K). The text of the CPG is included in this notice. This compliance guidance document is an update to the Compliance Policy Guides Manual (August 1996 edition). It is a new CPG, and it will be included in the next printing of the Compliance Policy Guides Manual. This CPG is intended for FDA personnel, and it is available electronically to the public.

  12. Identifying and Synchronizing Health Information Technology (HIT) Events from FDA Medical Device Reports.

    Science.gov (United States)

    Kang, Hong; Wang, Frank; Zhou, Sicheng; Miao, Qi; Gong, Yang

    2017-01-01

    Health information technology (HIT) events, a subtype of patient safety events, pose a major threat and barrier toward a safer healthcare system. It is crucial to gain a better understanding of the nature of the errors and adverse events caused by current HIT systems. The scarcity of HIT event-exclusive databases and event reporting systems indicates the challenge of identifying the HIT events from existing resources. FDA Manufacturer and User Facility Device Experience (MAUDE) database is a potential resource for HIT events. However, the low proportion and the rapid evolvement of HIT-related events present challenges for distinguishing them from other equipment failures and hazards. We proposed a strategy to identify and synchronize HIT events from MAUDE by using a filter based on structured features and classifiers based on unstructured features. The strategy will help us develop and grow an HIT event-exclusive database, keeping pace with updates to MAUDE toward shared learning.

  13. Chiron Vision files FDA application to market intraocular implant for CMV retinitis. Food and Drug Administration.

    Science.gov (United States)

    1995-07-01

    Chiron Corporation and Hoffman-LaRoche announced a filing of a New Drug Application with the Food and Drug Administration (FDA) to market Vitrasert, its intraocular implant which delivers ganciclovir directly to the eye for treatment of CMV retinitis. Clinical trials show that Vitrasert offers a clinical improvement versus intravenous ganciclovir in further delaying progression of CMV retinitis in the treated eye. One study reported that the median time to progression of CMV retinitis was 186 days for eyes receiving Vitrasert compared to 72 days for eyes receiving intravenous ganciclovir therapy. Chiron's intraocular implant contains ganciclovir embedded in a polymer-based system that slowly releases the drug into the eye for up to eight months. Two additional trials are underway. For further information contact the Professional Services Group at Chiron Corporation at (800) 244-7668, select 2.

  14. An analysis of the FDA Food Safety Modernization Act: protection for consumers and boon for business.

    Science.gov (United States)

    Strauss, Debra M

    2011-01-01

    This article analyzes components of the FDA Food Safety Modernization Act, which was prompted by incidents of food contamination, exploring the history of its passage and explaining its significance, as well as its limitations. As the first time in 70 years that food law has been changed substantially, this new law represents only an initial but significant step in the direction of improving food safety. With bipartisan support from both Congress and the President, this legislation embodies a mandate that food safety is at this moment becoming a priority. As a result, the time is ripe for a reassessment of other areas of food laws--particularly genetically modified foods and the use of milk and meat from cloned animals and their progeny--which are allowed under current U.S. law with no labeling, preapprovals, or post-market monitoring. These areas warrant special regulation consistent with the new proactive policy towards securing the safety of the food supply.

  15. Impact of the FDA warning of potential ceftriaxone and calcium interactions on drug use policy in clinical practice.

    Science.gov (United States)

    Esterly, John S; Steadman, Emily; Scheetz, Marc H

    2011-06-01

    In September 2007, the FDA issued an alert recommending that ceftriaxone and calcium-containing solutions should not be administered to any patient within 48 h of each other. Due to the widespread use of ceftriaxone, significant concern was expressed by the greater healthcare community about the warning, which the FDA eventually retracted in April of 2009. We sought to quantify the impact of the warning on healthcare institutions. A survey was administered to the membership of the Society of Infectious Diseases Pharmacists to quantify perceived changes in ceftriaxone use among healthcare institutions across the United States. A survey of Infectious Diseases experts was conducted. Participants were queried for hospital policies/drug use statistics during two times: immediately after the FDA warning and approximately 13 months post warning (preceding the FDA retraction). Related changes in formulary, drug-use policy, and the number of employee hours that were devoted to addressing the FDA warning were assessed. Ninety-four surveys representing 94 hospital systems were included in the analysis. Approximately half (n = 49, 52%) of respondent institutions enacted at least one drug-use policy change based on the warning; one institution removed ceftriaxone from a clinical protocol. Institutions' final interpretations of the warning differed slightly from initial understanding of the warning, and there was an overall minor decrease in the perceived use of ceftriaxone. The majority of those surveyed (n = 70, 74%) estimated that their respective institutions devoted between 1 and 49 employee hours to address the warning. Hospitals with ID pharmacists had minimal changes to ceftriaxone use after the 2007 FDA warning. Specialized pharmacists may be uniquely situated to help hospitals interpret global recommendations locally.

  16. Maternal characteristics associated with pregnancy exposure to FDA category C, D, and X drugs in a Canadian population.

    Science.gov (United States)

    Yang, Tubao; Walker, Mark C; Krewski, Daniel; Yang, Qiuying; Nimrod, Carl; Garner, Peter; Fraser, William; Olatunbosun, Olufemi; Wen, Shi Wu

    2008-03-01

    To estimate the frequency of exposure to prescription Food and Drug Administration (FDA) category C, D, and X drugs in pregnant women, and to analyze the maternal characteristics associated with such an exposure. A 50% random sample of women who gave a birth in Saskatchewan between January 1, 1997 and December 31, 2000 was chosen for the study. The rate of exposure to FDA category C, D, or X drugs recorded in the pharmacist database was estimated. Associations of exposure to FDA category C, D, and X drugs with maternal characteristics were evaluated using multiple logistical regression, with adjusted odds ratios (ORs) and its 95% confidence intervals (CIs) as the association measures. A total of 18 575 women were included in this study. Among them, 3604 (19.4%) had exposure to one or more FDA category C, D, and X drugs during pregnancy. Category C drugs were the most frequently used drugs (15.8%), followed by D drugs (5.2%), and X drugs (3.9%). Women with chronic health conditions had fourfold at increased risk of exposure than women without. Regardless of health status, women who were or =3, and who were on social assistance plan were at increased risk of pregnancy exposure to these drugs. About 19.4% pregnant women are exposed to FDA C, D or X drugs during pregnancy. Women with chronic diseases, younger age, increased parity, and under social assistance are at increased risk of exposure to FDA C, D, or X drugs. Copyright 2008 John Wiley & Sons, Ltd.

  17. QUADrATiC: scalable gene expression connectivity mapping for repurposing FDA-approved therapeutics.

    Science.gov (United States)

    O'Reilly, Paul G; Wen, Qing; Bankhead, Peter; Dunne, Philip D; McArt, Darragh G; McPherson, Suzanne; Hamilton, Peter W; Mills, Ken I; Zhang, Shu-Dong

    2016-05-04

    Gene expression connectivity mapping has proven to be a powerful and flexible tool for research. Its application has been shown in a broad range of research topics, most commonly as a means of identifying potential small molecule compounds, which may be further investigated as candidates for repurposing to treat diseases. The public release of voluminous data from the Library of Integrated Cellular Signatures (LINCS) programme further enhanced the utilities and potentials of gene expression connectivity mapping in biomedicine. We describe QUADrATiC ( http://go.qub.ac.uk/QUADrATiC ), a user-friendly tool for the exploration of gene expression connectivity on the subset of the LINCS data set corresponding to FDA-approved small molecule compounds. It enables the identification of compounds for repurposing therapeutic potentials. The software is designed to cope with the increased volume of data over existing tools, by taking advantage of multicore computing architectures to provide a scalable solution, which may be installed and operated on a range of computers, from laptops to servers. This scalability is provided by the use of the modern concurrent programming paradigm provided by the Akka framework. The QUADrATiC Graphical User Interface (GUI) has been developed using advanced Javascript frameworks, providing novel visualization capabilities for further analysis of connections. There is also a web services interface, allowing integration with other programs or scripts. QUADrATiC has been shown to provide an improvement over existing connectivity map software, in terms of scope (based on the LINCS data set), applicability (using FDA-approved compounds), usability and speed. It offers potential to biological researchers to analyze transcriptional data and generate potential therapeutics for focussed study in the lab. QUADrATiC represents a step change in the process of investigating gene expression connectivity and provides more biologically-relevant results than

  18. The FDA guidance for industry on PROs: the point of view of a pharmaceutical company.

    Science.gov (United States)

    Arpinelli, Fabio; Bamfi, Francesco

    2006-10-31

    The importance of the patients point of view on their health status is widely recognised. Patient-reported outcomes is a broad term encompassing a large variety of different health data reported by patients, as symptoms, functional status, Quality of Life and Health-Related Quality of Life. Measurements of Health-Related Quality of Life have been developed during many years of researches, and a lot of validated questionnaires exist. However, few attempts have been made to standardise the evaluation of instruments characteristics, no recommendations are made about interpretation on Health-Related Quality of Life results, especially regarding the clinical significance of a change leading a therapeutic approach. Moreover, the true value of Health-Related Quality of Life evaluations in clinical trials has not yet been completely defined. An important step towards a more structured and frequent use of Patient-Reported Outcomes in drug development is represented by the FDA Guidance, issued on February 2006. In our paper we aim to report some considerations on this Guidance. Our comments focus especially on the characteristics of instruments to use, the Minimal Important Difference, and the methods to calculate it. Furthermore, we present the advantages and opportunities of using the Patient-Reported Outcomes in drug development, as seen by a pharmaceutical company. The Patient-Reported Outcomes can provide additional data to make a drug more competitive than others of the same pharmacological class, and a well demonstrated positive impact on the patient' health status and daily life might allow a higher price and/or the inclusion in a reimbursement list. Applying extensively the FDA Guidance in the next trials could lead to a wider culture of subjective measurement, and to a greater consideration for the patient's opinions on his/her care. Moreover, prescribing doctors and payers could benefit from subjective information to better define the value of drugs.

  19. Comparison of FDA safety and efficacy data for KAMRA and Raindrop corneal inlays

    Directory of Open Access Journals (Sweden)

    Majid Moshirfar

    2017-09-01

    Full Text Available AIM: To provide a side-by-side analysis of the summary of safety and effectiveness data (SSED submitted to the FDA for the KAMRA and Raindrop corneal inlays for the correction of presbyopia. METHODS: SSED reports submitted to the FDA for KAMRA and Raindrop were compared with respect to loss of corrected distance visual acuity (CDVA, adverse event rates, induction of astigmatism, retention of contrast sensitivity, stability of manifest refractive spherical equivalent (MRSE, and achieved monocular uncorrected near visual acuity (UNVA at 24mo. RESULTS: Totally 442/508 of KAMRA patients and 344/373 Raindrop patients remained enrolled in the clinical trials at 24mo. The proportion of KAMRA and Raindrop patients who lost ≥2 lines of CDVA at 24mo was 3.4% and 1%, respectively. The adverse event rate was comparable between the devices. No significant inductions of astigmatism were noted. Both technologies induced a transient myopic shift in MRSE followed by a hyperopic shift and subsequent stabilization. Totally 87% of KAMRA and 98% of Raindrop patients attained a monocular UNVA of J5 (20/40 or better at 24mo, 28% of KAMRA and 67% of Raindrop patients attained a monocular UNVA of J1 (20/20 or better at 24mo. CONCLUSION: Both devices can be considered safe and effective, however, the results of corneal inlay implantation are mixed, and long-term patient satisfaction will likely depend on subjective expectations about the capabilities of the inlays. Variability in surgical technique and postoperative care within and between the two clinical trials diminishes the comparative power of this article.

  20. FDA approved drugs as potential Ebola treatments [v2; ref status: indexed, http://f1000r.es/554

    Directory of Open Access Journals (Sweden)

    Sean Ekins

    2015-03-01

    Full Text Available In the search for treatments for the Ebola Virus, multiple screens of FDA drugs have led to the identification of several with promising in vitro activity. These compounds were not originally developed as antivirals and some have been further tested in mouse in vivo models. We put forward the opinion that some of these drugs could be evaluated further and move into the clinic as they are already FDA approved and in many cases readily available. This may be important if there is a further outbreak in future and no other therapeutic is available.

  1. Famous puzzles of great mathematicians

    CERN Document Server

    Petković, Miodrag S

    2009-01-01

    This entertaining book presents a collection of 180 famous mathematical puzzles and intriguing elementary problems that great mathematicians have posed, discussed, and/or solved. The selected problems do not require advanced mathematics, making this book accessible to a variety of readers. Mathematical recreations offer a rich playground for both amateur and professional mathematicians. Believing that creative stimuli and aesthetic considerations are closely related, great mathematicians from ancient times to the present have always taken an interest in puzzles and diversions. The goal of this

  2. Could FDA approval of pre-exposure prophylaxis make a difference? A qualitative study of PrEP acceptability and FDA perceptions among men who have sex with men.

    Science.gov (United States)

    Underhill, Kristen; Morrow, Kathleen M; Operario, Don; Mayer, Kenneth H

    2014-02-01

    The FDA has approved tenofovir-emtricitabine for use as HIV pre-exposure prophylaxis, but it is unknown how approval may affect PrEP acceptability among US men who have sex with men. We conducted 8 focus groups among 38 Rhode Island MSM, including 3 groups among 16 male sex workers and 5 groups among 22 men in the general MSM community. Participants reported wide-ranging beliefs regarding consequences and meanings of FDA approval. Some participants would not use PrEP without approval, while others perceived approval as irrelevant or less significant than other sources of information. Our results suggest that FDA approval sends a signal that directly shapes PrEP acceptability among some MSM, while indirect influences of approval may affect uptake by others. Efforts to educate MSM about PrEP can increase acceptability by incorporating information about FDA approval, and outreach strategies should consider how this information may factor into personal decisions about PrEP use.

  3. Making a Great First Impression

    Science.gov (United States)

    Evenson, Renee

    2007-01-01

    Managers and business owners often base hiring decisions on first impressions. That is why it is so important to teach students to make a great first impression--before they go on that first job interview. Managers do not have unrealistic expectations, they just want to hire people who they believe can develop into valuable employees. A nice…

  4. Great Basin paleoenvironmental studies project

    International Nuclear Information System (INIS)

    1993-01-01

    Project goals, project tasks, progress on tasks, and problems encountered are described and discussed for each of the studies that make up the Great Basin Paleoenvironmental Studies Project for Yucca Mountain. These studies are: Paleobotany, Paleofauna, Geomorphology, and Transportation. Budget summaries are also given for each of the studies and for the overall project

  5. The Great Books and Economics.

    Science.gov (United States)

    Hartley, James E.

    2001-01-01

    Describes an introductory economics course in which all of the reading material is drawn from the Great Books of Western Civilization. Explains the rationale and mechanics of the course. Includes an annotated course syllabus that details how the reading material relates to the lecture material. (RLH)

  6. Great tit hatchling sex ratios

    NARCIS (Netherlands)

    Lessells, C.M.; Mateman, A.C.; Visser, J.

    1996-01-01

    The sex of Great Tit Parus major nestlings was determined using PCR RAPDs. Because this technique requires minute amounts of DNA, chicks could be sampled soon (0-2d) after hatching, before any nestling mortality occurred. The proportion of males among 752 chicks hatching in 102 broods (98.9% of

  7. The Great Gatsby. [Lesson Plan].

    Science.gov (United States)

    Zelasko, Ken

    Based on F. Scott Fitzgerald's novel "The Great Gatsby," this lesson plan presents activities designed to help students understand that adapting part of a novel into a dramatic reading makes students more intimate with the author's intentions and craft; and that a part of a novel may lend itself to various oral interpretations. The main activity…

  8. Great Basin wildlife disease concerns

    Science.gov (United States)

    Russ Mason

    2008-01-01

    In the Great Basin, wildlife diseases have always represented a significant challenge to wildlife managers, agricultural production, and human health and safety. One of the first priorities of the U.S. Department of Agriculture, Division of Fish and Wildlife Services was Congressionally directed action to eradicate vectors for zoonotic disease, particularly rabies, in...

  9. Awareness and trust of the FDA and CDC: Results from a national sample of US adults and adolescents.

    Directory of Open Access Journals (Sweden)

    Sarah D Kowitt

    Full Text Available Trust in government agencies plays a key role in advancing these organizations' agendas, influencing behaviors, and effectively implementing policies. However, few studies have examined the extent to which individuals are aware of and trust the leading United States agencies devoted to protecting the public's health. Using two national samples of adolescents (N = 1,125 and adults (N = 5,014, we examined demographic factors, with a focus on vulnerable groups, as correlates of awareness of and trust in the Centers for Disease Control and Prevention (CDC, Food and Drug Administration (FDA, and the federal government. From nine different weighted and adjusted logistic regression models, we found high levels of awareness of the existence of the FDA and CDC (ranging from 55.7% for adolescents' awareness of the CDC to 94.3% for adults' awareness of the FDA and moderate levels of trust (ranging from a low of 41.8% for adults' trust in the federal government and a high of 78.8% for adolescents' trust of the FDA. In the adolescent and adult samples, awareness was higher among non-Hispanic Blacks and respondents with low numeracy. With respect to trust, few consistent demographic differences emerged. Our findings provide novel insights regarding awareness and trust in the federal government and specific United States public health agencies. Our findings suggest groups to whom these agencies may want to selectively communicate to enhance trust and thus facilitate their communication and regulatory agendas.

  10. Modeling and simulation for medical product development and evaluation : highlights from the FDA-C-Path-ISOP 2013 workshop

    NARCIS (Netherlands)

    Romero, Klaus; Sinha, Vikram; Allerheiligen, Sandra; Danhof, Meindert; Pinheiro, Jose; Kruhlak, Naomi; Wang, Yaning; Wang, Sue-Jane; Sauer, John-Michael; Marier, J. F.; Corrigan, Brian; Rogers, James; Heerspink, H. J. Lambers; Gumbo, Tawanda; Vis, Peter; Watkins, Paul; Morrison, Tina; Gillespie, William; Gordon, Mark Forrest; Stephenson, Diane; Hanna, Debra; Pfister, Marc; Lalonde, Richard; Colatsky, Thomas

    2014-01-01

    Medical-product development has become increasingly challenging and resource-intensive. In 2004, the Food and Drug Administration (FDA) described critical challenges facing medical-product development by establishing the critical path initiative [1]. Priorities identified included the need for

  11. 76 FR 41506 - Draft Guidance for Industry and FDA Staff on In Vitro Companion Diagnostic Devices; Availability

    Science.gov (United States)

    2011-07-14

    ...., Bldg. 51, rm. 2201, Silver Spring, MD 20993- 0002, or Office of Communication, Outreach and Development... help make critical treatment decisions. FDA oversight of companion diagnostics will protect patients... current thinking on companion diagnostic devices. It does not create or confer any rights for or on any...

  12. 21 CFR 1.383 - What expedited procedures apply when FDA initiates a seizure action against a detained perishable...

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 1 2010-04-01 2010-04-01 false What expedited procedures apply when FDA initiates a seizure action against a detained perishable food? 1.383 Section 1.383 Food and Drugs FOOD AND... Administrative Detention of Food for Human or Animal Consumption General Provisions § 1.383 What expedited...

  13. The FDA's decision-making process: isn't it time to temper the principle of protective paternalism?

    Science.gov (United States)

    Brandt, Lawrence J

    2008-05-01

    The authors conducted a well-designed, multinational, large study of women younger than 65 yr of age with irritable bowel syndrome (IBS) with a mixed pattern of diarrhea and constipation (IBS-M) or constipation (IBS-C) and showed that a statistically greater percentage of patients in each group responded to tegaserod compared with patients treated with placebo. Practicality looms large, however, in that the Food and Drug Administration (FDA) disallowed the continued marketing of tegaserod because of cardiovascular safety concerns, and it now is only available under a restricted access program. The wisdom of this decision aside, it is disturbing that the FDA revealed a zero-tolerance for any significant risk of disease when a drug (e.g., tegaserod) was used for a nonlife-threatening condition; the FDA chose to neglect any potential benefit of significant improvement in quality of life, while at the same time allowing the continued availability of sildenifil for erectile dysfunction and other medications (e.g., rosiglitazone and nonsteroidal anti-inflammatory drugs [NSAIDs]), each with a far greater risk of cardiovascular complications. Whether tegaserod will be re-released and, if so, under what conditions, is yet to be determined, as is the question of whether the FDA will decide to allow a more transparent decision-making process with input from all interested parties affected by their decision.

  14. Association between change of health care providers and pregnancy exposure to FDA category C, D and X drugs.

    Science.gov (United States)

    Yang, Jianzhou; Xie, Rihua; Krewski, Daniel; Wang, Yongjin; Walker, Mark; Cao, Wenjun; Wen, Shi Wu

    2014-01-01

    Changing health care providers frequently breaks the continuity of care, which is associated with many health care problems. The purpose of this study was to examine the association between a change of health care providers and pregnancy exposure to FDA category C, D and X drugs. A 50% random sample of women who gave a birth in Saskatchewan between January 1, 1997 and December 31, 2000 were chosen for this study. The association between the number of changes in health care providers and with pregnancy exposure to category C, D, and X drugs for those women with and without chronic diseases were evaluated using multiple logistical regression, with adjusted odds ratios (ORs) and its 95% confidence intervals (CIs) as the association measures. A total of 18 568 women were included in this study. Rates of FDA C, D, and X drug uses were 14.35%, 17.07%, 21.72%, and 31.14%, in women with no change of provider, 1-2 changes, 3-5 changes, and more than 5 changes of health care providers. An association between the number of changes of health care providers and pregnancy exposure to FDA C, D, and X drugs existed in women without chronic diseases but not in women with chronic disease. Change of health care providers is associated with pregnancy exposure to FDA category C, D and X drugs in women without chronic diseases.

  15. 76 FR 13643 - FDA Food Safety Modernization Act: Title III-A New Paradigm for Importers; Public Meeting

    Science.gov (United States)

    2011-03-14

    ... Act: Title III--A New Paradigm for Importers; Public Meeting AGENCY: Food and Drug Administration, HHS... announcing a public meeting entitled ``FDA Food Safety Modernization Act: Title III--A New Paradigm for... provided. Request special accommodations due By March 22, 2011.... Patricia M. Kuntze, 301- to disability...

  16. The 2014 FDA assessment of commercial fish: practical considerations for improved dietary guidance.

    Science.gov (United States)

    McGuire, Jennifer; Kaplan, Jason; Lapolla, John; Kleiner, Rima

    2016-07-13

    The U.S. Food and Drug Administration (FDA) recently released its report: A Quantitative Assessment of the Net Effects on Fetal Neurodevelopment from Eating Commercial Fish (As Measured by IQ and also by Early Age Verbal Development in Children). By evaluating the benefits and potential concerns of eating fish during pregnancy and breastfeeding, the analysis suggests that pregnant women consuming two seafood meals (8-12 oz) per week could provide their child with an additional 3.3 IQ points by age 9. Recent insights from behavioral economics research indicate that other factors, such as concerns about price and methylmercury (MeHg) exposure, appear to reduce fish consumption in many individuals.To assess the net effects of eating commercial fish during pregnancy, we compared the consumption of select fish species necessary to achieve IQ benefits with the amount necessary to have adverse developmental effects due to MeHg exposure. For the species or market types evaluated, the number of servings necessary to reach MeHg exposure to observe an adverse effect was at least twice that the amount estimated to achieve peak developmental benefit. We then reported average costs of fresh and canned or pouched fish, and calculated the cost per week for pregnant women to achieve maximum IQ benefits for their gestating child. Canned light tuna was the least expensive option at $1.83 per week to achieve maximum IQ benefit.Due to their relatively low cost, canned and pouched fish products eaten with enough regularity are likely to provide peak cognitive benefits. Because of its popularity, canned and pouched tuna could provide some of the largest cognitive benefits from fish consumption in the U.S. Future FDA consumer advice and related educational initiatives could benefit from a broader perspective that highlights the importance of affordable and accessible fish choices. These observations underscore the importance of clear public health messaging that address both health

  17. Investigating drug repositioning opportunities in FDA drug labels through topic modeling.

    Science.gov (United States)

    Bisgin, Halil; Liu, Zhichao; Kelly, Reagan; Fang, Hong; Xu, Xiaowei; Tong, Weida

    2012-01-01

    Drug repositioning offers an opportunity to revitalize the slowing drug discovery pipeline by finding new uses for currently existing drugs. Our hypothesis is that drugs sharing similar side effect profiles are likely to be effective for the same disease, and thus repositioning opportunities can be identified by finding drug pairs with similar side effects documented in U.S. Food and Drug Administration (FDA) approved drug labels. The safety information in the drug labels is usually obtained in the clinical trial and augmented with the observations in the post-market use of the drug. Therefore, our drug repositioning approach can take the advantage of more comprehensive safety information comparing with conventional de novo approach. A probabilistic topic model was constructed based on the terms in the Medical Dictionary for Regulatory Activities (MedDRA) that appeared in the Boxed Warning, Warnings and Precautions, and Adverse Reactions sections of the labels of 870 drugs. Fifty-two unique topics, each containing a set of terms, were identified by using topic modeling. The resulting probabilistic topic associations were used to measure the distance (similarity) between drugs. The success of the proposed model was evaluated by comparing a drug and its nearest neighbor (i.e., a drug pair) for common indications found in the Indications and Usage Section of the drug labels. Given a drug with more than three indications, the model yielded a 75% recall, meaning 75% of drug pairs shared one or more common indications. This is significantly higher than the 22% recall rate achieved by random selection. Additionally, the recall rate grows rapidly as the number of drug indications increases and reaches 84% for drugs with 11 indications. The analysis also demonstrated that 65 drugs with a Boxed Warning, which indicates significant risk of serious and possibly life-threatening adverse effects, might be replaced with safer alternatives that do not have a Boxed Warning. In

  18. Direct-to-Consumer Broadcast Advertisements for Pharmaceuticals: Off-Label Promotion and Adherence to FDA Guidelines.

    Science.gov (United States)

    Klara, Kristina; Kim, Jeanie; Ross, Joseph S

    2018-05-01

    Direct-to-consumer (DTC) advertisements for prescription drugs in the United States are regulated by the Food and Drug Administration (FDA). Off-label promotion, or the advertisement of a drug for an indication not approved by the FDA, is prohibited. Our objective was to examine the presence of off-label promotion in broadcast DTC ads and to assess their adherence to FDA guidelines mandating fair balance in presentation of risks and benefits and prohibiting misleading advertisement claims. All English-language broadcast DTC ads for prescription drugs that aired in the United States from January 2015 to July 2016 were obtained from AdPharm, an online collection of healthcare advertisements. Ad length was measured and adherence to FDA guidelines was assessed for several categories: key regulatory items, indicators of false or misleading ads, and indicators of fair balance in presentation of risks and benefits. Our sample included 97 unique DTC ads, representing 60 unique drugs and 67 unique drug-indication combinations. No ads described drug risks quantitatively, whereas drug efficacy was presented quantitatively in 25 (26%) ads. Thirteen (13%) ads, all for diabetes medications, suggested off-label uses for weight loss and blood pressure reduction. The most commonly advertised drugs were indicated for the treatment of inflammatory conditions (n = 12; 18%), diabetes or diabetic neuropathy (n = 11; 16%), bowel or bladder dysfunction (n = 6; 9%), and infections or allergic reaction (n = 6; 9%). More than three-quarters (n = 51; 76%) advertised drugs to treat chronic conditions. Few broadcast DTC ads were fully compliant with FDA guidelines. The overall quality of information provided in ads was low, and suggestions of off-label promotion were common for diabetes medications. The impact of current DTC ads and off-label marketing on patient and prescriber decisions merits further scrutiny.

  19. Southern Great Plains Safety Orientation

    Energy Technology Data Exchange (ETDEWEB)

    Schatz, John

    2014-05-01

    Welcome to the Atmospheric Radiation Measurement (ARM) Climate Research Facility (ARM) Southern Great Plains (SGP) site. This U.S. Department of Energy (DOE) site is managed by Argonne National Laboratory (ANL). It is very important that all visitors comply with all DOE and ANL safety requirements, as well as those of the Occupational Safety and Health Administration (OSHA), the National Fire Protection Association, and the U.S. Environmental Protection Agency, and with other requirements as applicable.

  20. A History of the Sonocare CST-100: The First FDA-approved HIFU Device

    Science.gov (United States)

    Muratore, Robert

    2006-05-01

    The Sonocare CST-100 Therapeutic Ultrasound System, designed for the treatment of glaucoma, was developed in the 1980s and became the first high intensity focused ultrasound (HIFU) device to receive Food and Drug Administration approval. The system arose from studies done by F.L. Lizzi, Eng.Sc.D., of Riverside Research Institute and D.J. Coleman, M.D., of Cornell Medical Center/New York Hospital on the safety of ultrasound diagnosis of the eye. As safety limits were probed, therapeutic regimes were discovered. Optimization of operational parameters, clinical experience, and engineering design came together through a spin-off company, Sonocare, Inc., formed to produce and market the ophthalmic device. Various precedents were set during the approval process, including the acceptance by the FDA of radiation momentum imparted to an absorber as a measure of acoustic power. Many devices were sold, but the laser industry, grandfathered into the therapeutic field, eventually out-marketed Sonocare. The CST-100 remains as a model of elegant industrial design, and existing units are used daily in HIFU laboratory experiments.

  1. Towards a Computational Analysis of Status and Leadership Styles on FDA Panels

    Science.gov (United States)

    Broniatowski, David A.; Magee, Christopher L.

    Decisions by committees of technical experts are increasingly impacting society. These decision-makers are typically embedded within a web of social relations. Taken as a whole, these relations define an implicit social structure which can influence the decision outcome. Aspects of this structure are founded on interpersonal affinity between parties to the negotiation, on assigned roles, and on the recognition of status characteristics, such as relevant domain expertise. This paper build upon a methodology aimed at extracting an explicit representation of such social structures using meeting transcripts as a data source. Whereas earlier results demonstrated that the method presented here can identify groups of decision-makers with a contextual affinity (i.e., membership in a given medical specialty or voting clique), we now can extract meaningful status hierarchies, and can identify differing facilitation styles among committee chairs. Use of this method is demonstrated on the transcripts of U.S. Food and Drug Administration (FDA) advisory panel meeting transcripts; nevertheless, the approach presented here is extensible to other domains and requires only a meeting transcript as input.

  2. Medication Exposures and Subsequent Development of Ewing Sarcoma: A Review of FDA Adverse Event Reports

    Directory of Open Access Journals (Sweden)

    Judith U. Cope

    2015-01-01

    Full Text Available Background. Ewing sarcoma family of tumors (ESFT are rare but deadly cancers of unknown etiology. Few risk factors have been identified. This study was undertaken to ascertain any possible association between exposure to therapeutic drugs and ESFT. Methods. This is a retrospective, descriptive study. A query of the FDA Adverse Event Reporting System (FAERS was conducted for all reports of ESFT, January 1, 1998, through December 31, 2013. Report narratives were individually reviewed for patient characteristics, underlying conditions and drug exposures. Results. Over 16 years, 134 ESFT reports were identified, including 25 cases of ESFT following therapeutic drugs and biologics including immunosuppressive agents and hormones. Many cases were confounded by concomitant medications and other therapies. Conclusions. This study provides a closer look at medication use and underlying disorders in patients who later developed ESFT. While this study was not designed to demonstrate any clear causative association between ESFT and prior use of a single product or drug class, many drugs were used to treat immune-related disease and growth or hormonal disturbances. Further studies may be warranted to better understand possible immune or neuroendocrine abnormalities or exposure to specific classes of drugs that may predispose to the later development of ESFT.

  3. Repurposing the FDA-approved pinworm drug pyrvinium as a novel chemotherapeutic agent for intestinal polyposis.

    Directory of Open Access Journals (Sweden)

    Bin Li

    Full Text Available Mutations in the WNT-pathway regulator ADENOMATOUS POLYPOSIS COLI (APC promote aberrant activation of the WNT pathway that is responsible for APC-associated diseases such as Familial Adenomatous Polyposis (FAP and 85% of spontaneous colorectal cancers (CRC. FAP is characterized by multiple intestinal adenomas, which inexorably result in CRC. Surprisingly, given their common occurrence, there are few effective chemotherapeutic drugs for FAP. Here we show that the FDA-approved, anti-helminthic drug Pyrvinium attenuates the growth of WNT-dependent CRC cells and does so via activation of CK1α. Furthermore, we show that Pyrvinium can function as an in vivo inhibitor of WNT-signaling and polyposis in a mouse model of FAP: APCmin mice. Oral administration of Pyrvinium, a CK1α agonist, attenuated the levels of WNT-driven biomarkers and inhibited adenoma formation in APCmin mice. Considering its well-documented safe use for treating enterobiasis in humans, our findings suggest that Pyrvinium could be repurposed for the clinical treatment of APC-associated polyposes.

  4. Inhibition of Urease by Disulfiram, an FDA-Approved Thiol Reagent Used in Humans.

    Science.gov (United States)

    Díaz-Sánchez, Ángel Gabriel; Alvarez-Parrilla, Emilio; Martínez-Martínez, Alejandro; Aguirre-Reyes, Luis; Orozpe-Olvera, Jesica Aline; Ramos-Soto, Miguel Armando; Núñez-Gastélum, José Alberto; Alvarado-Tenorio, Bonifacio; de la Rosa, Laura Alejandra

    2016-11-26

    Urease is a nickel-dependent amidohydrolase that catalyses the decomposition of urea into carbamate and ammonia, a reaction that constitutes an important source of nitrogen for bacteria, fungi and plants. It is recognized as a potential antimicrobial target with an impact on medicine, agriculture, and the environment. The list of possible urease inhibitors is continuously increasing, with a special interest in those that interact with and block the flexible active site flap. We show that disulfiram inhibits urease in Citrullus vulgaris (CVU), following a non-competitive mechanism, and may be one of this kind of inhibitors. Disulfiram is a well-known thiol reagent that has been approved by the FDA for treatment of chronic alcoholism. We also found that other thiol reactive compounds (l-captopril and Bithionol) and quercetin inhibits CVU. These inhibitors protect the enzyme against its full inactivation by the thiol-specific reagent Aldrithiol (2,2'-dipyridyl disulphide, DPS), suggesting that the three drugs bind to the same subsite. Enzyme kinetics, competing inhibition experiments, auto-fluorescence binding experiments, and docking suggest that the disulfiram reactive site is Cys592, which has been proposed as a "hinge" located in the flexible active site flap. This study presents the basis for the use of disulfiram as one potential inhibitor to control urease activity.

  5. Tamoxifen: an FDA approved drug with neuroprotective effects for spinal cord injury recovery

    Directory of Open Access Journals (Sweden)

    Jennifer M Colón

    2016-01-01

    Full Text Available Spinal cord injury (SCI is a condition without a cure, affecting sensory and/or motor functions. The physical trauma to the spinal cord initiates a cascade of molecular and cellular events that generates a non-permissive environment for cell survival and axonal regeneration. Among these complex set of events are damage of the blood-brain barrier, edema formation, inflammation, oxidative stress, demyelination, reactive gliosis and apoptosis. The multiple events activated after SCI require a multi-active drug that could target most of these events and produce a permissive environment for cell survival, regeneration, vascular reorganization and synaptic formation. Tamoxifen, a selective estrogen receptor modulator, is an FDA approved drug with several neuroprotective properties that should be considered for the treatment of this devastating condition. Various investigators using different animal models and injury parameters have demonstrated the beneficial effects of this drug to improve functional locomotor recovery after SCI. Results suggest that the mechanism of action of Tamoxifen administration is to modulate anti-oxidant, anti-inflammatory and anti-gliotic responses. A gap of knowledge exists regarding the sex differences in response to Tamoxifen and the therapeutic window available to administer this treatment. In addition, the effects of Tamoxifen in axonal outgrowth or synapse formation needs to be investigated. This review will address some of the mechanisms activated by Tamoxifen after SCI and the results recently published by investigators in the field.

  6. The informational turn in food politics: The US FDA's nutrition label as information infrastructure.

    Science.gov (United States)

    Frohlich, Xaq

    2017-04-01

    This article traces the history of the US FDA regulation of nutrition labeling, identifying an 'informational turn' in the evolving politics of food, diet and health in America. Before nutrition labeling was introduced, regulators actively sought to segregate food markets from drug markets by largely prohibiting health information on food labels, believing such information would 'confuse' the ordinary food consumer. Nutrition labeling's emergence, first in the 1970s as consumer empowerment and then later in the 1990s as a solution to information overload, reflected the belief that it was better to manage markets indirectly through consumer information than directly through command-and-control regulatory architecture. By studying product labels as 'information infrastructure', rather than a 'knowledge fix', the article shows how labels are situated at the center of a legally constructed terrain of inter-textual references, both educational and promotional, that reflects a mix of market pragmatism and evolving legal thought about mass versus niche markets. A change to the label reaches out across a wide informational environment representing food and has direct material consequences for how food is produced, distributed, and consumed. One legacy of this informational turn has been an increasing focus by policymakers, industry, and arguably consumers on the politics of information in place of the politics of the food itself.

  7. Bringing smart pills to market: FDA regulation of ingestible drug/device combination products.

    Science.gov (United States)

    Avery, Matthew; Liu, Dan

    2011-01-01

    Imagine a pill that, after you swallow it, can track its position in your body. Or imagine a pill that can transmit a message to a doctor to tell him that you have taken your bitter medicine. Pills like this already exist. These so-called smart pills are an emerging type of medical therapy. However, this nascent technology has yet to reach the market and developers of these novel therapies face significant regulatory challenges. This article predicts how the Food and Drug Administration will regulate smart pills and shows how the current regulatory regime is inadequate. The article then proposes modifying the current regulatory regime to encourage development of smart pills and other innovative combination products by: (1) regulating combination products based on their "novel mode of action" rather than their "primary mode of action," (2) creating a marketing approval pathway specifically for combination products, and (3) eliminating regulations that require sponsors to get marketing approval from multiple centers within FDA and providing regulatory guidance specifically for ingestible drug/device combination products.

  8. Hepatitis B infection reported with cancer chemotherapy: analyzing the US FDA Adverse Event Reporting System.

    Science.gov (United States)

    Sanagawa, Akimasa; Hotta, Yuji; Kataoka, Tomoya; Maeda, Yasuhiro; Kondo, Masahiro; Kawade, Yoshihiro; Ogawa, Yoshihiro; Nishikawa, Ryohei; Tohkin, Masahiro; Kimura, Kazunori

    2018-04-16

    We conducted data mining using the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database on spontaneously reported adverse events to evaluate the association between anticancer drug therapy and hepatitis B infection. Reports of hepatitis B infection were retrieved from the FAERS database. The reporting odds ratio (ROR) was used to estimate the association between hepatitis B infection and various anticancer agents and drug combinations. We detected statistically significant risk signals of hepatitis B for 33 of 64 anticancer agents by ROR (26 cytotoxicity drugs and seven molecular-targeted drugs). We focused on molecular-targeted drugs and assessed the risk of hepatitis B from specific anticancer drug combinations. The frequency of hepatitis B infection was significantly high for drugs such as rituximab, bortezomib, imatinib, and everolimus. The addition of cyclophosphamide, doxorubicin, and fludarabine to drug combinations additively enhanced the frequency of hepatitis B infection. There were no reports on hepatitis B infection associated with trastuzumab or azacitidine monotherapy. However, trastuzumab-containing regimens (e.g., combinations with docetaxel or paclitaxel) were correlated with the incidence of hepatitis B infection, similar to azacitidine monotherapy. Our findings suggest that the concomitant use of anticancer drugs, such as trastuzumab, taxane, and azacitidine, may contribute to the risk of hepatitis B infection. The unique signals detected from the public database might provide clues to eliminate the threat of HBV in oncology. © 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

  9. The analysis of the market success of FDA approvals by probing top 100 bestselling drugs

    Science.gov (United States)

    Polanski, Jaroslaw; Bogocz, Jacek; Tkocz, Aleksandra

    2016-05-01

    Target-oriented drug discovery is the main research paradigm of contemporary drug discovery. In target-oriented approaches, we attempt to maximize in vitro drug potency by finding the optimal fit to the target. This can result in a higher molecular complexity, in particular, the higher molecular weight (MW) of the drugs. However, a comparison of the successful developments of pharmaceuticals with the general trends that can be observed in medicinal chemistry resulted in the conclusion that the so-called molecular obesity is an important reason for the attrition rate of drugs. When analyzing the list of top 100 drug bestsellers versus all of the FDA approvals, we discovered that on average lower-complexity (MW, ADMET score) drugs are winners of the top 100 list in terms of numbers but that, especially, up to some optimal MW value, a higher molecular complexity can pay off with higher incomes. This indicates that slim drugs are doing better but that fat drugs are bigger fishes to catch.

  10. Security and privacy qualities of medical devices: an analysis of FDA postmarket surveillance.

    Science.gov (United States)

    Kramer, Daniel B; Baker, Matthew; Ransford, Benjamin; Molina-Markham, Andres; Stewart, Quinn; Fu, Kevin; Reynolds, Matthew R

    2012-01-01

    Medical devices increasingly depend on computing functions such as wireless communication and Internet connectivity for software-based control of therapies and network-based transmission of patients' stored medical information. These computing capabilities introduce security and privacy risks, yet little is known about the prevalence of such risks within the clinical setting. We used three comprehensive, publicly available databases maintained by the Food and Drug Administration (FDA) to evaluate recalls and adverse events related to security and privacy risks of medical devices. Review of weekly enforcement reports identified 1,845 recalls; 605 (32.8%) of these included computers, 35 (1.9%) stored patient data, and 31 (1.7%) were capable of wireless communication. Searches of databases specific to recalls and adverse events identified only one event with a specific connection to security or privacy. Software-related recalls were relatively common, and most (81.8%) mentioned the possibility of upgrades, though only half of these provided specific instructions for the update mechanism. Our review of recalls and adverse events from federal government databases reveals sharp inconsistencies with databases at individual providers with respect to security and privacy risks. Recalls related to software may increase security risks because of unprotected update and correction mechanisms. To detect signals of security and privacy problems that adversely affect public health, federal postmarket surveillance strategies should rethink how to effectively and efficiently collect data on security and privacy problems in devices that increasingly depend on computing systems susceptible to malware.

  11. Cloned animal products in the human food chain: FDA should protect American consumers.

    Science.gov (United States)

    Butler, Jennifer E F

    2009-01-01

    Animal cloning is "complex process that lets one exactly copy the genetic, or inherited, traits of an animal." In 1997, Dolly the sheep was the first animal cloned and since then "scientists have used animal cloning to breed dairy cows, beef cattle, poultry, hogs and other species of livestock." Cloned animals are highly attractive to livestock breeders because "cloning essentially produces an identical copy of an animal with superior traits." The main purpose of cloning livestock is "more focused on efficiency and economic benefits of the producer rather than the overall effect of cloning on an animal's physical and mental welfare." The focus of this article is threefold. First, the science behind animal cloning is explained and some potential uses and risks of this technology are explored. Second, FDA's historical evolution, current regulatory authority, and limitations of that authority, is described. Lastly, a new regulatory vision recognizes the realities of 21st century global markets and the dynamic evolution of scientific discovery and technology.

  12. Pure- and Mixed-Gas Permeation Properties of Highly Selective and Plasticization Resistant Hydroxyl-Diamine-Based 6FDA Polyimides for CO2/CH4 Separation

    KAUST Repository

    Alaslai, Nasser Y.; Ghanem, Bader; Alghunaimi, Fahd; Litwiller, Eric; Pinnau, Ingo

    2016-01-01

    The effect of hydroxyl functionalization on the m-phenylene diamine moiety of 6FDA dianhydride-based polyimides was investigated for gas separation applications. Pure-gas permeability coefficients of He, H2, N2, O2, CH4, and CO2 were measured at 35 °C and 2 atm. The introduction of hydroxyl groups in the diamine moiety of 6FDA-diaminophenol (DAP) and 6FDA-diamino resorcinol (DAR) polyimides tightened the overall polymer structure due to increased charge transfer complex formation compared to unfunctionalized 6FDA-m-phenylene diamine (mPDA). The BET surface areas based on nitrogen adsorption of 6FDA-DAP (54 m2g−1) and of 6FDA-DAR (45 m2g−1) were ~18% and 32% lower than that of 6FDA-mPDA (66 m2g−1). 6FDA-mPDA had a pure-gas CO2 permeability of 14 Barrer and CO2/CH4 selectivity of 70. The hydroxyl-functionalized polyimides 6FDA-DAP and 6FDA-DAR exhibited very high pure-gas CO2/CH4 selectivities of 92 and 94 with moderate CO2 permeability of 11 and 8 Barrer, respectively. It was demonstrated that hydroxyl-containing polyimide membranes maintained very high CO2/CH4 selectivity (~ 75 at CO2 partial pressure of 10 atm) due to CO2 plasticization resistance when tested under high-pressure mixed-gas conditions. Functionalization with hydroxyl groups may thus be a promising strategy towards attaining highly selective polyimides for economical membrane-based natural gas sweetening.

  13. Pure- and Mixed-Gas Permeation Properties of Highly Selective and Plasticization Resistant Hydroxyl-Diamine-Based 6FDA Polyimides for CO2/CH4 Separation

    KAUST Repository

    Alaslai, Nasser Y.

    2016-01-05

    The effect of hydroxyl functionalization on the m-phenylene diamine moiety of 6FDA dianhydride-based polyimides was investigated for gas separation applications. Pure-gas permeability coefficients of He, H2, N2, O2, CH4, and CO2 were measured at 35 °C and 2 atm. The introduction of hydroxyl groups in the diamine moiety of 6FDA-diaminophenol (DAP) and 6FDA-diamino resorcinol (DAR) polyimides tightened the overall polymer structure due to increased charge transfer complex formation compared to unfunctionalized 6FDA-m-phenylene diamine (mPDA). The BET surface areas based on nitrogen adsorption of 6FDA-DAP (54 m2g−1) and of 6FDA-DAR (45 m2g−1) were ~18% and 32% lower than that of 6FDA-mPDA (66 m2g−1). 6FDA-mPDA had a pure-gas CO2 permeability of 14 Barrer and CO2/CH4 selectivity of 70. The hydroxyl-functionalized polyimides 6FDA-DAP and 6FDA-DAR exhibited very high pure-gas CO2/CH4 selectivities of 92 and 94 with moderate CO2 permeability of 11 and 8 Barrer, respectively. It was demonstrated that hydroxyl-containing polyimide membranes maintained very high CO2/CH4 selectivity (~ 75 at CO2 partial pressure of 10 atm) due to CO2 plasticization resistance when tested under high-pressure mixed-gas conditions. Functionalization with hydroxyl groups may thus be a promising strategy towards attaining highly selective polyimides for economical membrane-based natural gas sweetening.

  14. Learning and the Great Moderation

    OpenAIRE

    Bullard, James B.; Singh, Aarti

    2009-01-01

    We study a stylized theory of the volatility reduction in the U.S. after 1984 - the Great Moderation - which attributes part of the stabilization to less volatile shocks and another part to more difficult inference on the part of Bayesian households attempting to learn the latent state of the economy. We use a standard equilibrium business cycle model with technology following an unobserved regime-switching process. After 1984, according to Kim and Nelson (1999a), the variance of U.S. macroec...

  15. Pricing regulations in Great Britain

    International Nuclear Information System (INIS)

    Cicoletti, G.

    1993-01-01

    This paper briefly describes the structure and functions of Great Britain's essential electric power regulatory authority institutionalized by the 1989 British Electricity Act, i.e., the Office of Electricity Regulation, OFFER, and the responsibilities and tasks of the head of OFFER -the Director General of Electricity Supply (DGES). In particular, with regard to the latter, the paper describes how the DGES works together with regional electricity commissions to ensure the respect, by the various utilities, of consumer price caps and compliance with overall quality of service standards, as well as, to oversee 'pooling' activities by producers and distributors

  16. Pricing regulations in Great Britain

    International Nuclear Information System (INIS)

    Cicoletti, G.

    1993-01-01

    This paper briefly describes the structure and functions of Great Britain's essential electric power regulatory authority institutionalized by the 1989 British Electricity Act, i.e., the Office of Electricity Regulation, OFFER, and the responsibilities and tasks of the head of OFFER - the Director General of Electricity Supply (DGES). In particular, with regard to the latter, the paper describes how the DGES works together with regional electricity commissions to ensure the respect, by the various utilities, of consumer price caps and compliance with overall quality of service standards, as well as, to oversee 'pooling' activities by producers and distributors

  17. What killed Alexander the Great?

    Science.gov (United States)

    Battersby, Cameron

    2007-01-01

    The cause of the death of the Macedonian King, Alexander the Great, at Babylon in 323 BC has excited interest and conjecture throughout the ages. The information available in the surviving ancient sources, none of which is contemporaneous, has been reviewed and compared with modern knowledge as set out in several well-known recent surgical texts. The ancient sources record epic drinking by the Macedonian nobility since at least the time of Phillip II, Alexander's father. Alexander's sudden illness and death is likely to have resulted from a surgical complication of acute alcoholic excess.

  18. Commanders of the Great Victory

    Directory of Open Access Journals (Sweden)

    Anatoly Dmitriyevich Borshchov

    2015-01-01

    Full Text Available The honorary title of «commander» as well as the «admiral» is granted to a military or naval figure on the basis of public recognition of his personal contribution to the success of actions. Generals are usually individuals with creative thinking, the ability to foresee the development of military events. Generals usually have such personality traits as a strong will and determination, rich combat experience, credibility and high organizational skills. In an article dedicated to the 70th anniversary of the Soviet victory in the Great War examines the experience of formation and practice of the most talent-ed Soviet military leaders.

  19. Great apes prefer cooked food.

    Science.gov (United States)

    Wobber, Victoria; Hare, Brian; Wrangham, Richard

    2008-08-01

    The cooking hypothesis proposes that a diet of cooked food was responsible for diverse morphological and behavioral changes in human evolution. However, it does not predict whether a preference for cooked food evolved before or after the control of fire. This question is important because the greater the preference shown by a raw-food-eating hominid for the properties present in cooked food, the more easily cooking should have been adopted following the control of fire. Here we use great apes to model food preferences by Paleolithic hominids. We conducted preference tests with various plant and animal foods to determine whether great apes prefer food items raw or cooked. We found that several populations of captive apes tended to prefer their food cooked, though with important exceptions. These results suggest that Paleolithic hominids would likewise have spontaneously preferred cooked food to raw, exapting a pre-existing preference for high-quality, easily chewed foods onto these cooked items. The results, therefore, challenge the hypothesis that the control of fire preceded cooking by a significant period.

  20. Studying The Great Russian Revolution

    Directory of Open Access Journals (Sweden)

    A. V. Torkunov

    2017-01-01

    Full Text Available The article revises an established view of Russian Revolution as two separate events - February Revolution and October Revolution. The author supports the concept of the «Great Russian Revolution», which unites these two events in a single process of revolutionary development. The author draws attention to the following advantages of the concept under consideration. First, it conceptualizes the revolution as a process contingent of a local and global historical context. In this sense, the revolution is presented as the transition of society to the modern stage of development, meaning the transition to modernity. Second, revolutionary events in Russia are considered from the point of view of the evolution of the spatial and socioeconomic distribution and rearrangement of key social groups: peasantry, elites, national and ethnic minorities. Third, it takes into account the personal factor in the revolutionary events, the influence of individual personalities on escalation or the reduction of socio-political tensions. Fourth, it draws attention to the fact that revolutions imply the use of various forms of political violence. Each revolution is characterized by a unique correlation of forms and intensity of political violence. Finally, it gives a normative assessment of the Revolution, encouraging a national discussion on the results and consequences of this great event.

  1. An experimental investigation of masking in the US FDA adverse event reporting system database.

    Science.gov (United States)

    Wang, Hsin-wei; Hochberg, Alan M; Pearson, Ronald K; Hauben, Manfred

    2010-12-01

    A phenomenon of 'masking' or 'cloaking' in pharmacovigilance data mining has been described, which can potentially cause signals of disproportionate reporting (SDRs) to be missed, particularly in pharmaceutical company databases. Masking has been predicted theoretically, observed anecdotally or studied to a limited extent in both pharmaceutical company and health authority databases, but no previous publication systematically assesses its occurrence in a large health authority database. To explore the nature, extent and possible consequences of masking in the US FDA Adverse Event Reporting System (AERS) database by applying various experimental unmasking protocols to a set of drugs and events representing realistic pharmacovigilance analysis conditions. This study employed AERS data from 2001 through 2005. For a set of 63 Medical Dictionary for Regulatory Activities (MedDRA®) Preferred Terms (PTs), disproportionality analysis was carried out with respect to all drugs included in the AERS database, using a previously described urn-model-based algorithm. We specifically sought masking in which drug removal induced an increase in the statistical representation of a drug-event combination (DEC) that resulted in the emergence of a new SDR. We performed a series of unmasking experiments selecting drugs for removal using rational statistical decision rules based on the requirement of a reporting ratio (RR) >1, top-ranked statistical unexpectedness (SU) and relatedness as reflected in the WHO Anatomical Therapeutic Chemical level 4 (ATC4) grouping. In order to assess the possible extent of residual masking we performed two supplemental purely empirical analyses on a limited subset of data. This entailed testing every drug and drug group to determine which was most influential in uncovering masked SDRs. We assessed the strength of external evidence for a causal association for a small number of masked SDRs involving a subset of 29 drugs for which level of evidence

  2. Security and Privacy Qualities of Medical Devices: An Analysis of FDA Postmarket Surveillance

    Science.gov (United States)

    Kramer, Daniel B.; Baker, Matthew; Ransford, Benjamin; Molina-Markham, Andres; Stewart, Quinn; Fu, Kevin; Reynolds, Matthew R.

    2012-01-01

    Background Medical devices increasingly depend on computing functions such as wireless communication and Internet connectivity for software-based control of therapies and network-based transmission of patients’ stored medical information. These computing capabilities introduce security and privacy risks, yet little is known about the prevalence of such risks within the clinical setting. Methods We used three comprehensive, publicly available databases maintained by the Food and Drug Administration (FDA) to evaluate recalls and adverse events related to security and privacy risks of medical devices. Results Review of weekly enforcement reports identified 1,845 recalls; 605 (32.8%) of these included computers, 35 (1.9%) stored patient data, and 31 (1.7%) were capable of wireless communication. Searches of databases specific to recalls and adverse events identified only one event with a specific connection to security or privacy. Software-related recalls were relatively common, and most (81.8%) mentioned the possibility of upgrades, though only half of these provided specific instructions for the update mechanism. Conclusions Our review of recalls and adverse events from federal government databases reveals sharp inconsistencies with databases at individual providers with respect to security and privacy risks. Recalls related to software may increase security risks because of unprotected update and correction mechanisms. To detect signals of security and privacy problems that adversely affect public health, federal postmarket surveillance strategies should rethink how to effectively and efficiently collect data on security and privacy problems in devices that increasingly depend on computing systems susceptible to malware. PMID:22829874

  3. Monitoring Antimicrobial Resistance in the Food Supply Chain and Its Implications for FDA Policy Initiatives.

    Science.gov (United States)

    Zawack, Kelson; Li, Min; Booth, James G; Love, Will; Lanzas, Cristina; Gröhn, Yrjö T

    2016-09-01

    In response to concerning increases in antimicrobial resistance (AMR), the Food and Drug Administration (FDA) has decided to increase veterinary oversight requirements for antimicrobials and restrict their use in growth promotion. Given the high stakes of this policy for the food supply, economy, and human and veterinary health, it is important to rigorously assess the effects of this policy. We have undertaken a detailed analysis of data provided by the National Antimicrobial Resistance Monitoring System (NARMS). We examined the trends in both AMR proportion and MIC between 2004 and 2012 at slaughter and retail stages. We investigated the makeup of variation in these data and estimated the sample and effect size requirements necessary to distinguish an effect of the policy change. Finally, we applied our approach to take a detailed look at the 2005 withdrawal of approval for the fluoroquinolone enrofloxacin in poultry water. Slaughter and retail showed similar trends. Both AMR proportion and MIC were valuable in assessing AMR, capturing different information. Most variation was within years, not between years, and accounting for geographic location explained little additional variation. At current rates of data collection, a 1-fold change in MIC should be detectable in 5 years and a 6% decrease in percent resistance could be detected in 6 years following establishment of a new resistance rate. Analysis of the enrofloxacin policy change showed the complexities of the AMR policy with no statistically significant change in resistance of both Campylobacter jejuni and Campylobacter coli to ciprofloxacin, another second-generation fluoroquinolone. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  4. A Systematic Screen of FDA-Approved Drugs for Inhibitors of Biological Threat Agents

    Science.gov (United States)

    Madrid, Peter B.; Chopra, Sidharth; Manger, Ian D.; Gilfillan, Lynne; Keepers, Tiffany R.; Shurtleff, Amy C.; Green, Carol E.; Iyer, Lalitha V.; Dilks, Holli Hutcheson; Davey, Robert A.; Kolokoltsov, Andrey A.; Carrion, Ricardo; Patterson, Jean L.; Bavari, Sina; Panchal, Rekha G.; Warren, Travis K.; Wells, Jay B.; Moos, Walter H.; Burke, RaeLyn L.; Tanga, Mary J.

    2013-01-01

    Background The rapid development of effective medical countermeasures against potential biological threat agents is vital. Repurposing existing drugs that may have unanticipated activities as potential countermeasures is one way to meet this important goal, since currently approved drugs already have well-established safety and pharmacokinetic profiles in patients, as well as manufacturing and distribution networks. Therefore, approved drugs could rapidly be made available for a new indication in an emergency. Methodology/Principal Findings A large systematic effort to determine whether existing drugs can be used against high containment bacterial and viral pathogens is described. We assembled and screened 1012 FDA-approved drugs for off-label broad-spectrum efficacy against Bacillus anthracis; Francisella tularensis; Coxiella burnetii; and Ebola, Marburg, and Lassa fever viruses using in vitro cell culture assays. We found a variety of hits against two or more of these biological threat pathogens, which were validated in secondary assays. As expected, antibiotic compounds were highly active against bacterial agents, but we did not identify any non-antibiotic compounds with broad-spectrum antibacterial activity. Lomefloxacin and erythromycin were found to be the most potent compounds in vivo protecting mice against Bacillus anthracis challenge. While multiple virus-specific inhibitors were identified, the most noteworthy antiviral compound identified was chloroquine, which disrupted entry and replication of two or more viruses in vitro and protected mice against Ebola virus challenge in vivo. Conclusions/Significance The feasibility of repurposing existing drugs to face novel threats is demonstrated and this represents the first effort to apply this approach to high containment bacteria and viruses. PMID:23577127

  5. A systematic screen of FDA-approved drugs for inhibitors of biological threat agents.

    Directory of Open Access Journals (Sweden)

    Peter B Madrid

    Full Text Available BACKGROUND: The rapid development of effective medical countermeasures against potential biological threat agents is vital. Repurposing existing drugs that may have unanticipated activities as potential countermeasures is one way to meet this important goal, since currently approved drugs already have well-established safety and pharmacokinetic profiles in patients, as well as manufacturing and distribution networks. Therefore, approved drugs could rapidly be made available for a new indication in an emergency. METHODOLOGY/PRINCIPAL FINDINGS: A large systematic effort to determine whether existing drugs can be used against high containment bacterial and viral pathogens is described. We assembled and screened 1012 FDA-approved drugs for off-label broad-spectrum efficacy against Bacillus anthracis; Francisella tularensis; Coxiella burnetii; and Ebola, Marburg, and Lassa fever viruses using in vitro cell culture assays. We found a variety of hits against two or more of these biological threat pathogens, which were validated in secondary assays. As expected, antibiotic compounds were highly active against bacterial agents, but we did not identify any non-antibiotic compounds with broad-spectrum antibacterial activity. Lomefloxacin and erythromycin were found to be the most potent compounds in vivo protecting mice against Bacillus anthracis challenge. While multiple virus-specific inhibitors were identified, the most noteworthy antiviral compound identified was chloroquine, which disrupted entry and replication of two or more viruses in vitro and protected mice against Ebola virus challenge in vivo. CONCLUSIONS/SIGNIFICANCE: The feasibility of repurposing existing drugs to face novel threats is demonstrated and this represents the first effort to apply this approach to high containment bacteria and viruses.

  6. Effects of 31 FDA approved small-molecule kinase inhibitors on isolated rat liver mitochondria.

    Science.gov (United States)

    Zhang, Jun; Salminen, Alec; Yang, Xi; Luo, Yong; Wu, Qiangen; White, Matthew; Greenhaw, James; Ren, Lijun; Bryant, Matthew; Salminen, William; Papoian, Thomas; Mattes, William; Shi, Qiang

    2017-08-01

    The FDA has approved 31 small-molecule kinase inhibitors (KIs) for human use as of November 2016, with six having black box warnings for hepatotoxicity (BBW-H) in product labeling. The precise mechanisms and risk factors for KI-induced hepatotoxicity are poorly understood. Here, the 31 KIs were tested in isolated rat liver mitochondria, an in vitro system recently proposed to be a useful tool to predict drug-induced hepatotoxicity in humans. The KIs were incubated with mitochondria or submitochondrial particles at concentrations ranging from therapeutic maximal blood concentrations (Cmax) levels to 100-fold Cmax levels. Ten endpoints were measured, including oxygen consumption rate, inner membrane potential, cytochrome c release, swelling, reactive oxygen species, and individual respiratory chain complex (I-V) activities. Of the 31 KIs examined only three including sorafenib, regorafenib and pazopanib, all of which are hepatotoxic, caused significant mitochondrial toxicity at concentrations equal to the Cmax, indicating that mitochondrial toxicity likely contributes to the pathogenesis of hepatotoxicity associated with these KIs. At concentrations equal to 100-fold Cmax, 18 KIs were found to be toxic to mitochondria, and among six KIs with BBW-H, mitochondrial injury was induced by regorafenib, lapatinib, idelalisib, and pazopanib, but not ponatinib, or sunitinib. Mitochondrial liability at 100-fold Cmax had a positive predictive power (PPV) of 72% and negative predictive power (NPV) of 33% in predicting human KI hepatotoxicity as defined by product labeling, with the sensitivity and specificity being 62% and 44%, respectively. Similar predictive power was obtained using the criterion of Cmax ≥1.1 µM or daily dose ≥100 mg. Mitochondrial liability at 1-2.5-fold Cmax showed a 100% PPV and specificity, though the NPV and sensitivity were 32% and 14%, respectively. These data provide novel mechanistic insights into KI hepatotoxicity and indicate that

  7. Identification of Additional Anti-Persister Activity against Borrelia burgdorferi from an FDA Drug Library

    Directory of Open Access Journals (Sweden)

    Jie Feng

    2015-09-01

    Full Text Available Lyme disease is a leading vector-borne disease in the United States. Although the majority of Lyme patients can be cured with standard 2–4 week antibiotic treatment, 10%–20% of patients continue to suffer from prolonged post-treatment Lyme disease syndrome (PTLDS. While the cause for this is unclear, persisting organisms not killed by current Lyme antibiotics may be involved. In our previous study, we screened an FDA drug library and reported 27 top hits that showed high activity against Borrelia persisters. In this study, we present the results of an additional 113 active hits that have higher activity against the stationary phase B. burgdorferi than the currently used Lyme antibiotics. Many antimicrobial agents (antibiotics, antivirals, antifungals, anthelmintics or antiparasitics used for treating other infections were found to have better activity than the current Lyme antibiotics. These include antibacterials such as rifamycins (3-formal-rifamycin, rifaximin, rifamycin SV, thiostrepton, quinolone drugs (sarafloxacin, clinafloxacin, tosufloxacin, and cell wall inhibitors carbenicillin, tazobactam, aztreonam; antifungal agents such as fluconazole, mepartricin, bifonazole, climbazole, oxiconazole, nystatin; antiviral agents zanamivir, nevirapine, tilorone; antimalarial agents artemisinin, methylene blue, and quidaldine blue; antihelmintic and antiparasitic agents toltrazuril, tartar emetic, potassium antimonyl tartrate trihydrate, oxantel, closantel, hycanthone, pyrimethamine, and tetramisole. Interestingly, drugs used for treating other non-infectious conditions including verteporfin, oltipraz, pyroglutamic acid, pidolic acid, and dextrorphan tartrate, that act on the glutathione/γ-glutamyl pathway involved in protection against free radical damage, and also the antidepressant drug indatraline, were found to have high activity against stationary phase B. burgdorferi. Among the active hits, agents that affect cell membranes, energy

  8. Identification of Additional Anti-Persister Activity against Borrelia burgdorferi from an FDA Drug Library.

    Science.gov (United States)

    Feng, Jie; Weitner, Megan; Shi, Wanliang; Zhang, Shuo; Sullivan, David; Zhang, Ying

    2015-09-16

    Lyme disease is a leading vector-borne disease in the United States. Although the majority of Lyme patients can be cured with standard 2-4 week antibiotic treatment, 10%-20% of patients continue to suffer from prolonged post-treatment Lyme disease syndrome (PTLDS). While the cause for this is unclear, persisting organisms not killed by current Lyme antibiotics may be involved. In our previous study, we screened an FDA drug library and reported 27 top hits that showed high activity against Borrelia persisters. In this study, we present the results of an additional 113 active hits that have higher activity against the stationary phase B. burgdorferi than the currently used Lyme antibiotics. Many antimicrobial agents (antibiotics, antivirals, antifungals, anthelmintics or antiparasitics) used for treating other infections were found to have better activity than the current Lyme antibiotics. These include antibacterials such as rifamycins (3-formal-rifamycin, rifaximin, rifamycin SV), thiostrepton, quinolone drugs (sarafloxacin, clinafloxacin, tosufloxacin), and cell wall inhibitors carbenicillin, tazobactam, aztreonam; antifungal agents such as fluconazole, mepartricin, bifonazole, climbazole, oxiconazole, nystatin; antiviral agents zanamivir, nevirapine, tilorone; antimalarial agents artemisinin, methylene blue, and quidaldine blue; antihelmintic and antiparasitic agents toltrazuril, tartar emetic, potassium antimonyl tartrate trihydrate, oxantel, closantel, hycanthone, pyrimethamine, and tetramisole. Interestingly, drugs used for treating other non-infectious conditions including verteporfin, oltipraz, pyroglutamic acid, pidolic acid, and dextrorphan tartrate, that act on the glutathione/γ-glutamyl pathway involved in protection against free radical damage, and also the antidepressant drug indatraline, were found to have high activity against stationary phase B. burgdorferi. Among the active hits, agents that affect cell membranes, energy production, and reactive

  9. FDA-EPA Public Health Guidance on Fish Consumption: A Case Study on Informal Interagency Cooperation in "Shared Regulatory Space".

    Science.gov (United States)

    Holden, Mark

    2015-01-01

    This article is a case study on how administrative agencies interact with each other in cases of shared regulatory jurisdiction. The theoretical literature on the topic of overlapping jurisdiction both (1) makes predictions about how agencies are expected to behave when they share jurisdiction, and (2) in recent iterations argues that overlapping jurisdiction can confer unique policymaking benefits. Through the lens of that theoretical literature, this article examines the relations between the Food and Drug Administration (FDA) and the Environmental Protection Agency (EPA) regarding the public health risks posed by mercury in fish. It concludes that the FDA-EPA case study (1) corroborates the extant theoretical accounts of how agencies behave in cases of overlapping jurisdiction, (2) supports the conclusion of the recent scholarship that overlapping jurisdiction can confer unique policy benefits, and (3) reveals a few wrinkles not given adequate treatment in the extant literature.

  10. The liberal state and the rogue agency: FDA's regulation of drugs for mood disorders, 1950s-1970s.

    Science.gov (United States)

    Shorter, Edward

    2008-01-01

    The theory of the liberal state does not generally contemplate the possibility that regulatory agencies will turn into "rogues," regulating against the interests of their clients and, indeed, the public interest. In the years between circa 1955 and 1975 this seems to have happened to one of the prime regulatory agencies of the US federal government: the Food and Drug Administration (FDA). Intent upon transforming itself from a traditional "cop" agency to a regulatory giant, the FDA campaigned systematically to bring down some safe and effective drugs. This article concentrates on hearings in the area of psychopharmacology regarding several antianxiety drugs, namely meprobamate (Miltown), chlordiazepoxide (Librium) and diazepam (Valium). In addition, from 1967 to 1973 this regulatory vengefulness occurred on a broad scale in the Drug Efficacy Study Implementation (DESI), an administrative exercise that removed from the market almost half of the psychopharmacopoeia. The article explores possible bureaucratic motives for these actions.

  11. The first FDA marketing authorizations of next-generation sequencing technology and tests: challenges, solutions and impact for future assays.

    Science.gov (United States)

    Bijwaard, Karen; Dickey, Jennifer S; Kelm, Kellie; Težak, Živana

    2015-01-01

    The rapid emergence and clinical translation of novel high-throughput sequencing technologies created a need to clarify the regulatory pathway for the evaluation and authorization of these unique technologies. Recently, the US FDA authorized for marketing four next generation sequencing (NGS)-based diagnostic devices which consisted of two heritable disease-specific assays, library preparation reagents and a NGS platform that are intended for human germline targeted sequencing from whole blood. These first authorizations can serve as a case study in how different types of NGS-based technology are reviewed by the FDA. In this manuscript we describe challenges associated with the evaluation of these novel technologies and provide an overview of what was reviewed. Besides making validated NGS-based devices available for in vitro diagnostic use, these first authorizations create a regulatory path for similar future instruments and assays.

  12. FDA-approved drugs that are spermatotoxic in animals and the utility of animal testing for human risk prediction.

    Science.gov (United States)

    Rayburn, Elizabeth R; Gao, Liang; Ding, Jiayi; Ding, Hongxia; Shao, Jun; Li, Haibo

    2018-02-01

    This study reviews FDA-approved drugs that negatively impact spermatozoa in animals, as well as how these findings reflect on observations in human male gametes. The FDA drug warning labels included in the DailyMed database and the peer-reviewed literature in the PubMed database were searched for information to identify single-ingredient, FDA-approved prescription drugs with spermatotoxic effects. A total of 235 unique, single-ingredient, FDA-approved drugs reported to be spermatotoxic in animals were identified in the drug labels. Forty-nine of these had documented negative effects on humans in either the drug label or literature, while 31 had no effect or a positive impact on human sperm. For the other 155 drugs that were spermatotoxic in animals, no human data was available. The current animal models are not very effective for predicting human spermatotoxicity, and there is limited information available about the impact of many drugs on human spermatozoa. New approaches should be designed that more accurately reflect the findings in men, including more studies on human sperm in vitro and studies using other systems (ex vivo tissue culture, xenograft models, in silico studies, etc.). In addition, the present data is often incomplete or reported in a manner that prevents interpretation of their clinical relevance. Changes should be made to the requirements for pre-clinical testing, drug surveillance, and the warning labels of drugs to ensure that the potential risks to human fertility are clearly indicated.

  13. Trouble Spots in Online Direct-to-Consumer Prescription Drug Promotion: A Content Analysis of FDA Warning Letters.

    Science.gov (United States)

    Kim, Hyosun

    2015-08-25

    For the purpose of understanding the Food and Drug Administration's (FDA's) concerns regarding online promotion of prescription drugs advertised directly to consumers, this study examines notices of violations (NOVs) and warning letters issued by the FDA to pharmaceutical manufacturers. The FDA's warning letters and NOVs, which were issued to pharmaceutical companies over a 10-year period (2005 to 2014) regarding online promotional activities, were content-analyzed. Six violation categories were identified: risk information, efficacy information, indication information, product labeling, material information issues, and approval issues. The results reveal that approximately 95% of the alleged violations were found on branded drug websites, in online paid advertisements, and in online videos. Of the total 179 violations, the majority of the alleged violations were concerned with the lack of risk information and/or misrepresentation of efficacy information, suggesting that achieving a fair balance of benefit versus risk information is a major problem with regard to the direct-to-consumer advertising (DTCA) of prescription drugs. In addition, the character space limitations of online platforms, eg, sponsored links on search engines, pose challenges for pharmaceutical marketers with regard to adequately communicating important drug information, such as indication information, risk information, and product labeling. Presenting drug information in a fair and balanced manner remains a major problem. Industry guidance should consider addressing visibility and accessibility of information in the web environment to help pharmaceutical marketers meet the requirements for direct-to-consumer promotion and to protect consumers from misleading drug information. Promotion via social media warrants further attention, as pharmaceutical manufacturers have already begun actively establishing a social media presence, and the FDA has thus begun to keep tabs on social media promotions of

  14. The "natural" aversion: the FDA's reluctance to define a leading food-industry marketing claim, and the pressing need for a workable rule.

    Science.gov (United States)

    Farris, April L

    2010-01-01

    As of 2009, the "natural foods" industry has become a 22.3 billion dollar giant and "all-natural" is the second-leading marketing claim for all new food products. Even in such a flourishing market, the Food and Drug Administration (FDA) has never defined the term "natural" through rulemaking. FDA and the U.S. Department of Agriculture (USDA) have instead created separate, non-identical policy statements governing the use of the term "natural," and FDA has abandoned efforts to define "natural" through rulemaking in the face of more pressing priorities. In absence of any governing federal standard, consumer advocacy groups and warring food industries have attempted to define "natural" to fit their preferences through high-stakes litigation of state law claims, leaving courts free to apply diverging standards without the expertise of FDA. Recent case law from federal district courts and the Supreme Court leaves little hope that FDA's current policy statement will preempt state law causes of action. To prevent a potential patchwork of definitions varying by state, and to create a legitimate standard resting on informed scientific expertise rather than consumer whims, FDA should engage in rulemaking to define the term "natural." This paper concludes by sketching potential formulations for such a rule based on FDA's previous successful rule-making ventures and standards used by natural foods retailers.

  15. The Great Hedge of India

    International Nuclear Information System (INIS)

    Moxham, Roy

    2015-01-01

    The 'Great Hedge of India', a 3 700 kilometre-long hedge installed by the British customs to safeguard the colonial salt tax system and avoid salt smuggling totally faded from both memory and records (e.g. maps) in less than a century. Roy Moxham found traces of the hedge in a book footnote and searched it for several years until he found its meagre remains. The speaker wrote a book about this quest. He said that this story reveals how things disappear when they are no longer useful and, especially, when they are linked to parts of history that are not deemed particularly positive (the hedge was a means of colonial power)

  16. Gypsum karst in Great Britain

    Directory of Open Access Journals (Sweden)

    Cooper A.H.

    1996-01-01

    Full Text Available In Great Britain the most spectacular gypsum karst development is in the Zechstein gypsum (late Permian mainly in north-eastern England. The Midlands of England also has some karst developed in the Triassic gypsum in the vicinity of Nottingham. Along the north-east coast, south of Sunderland, well-developed palaeokarst, with magnificent breccia pipes, was produced by dissolution of Permian gypsum. In north-west England a small gypsum cave system of phreatic origin has been surveyed and recorded. A large actively evolving phreatic gypsum cave system has been postulated beneath the Ripon area on the basis of studies of subsidence and boreholes. The rate of gypsum dissolution here, and the associated collapse lead to difficult civil engineering and construction conditions, which can also be aggravated by water abstraction.

  17. Great-Britain at CERN

    CERN Multimedia

    C. Laignel

    2004-01-01

    From 23 to 25 November 2004 Administration Building Bldg 60/61 - ground and 1st floor 09.30 - 17.30 Twenty five companies will present their latest technology at the "Great-Britain at CERN" exhibition. British industry will exhibit products and technologies which are related to the field of particle physics. The main subjects are: electrical engineering, electronics, mechanical engineering, vacuum & low temperatures technologies, particles detectors and telecommunications. The exhibition is organised by BEAMA Exhibitions, The British Electrotechnical and Allied Manufacturer's Association There follows : the list of exhibitors. A detailed programme will be available in due course at : your Departemental secretariat, the reception information desk, Building 33, the exhibition. A detailed list of firms is available under the following FI link: http://fi-dep.web.cern.ch/fi-dep/structure/memberstates/exhibitions_visits.htm 1 Accles & Pollock 2 A S Scientific Products Ltd 3 C...

  18. Great Basin Experimental Range: Annotated bibliography

    Science.gov (United States)

    E. Durant McArthur; Bryce A. Richardson; Stanley G. Kitchen

    2013-01-01

    This annotated bibliography documents the research that has been conducted on the Great Basin Experimental Range (GBER, also known as the Utah Experiment Station, Great Basin Station, the Great Basin Branch Experiment Station, Great Basin Experimental Center, and other similar name variants) over the 102 years of its existence. Entries were drawn from the original...

  19. The origin of 'Great Walls'

    International Nuclear Information System (INIS)

    Shandarin, Sergei F.

    2009-01-01

    A new semi-analytical model that explains the formation and sizes of the 'great walls' - the largest structures observed in the universe is suggested. Although the basis of the model is the Zel'dovich approximation it has been used in a new way very different from the previous studies. Instead of traditional approach that evaluates the nonlinear density field it has been utilized for identification of the regions in Lagrangian space that after the mapping to real or redshift space (depending on the kind of structure is studied) end up in the regions where shell-crossing occurs. The set of these regions in Lagrangian space form the progenitor of the structure and after the mapping it determines the pattern of the structure in real or redshift space. The particle trajectories have crossed in such regions and the mapping is no longer unique there. The progenitor after mapping makes only one stream in the multi-stream flow regions therefore it does not comprise all the mass. Nevertheless, it approximately retains the shape of the structure. The progenitor of the structure in real space is determined by the linear density field along with two non-Gaussian fields derived from the initial potential. Its shape in Eulerian space is also affected by the displacement field. The progenitor of the structure in redshift space also depends on these fields but in addition it is strongly affected by two anisotropic fields that determine the pattern of great walls as well as their huge sizes. All the fields used in the mappings are derived from the linear potential smoothed at the current scale of nonlinearity which is R nl = 2.7 h −1 Mpc for the adopted parameters of the ΛCDM universe normalized to σ 8 = 0.8. The model predicts the existence of walls with sizes significantly greater than 500 h −1 Mpc that may be found in sufficiently large redshift surveys

  20. The Great Warming Brian Fagan

    Science.gov (United States)

    Fagan, B. M.

    2010-12-01

    The Great Warming is a journey back to the world of a thousand years ago, to the Medieval Warm Period. Five centuries of irregular warming from 800 to 1250 had beneficial effects in Europe and the North Atlantic, but brought prolonged droughts to much of the Americas and lands affected by the South Asian monsoon. The book describes these impacts of warming on medieval European societies, as well as the Norse and the Inuit of the far north, then analyzes the impact of harsh, lengthy droughts on hunting societies in western North America and the Ancestral Pueblo farmers of Chaco Canyon, New Mexico. These peoples reacted to drought by relocating entire communities. The Maya civilization was much more vulnerable that small-scale hunter-gatherer societies and subsistence farmers in North America. Maya rulers created huge water storage facilities, but their civilization partially collapsed under the stress of repeated multiyear droughts, while the Chimu lords of coastal Peru adapted with sophisticated irrigation works. The climatic villain was prolonged, cool La Niñalike conditions in the Pacific, which caused droughts from Venezuela to East Asia, and as far west as East Africa. The Great Warming argues that the warm centuries brought savage drought to much of humanity, from China to Peru. It also argues that drought is one of the most dangerous elements in today’s humanly created global warming, often ignored by preoccupied commentators, but with the potential to cause over a billion people to starve. Finally, I use the book to discuss the issues and problems of communicating multidisciplinary science to the general public.

  1. FDA Approval: Ibrutinib for Patients with Previously Treated Mantle Cell Lymphoma and Previously Treated Chronic Lymphocytic Leukemia.

    Science.gov (United States)

    de Claro, R Angelo; McGinn, Karen M; Verdun, Nicole; Lee, Shwu-Luan; Chiu, Haw-Jyh; Saber, Haleh; Brower, Margaret E; Chang, C J George; Pfuma, Elimika; Habtemariam, Bahru; Bullock, Julie; Wang, Yun; Nie, Lei; Chen, Xiao-Hong; Lu, Donghao Robert; Al-Hakim, Ali; Kane, Robert C; Kaminskas, Edvardas; Justice, Robert; Farrell, Ann T; Pazdur, Richard

    2015-08-15

    On November 13, 2013, the FDA granted accelerated approval to ibrutinib (IMBRUVICA capsules; Pharmacyclics, Inc.) for the treatment of patients with mantle cell lymphoma (MCL) who have received at least one prior therapy. On February 12, 2014, the FDA granted accelerated approval for the treatment of patients with chronic lymphocytic leukemia (CLL) who have received at least one prior therapy. Ibrutinib is a first-in-class Bruton's tyrosine kinase (BTK) inhibitor that received all four expedited programs of the FDA: Fast-Track designation, Breakthrough Therapy designation, Priority Review, and Accelerated Approval. Both approvals were based on overall response rate (ORR) and duration of response (DOR) in single-arm clinical trials in patients with prior treatment. In MCL (N = 111), the complete and partial response rates were 17.1% and 48.6%, respectively, for an ORR of 65.8% [95% confidence interval (CI), 56.2%-74.5%]. The median DOR was 17.5 months (95% CI, 15.8-not reached). In CLL (N = 48), the ORR was 58.3% (95% CI, 43.2%-72.4%), and the DOR ranged from 5.6 to 24.2 months. The most common adverse reactions (≥ 30% in either trial) were thrombocytopenia, diarrhea, neutropenia, bruising, upper respiratory tract infection, anemia, fatigue, musculoskeletal pain, peripheral edema, and nausea. ©2015 American Association for Cancer Research.

  2. Does the FDA have regulatory authority over adult autologous stem cell therapies? 21 CFR 1271 and the emperor's new clothes

    Directory of Open Access Journals (Sweden)

    Freeman Michael

    2012-03-01

    Full Text Available Abstract FDA has recently asserted that many autologous cell therapies once considered the practice of medicine are in fact drugs. These changes began with the creation of new sections of 21 CFR 1271 and a subsequent one word change where the FDA, without public commentary, altered a single word in its regulatory language regarding cell and tissue based therapies that asserted the authority to classify autologous tissue as drugs. The bright line between medical care and drug production can be delineated in many ways, but a simple metric that defines the dichotomy is the consent status of the patient. In healthcare, a patient can either be consented individually for a medical procedure or exposed to an unconsented risk where regulatory assurances are already in place. These new FDA policies apply rules meant to keep drugs safe in a drug factory (unconsented mass production risks to individually consented surgical procedures. We argue that there is little societal benefit to these changes and that they are already stifling medical innovation.

  3. Chloroquine, a FDA-approved Drug, Prevents Zika Virus Infection and its Associated Congenital Microcephaly in Mice.

    Science.gov (United States)

    Li, Chunfeng; Zhu, Xingliang; Ji, Xue; Quanquin, Natalie; Deng, Yong-Qiang; Tian, Min; Aliyari, Roghiyh; Zuo, Xiangyang; Yuan, Ling; Afridi, Shabbir Khan; Li, Xiao-Feng; Jung, Jae U; Nielsen-Saines, Karin; Qin, Frank Xiao-Feng; Qin, Cheng-Feng; Xu, Zhiheng; Cheng, Genhong

    2017-10-01

    Zika virus (ZIKV) has become a global public health emergency due to its rapidly expanding range and its ability to cause severe congenital defects such as microcephaly. However, there are no FDA-approved therapies or vaccines against ZIKV infection. Through our screening of viral entry inhibitors, we found that chloroquine (CQ), a commonly used antimalarial and a FDA-approved drug that has also been repurposed against other pathogens, could significantly inhibit ZIKV infection in vitro, by blocking virus internalization. We also demonstrated that CQ attenuates ZIKV-associated morbidity and mortality in mice. Finally, we proved that CQ protects fetal mice from microcephaly caused by ZIKV infection. Our methodology of focusing on previously identified antivirals in screens for effectiveness against ZIKV proved to be a rapid and efficient means of discovering new ZIKV therapeutics. Selecting drugs that were previously FDA-approved, such as CQ, also improves the likelihood that they may more quickly reach stages of clinical testing and use by the public. Copyright © 2017. Published by Elsevier B.V.

  4. High-risk medical devices, children and the FDA: regulatory challenges facing pediatric mechanical circulatory support devices.

    Science.gov (United States)

    Almond, Christopher S D; Chen, Eric A; Berman, Michael R; Less, Joanne R; Baldwin, J Timothy; Linde-Feucht, Sarah R; Hoke, Tracey R; Pearson, Gail D; Jenkins, Kathy; Duncan, Brian W; Zuckerman, Bram D

    2007-01-01

    Pediatric mechanical circulatory support is a critical unmet need in the United States. Infant- and child-sized ventricular assist devices are currently being developed largely through federal contracts and grants through the National Heart, Lung, and Blood Institute (NHLBI). Human testing and marketing of high-risk devices for children raises epidemiologic and regulatory issues that will need to be addressed. Leaders from the US Food and Drug Administration (FDA), NHLBI, academic pediatric community, and industry convened in January 2006 for the first FDA Workshop on the Regulatory Process for Pediatric Mechanical Circulatory Support Devices. The purpose was to provide the pediatric community with an overview of the federal regulatory process for high-risk medical devices and to review the challenges specific to the development and regulation of pediatric mechanical circulatory support devices. Pediatric mechanical circulatory support present significant epidemiologic, logistic, and financial challenges to industry, federal regulators, and the pediatric community. Early interactions with the FDA, shared appreciation of challenges, and careful planning will be critical to avoid unnecessary delays in making potentially life-saving devices available for children. Collaborative efforts to address these challenges are warranted.

  5. A clinical plan for MDMA (Ecstasy) in the treatment of posttraumatic stress disorder (PTSD): partnering with the FDA.

    Science.gov (United States)

    Doblin, Rick

    2002-01-01

    The FDA and the Spanish Ministry of Health have concluded that the risk/benefit ratio is favorable under certain circumstances for clinical studies investigating MDMA-assisted psychotherapy. Both agencies have approved pilot studies in chronic posttraumatic stress disorder (PTSD) patients who have failed to obtain relief from at least one course of conventional treatment. These studies, the only ones in the world into the therapeutic use of MDMA, are being funded by a nonprofit research and educational organization, the Multidisciplinary Association for Psychedelic Studies (MAPS, www.maps.org). A rationale is offered explaining why MAPS chose to focus its limited resources on MDMA, and also on PTSD patients. A Clinical Plan is elaborated for the conduct of the "adequate and well-controlled" trials necessary to evaluate the safety and efficacy of MDMA-assisted psychotherapy for PTSD, with the studies estimated to cost about 5 million dollars and to take about five years. The Clinical Plan has been developed, in part, through analysis of the studies conducted by Pfizer in its successful effort to have Zoloft approved by the FDA for use with PTSD patients, and through review of transcripts of the FDA's Psychopharmacologic Drugs Advisory Committee meeting that recommended approval of Zoloft for PTSD.

  6. The FDA Unapproved Drugs Initiative: An Observational Study of the Consequences for Drug Prices and Shortages in the United States.

    Science.gov (United States)

    Gupta, Ravi; Dhruva, Sanket S; Fox, Erin R; Ross, Joseph S

    2017-10-01

    Hundreds of drug products are currently marketed in the United States without approval from the FDA. The 2006 Unapproved Drugs Initiative (UDI) requires manufacturers to remove these drug products from the market or obtain FDA approval by demonstrating evidence of safety and efficacy. Once the FDA acts against an unapproved drug, fewer manufacturers remain in the market, potentially enabling drug price increases and greater susceptibility to drug shortages. There is a need for systematic study of the UDI's effect on prices and shortages of all targeted drugs. To examine the clinical evidence for approval and association with prices and shortages of previously unapproved prescription drugs after being addressed by the UDI. Previously unapproved prescription drugs that faced UDI regulatory action or with at least 1 product that received FDA approval through manufacturers' voluntary compliance with the UDI between 2006 and 2015 were identified. The clinical evidence was categorized as either newly conducted clinical trials or use of previously published literature and/or bioequivalence studies to demonstrate safety and efficacy. We determined the change in average wholesale price, presence of shortage, and duration of shortage for each drug during the 2 years before and after UDI regulatory action or approval through voluntary compliance. Between 2006 and 2015, 34 previously unapproved prescription drugs were addressed by the UDI. Nearly 90% of those with a drug product that received FDA approval were supported by literature reviews or bioequivalence studies, not new clinical trial evidence. Among the 26 drugs with available pricing data, average wholesale price during the 2 years before and after voluntary approval or UDI action increased by a median of 37% (interquartile range [IQR] = 23%-204%; P Innovation; from the Blue Cross Blue Shield Association to better understand medical technology evidence generation; from the Centers for Medicare & Medicaid Services to

  7. Synthesis and characterization of a microporous 6FDA-polyimide made from a novel carbocyclic pseudo Tröger's base diamine: Effect of bicyclic bridge on gas transport properties

    KAUST Repository

    Abdulhamid, Mahmoud A.; Ma, Xiaohua; Miao, Xiaohe; Pinnau, Ingo

    2017-01-01

    ,11-methanodibenzo[a,e][8]annulene (iCTBDA), were designed for the synthesis of microporous 6FDA-based polyimides (6FDA-CTBDA and 6FDA-iCTBDA). Both polyimides were soluble, exhibited excellent thermal stability of ∼490 °C, and had high surface areas of 587 m2 g−1 (6

  8. Twentieth Anniversary of Leptin discovery and the Approval of Myalept by FDA

    Directory of Open Access Journals (Sweden)

    Ata Mahmoodpoor

    2015-04-01

    Full Text Available Leptin is a 16 kDa hormone that is mainly expressed in adipose tissues (1. The major target of leptin is hypothalamus and it suppresses food intake and energy consumption, consequently diminishing adipose deposits and body weight (2, 3. The OB gene was isolated by Friedman in 1994 (4.  Based on the suggestion of Roger Guillemin, Friedman named this new hormone "leptin" from the Greek lepto meaning thin (5, 6. Since leptin discovery, numerous studies have been conducted on its physiological effects and its function in pathological conditions. Most of studies on leptin concentrated on its metabolic actions (7, receptors (8 and further broad functions such as immunity modulation (9 and memory processing (10. Considering such a vast range of functions, it is clear that patients with lack of leptin physiologically need pharmacological interventions. At this moment, we are in the twentieth year of leptin discovery. Finally, FDA approved a drug named Myalept (metreleptin for injection on February 2014 to treat rare metabolic disease caused by leptin deficiency. Congenital generalized lipodystrophy is a disorder with partial lack of fat tissues (11. The trial for the safety and effectiveness of Myalept demonstrated decrease in HbA1c, fasting blood glucose, and triglycerides (11. Nevertheless, there are some limitations to the usage of Myalept in HIV-related lipodystrophy and some metabolic disorders (11. Moreover, it may increase the risk of lymphoma by producing anti-metreleptin antibodies neutralizing endogenous leptin. Considering these concerns, Myalept is available only through a limited profile under a Risk Evaluation and Mitigation Strategy (REMS. Myalept is contraindicated in patients with general obesity not related to congenital leptin deficiency (12. Even though, Myalept has very limited indications for use in general population, it is considered a milestone towards the discovery of novel treatments for Leptin deficiencies and disorders

  9. Mining association patterns of drug-interactions using post marketing FDA's spontaneous reporting data.

    Science.gov (United States)

    Ibrahim, Heba; Saad, Amr; Abdo, Amany; Sharaf Eldin, A

    2016-04-01

    Pharmacovigilance (PhV) is an important clinical activity with strong implications for population health and clinical research. The main goal of PhV is the timely detection of adverse drug events (ADEs) that are novel in their clinical nature, severity and/or frequency. Drug interactions (DI) pose an important problem in the development of new drugs and post marketing PhV that contribute to 6-30% of all unexpected ADEs. Therefore, the early detection of DI is vital. Spontaneous reporting systems (SRS) have served as the core data collection system for post marketing PhV since the 1960s. The main objective of our study was to particularly identify signals of DI from SRS. In addition, we are presenting an optimized tailored mining algorithm called "hybrid Apriori". The proposed algorithm is based on an optimized and modified association rule mining (ARM) approach. A hybrid Apriori algorithm has been applied to the SRS of the United States Food and Drug Administration's (U.S. FDA) adverse events reporting system (FAERS) in order to extract significant association patterns of drug interaction-adverse event (DIAE). We have assessed the resulting DIAEs qualitatively and quantitatively using two different triage features: a three-element taxonomy and three performance metrics. These features were applied on two random samples of 100 interacting and 100 non-interacting DIAE patterns. Additionally, we have employed logistic regression (LR) statistic method to quantify the magnitude and direction of interactions in order to test for confounding by co-medication in unknown interacting DIAE patterns. Hybrid Apriori extracted 2933 interacting DIAE patterns (including 1256 serious ones) and 530 non-interacting DIAE patterns. Referring to the current knowledge using four different reliable resources of DI, the results showed that the proposed method can extract signals of serious interacting DIAEs. Various association patterns could be identified based on the relationships among

  10. Evaluation of an FDA approved library against laboratory models of human intestinal nematode infections.

    Science.gov (United States)

    Keiser, Jennifer; Panic, Gordana; Adelfio, Roberto; Cowan, Noemi; Vargas, Mireille; Scandale, Ivan

    2016-07-01

    Treatment options for infections with soil-transmitted helminths (STH) - Ascaris lumbricoides, Trichuris trichiura and the two hookworm species, Ancylostoma duodenale and Necator americanus - are limited despite their considerable global health burden. The aim of the present study was to test the activity of an openly available FDA library against laboratory models of human intestinal nematode infections. All 1,600 drugs were first screened against Ancylostoma ceylanicum third-stage larvae (L3). Active compounds were scrutinized and toxic compounds, drugs indicated solely for topical use, and already well-studied anthelmintics were excluded. The remaining hit compounds were tested in parallel against Trichuris muris first-stage larvae (L1), Heligmosomoides polygyrus third-stage larvae (L3), and adult stages of the three species in vitro. In vivo studies were performed in the H. polygyrus and T. muris mice models. Fifty-four of the 1,600 compounds tested revealed an activity of > 60 % against A. ceylanicum L3 (hit rate of 3.4 %), following incubation at 200 μM for 72 h. Twelve compounds progressed into further screens. Adult A. ceylanicum were the least affected (1/12 compounds active at 50 μM), while eight of the 12 test compounds revealed activity against T. muris L1 (100 μM) and adults (50 μM), and H. polygyrus L3 (200 μM). Trichlorfon was the only compound active against all stages of A. ceylanicum, H. polygyrus and T. muris. In addition, trichlorfon achieved high worm burden reductions of 80.1 and 98.9 %, following a single oral dose of 200 mg/kg in the T. muris and H. polygyrus mouse model, respectively. Drug screening on the larval stages of intestinal parasitic nematodes is feasible using small libraries and important given the empty drug discovery and development pipeline for STH infections. Differences and commonalities in drug activities across the different STH species and stages were confirmed. Hits identified might serve as a

  11. Use of the FDA nozzle model to illustrate validation techniques in computational fluid dynamics (CFD) simulations.

    Science.gov (United States)

    Hariharan, Prasanna; D'Souza, Gavin A; Horner, Marc; Morrison, Tina M; Malinauskas, Richard A; Myers, Matthew R

    2017-01-01

    A "credible" computational fluid dynamics (CFD) model has the potential to provide a meaningful evaluation of safety in medical devices. One major challenge in establishing "model credibility" is to determine the required degree of similarity between the model and experimental results for the model to be considered sufficiently validated. This study proposes a "threshold-based" validation approach that provides a well-defined acceptance criteria, which is a function of how close the simulation and experimental results are to the safety threshold, for establishing the model validity. The validation criteria developed following the threshold approach is not only a function of Comparison Error, E (which is the difference between experiments and simulations) but also takes in to account the risk to patient safety because of E. The method is applicable for scenarios in which a safety threshold can be clearly defined (e.g., the viscous shear-stress threshold for hemolysis in blood contacting devices). The applicability of the new validation approach was tested on the FDA nozzle geometry. The context of use (COU) was to evaluate if the instantaneous viscous shear stress in the nozzle geometry at Reynolds numbers (Re) of 3500 and 6500 was below the commonly accepted threshold for hemolysis. The CFD results ("S") of velocity and viscous shear stress were compared with inter-laboratory experimental measurements ("D"). The uncertainties in the CFD and experimental results due to input parameter uncertainties were quantified following the ASME V&V 20 standard. The CFD models for both Re = 3500 and 6500 could not be sufficiently validated by performing a direct comparison between CFD and experimental results using the Student's t-test. However, following the threshold-based approach, a Student's t-test comparing |S-D| and |Threshold-S| showed that relative to the threshold, the CFD and experimental datasets for Re = 3500 were statistically similar and the model could be

  12. The heart and great vessels

    International Nuclear Information System (INIS)

    Condon, V.

    1985-01-01

    Heart disease is the fifth most common cause of death in infants and children (preceded by anoxic and hypoxic conditions, gross congenital malformations, accidental death, and immaturity). Of all the cardiac lesions, congenital heart disease (CHD) makes up the gross majority, accounting for approximately 90% of all cardiac deaths. Approximately two-thirds of all infants who die from CHD do so within the first year of life; of these, approximately one-third die within the first month. The most common cause of death in the first month is hypoplastic left heart syndrome and lesions associated with it, i.e., aortic atresia/critical aortic stenosis and mitral atresia/critical mitral stenosis. Severe coarctation of the aorta (coarctation syndrome) and transposition of the great arteries are the other most important causes of death in this age group. CHD occurs as a familial condition in approximately 1-4% of cases; ventricular septal defects, patent ductus arteriosus, and atrial septal defect are particularly common forms. Parental age plays an important role, with a significantly increased risk of CHD in infants of mothers over 39 years of age. Patent ductus arteriosus is more prevalent in firstborn children, particularly those born prematurely to young mothers. Environmental factors, such as exposure to teratogenic agents, have also been shown to increase the incidence of CHD. Children with various syndromes also have increased incidence of CHD. Down syndrome is a classic example, as are other trisomies

  13. Tipping Points, Great and Small

    Science.gov (United States)

    Morrison, Foster

    2010-12-01

    The Forum by Jordan et al. [2010] addressed environmental problems of various scales in great detail, but getting the critical message through to the formulators of public policies requires going back to basics, namely, that exponential growth (of a population, an economy, or most anything else) is not sustainable. When have you heard any politician or economist from anywhere across the ideological spectrum say anything other than that more growth is essential? There is no need for computer models to demonstrate “limits to growth,” as was done in the 1960s. Of course, as one seeks more details, the complexity of modeling will rapidly outstrip the capabilities of both observation and computing. This is common with nonlinear systems, even simple ones. Thus, identifying all possible “tipping points,” as suggested by Jordan et al. [2010], and then stopping just short of them, is impractical if not impossible. The main thing needed to avoid environmental disasters is a bit of common sense.

  14. Transposition of the great arteries

    Directory of Open Access Journals (Sweden)

    Castela Eduardo

    2008-10-01

    Full Text Available Abstract Transposition of the great arteries (TGA, also referred to as complete transposition, is a congenital cardiac malformation characterised by atrioventricular concordance and ventriculoarterial (VA discordance. The incidence is estimated at 1 in 3,500–5,000 live births, with a male-to-female ratio 1.5 to 3.2:1. In 50% of cases, the VA discordance is an isolated finding. In 10% of cases, TGA is associated with noncardiac malformations. The association with other cardiac malformations such as ventricular septal defect (VSD and left ventricular outflow tract obstruction is frequent and dictates timing and clinical presentation, which consists of cyanosis with or without congestive heart failure. The onset and severity depend on anatomical and functional variants that influence the degree of mixing between the two circulations. If no obstructive lesions are present and there is a large VSD, cyanosis may go undetected and only be perceived during episodes of crying or agitation. In these cases, signs of congestive heart failure prevail. The exact aetiology remains unknown. Some associated risk factors (gestational diabetes mellitus, maternal exposure to rodenticides and herbicides, maternal use of antiepileptic drugs have been postulated. Mutations in growth differentiation factor-1 gene, the thyroid hormone receptor-associated protein-2 gene and the gene encoding the cryptic protein have been shown implicated in discordant VA connections, but they explain only a small minority of TGA cases. The diagnosis is confirmed by echocardiography, which also provides the morphological details required for future surgical management. Prenatal diagnosis by foetal echocardiography is possible and desirable, as it may improve the early neonatal management and reduce morbidity and mortality. Differential diagnosis includes other causes of central neonatal cyanosis. Palliative treatment with prostaglandin E1 and balloon atrial septostomy are usually

  15. The beach-seine fishery off Durban, KwaZulu-Natal

    African Journals Online (AJOL)

    1996-07-23

    Jul 23, 1996 ... the mean weight of a crate of fish, mean lengths of fish caught .... or beyond the Natal Sharks Board protective shark nets. (approximately 300 m offshore). ..... Spotfin flathead. White karanteen ... Great barracuda. Yellow stripe ...

  16. Cosmic Reason of Great Glaciation

    Science.gov (United States)

    Bagrov, Alexander; Murtazov, Andrey

    The origin of long-time and global glaciations in the past of our planet, which have been named «great», is still not clear. Both the advance of glaciers and their subsequent melting must be connected with some energy consuming processes. There is a powerful energy source permanently functioning throughout the Earth’s history - the solar radiation. The equality of the incoming shortwave solar energy and the transformed long-wave energy emitted by the Earth provides for the whole ecosphere’s sustainable evolution. Great glaciations might be caused by space body falls into the world oceans. If the body is large enough, it can stir waters down to the bottom. The world waters are part of the global heat transfer from the planet’s equator to its poles (nowadays, mostly to the North Pole). The mixing of the bottom and surface waters breaks the circulation of flows and they stop. The termination of heat transfer to the poles will result in an icecap at high latitudes which in its turn will decrease the total solar heat inflow to the planet and shift the pole ice boarder to the equator. This positive feedback may last long and result in long-time glaciations. The oceanic currents will remain only near the equator. The factor obstructing the global cooling is the greenhouse effect. Volcanic eruptions supply a lot of carbon dioxide into the atmosphere. When due to the increased albedo the planet receives less solar heat, plants bind less carbon oxide into biomass and more of it retains in the atmosphere. Therefore, the outflow of heat from the planet decreases and glaciations does not involve the whole planet. The balance established between the heat inflow and heat losses is unstable. Any imbalance acts as a positive feed-back factor. If the volcanic activity grows, the inflow of the carbon dioxide into the atmosphere will cause its heating-up (plants will fail to reproduce themselves quickly enough to utilize the carbonic acid). The temperature growth will lead to

  17. Repositioning FDA Drugs as Potential Cruzain Inhibitors from Trypanosoma cruzi: Virtual Screening, In Vitro and In Vivo Studies

    Directory of Open Access Journals (Sweden)

    Isidro Palos

    2017-06-01

    Full Text Available Chagas disease (CD is a neglected disease caused by the parasite Trypanosoma cruzi, which affects underdeveloped countries. The current drugs of choice are nifurtimox and benznidazole, but both have severe adverse effects and less effectivity in chronic infections; therefore, the need to discover new drugs is essential. A computer-guided drug repositioning method was applied to identify potential FDA drugs (approved and withdrawn as cruzain (Cz inhibitors and trypanocidal effects were confirmed by in vitro and in vivo studies. 3180 FDA drugs were virtually screened using a structure-based approach. From a first molecular docking analysis, a set of 33 compounds with the best binding energies were selected. Subsequent consensus affinity binding, ligand amino acid contact clustering analysis, and ranked position were used to choose four known pharmacological compounds to be tested in vitro. Mouse blood samples infected with trypomastigotes from INC-5 and NINOA strains were used to test the trypanocidal effect of four selected compounds. Among these drugs, one fibrate antilipemic (etofyllin clofibrate and three β-lactam antibiotics (piperacillin, cefoperazone, and flucloxacillin showed better trypanocidal effects (LC50 range 15.8–26.1 μg/mL in comparison with benznidazole and nifurtimox (LC50 range 33.1–46.7 μg/mL. A short-term in vivo evaluation of these compounds showed a reduction of parasitemia in infected mice (range 90–60% at 6 h, but this was low compared to benznidazole (50%. This work suggests that four known FDA drugs could be used to design and obtain new trypanocidal agents.

  18. An analysis of the warning letters issued by the FDA to pharmaceutical manufacturers regarding misleading health outcomes claims

    Directory of Open Access Journals (Sweden)

    Chatterjee S

    2012-12-01

    Full Text Available Objective: To evaluate the number and type of warning letters issued by the US Food and Drug Administration (FDA to pharmaceutical manufacturers for promotional violations.Methods: Two reviewers downloaded, printed and independently evaluated warning letters issued by the FDA to pharmaceutical manufacturers from years 2003-2008. Misleading claims were broadly classified as clinical, Quality-of-Life (QoL, and economic claims. Clinical claims included claims regarding unsubstantiated efficacy, safety and tolerability, superiority, broadening of indication and/or omission of risk information. QoL claims included unsubstantiated quality of life and/or health-related quality of life claims. Economic claims included any form of claim made on behalf of the pharmaceutical companies related to cost superiority of or cost savings from the drug compared to other drugs in the market.Results: In the 6-year study period, 65 warning letters were issued by FDA, which contained 144 clinical, three QoL, and one economic claim. On an average, 11 warning letters were issued per year. Omission of risk information was the most frequently violated claim (30.6% followed by unsubstantiated efficacy claims (18.6%. Warning letters were primarily directed to manufacturers of cardiovascular (14.6%, anti-microbial (14.6%, and CNS (12.5% drugs. Majority of the claims referenced in warning letters contained promotional materials directed to physicians (57%. Conclusion: The study found that misleading clinical outcome claims formed the majority of the promotional violations, and majority of the claims were directed to physicians. Since inadequate promotion of medications may lead to irrational prescribing, the study emphasizes the importance of disseminating reliable, credible, and scientific information to patients, and more importantly, physicians to protect public health.

  19. Parallel screening of FDA-approved antineoplastic drugs for identifying sensitizers of TRAIL-induced apoptosis in cancer cells

    International Nuclear Information System (INIS)

    Taylor, David J; Parsons, Christine E; Han, Haiyong; Jayaraman, Arul; Rege, Kaushal

    2011-01-01

    Tumor Necrosis Factor-α Related Apoptosis Inducing Ligand (TRAIL) and agonistic antibodies to death receptor 4 and 5 are promising candidates for cancer therapy due to their ability to induce apoptosis selectively in a variety of human cancer cells, while demonstrating little cytotoxicity in normal cells. Although TRAIL and agonistic antibodies to DR4 and DR5 are considered safe and promising candidates in cancer therapy, many malignant cells are resistant to DR-mediated, TRAIL-induced apoptosis. In the current work, we screened a small library of fifty-five FDA and foreign-approved anti-neoplastic drugs in order to identify candidates that sensitized resistant prostate and pancreatic cancer cells to TRAIL-induced apoptosis. FDA-approved drugs were screened for their ability to sensitize TRAIL resistant prostate cancer cells to TRAIL using an MTT assay for cell viability. Analysis of variance was used to identify drugs that exhibited synergy with TRAIL. Drugs demonstrating the highest synergy were selected as leads and tested in different prostate and pancreatic cancer cell lines, and one immortalized human pancreatic epithelial cell line. Sequential and simultaneous dosing modalities were investigated and the annexin V/propidium iodide assay, in concert with fluorescence microscopy, was employed to visualize cells undergoing apoptosis. Fourteen drugs were identified as having synergy with TRAIL, including those whose TRAIL sensitization activities were previously unknown in either prostate or pancreatic cancer cells or both. Five leads were tested in additional cancer cell lines of which, doxorubicin, mitoxantrone, and mithramycin demonstrated synergy in all lines. In particular, mitoxantrone and mithramycin demonstrated significant synergy with TRAIL and led to reduction of cancer cell viability at concentrations lower than 1 μM. At these low concentrations, mitoxantrone demonstrated selectivity toward malignant cells over normal pancreatic epithelial cells

  20. Parallel screening of FDA-approved antineoplastic drugs for identifying sensitizers of TRAIL-induced apoptosis in cancer cells

    Directory of Open Access Journals (Sweden)

    Taylor David J

    2011-11-01

    Full Text Available Abstract Background Tumor Necrosis Factor-α Related Apoptosis Inducing Ligand (TRAIL and agonistic antibodies to death receptor 4 and 5 are promising candidates for cancer therapy due to their ability to induce apoptosis selectively in a variety of human cancer cells, while demonstrating little cytotoxicity in normal cells. Although TRAIL and agonistic antibodies to DR4 and DR5 are considered safe and promising candidates in cancer therapy, many malignant cells are resistant to DR-mediated, TRAIL-induced apoptosis. In the current work, we screened a small library of fifty-five FDA and foreign-approved anti-neoplastic drugs in order to identify candidates that sensitized resistant prostate and pancreatic cancer cells to TRAIL-induced apoptosis. Methods FDA-approved drugs were screened for their ability to sensitize TRAIL resistant prostate cancer cells to TRAIL using an MTT assay for cell viability. Analysis of variance was used to identify drugs that exhibited synergy with TRAIL. Drugs demonstrating the highest synergy were selected as leads and tested in different prostate and pancreatic cancer cell lines, and one immortalized human pancreatic epithelial cell line. Sequential and simultaneous dosing modalities were investigated and the annexin V/propidium iodide assay, in concert with fluorescence microscopy, was employed to visualize cells undergoing apoptosis. Results Fourteen drugs were identified as having synergy with TRAIL, including those whose TRAIL sensitization activities were previously unknown in either prostate or pancreatic cancer cells or both. Five leads were tested in additional cancer cell lines of which, doxorubicin, mitoxantrone, and mithramycin demonstrated synergy in all lines. In particular, mitoxantrone and mithramycin demonstrated significant synergy with TRAIL and led to reduction of cancer cell viability at concentrations lower than 1 μM. At these low concentrations, mitoxantrone demonstrated selectivity toward

  1. 4th Global CRO Council for Bioanalysis: coadministered drugs stability, EMA/US FDA guidelines, 483s and carryover.

    Science.gov (United States)

    Lowes, Steve; Jersey, Jim; Shoup, Ronald; Garofolo, Fabio; Needham, Shane; Couerbe, Philippe; Lansing, Tim; Bhatti, Masood; Sheldon, Curtis; Hayes, Roger; Islam, Rafiq; Lin, Zhongping; Garofolo, Wei; Moussallie, Marc; Teixeira, Leonardo de Souza; Rocha, Thais; Jardieu, Paula; Truog, James; Lin, Jenny; Lundberg, Richard; Breau, Alan; Dilger, Carmen; Bouhajib, Mohammed; Levesque, Ann; Gagnon-Carignan, Sofi; Jenkins, Rand; Nicholson, Robert; Lin, Ming Hung; Karnik, Shane; DeMaio, William; Smith, Kirk; Cojocaru, Laura; Allen, Mike; Fatmi, Saadya; Sayyarpour, Farhad; Malone, Michele; Fang, Xinping

    2012-04-01

    The Global CRO Council for Bioanalysis (GCC) was formed in September 2010. Since then, the representatives of the member companies come together periodically to openly discuss bioanalysis and the regulatory challenges unique to the outsourcing industry. The 4th GCC Closed Forum brought together experts from bioanalytical CROs to share and discuss recent issues in regulated bioanalysis, such as the impact of coadministered drugs on stability, some differences between European Medicines Agency and US FDA bioanalytical guidance documents and lessons learned following recent Untitled Letters. Recent 483s and agency findings, as well as issues on method carryover, were also part of the topics discussed.

  2. Mechanistic Oral Absorption Modeling and Simulation for Formulation Development and Bioequivalence Evaluation: Report of an FDA Public Workshop.

    Science.gov (United States)

    Zhang, X; Duan, J; Kesisoglou, F; Novakovic, J; Amidon, G L; Jamei, M; Lukacova, V; Eissing, T; Tsakalozou, E; Zhao, L; Lionberger, R

    2017-08-01

    On May 19, 2016, the US Food and Drug Administration (FDA) hosted a public workshop, entitled "Mechanistic Oral Absorption Modeling and Simulation for Formulation Development and Bioequivalence Evaluation." The topic of mechanistic oral absorption modeling, which is one of the major applications of physiologically based pharmacokinetic (PBPK) modeling and simulation, focuses on predicting oral absorption by mechanistically integrating gastrointestinal transit, dissolution, and permeation processes, incorporating systems, active pharmaceutical ingredient (API), and the drug product information, into a systemic mathematical whole-body framework. © 2017 The Authors CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.

  3. FDA-CDC Antimicrobial Resistance Isolate Bank: a Publicly Available Resource To Support Research, Development, and Regulatory Requirements.

    Science.gov (United States)

    Lutgring, Joseph D; Machado, María-José; Benahmed, Faiza H; Conville, Patricia; Shawar, Ribhi M; Patel, Jean; Brown, Allison C

    2018-02-01

    The FDA-CDC Antimicrobial Resistance Isolate Bank was created in July 2015 as a publicly available resource to combat antimicrobial resistance. It is a curated repository of bacterial isolates with an assortment of clinically important resistance mechanisms that have been phenotypically and genotypically characterized. In the first 2 years of operation, the bank offered 14 panels comprising 496 unique isolates and had filled 486 orders from 394 institutions throughout the United States. New panels are being added. Copyright © 2018 American Society for Microbiology.

  4. [Guidance of FDA risk evaluation and mitigation strategy and enlightenment to drug risk management of post-marketing Chinese medicine].

    Science.gov (United States)

    Li, Yuanyuan; Xie, Yanming

    2011-10-01

    The FDA risk evaluation and mitigation strategy (REMS) aims to drugs or biological products known or potential serious risk management. Analysis with the example of the content of the Onsolis REMS named FOCOS. Our country can be reference for the analysis of relevant experience and establish a scientific evaluation mechanism, strengthen the drug risk consciousness, promote the rational drug use, organic combined with the before-marketing and post-marketing evaluation of traditional Chinese medicine, and promote the evaluation of risk management of the drug development and improvement.

  5. FDA (Food and Drug Administration) Compliance Program Guidance Manual (FY 88). Section 4. Medical and radiological devices

    International Nuclear Information System (INIS)

    1988-01-01

    The FDA Compliance Program Guidance Manual provides a system for issuing and filing program plans and instructions directed to Food and Drug Administration Field operations for project implementation. Section IV provides those chapters of the Compliance Program Guidance Manual which pertain to the areas of medical and radiological devices. Some of the areas of coverage include laser and sunlamp standards inspections, compliance testing of various radiation-emitting products such as television receivers and microwave ovens, emergency response planning and policy, premarket approval and device manufacturers inspections, device problem reporting, sterilization of devices, and consumer education programs on medical and radiological devices

  6. Agreements and Discrepancies between FDA Reports and Journal Papers on Biologic Agents Approved for Rheumatoid Arthritis: A Meta-Research Project.

    Directory of Open Access Journals (Sweden)

    Gil Amarilyo

    Full Text Available Sponsors that seek to commercialize new drugs apply to the Food and Drug Administration (FDA which independently analyzes the raw data and reports the results on its website.This study sought to determine if there are differences between the FDA assessments and journal reports on biologic agents developed for the treatment of rheumatoid arthritis.Available data on FDA-approved drugs were extracted from the website, and a systematic literature search was conducted to identify matching studies in peer-reviewed medical journals. Outcome measures were the American College of Rheumatology response criteria ACR20 (efficacy and withdrawal due to adverse events (safety. As effect size odds ratios were estimated for each active trial arm vs. control arm (i.e. for both sources: FDA and journal report, followed by calculation of the ratios of the FDA and journal report odds ratios. A ratio of odds ratios not equal to 1 was categorized as a discrepancy.FDA reports were available for 8 of 9 FDA-approved biologic agents for rheumatoid arthritis; all identified trials (34 except one were published in peer-reviewed journals. Overall, discrepancies were noted for 20 of the 33 evaluated trials. Differences in the apparent benefit reporting were found in 39% (24/61 pairwise comparisons and in 11 cases these were statistically significant; the FDA report showed greater benefit than the journal publication in 15 comparisons and lesser benefit in 9. Differences in the reported harms were found in 51% (28/55 pairwise comparisons and were statistically significant in 5. The "signal" in FDA reports showed a less harmful effect than the journal publication in 17 comparisons whereas a more harmful effect in 11. The differences were attributed to differences in analytic approach, patient inclusion, rounding effect, and counting discrepancies. However, no differences were categorized as critical.There was no empirical evidence to suggest biased estimates between the two

  7. FDA Approval: Palbociclib for the Treatment of Postmenopausal Patients with Estrogen Receptor-Positive, HER2-Negative Metastatic Breast Cancer.

    Science.gov (United States)

    Beaver, Julia A; Amiri-Kordestani, Laleh; Charlab, Rosane; Chen, Wei; Palmby, Todd; Tilley, Amy; Zirkelbach, Jeanne Fourie; Yu, Jingyu; Liu, Qi; Zhao, Liang; Crich, Joyce; Chen, Xiao Hong; Hughes, Minerva; Bloomquist, Erik; Tang, Shenghui; Sridhara, Rajeshwari; Kluetz, Paul G; Kim, Geoffrey; Ibrahim, Amna; Pazdur, Richard; Cortazar, Patricia

    2015-11-01

    On February 3, 2015, the FDA granted accelerated approval to palbociclib (IBRANCE, Pfizer Inc.), an inhibitor of cyclin-dependent kinases 4 and 6 (CDK4 and CDK6), for use in combination with letrozole for the treatment of postmenopausal women with estrogen receptor (ER)-positive, HER2-negative advanced breast cancer as initial endocrine-based therapy for their metastatic disease. The approval is based on a randomized, multicenter, open-label phase I/II trial (PALOMA-1) in 165 patients randomized to palbociclib (125 mg orally daily for 21 consecutive days, followed by 7 days off treatment) plus letrozole (2.5 mg orally daily) or letrozole alone. The phase II portion of the trial was divided into two cohorts: cohort 1 enrolled 66 biomarker-unselected patients and cohort 2 enrolled 99 biomarker-positive patients. The major efficacy outcome measure was investigator-assessed progression-free survival (PFS). A large magnitude of improvement in PFS was observed in patients receiving palbociclib plus letrozole compared with patients receiving letrozole alone (HR, 0.488; 95% confidence interval, 0.319-0.748). Multiple sensitivity analyses were supportive of clinical benefit. The most common adverse reaction in patients receiving palbociclib plus letrozole was neutropenia. This article summarizes the FDA thought process and data supporting accelerated approval based on PALOMA-1 that may be contingent upon verification and description of clinical benefit in the ongoing and fully accrued confirmatory trial PALOMA-2. ©2015 American Association for Cancer Research.

  8. Drug disposition and drug-drug interaction data in 2013 FDA new drug applications: a systematic review.

    Science.gov (United States)

    Yu, Jingjing; Ritchie, Tasha K; Mulgaonkar, Aditi; Ragueneau-Majlessi, Isabelle

    2014-12-01

    The aim of the present work was to perform a systematic review of drug metabolism, transport, pharmacokinetics, and DDI data available in the NDAs approved by the FDA in 2013, using the University of Washington Drug Interaction Database, and to highlight significant findings. Among 27 NMEs approved, 22 (81%) were well characterized with regard to drug metabolism, transport, or organ impairment, in accordance with the FDA drug interaction guidance (2012) and were fully analyzed in this review. In vitro, a majority of the NMEs were found to be substrates or inhibitors/inducers of at least one drug metabolizing enzyme or transporter. However, in vivo, only half (n = 11) showed clinically relevant drug interactions, with most related to the NMEs as victim drugs and CYP3A being the most affected enzyme. As perpetrators, the overall effects for NMEs were much less pronounced, compared with when they served as victims. In addition, the pharmacokinetic evaluation in patients with hepatic or renal impairment provided useful information for further understanding of the drugs' disposition. Copyright © 2014 by The American Society for Pharmacology and Experimental Therapeutics.

  9. Hypersensitivity reactions to anticancer agents: Data mining of the public version of the FDA adverse event reporting system, AERS

    Directory of Open Access Journals (Sweden)

    Sakaeda Toshiyuki

    2011-10-01

    Full Text Available Abstract Background Previously, adverse event reports (AERs submitted to the US Food and Drug Administration (FDA database were reviewed to confirm platinum agent-associated hypersensitivity reactions. The present study was performed to confirm whether the database could suggest the hypersensitivity reactions caused by anticancer agents, paclitaxel, docetaxel, procarbazine, asparaginase, teniposide, and etoposide. Methods After a revision of arbitrary drug names and the deletion of duplicated submissions, AERs involving candidate agents were analyzed. The National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 was applied to evaluate the susceptibility to hypersensitivity reactions, and standardized official pharmacovigilance tools were used for quantitative detection of signals, i.e., drug-associated adverse events, including the proportional reporting ratio, the reporting odds ratio, the information component given by a Bayesian confidence propagation neural network, and the empirical Bayes geometric mean. Results Based on 1,644,220 AERs from 2004 to 2009, the signals were detected for paclitaxel-associated mild, severe, and lethal hypersensitivity reactions, and docetaxel-associated lethal reactions. However, the total number of adverse events occurring with procarbazine, asparaginase, teniposide, or etoposide was not large enough to detect signals. Conclusions The FDA's adverse event reporting system, AERS, and the data mining methods used herein are useful for confirming drug-associated adverse events, but the number of co-occurrences is an important factor in signal detection.

  10. U.S. FDA Approval Summary: Nivolumab for Treatment of Unresectable or Metastatic Melanoma Following Progression on Ipilimumab.

    Science.gov (United States)

    Hazarika, Maitreyee; Chuk, Meredith K; Theoret, Marc R; Mushti, Sirisha; He, Kun; Weis, Shawna L; Putman, Alexander H; Helms, Whitney S; Cao, Xianhua; Li, Hongshan; Zhao, Hong; Zhao, Liang; Welch, Joel; Graham, Laurie; Libeg, Meredith; Sridhara, Rajeshwari; Keegan, Patricia; Pazdur, Richard

    2017-07-15

    On December 22, 2014, the FDA granted accelerated approval to nivolumab (OPDIVO; Bristol-Myers Squibb) for the treatment of patients with unresectable or metastatic melanoma and disease progression following ipilimumab and, if BRAF V600 mutation positive, a BRAF inhibitor. Approval was based on a clinically meaningful, durable objective response rate (ORR) in a non-comparative analysis of 120 patients who received 3 mg/kg of nivolumab intravenously every 2 weeks with at least 6-month follow-up in an ongoing, randomized, open-label, active-controlled clinical trial. The ORR as assessed by a blinded independent review committee per RECIST v1.1 was 31.7% (95% confidence interval, 23.5-40.8). Ongoing responses were observed in 87% of responding patients, ranging from 2.6+ to 10+ months. In 13 patients, the response duration was 6 months or longer. The risks of nivolumab, including clinically significant immune-mediated adverse reactions (imARs), were assessed in 268 patients who received at least one dose of nivolumab. The FDA review considered whether the ORR and durations of responses were reasonably likely to predict clinical benefit, the adequacy of the safety database, and systematic approaches to the identification, description, and patient management for imARs in product labeling. Clin Cancer Res; 23(14); 3484-8. ©2017 AACR . ©2017 American Association for Cancer Research.

  11. Software-Related Recalls of Health Information Technology and Other Medical Devices: Implications for FDA Regulation of Digital Health.

    Science.gov (United States)

    Ronquillo, Jay G; Zuckerman, Diana M

    2017-09-01

    Policy Points: Medical software has become an increasingly critical component of health care, yet the regulation of these devices is inconsistent and controversial. No studies of medical devices and software assess the impact on patient safety of the FDA's current regulatory safeguards and new legislative changes to those standards. Our analysis quantifies the impact of software problems in regulated medical devices and indicates that current regulations are necessary but not sufficient for ensuring patient safety by identifying and eliminating dangerous defects in software currently on the market. New legislative changes will further deregulate health IT, reducing safeguards that facilitate the reporting and timely recall of flawed medical software that could harm patients. Medical software has become an increasingly critical component of health care, yet the regulatory landscape for digital health is inconsistent and controversial. To understand which policies might best protect patients, we examined the impact of the US Food and Drug Administration's (FDA's) regulatory safeguards on software-related technologies in recent years and the implications for newly passed legislative changes in regulatory policy. Using FDA databases, we identified all medical devices that were recalled from 2011 through 2015 primarily because of software defects. We counted all software-related recalls for each FDA risk category and evaluated each high-risk and moderate-risk recall of electronic medical records to determine the manufacturer, device classification, submission type, number of units, and product details. A total of 627 software devices (1.4 million units) were subject to recalls, with 12 of these devices (190,596 units) subject to the highest-risk recalls. Eleven of the devices recalled as high risk had entered the market through the FDA review process that does not require evidence of safety or effectiveness, and one device was completely exempt from regulatory review

  12. FDA/DEA/PDMP/UDT: alphabet soup or sensible and integrated risk management?

    Science.gov (United States)

    Passik, Steven D; Kirsh, Kenneth L; Twillman, Robert K

    2015-01-01

    Both prescription drug monitoring programs (PDMP) and urine drug testing (UDT) are recommended as parts of an ongoing risk management approach for controlled substance prescribing. The authors provide an editorial and commentary to discuss the unique contributions of each to promote better clinical decision making for prescribers. A commentary is employed along with brief discussion comparing four states with an active PDMP in place to three states without an active PDMP as it relates back to findings on UDT in those states from a laboratory conducting liquid chromatography tandem mass spectrometry. The commentary focuses on the place of both tools (UDT and PDMP) in risk management efforts. The argument is made that relying on a PDMP alone would lead to clinical decisions that may miss a great deal of problematic or aberrant behaviors.

  13. Synthesis and characterization of a microporous 6FDA-polyimide made from a novel carbocyclic pseudo Tröger's base diamine: Effect of bicyclic bridge on gas transport properties

    KAUST Repository

    Abdulhamid, Mahmoud A.

    2017-10-12

    A newly designed carbocyclic pseudo Tröger\\'s base diamine (CTB) monomer, 2,8-dimethyl-3,9-diamino-5,6,11,12-tetrahydro-5,11-methanodibenzo[a,e][8]annulene (CTBDA) and its isomeric analogue 2,8-dimethyl-(1,7)(4,10)(3,9)-diamino-5,6,11,12-tetrahydro-5,11-methanodibenzo[a,e][8]annulene (iCTBDA), were designed for the synthesis of microporous 6FDA-based polyimides (6FDA-CTBDA and 6FDA-iCTBDA). Both polyimides were soluble, exhibited excellent thermal stability of ∼490 °C, and had high surface areas of 587 m2 g−1 (6FDA-CTBDA) and 562 m2 g−1 (6FDA-iCTBDA). A 6FDA-based polyimide derived from 4,10-dimethyl-3,9-diamino-6H,12H-5,11-methanodibenzo[b,f][1,5]-diazocine (6FDA-TBDA) was made for comparison to investigate the effects of the basic tertiary nitrogen functionality in the Tröger\\'s base diamine on the polymer properties relative to the carbocyclic 6FDA-CTBDA analogue. 6FDA-TBDA displayed lower gas permeabilities but moderately higher gas-pair permselectivities than 6FDA-CTBDA. The enhanced permselectivity of 6FDA-TBDA resulted exclusively from higher diffusion-based selectivity. Direct gas sorption measurements demonstrated that the basicity in the Tröger\\'s base bridge moiety enhanced the sorption capacity of CO2 only slightly and had no effect on the CO2/CH4 solubility selectivity in 6FDA-TBDA vs. 6FDA-CTBDA.

  14. 'Great Power Style' in China's Economic Policy

    DEFF Research Database (Denmark)

    Jiang, Yang

    2011-01-01

    China’s ascendance attracts concern, even though Beijing claims to be a responsible great power and tries to demonstrate its ‘great power style’ in economic diplomacy. This article therefore discusses the following questions: to what extent does the current notion and practice of Chinese ‘great...... power style’ in economic diplomacy comply with, or differ from, the criteria of benign hegemony; and what are the major constraining factors? Conceptually, China’s ‘great power style’ is rooted in ancient Chinese political philosophy and institution, but it highly resembles the Western notion of benign...

  15. Great Expectations for Middle School Counselors

    Science.gov (United States)

    Wright, Robert J.

    2012-01-01

    During the Great Recession, 2008 to 2010, school systems scrambled to balance budgets, and the ratio of counselors to students became even larger. To make matters worse, the Great Recession had a major impact on cuts in educational funding. Budget cutbacks tend to occur where the public will be least likely to notice. The loss of teachers and the…

  16. Great Books. What Works Clearinghouse Intervention Report

    Science.gov (United States)

    What Works Clearinghouse, 2011

    2011-01-01

    "Great Books" is a program that aims to improve the reading, writing, and critical thinking skills of students in kindergarten through high school. The program is implemented as a core or complementary curriculum and is based on the Shared Inquiry[TM] method of learning. The purpose of "Great Books" is to engage students in…

  17. Great ape genetic diversity and population history

    DEFF Research Database (Denmark)

    Prado-Martinez, Javier; Sudmant, Peter H; Kidd, Jeffrey M

    2013-01-01

    Most great ape genetic variation remains uncharacterized; however, its study is critical for understanding population history, recombination, selection and susceptibility to disease. Here we sequence to high coverage a total of 79 wild- and captive-born individuals representing all six great ape...

  18. Libraries Achieving Greatness: Technology at the Helm

    Science.gov (United States)

    Muir, Scott P.

    2009-01-01

    Libraries have been around for thousands of years. Many of them are considered great because of their magnificent architecture or because of the size of their collections. This paper offers ten case studies of libraries that have used technology to achieve greatness. Because almost any library can implement technology, a library does not have to…

  19. Recensie "The Great Reset" : Richard Florida

    NARCIS (Netherlands)

    Roy van Dalm

    2010-01-01

    Like the Great Depression and the Long Depression before it, experts have viewed prolonged economic downturns as crises. In The Great Reset , bestselling author Richard Florida argues that we should instead see the recent recession as an opportunity to create entirely new ways of working and living

  20. Beyond C, H, O, and N! Analysis of the elemental composition of U.S. FDA approved drug architectures.

    Science.gov (United States)

    Smith, Brandon R; Eastman, Candice M; Njardarson, Jon T

    2014-12-11

    The diversity of elements among U.S. Food and Drug Administration (FDA) approved pharmaceuticals is analyzed and reported, with a focus on atoms other than carbon, hydrogen, oxygen, and nitrogen. Our analysis reveals that sulfur, chlorine, fluorine, and phosphorous represent about 90% of elemental substitutions, with sulfur being the fifth most used element followed closely by chlorine, then fluorine and finally phosphorous in the eighth place. The remaining 10% of substitutions are represented by 16 other elements of which bromine, iodine, and iron occur most frequently. The most detailed parts of our analysis are focused on chlorinated drugs as a function of approval date, disease condition, chlorine attachment, and structure. To better aid our chlorine drug analyses, a new poster showcasing the structures of chlorinated pharmaceuticals was created specifically for this study. Phosphorus, bromine, and iodine containing drugs are analyzed closely as well, followed by a discussion about other elements.

  1. An FDA-Drug Library Screen for Compounds with Bioactivities against Meticillin-Resistant Staphylococcus aureus (MRSA

    Directory of Open Access Journals (Sweden)

    Qiu Ying Lau

    2015-10-01

    Full Text Available The lack of new antibacterial drugs entering the market and their misuse have resulted in the emergence of drug-resistant bacteria, posing a major health crisis worldwide. In particular, meticillin-resistant Staphylococcus aureus (MRSA, a pathogen responsible for numerous human infections, has become endemic in hospitals worldwide. Drug repurposing, the finding of new therapeutic indications for approved drugs, is deemed a plausible solution to accelerate drug discovery and development in this area. Towards this end, we screened 1163 drugs approved by the Food and Drug Administration (FDA for bioactivities against MRSA in a 10 μM single-point assay. After excluding known antibiotics and antiseptics, six compounds were identified and their MICs were determined against a panel of clinical MRSA strains. A toxicity assay using human keratinocytes was also conducted to gauge their potential for repurposing as topical agents for treating MRSA skin infections.

  2. Fabrication of 50-mg 252Cf neutron sources for the FDA [Food and Drug Administration] activation analysis facility

    International Nuclear Information System (INIS)

    Bigelow, J.E.; Cagle, E.B.; Knauer, J.B.

    1987-01-01

    The Transuranium Processing Plant (TPP) at ORNL has been requested by the Food and Drug Administration (FDA) to furnish 200 mg of 252 Cf for use in their new activation analysis facility. This paper discusses the procedure to be employed in fabricating the californium into four neutron sources, each containing a nominal 50-mg of 252 Cf. The ORNL Model LSD (Large, Stainless steel, Doubly encapsulated) neutron source consists of a 6.33-mm-diam aluminum pellet doubly encapsulated in Type 304L stainless steel. The pellet is comprised of an aluminum tube holding Cf 2 O 2 SO 4 microspheres confined by pressed aluminum powder. The microspheres are prepared in a separate vessel and then transferred into the specially designed aluminum tube prior to pressing

  3. A Descriptive Longitudinal Study of Changes in Vape Shop Characteristics and Store Policies in Anticipation of the 2016 FDA Regulations of Tobacco Products, Including E-Cigarettes.

    Science.gov (United States)

    Yu, Sheila; Escobedo, Patricia; Garcia, Robert; Cruz, Tess Boley; Unger, Jennifer B; Baezconde-Garbanati, Lourdes; Meza, Leah; Sussman, Steve

    2018-02-11

    After proposing the "Deeming Rule" in 2014, the U.S. Food and Drug Administration (FDA) began regulating the manufacturing, marketing, and sales of electronic cigarette (e-cigarette) products as tobacco products in 2016. The current study conducted vape shop store observations and surveyed Los Angeles-area shop employees (assessing their beliefs, awareness, and perceptions of e-cigarettes and related FDA regulations) at two time points one year apart to better understand what vape shop retailers would do given FDA's soon-to-be-enacted Deeming Rule. The study also compared retailer beliefs/awareness/actions and store characteristics immediately after the Deeming Rule proposal versus a year after the Rule had been proposed, right before its enactment. Two data collection waves occurred before the Deeming Rule enactment, with Year 1 surveying 77 shops (2014) and Year 2 surveying 61 shops (2015-2016). Between the data collection points, 16 shops had closed. Among the shops that were open at both time points, the majority (95% in Year 1; 74% in Year 2) were aware of some FDA regulations or other policies applying to vape shops. However, overall awareness of FDA regulations and state/local policies governing e-cigarettes significantly decreased from Year 1 to Year 2. At both time points, all shops offered customers free puffs of nicotine-containing e-liquids (prohibited by the then upcoming Deeming Rule). Perceptions of e-cigarette safety also significantly decreased between the years. Exploring vape shop retailer perceptions and store policies (i.e., free puffs/samples displays, perceptions of e-cigarette safety, etc.) over time will help the FDA assess the needs of the vape shop community and develop more effective retailer education campaigns and materials targeted to increase compliance with the newly enacted regulations.

  4. Trends in utilization of smoking cessation agents before and after the passage of FDA boxed warning in the United States.

    Science.gov (United States)

    Shah, Drishti; Shah, Anuj; Tan, Xi; Sambamoorthi, Usha

    2017-08-01

    In 2009, the FDA required a black box warning (BBW) on bupropion and varenicline, the two commonly prescribed smoking cessation agents due to reports of adverse neuropsychiatric events. We investigated if there was a decline in use of bupropion and varenicline after the BBW by comparing the percent using these medications before and after BBW. We conducted a retrospective observational study using data from the Medical Expenditure Panel Survey from 2007 to 2014. The study sample consisted of adult smokers, who were advised by their physicians to quit smoking. We divided the time period into "pre-warning", "post-warning: immediate", and "post-warning: late." Unadjusted analysis using chi-square tests and adjusted analyses using logistic regressions were conducted to evaluate the change in bupropion and varenicline use before and after the BBW. Secondary analyses using piecewise regression were also conducted. On an average, 49.04% of smokers were advised by their physicians to quit smoking. We observed a statistically significant decline in varenicline use from 22.1% in year 2007 to 9.23% in 2014 (p valuesmoking by their physicians were less likely to use varenicline in the immediate post-BBW period as compared to pre-BBW period. While the use of varenicline continued to be significantly low in the late post-BBW period (AOR=0.45, 95% CI=0.31-0.64) as compared to the pre-BBW period, the trend in use as seen in piecewise regression remained stable (OR=0.90, 95% CI=0.75-1.06). We did not observe significant differences in bupropion use between the pre- and post-BBW periods. The passage of the FDA boxed warning was associated with a significant decline in the use of varenicline, but not in the use of bupropion. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Trouble Spots in Online Direct-to-Consumer Prescription Drug Promotion: A Content Analysis of FDA Warning Letters

    Directory of Open Access Journals (Sweden)

    Hyosun Kim

    2015-12-01

    Full Text Available Background For the purpose of understanding the Food and Drug Administration’s (FDA’s concerns regarding online promotion of prescription drugs advertised directly to consumers, this study examines notices of violations (NOVs and warning letters issued by the FDA to pharmaceutical manufacturers. Methods The FDA’s warning letters and NOVs, which were issued to pharmaceutical companies over a 10-year period (2005 to 2014 regarding online promotional activities, were content-analyzed. Results Six violation categories were identified: risk information, efficacy information, indication information, product labeling, material information issues, and approval issues. The results reveal that approximately 95% of the alleged violations were found on branded drug websites, in online paid advertisements, and in online videos. Of the total 179 violations, the majority of the alleged violations were concerned with the lack of risk information and/or misrepresentation of efficacy information, suggesting that achieving a fair balance of benefit versus risk information is a major problem with regard to the direct-to-consumer advertising (DTCA of prescription drugs. In addition, the character space limitations of online platforms, eg, sponsored links on search engines, pose challenges for pharmaceutical marketers with regard to adequately communicating important drug information, such as indication information, risk information, and product labeling. Conclusion Presenting drug information in a fair and balanced manner remains a major problem. Industry guidance should consider addressing visibility and accessibility of information in the web environment to help pharmaceutical marketers meet the requirements for direct-to-consumer promotion and to protect consumers from misleading drug information. Promotion via social media warrants further attention, as pharmaceutical manufacturers have already begun actively establishing a social media presence, and the

  6. Survival benefit of glioblastoma patients after FDA approval of temozolomide concomitant with radiation and bevacizumab: A population-based study.

    Science.gov (United States)

    Zhu, Ping; Du, Xianglin L; Lu, Guangrong; Zhu, Jay-Jiguang

    2017-07-04

    Few population-based analyses have investigated survival change in glioblastoma multiforme (GBM) patients treated with concomitant radiotherapy-temozolomide (RT-TMZ) and adjuvant temozolomide (TMZ) and then bevacizumab (BEV) after Food and Drug Administration (FDA) approval, respectively. We aimed to explore the effects on survival with RT-TMZ, adjuvant TMZ and BEV in general GBM population based on the Surveillance, Epidemiology, and End Results (SEER) and Texas Cancer Registry (TCR) databases. A total of 28933 GBM patients from SEER (N = 24578) and TCR (N = 4355) between January 2000 and December 2013 were included. Patients were grouped into three calendar periods based on date of diagnosis: pre-RT-TMZ and pre-BEV (1/2000-2/2005, P1), post-RT-TMZ and pre-BEV (3/2005-4/2009, P2), and post-RT-TMZ and post-BEV (5/2009-12/2013, P3). The association between calendar period of diagnosis and survival was analyzed in SEER and TCR, separately, by the Kaplan-Meier method and Cox proportional hazards model. We found a significant increase in median overall survival (OS) across the three periods in both populations. In multivariate models, the risk of death was significantly reduced during P2 and further decreased in P3, which remained unchanged after stratification. Comparison and validation analysis were performed in the combined dataset, and consistent results were observed. We conclude that the OS of GBM patients in a "real-world" setting has been steadily improved from January 2000 to December 2013, which likely resulted from the administrations of TMZ concomitant with RT and adjuvant TMZ for newly diagnosed GBM and then BEV for recurrent GBM after respective FDA approval.

  7. NCI-FDA Interagency Oncology Task Force Workshop Provides Guidance for Analytical Validation of Protein-based Multiplex Assays | Office of Cancer Clinical Proteomics Research

    Science.gov (United States)

    An NCI-FDA Interagency Oncology Task Force (IOTF) Molecular Diagnostics Workshop was held on October 30, 2008 in Cambridge, MA, to discuss requirements for analytical validation of protein-based multiplex technologies in the context of its intended use. This workshop developed through NCI's Clinical Proteomic Technologies for Cancer initiative and the FDA focused on technology-specific analytical validation processes to be addressed prior to use in clinical settings. In making this workshop unique, a case study approach was used to discuss issues related to

  8. Pacific salmonines in the Great Lakes Basin

    Science.gov (United States)

    Claramunt, Randall M.; Madenjian, Charles P.; Clapp, David; Taylor, William W.; Lynch, Abigail J.; Léonard, Nancy J.

    2012-01-01

    Pacific salmon (genus Oncorhynchus) are a valuable resource, both within their native range in the North Pacific rim and in the Great Lakes basin. Understanding their value from a biological and economic perspective in the Great Lakes, however, requires an understanding of changes in the ecosystem and of management actions that have been taken to promote system stability, integrity, and sustainable fisheries. Pacific salmonine introductions to the Great Lakes are comprised mainly of Chinook salmon, coho salmon, and steelhead and have accounted for 421, 177, and 247 million fish, respectively, stocked during 1966-2007. Stocking of Pacific salmonines has been effective in substantially reducing exotic prey fish abundances in several of the Great Lakes (e.g., lakes Michigan, Huron, and Ontario). The goal of our evaluation was to highlight differences in management strategies and perspectives across the basin, and to evaluate policies for Pacific salmonine management in the Great Lakes. Currently, a potential conflict exists between Pacific salmonine management and native fish rehabilitation goals because of the desire to sustain recreational fisheries and to develop self-sustaining populations of stocked Pacific salmonines in the Great Lakes. We provide evidence that suggests Pacific salmonines have not only become naturalized to the food webs of the Great Lakes, but that their populations (specifically Chinook salmon) may be fluctuating in concert with specific prey (i.e., alewives) whose populations are changing relative to environmental conditions and ecosystem disturbances. Remaining questions, however, are whether or not “natural” fluctuations in predator and prey provide enough “stability” in the Great Lakes food webs, and even more importantly, would a choice by managers to attempt to reduce the severity of predator-prey oscillations be antagonistic to native fish restoration efforts. We argue that, on each of the Great Lakes, managers are pursuing

  9. Great Lakes Restoration Initiative Great Lakes Mussel Watch(2009-2014)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Following the inception of the Great Lakes Restoration Initiative (GLRI) to address the significant environmental issues plaguing the Great Lakes region, the...

  10. Credit spread variability in U.S. business cycles: the Great Moderation versus the Great Recession

    OpenAIRE

    Hylton Hollander; Guangling Liu

    2014-01-01

    This paper establishes the prevailing financial factors that influence credit spread variability, and its impact on the U.S. business cycle over the Great Moderation and Great Recession periods. To do so, we develop a dynamic general equilibrium framework with a central role of financial intermediation and equity assets. Over the Great Moderation and Great Recession periods, we find an important role for bank market power (sticky rate adjustments and loan rate markups) on credit spread variab...

  11. Credit spread variability in U.S. business cycles: The Great Moderation versus the Great Recession

    OpenAIRE

    Hylton Hollander and Guangling Liu

    2014-01-01

    This paper establishes the prevailing financial factors that influence credit spread variability, and its impact on the U.S. business cycle over the Great Moderation and Great Recession periods. To do so, we develop a dynamic general equilibrium framework with a central role of financial intermediation and equity assets. Over the Great Moderation and Great Recession periods, we find an important role for bank market power (sticky rate adjustments and loan rate markups) on credit spread variab...

  12. 75 FR 6354 - NOAA Great Lakes Habitat Restoration Program Project Grants under the Great Lakes Restoration...

    Science.gov (United States)

    2010-02-09

    ...-04] RIN 0648-ZC10 NOAA Great Lakes Habitat Restoration Program Project Grants under the Great Lakes... Atmospheric Administration (NOAA), Department of Commerce. ACTION: Notice of funding availability; Date... on January 19, 2010. That notice announced the NOAA Great Lakes Habitat Restoration Program Project...

  13. The Great Recession and confidence in homeownership

    OpenAIRE

    Anat Bracha; Julian Jamison

    2013-01-01

    Confidence in homeownership shifts for those who personally experienced real estate loss during the Great Recession. Older Americans are confident in the value of homeownership. Younger Americans are less confident.

  14. Great Lakes CoastWatch Node

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — CoastWatch is a nationwide National Oceanic and Atmospheric Administration (NOAA) program within which the Great Lakes Environmental Research Laboratory (GLERL)...

  15. The Making of a Great Captain

    National Research Council Canada - National Science Library

    Weibel, Theodore G

    2006-01-01

    ... judgement. This paper examines the hypothesis that Great Captains are a product of their families, are highly educated from an early age, possess the qualities of a genius, encounter grand life experiences...

  16. Thirty years of great ape gestures.

    Science.gov (United States)

    Tomasello, Michael; Call, Josep

    2018-02-21

    We and our colleagues have been doing studies of great ape gestural communication for more than 30 years. Here we attempt to spell out what we have learned. Some aspects of the process have been reliably established by multiple researchers, for example, its intentional structure and its sensitivity to the attentional state of the recipient. Other aspects are more controversial. We argue here that it is a mistake to assimilate great ape gestures to the species-typical displays of other mammals by claiming that they are fixed action patterns, as there are many differences, including the use of attention-getters. It is also a mistake, we argue, to assimilate great ape gestures to human gestures by claiming that they are used referentially and declaratively in a human-like manner, as apes' "pointing" gesture has many limitations and they do not gesture iconically. Great ape gestures constitute a unique form of primate communication with their own unique qualities.

  17. Southern Great Plains Atmospheric Radiation Measurement Site

    Data.gov (United States)

    Federal Laboratory Consortium — The Southern Great Plains Atmospheric Radiation Measurement Site (SGP-ARM) is the oldest and largest of DOE's Arm sites. It was established in 1992. It consists of...

  18. Theodosius Dohzhansky: A Great Inspirer 1

    Indian Academy of Sciences (India)

    the direct personal influence of some of these great scientists on their peers and successors is re~atively small. A very small number of scientists ... studying the evolutionary genetics of speciation in Drosophila. --------~--------43. RESONANCE I ...

  19. Great Lakes rivermouths: a primer for managers

    Science.gov (United States)

    Pebbles, Victoria; Larson, James; Seelbach, Paul; Pebbles, Victoria; Larson, James; Seelbach, Paul

    2013-01-01

    Between the North American Great Lakes and their tributaries are the places where the confluence of river and lake waters creates a distinct ecosystem: the rivermouth ecosystem. Human development has often centered around these rivermouths, in part, because they provide a rich array of ecosystem services. Not surprisingly, centuries of intense human activity have led to substantial pressures on, and alterations to, these ecosystems, often diminishing or degrading their ecological functions and associated ecological services. Many Great Lakes rivermouths are the focus of intense restoration efforts. For example, 36 of the active Great Lakes Areas of Concern (AOCs) are rivermouths or areas that include one or more rivermouths. Historically, research of rivermouth ecosystems has been piecemeal, focused on the Great Lakes proper or on the upper reaches of tributaries, with little direct study of the rivermouth itself. Researchers have been divided among disciplines, agencies and institutions; and they often work independently and use disparate venues to communicate their work. Management has also been fragmented with a focus on smaller, localized, sub-habitat units and socio-political or economic elements, rather than system-level consideration. This Primer presents the case for a more holistic approach to rivermouth science and management that can enable restoration of ecosystem services with multiple benefits to humans and the Great Lakes ecosystem. A conceptual model is presented with supporting text that describes the structures and processes common to all rivermouths, substantiating the case for treating these ecosystems as an identifiable class.1 Ecological services provided by rivermouths and changes in how humans value those services over time are illustrated through case studies of two Great Lakes rivermouths—the St. Louis River and the Maumee River. Specific ecosystem services are identified in italics throughout this Primer and follow definitions described

  20. Understanding Great Earthquakes in Japan's Kanto Region

    Science.gov (United States)

    Kobayashi, Reiji; Curewitz, Daniel

    2008-10-01

    Third International Workshop on the Kanto Asperity Project; Chiba, Japan, 16-19 February 2008; The 1703 (Genroku) and 1923 (Taisho) earthquakes in Japan's Kanto region (M 8.2 and M 7.9, respectively) caused severe damage in the Tokyo metropolitan area. These great earthquakes occurred along the Sagami Trough, where the Philippine Sea slab is subducting beneath Japan. Historical records, paleoseismological research, and geophysical/geodetic monitoring in the region indicate that such great earthquakes will repeat in the future.

  1. The diverse impacts of the great recession

    OpenAIRE

    Makoto Nakajima

    2013-01-01

    The Great Recession had a large negative impact on the U.S. economy. Asset prices, most notably stock and house prices, declined substantially, resulting in a loss in wealth for many American households. In this article, Makoto Nakajima documents how diverse households were affected in a variety of dimensions during the Great Recession, in particular between 2007 and 2009, using newly available data from the 2007-2009 Survey of Consumer Finances. He discusses why it is important to look at th...

  2. The Great War and German Memory

    DEFF Research Database (Denmark)

    Leese, Peter

    2012-01-01

    Review essay on Jason Crouthamel, The Great War and German Memory. Society, Politics and Psychological Trauma, 1914-18 (2009) and Anton Kaes, Shell Shock Cinema: Weimar Culture and the Wounds of War (2009)......Review essay on Jason Crouthamel, The Great War and German Memory. Society, Politics and Psychological Trauma, 1914-18 (2009) and Anton Kaes, Shell Shock Cinema: Weimar Culture and the Wounds of War (2009)...

  3. Climate variability and Great Plains agriculture

    International Nuclear Information System (INIS)

    Rosenberg, N.J.; Katz, L.A.

    1991-01-01

    The ways in which inhabitants of the Great Plains, including Indians, early settlers, and 20th century farmers, have adapted to climate changes on the Great Plains are explored. The climate of the Great Plains, because of its variability and extremes, can be very stressful to plants, animals and people. It is suggested that agriculture and society on the Great Plains have, during the last century, become less vulnerable to the stresses imposed by climate. Opinions as to the sustainability of agriculture on the Great Plains vary substantially. Lockeretz (1981) suggests that large scale, high cost technologies have stressed farmers by creating surpluses and by requiring large investments. Opie (1989) sees irrigation as a climate substitute, however he stresses that the Ogallala aquifer must inevitably become depleted. Deborah and Frank Popper (1987) believe that farming on the Plains is unsustainable, and destruction of shelterbelts, out-migration of the rural population and environmental problems will lead to total collapse. With global warming, water in the Great Plains is expected to become scarcer, and although improvements in irrigation efficiency may slow depletion of the Ogallala aquifer, ultimately the acreage under irrigation must decrease to levels that can be sustained by natural recharge and reliable surface flows. 23 refs., 2 figs

  4. Biochemical markers and the FDA Critical Path: how biomarkers may contribute to the understanding of pathophysiology and provide unique and necessary tools for drug development

    DEFF Research Database (Denmark)

    Karsdal, M A; Henriksen, K; Leeming, D J

    2009-01-01

    The aim of this review is to discuss the potential usefulness of a novel class of biochemical markers, neoepitopes, in the context of the US Food and Drug Administration (FDA) Critical Path Initiative, which emphasizes biomarkers of safety and efficacy as areas of pivotal interest. Examples...

  5. Missed Opportunities in the Patient-Focused Drug Development Public Meeting and Scientific Workshop on Female Sexual Dysfunction Held at the FDA, October 2014

    NARCIS (Netherlands)

    Tiefer, Leonore; Laan, Ellen; Basson, Rosemary

    2015-01-01

    There were numerous missed opportunities at the October 2014 U.S. Food and Drug Administration (FDA) meeting on female sexual dysfunction (FSD). They included opportunities to hear from a diverse range of patients and to engage in evidence-based discussions of unmet medical needs, diagnostic

  6. Spin in RCTs of anxiety medication with a positive primary outcome : A comparison of concerns expressed by the US FDA and in the published literature

    NARCIS (Netherlands)

    Beijers, Lian; Jeronimus, Bertus F; Turner, Erick H; de Jonge, Peter; Roest, Annelieke M

    2017-01-01

    Objectives: This study aimed to determine the presence of spin in papers on positive randomised clinical trials (RCTs) of antidepressant medication for anxiety disorders by comparing concerns expressed in the Food and Drug Administration (FDA) reviews with those expressed in the published paper.

  7. Center for Cancer Research plays key role in first FDA-approved drug for treatment of Merkel cell carcinoma | Center for Cancer Research

    Science.gov (United States)

    The Center for Cancer Research’s ability to rapidly deploy integrated basic and clinical research teams at a single site facilitated the rapid FDA approval of the immunotherapy drug avelumab for metastatic Merkel cell carcinoma, a rare, aggressive form of skin cancer. Learn more...  

  8. The evolution of FDA policy on silicone breast implants: a case study of politics, bureaucracy, and business in the process of decision-making.

    Science.gov (United States)

    Palley, H A

    1995-01-01

    The central issue facing federal regulation of breast implants is that while such devices are not functionally necessary or needed for survival, the side effects may be harmful and have not been proven unharmful. The Medical Device Amendments of 1976 appear to require such evidence prior to the FDA permitting the unrestricted marketing of these devices. However, only recently have such requirements been imposed by the FDA. The author examines the FDA's decision-making process, particularly as applied to silicone breast implants, and the factors that appears to have affected such decisions. In pursuing this study, the activities of a number of interest-group actors, as well as congressional responses and the role of federal bureaucratic actors, were examined. In 1992, the FDA established a regulatory protocol that effectively withdrew most silicone breast implants from the market for the purpose of breast augmentation and allows for the monitoring of the impact of new implants on women's health. This increase concern for determining the safety of breast implants is due to a number of factors, which are examined in this article.

  9. Energy and water in the Great Lakes.

    Energy Technology Data Exchange (ETDEWEB)

    Tidwell, Vincent Carroll

    2011-11-01

    The nexus between thermoelectric power production and water use is not uniform across the U.S., but rather differs according to regional physiography, demography, power plant fleet composition, and the transmission network. That is, in some regions water demand for thermoelectric production is relatively small while in other regions it represents the dominate use. The later is the case for the Great Lakes region, which has important implications for the water resources and aquatic ecology of the Great Lakes watershed. This is today, but what about the future? Projected demographic trends, shifting lifestyles, and economic growth coupled with the threat of global climate change and mounting pressure for greater U.S. energy security could have profound effects on the region's energy future. Planning for such an uncertain future is further complicated by the fact that energy and environmental planning and regulatory decisionmaking is largely bifurcated in the region, with environmental and water resource concerns generally taken into account after new energy facilities and technologies have been proposed, or practices are already in place. Based on these confounding needs, the objective of this effort is to develop Great Lakes-specific methods and tools to integrate energy and water resource planning and thereby support the dual goals of smarter energy planning and development, and protection of Great Lakes water resources. Guiding policies for this planning are the Great Lakes and St. Lawrence River Basin Water Resources Compact and the Great Lakes Water Quality Agreement. The desired outcome of integrated energy-water-aquatic resource planning is a more sustainable regional energy mix for the Great Lakes basin ecosystem.

  10. Generic lamotrigine versus brand-name Lamictal bioequivalence in patients with epilepsy: A field test of the FDA bioequivalence standard.

    Science.gov (United States)

    Ting, Tricia Y; Jiang, Wenlei; Lionberger, Robert; Wong, Jessica; Jones, Jace W; Kane, Maureen A; Krumholz, Allan; Temple, Robert; Polli, James E

    2015-09-01

    To test the current U.S. Food and Drug Administration (FDA) bioequivalence standard in a comparison of generic and brand-name drug pharmacokinetic (PK) performance in "generic-brittle" patients with epilepsy under clinical use conditions. This randomized, double-blind, multiple-dose, steady-state, fully replicated bioequivalence study compared generic lamotrigine to brand-name Lamictal in "generic-brittle" patients with epilepsy (n = 34) who were already taking lamotrigine. Patients were repeatedly switched between masked Lamictal and generic lamotrigine. Intensive PK blood sampling at the end of each 2-week treatment period yielded two 12-h PK profiles for brand-name and generic forms for each patient. Steady-state area under the curve (AUC), peak plasma concentration (Cmax ), and minimum plasma concentration (Cmin ) data were subjected to conventional average bioequivalence (ABE) analysis, reference-scaled ABE analysis, and within-subject variability (WSV) comparisons. In addition, generic-versus-brand comparisons in individual patients were performed. Secondary clinical outcomes included seizure frequency and adverse events. Generic demonstrated bioequivalence to brand. The 90% confidence intervals of the mean for steady-state AUC, Cmax , and Cmin for generic-versus-brand were 97.2-101.6%, 98.8-104.5%, and 93.4-101.0%, respectively. The WSV of generic and brand were also similar. Individual patient PK ratios for generic-versus-brand were similar but not identical, in part because brand-versus-brand profiles were not identical, even though subjects were rechallenged with the same product. Few subjects had seizure exacerbations or tolerability issues with product switching. One subject, however, reported 267 focal motor seizures, primarily on generic, although his brand and generic PK profiles were practically identical. Some neurologists question whether bioequivalence in healthy volunteers ensures therapeutic equivalence of brand and generic antiepileptic drugs

  11. Identification and content validation of wound therapy clinical endpoints relevant to clinical practice and patient values for FDA approval. Part 1. Survey of the wound care community.

    Science.gov (United States)

    Driver, Vickie R; Gould, Lisa J; Dotson, Peggy; Gibbons, Gary W; Li, William W; Ennis, William J; Kirsner, Robert S; Eaglstein, William H; Bolton, Laura L; Carter, Marissa J

    2017-05-01

    Wounds that exhibit delayed healing add extraordinary clinical, economic, and personal burdens to patients, as well as to increasing financial costs to health systems. New interventions designed to ease such burdens for patients with cancer, renal, or ophthalmologic conditions are often cleared for approval by the U.S. Food and Drug Administration (FDA) using multiple endpoints but the requirement of complete healing as a primary endpoint for wound products impedes FDA clearance of interventions that can provide other clinical or patient-centered benefits for persons with wounds. A multidisciplinary group of wound experts undertook an initiative, in collaboration with the FDA, to identify and content validate supporting FDA criteria for qualifying wound endpoints relevant to clinical practice (CP) and patient-centered outcomes (PCO) as primary outcomes in clinical trials. As part of the initiative, a research study was conducted involving 628 multidisciplinary expert wound clinicians and researchers from 4 different groups: the interdisciplinary core advisory team; attendees of the Spring 2015 Symposium on Advanced Wound Care (SAWC); clinicians employed by a national network of specialty clinics focused on comprehensive wound care; and Association for the Advancement of Wound Care (AAWC) and Wound Healing Society (WHS) members who had not previously completed the survey. The online survey assessed 28 literature-based wound care endpoints for their relevance and importance to clinical practice and clinical research. Fifteen of the endpoints were evaluated for their relevance to improving quality of life. Twenty-two endpoints had content validity indexes (CVI) ≥ 0.75, and 15 were selected as meriting potential inclusion as additional endpoints for FDA approval of future wound care interventions. This study represents an important first step in identifying and validating new measurable wound care endpoints for clinical research and practice and for regulatory

  12. A Descriptive Longitudinal Study of Changes in Vape Shop Characteristics and Store Policies in Anticipation of the 2016 FDA Regulations of Tobacco Products, Including E-Cigarettes

    Directory of Open Access Journals (Sweden)

    Sheila Yu

    2018-02-01

    Full Text Available After proposing the “Deeming Rule” in 2014, the U.S. Food and Drug Administration (FDA began regulating the manufacturing, marketing, and sales of electronic cigarette (e-cigarette products as tobacco products in 2016. The current study conducted vape shop store observations and surveyed Los Angeles–area shop employees (assessing their beliefs, awareness, and perceptions of e-cigarettes and related FDA regulations at two time points one year apart to better understand what vape shop retailers would do given FDA’s soon-to-be-enacted Deeming Rule. The study also compared retailer beliefs/awareness/actions and store characteristics immediately after the Deeming Rule proposal versus a year after the Rule had been proposed, right before its enactment. Two data collection waves occurred before the Deeming Rule enactment, with Year 1 surveying 77 shops (2014 and Year 2 surveying 61 shops (2015–2016. Between the data collection points, 16 shops had closed. Among the shops that were open at both time points, the majority (95% in Year 1; 74% in Year 2 were aware of some FDA regulations or other policies applying to vape shops. However, overall awareness of FDA regulations and state/local policies governing e-cigarettes significantly decreased from Year 1 to Year 2. At both time points, all shops offered customers free puffs of nicotine-containing e-liquids (prohibited by the then upcoming Deeming Rule. Perceptions of e-cigarette safety also significantly decreased between the years. Exploring vape shop retailer perceptions and store policies (i.e., free puffs/samples displays, perceptions of e-cigarette safety, etc. over time will help the FDA assess the needs of the vape shop community and develop more effective retailer education campaigns and materials targeted to increase compliance with the newly enacted regulations.

  13. Trends in internet search activity, media coverage, and patient-centered health information after the FDA safety communications on surgical mesh for pelvic organ prolapse.

    Science.gov (United States)

    Stone, Benjamin V; Forde, James C; Levit, Valerie B; Lee, Richard K; Te, Alexis E; Chughtai, Bilal

    2016-11-01

    In July 2011, the US Food and Drug Administration (FDA) issued a safety communication regarding serious complications associated with surgical mesh for pelvic organ prolapse, prompting increased media and public attention. This study sought to analyze internet search activity and news article volume after this FDA warning and to evaluate the quality of websites providing patient-centered information. Google Trends™ was utilized to evaluate search engine trends for the term "pelvic organ prolapse" and associated terms between 1 January 2004 and 31 December 2014. Google News™ was utilized to quantify the number of news articles annually under the term "pelvic organ prolapse." The search results for the term "pelvic organ prolapse" were assessed for quality using the Health On the Net Foundation (HON) certification. There was a significant increase in search activity from 37.42 in 2010 to 57.75 in 2011, at the time of the FDA communication (p = 0.021). No other annual interval had a statistically significant increase in search activity. The single highest monthly search activity, given the value of 100, was August 2011, immediately following the July 2011 notification, with the next highest value being 98 in July 2011. Linear regression analysis of news articles per year since the FDA communication revealed r 2  = 0.88, with a coefficient of 186. Quality assessment demonstrated that 42 % of websites were HON-certified, with .gov sites providing the highest quality information. Although the 2011 FDA safety communication on surgical mesh was associated with increased public and media attention, the quality of relevant health information on the internet remains of poor quality. Future quality assurance measures may be critical in enabling patients to play active roles in their own healthcare.

  14. The Great London Smog of 1952.

    Science.gov (United States)

    Polivka, Barbara J

    2018-04-01

    : The Great London Smog of December 1952 lasted five days and killed up to 12,000 people. The smog developed primarily because of extensive burning of high-sulfur coal. The health effects were both immediate and long lasting, with a recent study revealing an increased likelihood of childhood asthma development in those exposed to the Great Smog while in utero or during their first year of life. Subsequent pollution legislation-including the U.S. Clean Air Act and its amendments-have demonstrably reduced air pollution and positively impacted health outcomes. With poor air quality events like the Great Smog continuing to occur today, nurses need to be aware of the impact such environmental disasters can have on human health.

  15. ["Great jobs"-also in psychiatry?].

    Science.gov (United States)

    Spiessl, H; Hübner-Liebermann, B

    2003-09-01

    Against the background of a beginning shortage of psychiatrists, results from interviews with 112 employees of an automotive company with the topic "Great Job" are presented to discuss their relevance to psychiatry. The interviews were analysed by means of a qualitative content analysis. Most employees assigned importance to great pay, constructive collaboration with colleagues, and work appealing to personal interests. Further statements particularly relevant to psychiatry were: successful career, flexible working hours, manageable job, work-life balance, well-founded training, no bureaucracy within the company, and personal status in society. The well-known economic restrictions in health care and the still negative attitude towards psychiatry currently reduce the attraction of psychiatry as a profession. From the viewpoint of personnel management, the attractors of a great job revealed in this study are proposed as important clues for the recruitment of medical students for psychiatry and the development of psychiatric staff.

  16. Great Basin geologic framework and uranium favorability

    International Nuclear Information System (INIS)

    Larson, L.T.; Beal, L.H.

    1978-01-01

    Work on this report has been done by a team of seven investigators assisted over the project span by twenty-three undergraduate and graduate students from May 18, 1976 to August 19, 1977. The report is presented in one volume of text, one volume or Folio of Maps, and two volumes of bibliography. The bibliography contains approximately 5300 references on geologic subjects pertinent to the search for uranium in the Great Basin. Volume I of the bibliography lists articles by author alphabetically and Volume II cross-indexes these articles by location and key word. Chapters I through IV of the Text volume and accompanying Folio Map Sets 1, 2, 3, 4, and 5, discuss the relationship of uranium to rock and structural environments which dominate the Great Basin. Chapter 5 and Map Sets 6 and 7 provide a geochemical association/metallogenic grouping of mineral occurrences in the Great Basin along with information on rock types hosting uranium. Chapter VI summarizes the results of a court house claim record search for 'new' claiming areas for uranium, and Chapter VII along with Folio Map Set 8 gives all published geochronological data available through April 1, 1977 on rocks of the Great Basin. Chapter VIII provides an introduction to a computer analysis of characteristics of certain major uranium deposits in crystalline rocks (worldwide) and is offered as a suggestion of what might be done with uranium in all geologic environments. We believe such analysis will assist materially in constructing exploration models. Chapter IX summarizes criteria used and conclusions reached as to the favorability of uranium environments which we believe to exist in the Great Basin and concludes with recommendations for both exploration and future research. A general summary conclusion is that there are several geologic environments within the Great Basin which have considerable potential and that few, if any, have been sufficiently tested

  17. Great Lakes Research Review, 1982. Appendices.

    Science.gov (United States)

    1982-11-01

    7D-i53 28 GREAT LAKES RESEARCH REVIEW 1982 PPENDICES (U) / PETROLEUM REFINERY PO INT SOURCE TASK FORCE WINDSOR (ONTARIO) NOV 82UNCLASSIFIED F/G 8...C7 U. 3 X 7 45 1 2 0. ODm C of. C.’ WC.’ L. LI 7 R-Ri53 62B GREAT LKES RESEARCH REVIEW 1982 PPENDICES (U) 2/3 PETROLEUM REFINERY POINT SOURCE TASK...NUMBER ORGANIZATION* TITLE OF PROJECT 001 A** 0300 ERL-D Acute and Early Life Stage Toxicity Testing of Priority Pollutant Chemicals 002 A 0302 ERL-D

  18. Great Importance Attached to Intangible Cultural Heritage

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    @@ Intangible Cultural Heritage on Verge of Extinction? With the acceleration of globalization and modernization, dramatic changes have taken place in China's cultural ecology: intangible cultural heritage is confronted with great challenges and a lot of orally and behaviorally transmitted cultural heritage disappear one after another; a great deal of traditional craftsmanship is on the verge of extinction; a large number of precious objects and materials of historical and cultural values are destroyed,deserted or lost in foreign countries; arbitrary misuse and excessive exploitation of intangible cultural heritage occur from time to time. Therefore, the protection of intangible cultural heritage brooks no delay.

  19. ILP-2 modeling and virtual screening of an FDA-approved library:a possible anticancer therapy.

    Science.gov (United States)

    Khalili, Saeed; Mohammadpour, Hemn; Shokrollahi Barough, Mahideh; Kokhaei, Parviz

    2016-06-23

    The members of the inhibitors of apoptosis protein (IAP) family inhibit diverse components of the caspase signaling pathway, notably caspase 3, 7, and 9. ILP-2 (BIRC-8) is the most recently identified member of the IAPs, mainly interacting with caspase 9. This interaction would eventually lead to death resistance in the case of cancerous cells. Therefore, structural modeling of ILP-2 and finding applicable inhibitors of its interaction with caspase 9 are a compelling challenge. Three main protein modeling approaches along with various model refinement measures were harnessed to achieve a reliable 3D model, using state-of-the-art software. Thereafter, the selected model was employed to perform virtual screening of an FDA approved library. A model built by a combinatorial approach (homology and ab initio approaches) was chosen as the best model. Model refinement processes successfully bolstered the model quality. Virtual screening of the compound library introduced several high affinity inhibitor candidates that interact with functional residues of ILP2. Given the 3D structure of the ILP2 molecule, we found promising inhibitory molecules. In addition to high affinity towards the ILP2 molecule, these molecules interact with residues that play pivotal rules in ILP2-caspase interaction. These molecules would inhibit ILP2-caspase interaction and consequently would lead to reactivated cell apoptosis through the caspases pathway.

  20. Gas separation performance of carbon molecular sieve membranes based on 6FDA-mPDA/DABA (3:2) polyimide.

    Science.gov (United States)

    Qiu, Wulin; Zhang, Kuang; Li, Fuyue Stephanie; Zhang, Ke; Koros, William J

    2014-04-01

    6FDA-mPDA/DABA (3:2) polyimide was synthesized and characterized for uncross-linked, thermally crosslinked, and carbon molecular sieve (CMS) membranes. The membranes were characterized with thermogravimetric analysis, FTIR spectroscopy, wide-angle X-ray diffraction, and gas permeation tests. Variations in the d spacing, the formation of pore structures, and changes in the pore sizes of the CMS membranes were discussed in relation to pyrolysis protocols. The uncross-linked polymer membranes showed high CO2 /CH4 selectivity, whereas thermally crosslinked membranes exhibited significantly improved CO2 permeability and excellent CO2 plasticization resistance. The CMS membranes showed even higher CO2 permeability and CO2 /CH4 selectivity. An increase in the pyrolysis temperature resulted in CMS membranes with lower gas permeability but higher selectivity. The 550 °C pyrolyzed CMS membranes showed CO2 permeability as high as 14 750 Barrer with CO2 /CH4 selectivity of approximately 52. Even 800 °C pyrolyzed CMS membranes still showed high CO2 permeability of 2610 Barrer with high CO2 /CH4 selectivity of approximately 118. Both polymer membranes and the CMS membranes are very attractive in aggressive natural gas purification applications. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. [Vaginal mesh operations in the urogynecological practice after the FDA warnings. Use or not to use mesh?

    Science.gov (United States)

    Fekete, Zoltán; Körösi, Szilvia; Németh, Gábor

    2018-03-01

    The prevalence of pelvic organ prolapse (POP) with aging is escalating alarmingly, and now becoming a growing epidemic among the elderly. Synthetic transvaginal mesh (TVM) has been employed with increasing popularity in the treatment of POP until the end of the last decade. After the U.S. Drug and Food Administration (FDA) warnings in the years 2008 and 2011, the number of vaginal mesh operations has decreased dramatically. The aim of the study was to evaluate and compare the anti-POP effectivity, the anti-stress incontinence (anti-SUI) efficacy, and the late (36 months) post-operative complications of the anterior vaginoplasty and the TVM operations. We analysed the clinical data from 120 patients with stage II-III anterior prolapse and concomitant SUI who had undergone surgery at a tertiary referral centre in Hungary between January 2013 and January 2014. Sixty patients underwent Kelly-Stoeckel vaginoplasty and the other 60 cases had TVM operation. The surgical complications were classified using the Clavien-Dindo (CD) classification system. The anti-POP (91.6% vs. 63.3%; pmesh surgery represents an effective procedure for prolapse and concomitant SUI with a decreased risk of short- and long-term complications. Orv Hetil. 2018; 159(10): 397-404.

  2. Montana Advanced Biofuels Great Falls Approval

    Science.gov (United States)

    This November 20, 2015 letter from EPA approves the petition from Montana Advanced Biofuels, LLC, Great Falls facility, regarding ethanol produced through a dry mill process, qualifying under the Clean Air Act for advanced biofuel (D-code 5) and renewable

  3. Alfanet Worked Example: What is Greatness?

    NARCIS (Netherlands)

    dr. Pierre Gorissen

    2004-01-01

    This document consists of an example of a Learning Design based on the What is Greatness example originally created by James Dalziel from WebMCQ using LAMS. Note: The example has been created in parallel with the actual development of the Alfanet system. So no claims can be made that the example

  4. Nevada, the Great Recession, and Education

    Science.gov (United States)

    Verstegen, Deborah A.

    2013-01-01

    The impact of the Great Recession and its aftermath has been devastating in Nevada, especially for public education. This article discusses the budget shortfalls and the impact of the economic crisis in Nevada using case study methodology. It provides a review of documents, including Governor Gibbon's proposals for the public K-12 education system…

  5. Professor Witold Nowicki - a greatly spirited pathologist.

    Science.gov (United States)

    Wincewicz, A; Szepietowska, A; Sulkowski, S

    2016-06-01

    This paper presents a complete overview of the scientific, professional and social activity of a great Polish pathologist, Witold Nowicki (1878-1941), from mainly Polish-written, original sources with a major impact on mostly his own publications. The biographical commemoration of this eminent professor is not only due to the fact that he provided a profound microscopic characterization of pneumatosis cystoides in 1909 and 1924. Nowicki greatly influenced the development of anatomical pathology in Poland, having authored over 82 publications, with special reference to tuberculosis, lung cancer, sarcomatous carcinomas, scleroma and others. However, the first of all his merits for the readership of Polish pathologists was his textbook titled Anatomical Pathology, which was a basic pathology manual in pre-war Poland. Witold Nowicki - as the head of the academic pathological anatomy department and former dean of the medical faculty - was shot with other professors by Nazi Germans in the Wuleckie hills in Lvov during World War Two. Professor Nowicki was described as being "small in size but great in spirit" by one of his associates, and remains an outstanding example of a meticulous pathologist, a patient tutor and a great social activist to follow.

  6. 76 FR 32857 - Great Outdoors Month, 2011

    Science.gov (United States)

    2011-06-07

    ... protecting an iconic vast public land, or by creating a community garden or an urban park. Last year, I was... leaders, students, and community groups led to a report unveiled in February, America's Great Outdoors: A Promise to Future Generations, which lays the foundation for smarter, more community-driven action to...

  7. Dramatic Change in Jupiter's Great Red Spot

    Science.gov (United States)

    Simon, A. A.; Wong, M. H.; Rogers, J. H.; Orton, G. S.; de Pater, I.; Asay-Davis, X.; Carlson, R. W.; Marcus, P. S.

    2015-01-01

    Jupiter's Great Red Spot (GRS) is one of its most distinct and enduring features, having been continuously observed since the 1800's. It currently spans the smallest latitude and longitude size ever recorded. Here we show analyses of 2014 Hubble spectral imaging data to study the color, structure and internal dynamics of this long-live storm.

  8. Financial fragility in the Great Moderation

    NARCIS (Netherlands)

    Bezemer, Dirk; Grydaki, Maria

    2014-01-01

    A nascent literature explores the measurement of financial fragility. This paper considers evidence for rising financial fragility during the 1984-2007 Great Moderation in the U.S. The literature suggests that macroeconomic stability combined with strong growth of credit to asset markets, in asset

  9. The Great Work of the New Millennium

    Science.gov (United States)

    Berry, Thomas

    2013-01-01

    Thomas Berry explores the meaning of work from the standpoint of human civilization responding to the call of the universe, replacing use and exploitation of nature with the wonder, rapport, and intimacy so important to the psychic balance of the developing human and natural harmony of life on Earth. The Great Work is defined as the work of…

  10. Teaching Group Work with "The Great Debaters"

    Science.gov (United States)

    Moe, Jeffry; Autry, Linda; Olson, Joann S.; Johnson, Kaprea F.

    2014-01-01

    An experiential learning activity, based on the film "The Great Debaters" (Washington, D., 2007), was used during a group work class. Description and preliminary evaluation of the activity is provided, including analysis of participant scores on the group leader self-efficacy instrument at multiple points. Implications and future…

  11. A great potential for market power

    International Nuclear Information System (INIS)

    Trong, Maj Dang

    2003-01-01

    In a report the competition authorities of Norway, Sweden and Denmark conclude that there is a great potential for exerting market power in the Nordic countries. Bottlenecks in the transmission grid divide the Nordic market in shifting constellations of geographic markets and the market concentration in each market may therefore become very high

  12. The great neurosis of Dr. Joseph Gerard.

    Science.gov (United States)

    Lefrère, Jean-Jacques; Rouillon, Frédéric

    2013-01-01

    The Great Neurosis, of Dr. Joseph Gerard, was published in 1889 in Paris. The book, intended for the general public, shows the different varieties of neuroses through picturesque and instructive examples. Its scientific and medical value is poor, but provides us with the various meanings of the word 'neurosis' in the late nineteenth century. Copyright © 2013 S. Karger AG, Basel.

  13. The Technological Diegesis in "The Great Gatsby"

    Science.gov (United States)

    Zhang, Mingquan

    2008-01-01

    This paper explores the technological diegesis in "The Great Gatsby." In the novel, Fitzgerald cleverly integrates the technological forces into his writing. He particularly relies on the two main props of automobile and telephone to arrange his fragmented plots into a whole. By the deliberate juxtaposition of men and women and machines…

  14. The Classical Plotline of "The Great Gatsby"

    Science.gov (United States)

    Slattery, Dennis P.

    1975-01-01

    Argues that an understanding of the craft of fiction is furthered by a return to the original creation, concluding that "The Great Gatsby" is one of the best examples of Aristotle's description of tragedy as set forth in "The Poetics." (RB)

  15. History of Great Ideas: An Honors Seminar.

    Science.gov (United States)

    Terrill, Marty; And Others

    The History of Great Ideas is an interdisciplinary seminar course for sophomore honor students at North Arkansas Community Technical College that teaches the intellectual history of western civilization. Each semester, students study 14 ideas from science, philosophy, history, religion, sociology, and economics to discover how philosophical…

  16. 77 FR 33597 - Great Outdoors Month, 2012

    Science.gov (United States)

    2012-06-07

    ... Outdoors Month, 2012 By the President of the United States of America A Proclamation America's natural... launch the America's Great Outdoors Initiative. Building on input from tens of thousands of people across... engine of growth. As part of our National Travel and Tourism Strategy, my Administration is working to...

  17. GreatSchools.org Finds Its Niche

    Science.gov (United States)

    Samuels, Christina A.

    2012-01-01

    GreatSchools.org neatly ranks more than 136,000 traditional public, private, and charter schools nationwide on a scale of 1 to 10, based on state test scores. But what often draws readers are the gossipy insider comments posted by parents, students, and teachers, and the star ratings those commenters contribute. The growth of online school rating…

  18. Great plains regional climate assessment technical report

    Science.gov (United States)

    The Great Plains region (GP) plays important role in providing food and energy to the economy of the United States. Multiple climatic and non-climatic stressors put multiple sectors, livelihoods and communities at risk, including agriculture, water, ecosystems and rural and tribal communities. The G...

  19. The Last Great American Picture Show

    NARCIS (Netherlands)

    Elsaesser, Thomas; King, Noel; Horwath, Alexander

    2004-01-01

    The Last Great American Picture Show brings together essays by scholars and writers who chart the changing evaluations of the American cinema of the 1970s, sometimes referred to as the decade of the lost generation, but now more and more recognized as the first New Hollywood, without which the

  20. How To Become a Great Public Space.

    Science.gov (United States)

    Block, Marylaine

    2003-01-01

    Presents interviews with Fred Kent, founder of the Project for Public Spaces (PPS) and Phil Myrick, PPS's assistant vice president, about transforming libraries into desirable public spaces. Discusses qualities people value in public spaces; great library buildings and what they are doing right; the first thing library directors should do when…

  1. Chapter 17. Information needs: Great gray owls

    Science.gov (United States)

    Gregory D. Hayward

    1994-01-01

    Current understanding of great gray owl biology and ecology is based on studies of less than five populations. In an ideal world, a strong conservation strategy would require significant new information. However, current knowledge suggests that conservation of this forest owl should involve fewer conflicts than either the boreal or flammulated owl. The mix of forest...

  2. Great Depression a Timely Class Topic

    Science.gov (United States)

    Zehr, Mary Ann

    2009-01-01

    This article reports that a number of history and social studies teachers have found that because of the parallels they're able to draw between the current economic crisis and the Great Depression, their students are seeing that history is relevant. They're engaging more deeply in history lessons than they have in previous years. The teachers say…

  3. Ecosystem services in the Great Lakes

    Science.gov (United States)

    A comprehensive inventory of ecosystem services across the entire Great Lakes basin is currently lacking and is needed to make informed management decisions. A greater appreciation and understanding of ecosystem services, including both use and non-use services, may have avoided ...

  4. Comparison of treatment effect sizes from pivotal and postapproval trials of novel therapeutics approved by the FDA based on surrogate markers of disease: a meta-epidemiological study.

    Science.gov (United States)

    Wallach, Joshua D; Ciani, Oriana; Pease, Alison M; Gonsalves, Gregg S; Krumholz, Harlan M; Taylor, Rod S; Ross, Joseph S

    2018-03-21

    The U.S. Food and Drug Administration (FDA) often approves new drugs based on trials that use surrogate markers for endpoints, which involve certain trade-offs and may risk making erroneous inferences about the medical product's actual clinical effect. This study aims to compare the treatment effects among pivotal trials supporting FDA approval of novel therapeutics based on surrogate markers of disease with those observed among postapproval trials for the same indication. We searched Drugs@FDA and PubMed to identify published randomized superiority design pivotal trials for all novel drugs initially approved by the FDA between 2005 and 2012 based on surrogate markers as primary endpoints and published postapproval trials using the same surrogate markers or patient-relevant outcomes as endpoints. Summary ratio of odds ratios (RORs) and difference between standardized mean differences (dSMDs) were used to quantify the average difference in treatment effects between pivotal and matched postapproval trials. Between 2005 and 2012, the FDA approved 88 novel drugs for 90 indications based on one or multiple pivotal trials using surrogate markers of disease. Of these, 27 novel drugs for 27 indications were approved based on pivotal trials using surrogate markers as primary endpoints that could be matched to at least one postapproval trial, for a total of 43 matches. For nine (75.0%) of the 12 matches using the same non-continuous surrogate markers as trial endpoints, pivotal trials had larger treatment effects than postapproval trials. On average, treatment effects were 50% higher (more beneficial) in the pivotal than the postapproval trials (ROR 1.5; 95% confidence interval CI 1.01-2.23). For 17 (54.8%) of the 31 matches using the same continuous surrogate markers as trial endpoints, pivotal trials had larger treatment effects than the postapproval trials. On average, there was no difference in treatment effects between pivotal and postapproval trials (dSMDs 0.01; 95

  5. What Makes a Great Journal Great in Economics? The Singer Not the Song.

    NARCIS (Netherlands)

    C-L. Chang (Chia-Lin); M.J. McAleer (Michael); L. Oxley (Les)

    2010-01-01

    textabstractThe paper is concerned with analysing what makes a great journal great in economics, based on quantifiable measures. Alternative Research Assessment Measures (RAM) are discussed, with an emphasis on the Thomson Reuters ISI Web of Science database (hereafter ISI). The various ISI RAM that

  6. FDA Kids' Home Page

    Science.gov (United States)

    ... Consumers Consumer Information by Audience For Kids For Kids Share Tweet Linkedin Pin it More sharing options ... Compliance Federal, State & Local Officials Consumers Health Professionals Science & Research Industry Scroll back to top Popular Content ...

  7. FDA Online Label Repository

    Data.gov (United States)

    U.S. Department of Health & Human Services — The drug labels and other drug-specific information on this Web site represent the most recent drug listing information companies have submitted to the Food and Drug...

  8. FDA 101: Dietary Supplements

    Science.gov (United States)

    ... to get the agency's approval before producing or selling these products. It is not legal to market ... when used in combination with certain other drugs, substances, or foods. Do not self-diagnose any health ...

  9. Recent FDA Regulatory Measures

    NARCIS (Netherlands)

    Grossman, M.R.

    2014-01-01

    The use of antimicrobial drugs (antibiotics) in animal feed or drinking water helps animals to gain weight more efficiently, but also contributes to antimicrobial resistance, which makes important antibiotics less effective and threatens public health.

  10. Still the Great Debate – “Fair Balance” in Direct-to-Consumer Prescription Drug Advertising; Comment on “Trouble Spots in Online Direct-to-Consumer Prescription Drug Promotion: A Content Analysis of FDA Warning Letters”

    Directory of Open Access Journals (Sweden)

    Brent L. Rollins

    2016-04-01

    Full Text Available The above titled paper examined the Food and Drug Administration’s (FDA’s warning letters and notice of violations (NOV over a 10-year period. Findings from this content analysis reinforced what has been the primary issue for prescription direct-to-consumer advertising (DTCA since its beginning, the fair balance of risk and benefit information. As opposed to another analysis in 2026 about this still being an issue, is there anything that can be done to prevent this problem from continuing?

  11. Impact of FDA-Approved Drugs on the Prostaglandin Transporter OATP2A1/SLCO2A1.

    Science.gov (United States)

    Kamo, Shunsuke; Nakanishi, Takeo; Aotani, Rika; Nakamura, Yoshinobu; Gose, Tomoka; Tamai, Ikumi

    2017-09-01

    To understand interaction of drugs with the prostaglandin transporter OATP2A1/SLCO2A1 that regulates disposition of prostaglandins, we explored the impact of 636 drugs in an FDA-approved drug library on 6-carboxyfluorescein (6-CF) uptake by OATP2A1-expressing HEK293 cells (HEK/2A1). Fifty-one and 10 drugs were found to inhibit and enhance 6-CF uptake by more than 50%, respectively. Effect of the 51 drugs on 6-CF uptake was positively correlated with that on PGE 2 uptake (r = 0.64, p < 0.001). Among those, 5 drugs not structurally related to prostaglandins, suramin, pranlukast, zafirlukast, olmesartan medoxomil, and losartan potassium, exhibited more than 90% PGE 2 uptake inhibition. Inhibitory affinity of suramin to OATP2A1 was the highest (IC 50,2A1 of 0.17 μM), and its IC 50 values to MRP4-mediated PGE 2 transport (IC 50,MRP4 ) and PGE 2 synthesis in human U-937 cells treated with phorbol 12-myristate 13-acetate (IC 50,Syn ) were 73.6 and 336.7 times higher than IC 50,2A1 , respectively. Moreover, structure-activity relationship study in 29 nonsteroidal anti-inflammatory drugs contained in the library displayed inhibitory activities of anthranilic acid derivatives, but enhancing effects of propionic acid derivatives. These results demonstrate that suramin is a potent selective inhibitor of OATP2A1, providing a comprehensive information about drugs in clinical use that interact with OATP2A1. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  12. A survey of the FDA's AERS database regarding muscle and tendon adverse events linked to the statin drug class.

    Directory of Open Access Journals (Sweden)

    Keith B Hoffman

    Full Text Available BACKGROUND: Cholesterol management drugs known as statins are widely used and often well tolerated; however, a variety of muscle-related side effects can arise. These adverse events (AEs can have serious impact, and form a significant barrier to therapy adherence. Surveillance of post-marketing AEs is of vital importance to understand real-world AEs and reporting differences between individual statin drugs. We conducted a review of post-approval muscle and tendon AE reports in association with statin use, to assess differences within the drug class. METHODS: We analyzed all case reports from the FDA AE Reporting System (AERS database linking muscle-related AEs to statin use (07/01/2005-03/31/2011. Drugs examined were: atorvastatin, simvastatin, lovastatin, pravastatin, rosuvastatin, and fluvastatin. RESULTS: Relative risk rates for rosuvastatin were consistently higher than other statins. Atorvastatin and simvastatin showed intermediate risks, while pravastatin and lovastatin appeared to have the lowest risk rates. Relative risk of muscle-related AEs, therefore, approximately tracked with per milligram LDL-lowering potency, with fluvastatin an apparent exception. Incorporating all muscle categories, rates for atorvastatin, simvastatin, pravastatin, and lovastatin were, respectively, 55%, 26%, 17%, and 7.5% as high, as rosuvastatin, approximately tracking per milligram potency (Rosuvastatin>Atorvastatin>Simvastatin>Pravastatin ≈ Lovastatin and comporting with findings of other studies. Relative potency, therefore, appears to be a fundamental predictor of muscle-related AE risk, with fluvastatin, the least potent statin, an apparent exception (risk 74% vs rosuvastatin. INTERPRETATION: AE reporting rates differed strikingly for drugs within the statin class, with relative reporting aligning substantially with potency. The data presented in this report offer important reference points for the selection of statins for cholesterol management in

  13. Evaluation of Adverse Events in Total Disc Replacement: A Meta-Analysis of FDA Summary of Safety and Effectiveness Data.

    Science.gov (United States)

    Anderson, Paul A; Nassr, Ahmad; Currier, Bradford L; Sebastian, Arjun S; Arnold, Paul M; Fehlings, Michael G; Mroz, Thomas E; Riew, K Daniel

    2017-04-01

    Systematic review and meta-analysis. The safety of new technology such as cervical total disc replacement (TDR) is of paramount importance and is best evaluated in randomized clinical trials (RCT). We compared complication risks of TDR to fusion using data from Investigational Device Exemptions. A systematic review of FDA Summary of Safety and Effectiveness reports of the 8 approved cervical TDRs was performed. These were all randomized controlled trials comparing anterior cervical discectomy and fusion (ACDF) to TDR. Important outcome variables were dysphagia, wound infection, neurologic injuries, heterotopic ossification, death, and secondary surgeries. A random effects model was selected a priori. Data on adverse events was abstracted and analyzed by calculating relative risk of ACDF to TDR by meta-analysis techniques. The study included 3027 patients with 1377 randomized to ACDF and 1652 to TDR. No statistical differences were present between the 2 groups in dysphagia/dysphonia, hardware related, heterotopic ossification, death, and overall neurologic adverse events and incidence of neurologic deterioration. The relative risk of wound-related problems ACDF to TDR was 0.76 (95% confidence interval [CI] = 0.59, 0.98) favoring ACDF, which was statistically significant, but these were minor and never required a second surgical procedure for deep wound infection. The relative risk of ACDF to TDR in surgical-related neurologic events and secondary surgeries was 1.62 (95% CI = 1.04, 2.53) and 1.79 (95% CI = 1.17, 2.74), both favoring TDR. Cervical TDR appears to be as safe as or safer than ACDF at 2-year follow-up.

  14. Gas Separation Performance of Carbon Molecular Sieve Membranes Based on 6FDA-mPDA/DABA (3:2) Polyimide

    KAUST Repository

    Qiu, Wulin

    2014-02-23

    6FDA-mPDA/DABA (3:2) polyimide was synthesized and characterized for uncross-linked, thermally crosslinked, and carbon molecular sieve (CMS) membranes. The membranes were characterized with thermogravimetric analysis, FTIR spectroscopy, wide-angle X-ray diffraction, and gas permeation tests. Variations in the d spacing, the formation of pore structures, and changes in the pore sizes of the CMS membranes were discussed in relation to pyrolysis protocols. The uncross-linked polymer membranes showed high CO 2/CH4 selectivity, whereas thermally crosslinked membranes exhibited significantly improved CO2 permeability and excellent CO2 plasticization resistance. The CMS membranes showed even higher CO2 permeability and CO2/CH4 selectivity. An increase in the pyrolysis temperature resulted in CMS membranes with lower gas permeability but higher selectivity. The 550 °C pyrolyzed CMS membranes showed CO2 permeability as high as 14 750 Barrer with CO 2/CH4 selectivity of approximately 52. Even 800 °C pyrolyzed CMS membranes still showed high CO2 permeability of 2610 Barrer with high CO2/CH4 selectivity of approximately 118. Both polymer membranes and the CMS membranes are very attractive in aggressive natural gas purification applications. Permeating through: Polyimide-based uncross-linked, thermally crosslinked, and carbon molecular sieve (CMS) membranes are prepared. Variations in the d spacing, the formation of pore structures, and changes in the pore sizes of the CMS membranes are discussed in relation to pyrolysis protocols. Both the polymer and CMS membranes are very attractive in aggressive natural gas purification applications. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. Effectiveness of FDA's new over-the-counter acetaminophen warning label in improving consumer risk perception of liver damage.

    Science.gov (United States)

    Goyal, R K; Rajan, S S; Essien, E J; Sansgiry, S S

    2012-12-01

    The Food and Drug Administration (FDA) issued new organ-specific warning label requirements for over-the-counter (OTC) analgesic products in order to make consumers aware of the risk of liver damage when using acetaminophen. However, awareness of a health risk alone cannot ensure consumers' engagement in safe and preventive behaviour. In this study, we attempted to: (i) measure consumer risk perception of liver damage due to the OTC acetaminophen products and (ii) analyse the effectiveness of the new organ-specific warning label in improving consumer risk perception of liver damage and intention to perform protective behaviours while using OTC acetaminophen products. This within-subject experimental study used a convenience sample of English-speaking adults visiting OTC segments of selected pharmacy stores in Houston. Participants were randomly exposed to the old and new warning labels and their respective risk perception (measured on a visual analogue scale, 0%, no risk, to 100%, extreme risk) and behavioural intention (measured on a 7-point Likert scale) were recorded using a validated, self-administered questionnaire. Descriptive statistics and non-parametric Wilcoxon signed-rank tests were performed using sas statistical software (v 9.2) at a priori significance level of 0.05. Majority of participants (74.4%) were not aware of the new warnings; however, majority (67.8%) had prior knowledge of the risk. The mean risk perception score for the new warning label was found to be significantly higher (72.2% vs. 65.9%, P risk perception of potential liver damage and may encourage protective behaviour. However, future studies are essential to assess the impact of the new label on actual changes in consumer behaviour and subsequent reduction in acetaminophen-related morbidity and mortality. © 2012 Blackwell Publishing Ltd.

  16. FDA Approval: Alectinib for the Treatment of Metastatic, ALK-Positive Non-Small Cell Lung Cancer Following Crizotinib.

    Science.gov (United States)

    Larkins, Erin; Blumenthal, Gideon M; Chen, Huanyu; He, Kun; Agarwal, Rajiv; Gieser, Gerlie; Stephens, Olen; Zahalka, Eias; Ringgold, Kimberly; Helms, Whitney; Shord, Stacy; Yu, Jingyu; Zhao, Hong; Davis, Gina; McKee, Amy E; Keegan, Patricia; Pazdur, Richard

    2016-11-01

    On December 11, 2015, the FDA granted accelerated approval to alectinib (Alecensa; Genentech) for the treatment of patients with anaplastic lymphoma receptor tyrosine kinase (ALK)-positive, metastatic non-small cell lung cancer (NSCLC) who have progressed on or are intolerant to crizotinib. This approval was based on two single-arm trials including 225 patients treated with alectinib 600 mg orally twice daily. The objective response rates (ORR) by an independent review committee in these studies were 38% [95% confidence interval (CI), 28-49] and 44% (95% CI, 36-53); the median durations of response (DOR) were 7.5 months and 11.2 months. In a pooled analysis of 51 patients with measurable disease in the central nervous system (CNS) at baseline, the CNS ORR was 61% (95% CI, 46-74); the CNS DOR was 9.1 months. The primary safety analysis population included 253 patients. The most common adverse reactions were fatigue (41%), constipation (34%), edema (30%), and myalgia (29%). The most common laboratory abnormalities were anemia (56%), increased aspartate aminotransferase (51%), increased alkaline phosphatase (47%), increased creatine phosphokinase (43%), hyperbilirubinemia (39%), hyperglycemia (36%), increased alanine aminotransferase (34%), and hypocalcemia (32%). Dose reductions due to adverse reactions occurred in 12% of patients, whereas 27% of patients had alectinib dosing interrupted for adverse reactions. Permanent discontinuation of alectinib due to adverse reactions occurred in only 6% of patients. With the clinically meaningful ORR and DOR as well as the safety profile observed in these trials, alectinib was determined to have a favorable benefit-risk profile for the treatment of the indicated population. Clin Cancer Res; 22(21); 5171-6. ©2016 AACR. ©2016 American Association for Cancer Research.

  17. Analysis of the Interaction between Clopidogrel, Aspirin, and Proton Pump Inhibitors Using the FDA Adverse Event Reporting System Database.

    Science.gov (United States)

    Suzuki, Yukiya; Suzuki, Honami; Umetsu, Ryogo; Uranishi, Hiroaki; Abe, Junko; Nishibata, Yuri; Sekiya, Yasuaki; Miyamura, Nobuteru; Hara, Hideaki; Tsuchiya, Teruo; Kinosada, Yasutomi; Nakamura, Mitsuhiro

    2015-01-01

    Clopidogrel is an antiplatelet agent widely used in combination with aspirin to limit the occurrence of cardiovascular (embolic/thrombotic) events. Consensus guidelines recommend proton pump inhibitors (PPIs) as a gastrointestinal (GI) prophylactic measure for all patients receiving dual antiplatelet therapy with clopidogrel and aspirin. The objective of this study was to analyze the effect of the simultaneous use of clopidogrel, aspirin, and PPIs on hemorrhagic and embolic/thrombotic events using the U.S. Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database. Reports of hemorrhagic and embolic/thrombotic events between 2004 and 2013 were analyzed with a reporting odds ratio (ROR) algorithm and logistic regression methods. The Medical Dictionary for Regulatory Activities Preferred Terms was used to identify such events. Regarding hemorrhagic events, the adjusted RORs of the concomitant use of aspirin and clopidogrel and those of PPIs prescribed with aspirin and clopidogrel were 4.40 (95% confidence interval [CI], 4.02-4.81) and 3.40 (95% CI, 2.84-4.06), respectively. For embolic/thrombotic events, the adjusted RORs of the concomitant use of aspirin and clopidogrel and those of PPIs prescribed with aspirin and clopidogrel were 2.37 (95% CI, 2.16-2.59) and 2.38 (95% CI, 2.00-2.84), respectively. Among patients included in the FAERS database, the concurrent use of aspirin and clopidogrel with PPIs reduced the adjusted ROR of GI hemorrhagic events. PPIs had little influence on the adjusted ROR of embolic/thrombotic events. These results support the use of PPIs as a preventive measure against GI hemorrhagic events for patients receiving clopidogrel and aspirin.

  18. Hospital Capital Investment During the Great Recession.

    Science.gov (United States)

    Choi, Sung

    2017-01-01

    Hospital capital investment is important for acquiring and maintaining technology and equipment needed to provide health care. Reduction in capital investment by a hospital has negative implications for patient outcomes. Most hospitals rely on debt and internal cash flow to fund capital investment. The great recession may have made it difficult for hospitals to borrow, thus reducing their capital investment. I investigated the impact of the great recession on capital investment made by California hospitals. Modeling how hospital capital investment may have been liquidity constrained during the recession is a novel contribution to the literature. I estimated the model with California Office of Statewide Health Planning and Development data and system generalized method of moments. Findings suggest that not-for-profit and public hospitals were liquidity constrained during the recession. Comparing the changes in hospital capital investment between 2006 and 2009 showed that hospitals used cash flow to increase capital investment by $2.45 million, other things equal.

  19. Great red spot dependence on solar activity

    International Nuclear Information System (INIS)

    Schatten, K.H.

    1979-01-01

    A new inquiry has been made into the question of whether Jupiter's Great Red Spot shows a solar activity dependence. From 1892 to 1947 a clear correlation was present. A dearth of sightings in the seventeenth century, along with the Maunder Minimum, further supports the relation. An anticorrelation, however, from l948 to l967 removed support for such an effect. The old observations have reexamined and recent observations have also been studied. The author reexamines this difficult question and suggests a possible physical mechanism for a Sun-Jovian weather relation. Prinn and Lewis' conversion reaction of Phosphine gas to triclinic red phosphorous crystals is a reaction dependent upon solar radiation. It may explain the dependence found, as well as the striking appearance of the Great Red Spot in the UV

  20. CT of the heart and great vessels

    International Nuclear Information System (INIS)

    Masuda, Yoshiaki; Inagaki, Yoshiaki

    1982-01-01

    Diseases of the heart and great vessels were diagnosed by CT through comparison of the pictures with that of control. Indications for CT included pericardiac diseases such as pericardial effusion, pericardiac cyst, pericardiac defect, pericardiac fat pad, and dilated or hypertrophic ventriculus. Of coronary artery diseases, myocardial infarction is the best indication for CT; and coronary artery calcification and coronary artery bypass graft for checking up the patency were also indications for this method. CT was useful for diagnosis of valvular diseases, especially mitral valve diseases, congenital heart diseases with structural abnormalities, abnormalities of the aorta and great veins, and of the pulmonary arteries and veins, and for follow-up of pulmonary congestion. (Ueda, J.)

  1. The power mix in Great-Britain

    International Nuclear Information System (INIS)

    Trebuchet, Charlotte

    2012-11-01

    This study addresses a new reform of the electric power sector in Great Britain: RIIO (Revenue = Incentives + Innovations + Outputs). The author discusses aspects related to market organisation and aspects related to the grid. First, she gives an overview of the situation of the electricity sector in Great-Britain by describing its evolution from the start of the liberalisation policy until our days, and by presenting the regulation of the electric power transport network. In a second part, she analyses which changes will be introduced by RIIO. She comments the general principles of this reform and discusses its implications for the sector. Appendices describe the LCN Fund (Low carbon network Fund) mechanism which is a specific bidding and selection process, and briefly indicate the projects selected by this fund in 2010 and 2011

  2. Why are there no great women chefs?

    Science.gov (United States)

    Druckman, Charlotte

    2010-01-01

    This article applies the rhetorical and deliberately provocative approach of the watershed essay art historian Linda Nochlin wrote in 1971—“Why Have there Been No Great Women Artists?”—to today's culinary industry. Nochlin used the question her title posed as a theoretical trap that would draw attention not only to the inherent sexism or prejudice that pervades the way the public perceives art, but also to those same issues' existence within and impact on academia and the other cultural institutions responsible for posing these sorts of questions. Nochlin bypassed the obvious and irrelevant debate over women's being less or differently talented and, in so doing, exposed that debate for being a distraction from the heart of the matter: how, sociologically (media) or institutionally (museums, foundations, etc.), people define a “great artist.” Although it's 40 years later, the polemic is as effective when used to understand the gender divide in the food world.

  3. Alexander the Great's relationship with alcohol.

    Science.gov (United States)

    Liappas, J A; Lascaratos, J; Fafouti, S; Christodoulou, G N

    2003-05-01

    This study sought to clarify if Alexander the Great indulged pathologically in alcohol and whether it contributed to his death. The texts of the historians Diodorus of Sicily, Plutarch, Arrian, Curtius Rufus, Athenaeus, Aelian and Justin were studied, with their information concerning wine consumption by Macedonians, and especially Alexander, and were evaluated. The surviving historical texts, all later than Alexander's epoch, are based on a series of contemporary histories and especially on the 'Royal Journals', an official diary written in the imperial court. Alexander consumed large quantities of undiluted wine periodically, reaching pathological intoxication. However, the existing data do not provide convincing evidence that Alexander the Great manifested abuse of or dependence on alcohol according to DSM-IV or ICD-10 criteria and it seems unlikely that alcohol was involved in his untimely death.

  4. Ultrasound assessment of great saphenous vein insufficiency

    Directory of Open Access Journals (Sweden)

    Chander RK

    2015-06-01

    Full Text Available Rajiv K Chander,1 Thomas S Monahan1,2 1Section of Vascular Surgery, Department of Surgery, University of Maryland School of Medicine, 2Department of Surgery, Baltimore Veterans Affairs Medical Center, Baltimore, MD, USA Abstract: Duplex ultrasonography is the ideal modality to assess great saphenous vein insufficiency. Duplex ultrasonography incorporates both gray scale images to delineate anatomy and color-Doppler imaging that visualizes the flow of blood in a structure. Assessment of great saphenous vein requires definition of the anatomy, augmentation of flow, evaluation for both superficial and deep vein thrombosis, and determining the presence of reflux. Currently, evolution in the treatment of reflux also relies on ultrasound for the treatment of the disease. Understanding the utilization of the ultrasound for the diagnosis and treatment of greater saphenous vein reflux is important for practitioners treating reflux disease. Keywords: duplex ultrasonography, small saphenous vein 

  5. Geoarchaeology of water management at Great Zimbabwe

    DEFF Research Database (Denmark)

    Sulas, Federica; Pikirayi, Innocent; Sagiya, Munyaradzi Elton

    In Africa, research on water management in urban contexts has often focussed rainfall, and the occurrence floods and droughts, whereas small-scale catchment systems and soil moisture regimes have received far less attention. This paper sets out to re-address the issue by examining the occurrence......, distribution and use of multiple water resources at the ancient urban landscape of Great Zimbabwe. Here, the rise and demise of the urban site have been linked to changing rainfall in the 1st mill. AD. Accordingly, rainfall shortages and consequent droughts eventually leading to the decline and abandonment...... of Great Zimbabwe at around 1550 AD. However, new research findings suggest a different scenario. Combining geoarchaeolological investigations, soil micromorphology and geochemistry with the study of historical sources and ethnographic records, new datasets indicate prolonged availability and diversified...

  6. Hospital Capital Investment During the Great Recession

    Science.gov (United States)

    Choi, Sung

    2017-01-01

    Hospital capital investment is important for acquiring and maintaining technology and equipment needed to provide health care. Reduction in capital investment by a hospital has negative implications for patient outcomes. Most hospitals rely on debt and internal cash flow to fund capital investment. The great recession may have made it difficult for hospitals to borrow, thus reducing their capital investment. I investigated the impact of the great recession on capital investment made by California hospitals. Modeling how hospital capital investment may have been liquidity constrained during the recession is a novel contribution to the literature. I estimated the model with California Office of Statewide Health Planning and Development data and system generalized method of moments. Findings suggest that not-for-profit and public hospitals were liquidity constrained during the recession. Comparing the changes in hospital capital investment between 2006 and 2009 showed that hospitals used cash flow to increase capital investment by $2.45 million, other things equal. PMID:28617202

  7. Fabrication of 6FDA-durene membrane incorporated with zeolite T and aminosilane grafted zeolite T for CO2/CH4 separation

    Science.gov (United States)

    Jusoh, Norwahyu; Fong Yeong, Yin; Keong Lau, Kok; Shariff, Azmi Mohd

    2017-08-01

    In the present work, zeolite T and aminosilane grafted zeolite T are embedded into 6FDA-durene polyimide phase for the fabrication of mixed matrix membranes (MMMs). FESEM images demonstrated that the improvement of interfacial adhesion between zeolite and polymer phases in MMM loaded with aminosilane grafted zeolite T was not significant as compared to zeolite T/6FDA-durene MMM. From the gas permeation test, CO2/CH4 selectivity up to 26.4 was achieved using MMM containing aminosilane grafted zeolite T, while MMM loaded with ungrafted zeolite T showed CO2/CH4 selectivity of 19.1. In addition, MMM incorporated with aminosilane grafted zeolite T particles successfully lies on Robeson upper bound 2008, which makes it an attractive candidate for CO2/CH4 separation.

  8. Electrofishing survey of the Great Miami River

    International Nuclear Information System (INIS)

    Stocker, L.E.; Miller, M.C.; Engman, J.; Evans, R.L.; Koch, R.W.; Brence, W.A.

    1994-01-01

    Fish sampling by electroshocking in the Great Miami River above and below the Fernald sit was designed to determine changes in the health of the fish community compared to the previous nine years and to collect samples for uranium analysis in fish filets. This document contains information describing the findings of this program. Topics discussed include: physical and chemical parameters, species richness, species diversity, and water analysis

  9. The Rule of Saint Basil the Great

    Directory of Open Access Journals (Sweden)

    Piotr Pietrow

    2014-11-01

    Full Text Available The rules of monasticism were collected and published in a single work entitled Asketikon by Saint Basil the Great. It is arranged in the form of questions and answers to create one coherent work. It has two different publications.The first publication named The Small Asketikon dates to 370-370. It is the fruit of the Saint’s work among Pontic communities and consists of 203 questions and answers. The orignial Greek manuscript has not survived and it is available only in two translations: the Latin Rufin and fragments in Syrian language. The second publication named The Great Asketikon appeard in about 377 and presents the most mature step of cenobitic monasticismin Basil’s elaboration. The Great Asketikon was created by adding new questions to The Small Asketikon and consists of two parts called the The Longer Rules and The Shorter Rules. The Longer Rules are primarily a set of questions and answers. It includes a wide range of rules and norms of the overall life in community. It refers to the fundamental rules of spirituality, such as love, sacrifice, obedience and rudimental problems connected withcommunity organization, cenobitic monasticism and the role of the superior, work and prayer. The second part of The Great Asketikon consists of shorter rules. Two publications are known: the first one originated in Pont andincludes 286 questions and answers and second arose in Cezarei and includes 318 questions and answers. In this work, the Hierarch explains in detail issues regarding community life and solves difficult problems connected with conscience. He writes about behavior towards brothers and explains the significance of weaknesses and virtues.

  10. Network Interactions in the Great Altai Region

    Directory of Open Access Journals (Sweden)

    Lev Aleksandrovich Korshunov

    2017-12-01

    Full Text Available To improve the efficiency and competitiveness of the regional economy, an effective interaction between educational institutions in the Great Altai region is needed. The innovation growth can enhancing this interaction. The article explores the state of network structures in the economy and higher education in the border territories of the countries of Great Altai. The authors propose an updated approach to the three-level classification of network interaction. We analyze growing influence of the countries with emerging economies. We define the factors that impede the more stable and multifaceted regional development of these countries. Further, the authors determine indicators of the higher education systems and cooperation systems at the university level between the Shanghai Cooperation Organization countries (SCO and BRICS countries, showing the international rankings of the universities in these countries. The teaching language is important to overcome the obstacles in the interregional cooperation. The authors specify the problems of the development of the universities of the SCO and BRICS countries as global educational networks. The research applies basic scientific logical methods of analysis and synthesis, induction and deduction, as well as the SWOT analysis method. We have indentified and analyzed the existing economic and educational relations. To promote the economic innovation development of the border territories of the Great Altai, we propose a model of regional network university. Modern universities function in a new economic environment. Thus, in a great extent, they form the technological and social aspects of this environment. Innovative network structures contribute to the formation of a new network institutional environment of the regional economy, which impacts the macro- and microeconomic performance of the region as a whole. The results of the research can help to optimize the regional economies of the border

  11. Academic Performance and the Great Recession

    OpenAIRE

    Adamopoulou, Effrosyni; Tanzi, Giulia M.

    2014-01-01

    In this paper we study how the Great Recession affected university students in terms of performance, with a special focus on the dropout probability. To do so, we use individual-level data on a representative sample of university students in Italy in 2007 and 2011. We measure the severity of the recession in terms of increases in adult and youth unemployment rate and we exploit geographical variation to achieve identification. On the one hand, an increase in adult male unemployment rate deter...

  12. Employment services in Great Britain and Turkey

    OpenAIRE

    ÖZKANLI, Özlem

    2001-01-01

    This artiele criticaUy compares the institutions and procedures for the employment services of Great Britain (GB) and Turkey. The similarities and differences of two employment organisations, the Department for Education and Employment in GB and the Turkish Employment Organisation, are examined. Data is collected in field study from these organisations, based in London and Ankara, through interviews and observation techniques. Field study in London is financed by the World Bank. After briefly...

  13. Introduction: Mobilizing Shakespeare During the Great War

    OpenAIRE

    Smialkowska, Monika

    2014-01-01

    This introduction situates this special issue in the context of ongoing debates surrounding the “cultural mobilization” of Shakespeare during the Great War. The key areas of these debates include the degree to which Shakespeare could successfully be appropriated during the war for totalizing – nationalist and imperialist – purposes; the challenges to such appropriations (for instance, from the colonized nations); ideological fractures produced by seeing Shakespeare, simultaneously, as “univer...

  14. Estimating Spring Condensation on the Great Lakes

    Science.gov (United States)

    Meyer, A.; Welp, L.

    2017-12-01

    The Laurentian Great Lakes region provides opportunities for shipping, recreation, and consumptive water use to a large part of the United States and Canada. Water levels in the lakes fluctuate yearly, but attempts to model the system are inadequate because the water and energy budgets are still not fully understood. For example, water levels in the Great Lakes experienced a 15-year low period ending in 2013, the recovery of which has been attributed partially to decreased evaporation and increased precipitation and runoff. Unlike precipitation, the exchange of water vapor between the lake and the atmosphere through evaporation or condensation is difficult to measure directly. However, estimates have been constructed using off-shore eddy covariance direct measurements of latent heat fluxes, remote sensing observations, and a small network of monitoring buoys. When the lake surface temperature is colder than air temperature as it is in spring, condensation is larger than evaporation. This is a relatively small component of the net annual water budget of the lakes, but the total amount of condensation may be important for seasonal energy fluxes and atmospheric deposition of pollutants and nutrients to the lakes. Seasonal energy fluxes determine, and are influenced by, ice cover, water and air temperatures, and evaporation in the Great Lakes. We aim to quantify the amount of spring condensation on the Great Lakes using the National Center for Atmospheric Prediction North American Regional Reanalysis (NCEP NARR) Data for Winter 2013 to Spring 2017 and compare the condensation values of spring seasons following high volume, high duration and low volume, low duration ice cover.

  15. Determining Wind Erosion in the Great Plains

    OpenAIRE

    Elwin G. Smith; Burton C. English

    1982-01-01

    Wind erosion is defined as the movement of soil particles resulting from strong turbulent winds. The movement of soil particles can be categorized as suspension, saltation, or surface creep. Fine soil particles can be suspended in the atmosphere and carried for great distances. Particles too large to be suspended move in a jumping action along the soil surface, known as saltation. Heavier particles have a rolling movement along the surface and this type of erosion is surface creep.

  16. Precipitation Dynamical Downscaling Over the Great Plains

    Science.gov (United States)

    Hu, Xiao-Ming; Xue, Ming; McPherson, Renee A.; Martin, Elinor; Rosendahl, Derek H.; Qiao, Lei

    2018-02-01

    Detailed, regional climate projections, particularly for precipitation, are critical for many applications. Accurate precipitation downscaling in the United States Great Plains remains a great challenge for most Regional Climate Models, particularly for warm months. Most previous dynamic downscaling simulations significantly underestimate warm-season precipitation in the region. This study aims to achieve a better precipitation downscaling in the Great Plains with the Weather Research and Forecast (WRF) model. To this end, WRF simulations with different physics schemes and nudging strategies are first conducted for a representative warm season. Results show that different cumulus schemes lead to more pronounced difference in simulated precipitation than other tested physics schemes. Simply choosing different physics schemes is not enough to alleviate the dry bias over the southern Great Plains, which is related to an anticyclonic circulation anomaly over the central and western parts of continental U.S. in the simulations. Spectral nudging emerges as an effective solution for alleviating the precipitation bias. Spectral nudging ensures that large and synoptic-scale circulations are faithfully reproduced while still allowing WRF to develop small-scale dynamics, thus effectively suppressing the large-scale circulation anomaly in the downscaling. As a result, a better precipitation downscaling is achieved. With the carefully validated configurations, WRF downscaling is conducted for 1980-2015. The downscaling captures well the spatial distribution of monthly climatology precipitation and the monthly/yearly variability, showing improvement over at least two previously published precipitation downscaling studies. With the improved precipitation downscaling, a better hydrological simulation over the trans-state Oologah watershed is also achieved.

  17. Corrected transposition of the great arteries

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Young Hi; Park, Jae Hyung; Han, Man Chung [Seoul National University College of Medicine, Seoul (Korea, Republic of)

    1981-12-15

    The corrected transposition of the great arteries is an usual congenital cardiac malformation, which consists of transposition of great arteries and ventricular inversion, and which is caused by abnormal development of conotruncus and ventricular looping. High frequency of associated cardiac malformations makes it difficult to get accurate morphologic diagnosis. A total of 18 cases of corrected transposition of the great arteries is presented, in which cardiac catheterization and angiocardiography were done at the Department of Radiology, Seoul National University Hospital between September 1976 and June 1981. The clinical, radiographic, and operative findings with the emphasis on the angiocardiographic findings were analyzed. The results are as follows: 1. Among 18 cases, 13 cases have normal cardiac position, 2 cases have dextrocardia with situs solitus, 2 cases have dextrocardia with situs inversus and 1 case has levocardia with situs inversus. 2. Segmental sets are (S, L, L) in 15 cases, and (I, D,D) in 3 cases and there is no exception to loop rule. 3. Side by side interrelationships of both ventricles and both semilunar valves are noticed in 10 and 12 cases respectively. 4. Subaortic type conus is noted in all 18 cases. 5. Associated cardic malformations are VSD in 14 cases, PS in 11, PDA in 3, PFO in 3, ASD in 2, right aortic arch in 2, tricuspid insufficiency, mitral prolapse, persistent left SVC and persistent right SVC in 1 case respectively. 6. For accurate diagnosis of corrected TGA, selective biventriculography using biplane cineradiography is an essential procedure.

  18. Corrected transposition of the great arteries

    International Nuclear Information System (INIS)

    Choi, Young Hi; Park, Jae Hyung; Han, Man Chung

    1981-01-01

    The corrected transposition of the great arteries is an usual congenital cardiac malformation, which consists of transposition of great arteries and ventricular inversion, and which is caused by abnormal development of conotruncus and ventricular looping. High frequency of associated cardiac malformations makes it difficult to get accurate morphologic diagnosis. A total of 18 cases of corrected transposition of the great arteries is presented, in which cardiac catheterization and angiocardiography were done at the Department of Radiology, Seoul National University Hospital between September 1976 and June 1981. The clinical, radiographic, and operative findings with the emphasis on the angiocardiographic findings were analyzed. The results are as follows: 1. Among 18 cases, 13 cases have normal cardiac position, 2 cases have dextrocardia with situs solitus, 2 cases have dextrocardia with situs inversus and 1 case has levocardia with situs inversus. 2. Segmental sets are (S, L, L) in 15 cases, and (I, D,D) in 3 cases and there is no exception to loop rule. 3. Side by side interrelationships of both ventricles and both semilunar valves are noticed in 10 and 12 cases respectively. 4. Subaortic type conus is noted in all 18 cases. 5. Associated cardic malformations are VSD in 14 cases, PS in 11, PDA in 3, PFO in 3, ASD in 2, right aortic arch in 2, tricuspid insufficiency, mitral prolapse, persistent left SVC and persistent right SVC in 1 case respectively. 6. For accurate diagnosis of corrected TGA, selective biventriculography using biplane cineradiography is an essential procedure

  19. OF THE GREAT TEMPLE OF BEL

    Directory of Open Access Journals (Sweden)

    A. Denker

    2017-02-01

    Full Text Available The Great Temple of Bel in Palmyra was a unique edifice which had blended the well established lines of Greco-Roman architecture with the art and taste of the Orient. With the gilded bronze capitals of its 41 Corinthian columns it was the product of enormous effort and budget. It was the gem of a remarkable epoch of wealthy Palmyra and mighty Roma. With its splendidly decorated adyta ceilings it became a source of inspiration and imagination for Western architecture and decorative arts. While continuing to captivate the World, it was leveled and vanished as a grim result of conflict based vandalism. The aim of this work is to piece together this, the most eloquent and stupendous monument of the Roman East, from its ruins and reconstruct it as it was once extant. Its loss is irreplacable, but its photo-realistic reconstruction can offer some solace by waking the memories of the great temple as in the past. The lost reality of the Great Temple of Bel is revived here by digitally constructing its “ghost images".

  20. Great auricular neuropraxia with beach chair position

    Directory of Open Access Journals (Sweden)

    Joshi M

    2017-07-01

    Full Text Available Minal Joshi,1 Ruth Cheng,2 Hattiyangadi Kamath,1 Joel Yarmush1 1Department of Anesthesiology, New York Methodist Hospital, New York, NY, USA; 2School of Medicine, St. George’s University, Grenada, West Indies Abstract: Shoulder arthroscopy has been shown to be the procedure of choice for many diagnostic and therapeutic interventions. Neuropraxia of the great auricular nerve (GAN is an uncommon complication of shoulder surgery, with the patient in the beach chair position. We report a case of great auricular neuropraxia associated with direct compression by a horseshoe headrest, used in routine positioning for uncomplicated shoulder surgery. In this case, an arthroscopic approach was taken, under regional anesthesia with sedation in the beach chair position. The GAN, a superficial branch of the cervical plexus, is vulnerable to neuropraxia due to its superficial anatomical location. We recommend that for the procedures of the beach chair position, the auricle be protected and covered with cotton and gauze to avoid direct compression and the position of the head and neck be checked and corrected frequently. Keywords: neuropraxia, anesthesia, arthroscopy, great auricular nerve

  1. Moral reasoning about great apes in research

    Science.gov (United States)

    Okamoto, Carol Midori

    2006-04-01

    This study explored how individuals (biomedical scientists, Great Ape Project activists, lay adults, undergraduate biology and environmental studies students, and Grade 12 and 9 biology students) morally judge and reason about using great apes in biomedical and language research. How these groups perceived great apes' mental capacities (e.g., pain, logical thinking) and how these perceptions related to their judgments were investigated through two scenarios. In addition, the kinds of informational statements (e.g., biology, economics) that may affect individuals' scenario judgments were investigated. A negative correlation was found between mental attributions and scenario judgments while no clear pattern occurred for the informational statements. For the biomedical scenario, all groups significantly differed in mean judgment ratings except for the biomedical scientists, GAP activists and Grade 9 students. For the language scenario, all groups differed except for the GAP activists, and undergraduate environmental studies and Grade 9 students. An in-depth qualitative analysis showed that although the biomedical scientists, GAP activists and Grade 9 students had similar judgments, they produced different mean percentages of justifications under four moral frameworks (virtue, utilitarianism, deontology, and welfare). The GAP activists used more virtue reasoning while the biomedical scientists and Grade 9 students used more utilitarian and welfare reasoning, respectively. The results are discussed in terms of developing environmental/humane education curricula.

  2. How do the EMA and FDA decide which anticancer drugs make it to the market? A comparative qualitative study on decision makers' views.

    Science.gov (United States)

    Tafuri, G; Stolk, P; Trotta, F; Putzeist, M; Leufkens, H G; Laing, R O; De Allegri, M

    2014-01-01

    The process leading to a regulatory outcome is guided by factors both related and unrelated to the data package, defined in this analysis as 'formal and informal factors', respectively. The aim of this qualitative study was to analyse which formal and informal factors drive the decision-making process of the European Medicines Agency (EMA) and Food and Drug Administration (FDA) regulators with regard to anticancer drugs, using in-depth semi-structured interviews with regulators of the two agencies. In line with the theory and practice of qualitative research, no set sample size was defined a priori. Respondent enrolment continued until saturation and redundancy were reached. Data were collected through means of in-depth semi-structured interviews conducted either in a face-to-face setting or via Skype(®) with each regulator. The interviews were audio-recorded and verbatim transcribed. The analysis was manually carried out on the transcribed text. Data were independently coded and categorized by two researchers. Interpretation of the findings emerged through a process of triangulation between the two. Seven EMA and six FDA regulators, who had extensive experience with making decisions about anticancer medicines, were interviewed between April and June 2012. There is an open dialogue between the FDA and EMA, with the two moving closer and exchanging information, not opinions. Differences in decision-making between the agencies may be due to a different evaluation of end points. Different interaction modalities with industry and patients represent an additional source of divergence with a potential impact on decision-making. The key message of our respondents was that the agencies manage uncertainty in a different way: unlike the EMA, the FDA has a prevailing attitude to take risks in order to guarantee quicker access to new treatments. Although formal factors are the main drivers for regulatory decisions, the influence of informal factors plays an important role in

  3. The Conundrum of Online Prescription Drug Promotion Comment on "Trouble Spots in Online Direct-to-Consumer Prescription Drug Promotion: A Content Analysis of FDA Warning Letters".

    Science.gov (United States)

    Wanasika, Isaac

    2016-03-26

    This commentary discusses pertinent issues from Hyosun Kim's paper on online prescription drug promotion. The study is well-designed and the findings highlight some of the consequences of the Food and Drug Administration's (FDA's) decision to deregulate online advertising of prescription drugs. While Kim's findings confirm some of the early concerns, they also provide a perspective of implementation challenges in the ever-changing technological environment. © 2016 by Kerman University of Medical Sciences.

  4. Bureau of Radiological Health...a look at Food and Drug Administration's (FDA's) program to protect the American consumer from radiaton. Final report

    International Nuclear Information System (INIS)

    Eccleston, R.C.; Barnett, M.H.

    1977-04-01

    The report provides a brief overview of the FDA's major regulatory and voluntary efforts in the area of radiation control, and examines the impact of the Agency's programs to eliminate unproductive radiation exposure to the American consumer. It concludes with a summary of present and future concerns about newly emerging radiation-emitting products and uses, and the potential public health problems which they may engender

  5. Novel 6FDA-based polyimides derived from sterically hindered Tröger's base diamines: Synthesis and gas permeation properties

    KAUST Repository

    Ghanem, Bader

    2016-04-30

    Two novel Tröger\\'s base-based di-o-substituted diamine monomers were synthesized and used to prepare two intrinsically microporous 6FDA-based polyimides (PIM-PI-TB-1 and PIM-PI-TB-2) with high molecular weight, high thermal stability and excellent solubility in common organic solvents. Compared to previously reported methods for preparing TB-based diamines, which are based on reduction of dimerized nitro-substituted anilines or condensation of phenylenediamine derivatives with dianhydrides, the novel protocol can be used to prepare different functionalized TB-based diamine monomers from a wide variety of aniline derivatives. PIM-PI-TB-1 (made from 6FDA and dibromo-tetramethyl-substituted TB diamine) and PIM-PI-TB-2 (made from 6FDA and tetramethyl-substituted TB diamine) are intrinsically microporous polymers with high BET surface areas of 440 m2/g and 580 m2/g, respectively. Pure-gas permeability coefficients of He, H2, N2, O2, CH4, and CO2 were measured at 35 °C and 2 bar for fresh and 180 days aged films. Both TB-based polyimides exhibited high gas permeability with moderate selectivity. The gas permeability dropped significantly coupled with a moderate increase in selectivity after long-term physical aging of 180 days.

  6. A common feature pharmacophore for FDA-approved drugs inhibiting the Ebola virus [v2; ref status: indexed, http://f1000r.es/4wt

    Directory of Open Access Journals (Sweden)

    Sean Ekins

    2014-12-01

    Full Text Available We are currently faced with a global infectious disease crisis which has been anticipated for decades. While many promising biotherapeutics are being tested, the search for a small molecule has yet to deliver an approved drug or therapeutic for the Ebola or similar filoviruses that cause haemorrhagic fever. Two recent high throughput screens published in 2013 did however identify several hits that progressed to animal studies that are FDA approved drugs used for other indications. The current computational analysis uses these molecules from two different structural classes to construct a common features pharmacophore. This ligand-based pharmacophore implicates a possible common target or mechanism that could be further explored. A recent structure based design project yielded nine co-crystal structures of pyrrolidinone inhibitors bound to the viral protein 35 (VP35. When receptor-ligand pharmacophores based on the analogs of these molecules and the protein structures were constructed, the molecular features partially overlapped with the common features of solely ligand-based pharmacophore models based on FDA approved drugs. These previously identified FDA approved drugs with activity against Ebola were therefore docked into this protein. The antimalarials chloroquine and amodiaquine docked favorably in VP35. We propose that these drugs identified to date as inhibitors of the Ebola virus may be targeting VP35. These computational models may provide preliminary insights into the molecular features that are responsible for their activity against Ebola virus in vitro and in vivo and we propose that this hypothesis could be readily tested.

  7. A common feature pharmacophore for FDA-approved drugs inhibiting the Ebola virus [v1; ref status: indexed, http://f1000r.es/4qh

    Directory of Open Access Journals (Sweden)

    Sean Ekins

    2014-11-01

    Full Text Available We are currently faced with a global infectious disease crisis which has been anticipated for decades. While many promising biotherapeutics are being tested, the search for a small molecule has yet to deliver an approved drug or therapeutic for the Ebola or similar filoviruses that cause haemorrhagic fever. Two recent high throughput screens published in 2013 did however identify several hits that progressed to animal studies that are FDA approved drugs used for other indications. The current computational analysis uses these molecules from two different structural classes to construct a common features pharmacophore. This ligand-based pharmacophore implicates a possible common target or mechanism that could be further explored. A recent structure based design project yielded nine co-crystal structures of pyrrolidinone inhibitors bound to the viral protein 35 (VP35. When receptor-ligand pharmacophores based on the analogs of these molecules and the protein structures were constructed, the molecular features partially overlapped with the common features of solely ligand-based pharmacophore models based on FDA approved drugs. These previously identified FDA approved drugs with activity against Ebola were therefore docked into this protein. The antimalarials chloroquine and amodiaquine docked favorably in VP35. We propose that these drugs identified to date as inhibitors of the Ebola virus may be targeting VP35. These computational models may provide preliminary insights into the molecular features that are responsible for their activity against Ebola virus in vitro and in vivo and we propose that this hypothesis could be readily tested.

  8. Novel 6FDA-based polyimides derived from sterically hindered Tröger's base diamines: Synthesis and gas permeation properties

    KAUST Repository

    Ghanem, Bader; Alaslai, Nasser Y.; Miao, Xiaohe; Pinnau, Ingo

    2016-01-01

    Two novel Tröger's base-based di-o-substituted diamine monomers were synthesized and used to prepare two intrinsically microporous 6FDA-based polyimides (PIM-PI-TB-1 and PIM-PI-TB-2) with high molecular weight, high thermal stability and excellent solubility in common organic solvents. Compared to previously reported methods for preparing TB-based diamines, which are based on reduction of dimerized nitro-substituted anilines or condensation of phenylenediamine derivatives with dianhydrides, the novel protocol can be used to prepare different functionalized TB-based diamine monomers from a wide variety of aniline derivatives. PIM-PI-TB-1 (made from 6FDA and dibromo-tetramethyl-substituted TB diamine) and PIM-PI-TB-2 (made from 6FDA and tetramethyl-substituted TB diamine) are intrinsically microporous polymers with high BET surface areas of 440 m2/g and 580 m2/g, respectively. Pure-gas permeability coefficients of He, H2, N2, O2, CH4, and CO2 were measured at 35 °C and 2 bar for fresh and 180 days aged films. Both TB-based polyimides exhibited high gas permeability with moderate selectivity. The gas permeability dropped significantly coupled with a moderate increase in selectivity after long-term physical aging of 180 days.

  9. The Great Firewall of China: A Critical Analysis

    National Research Council Canada - National Science Library

    Whiting, Michael D

    2008-01-01

    Censorship has a great impact on society as we enter the cyber environment. The Chinese "Great Firewall", as it is commonly called, brings great attention to China as they enter into the global economy...

  10. Clinical trial registration, reporting, publication and FDAAA compliance: a cross-sectional analysis and ranking of new drugs approved by the FDA in 2012

    Science.gov (United States)

    Miller, Jennifer E; Korn, David; Ross, Joseph S

    2015-01-01

    Objective To evaluate clinical trial registration, reporting and publication rates for new drugs by: (1) legal requirements and (2) the ethical standard that all human subjects research should be publicly accessible to contribute to generalisable knowledge. Design Cross-sectional analysis of all clinical trials submitted to the Food and Drug Administration (FDA) for drugs approved in 2012, sponsored by large biopharmaceutical companies. Data sources Information from Drugs@FDA, ClinicalTrials.gov, MEDLINE-indexed journals and drug company communications. Main outcome measures Clinical trial registration and results reporting in ClinicalTrials.gov, publication in the medical literature, and compliance with the 2007 FDA Amendments Acts (FDAAA), analysed on the drug level. Results The FDA approved 15 drugs sponsored by 10 large companies in 2012. We identified 318 relevant trials involving 99 599 research participants. Per drug, a median of 57% (IQR 32–83%) of trials were registered, 20% (IQR 12–28%) reported results in ClinicalTrials.gov, 56% (IQR 41–83%) were published, and 65% (IQR 41–83%) were either published or reported results. Almost half of all reviewed drugs had at least one undisclosed phase II or III trial. Per drug, a median of 17% (IQR 8–20%) of trials supporting FDA approvals were subject to FDAAA mandated public disclosure; of these, a median of 67% (IQR 0–100%) were FDAAA-compliant. 68% of research participants (67 629 of 99 599) participated in FDAAA-subject trials, with 51% (33 405 of 67 629) enrolled in non-compliant trials. Transparency varied widely among companies. Conclusions Trial disclosures for new drugs remain below legal and ethics standards, with wide variation in practices among drugs and their sponsors. Best practices are emerging. 2 of our 10 reviewed companies disclosed all trials and complied with legal disclosure requirements for their 2012 approved drugs. Ranking new drugs on transparency criteria may improve

  11. New Advantage 24 contraceptive gel claims 24-hour effectiveness. But proposed FDA rule could put N-9 products to the test.

    Science.gov (United States)

    1995-04-01

    Advantage 24 is a new contraceptive gel that makes use of bioadhesive technology to offer 24 hours of protection relying on the spermicide nonoxynol-9 (N-9) in lower concentrations. If a proposed US Food and Drug Administration (FDA) rule is enforced N-9 may be examined closely. The manufacturer, Whitehall-Robins Healthcare in New Jersey, stopped production of the Today contraceptive sponge because of the costs of complying with FDA standards. The Advantage 24 gel costs twice as much as the sponge. It is made in Switzerland and distributed by an Illinois company. Any vaginal contraceptive containing N-9 would be approved by the FDA as long as it complied with guidelines laid down in an FDA monograph. However, the registration of the gel could not be confirmed. The product uses a bioadhesive technology concept that natural substances adhere to epithelial and mucosal tissues in the body. Polycarbofil is mixed with water, N-9, and mineral oil to create an emulsion that allows for a time-release mechanism, but at any given time only 2 mg of N-9 is available to kill sperm. The final formula for Advantage 24 is 52.5 mg per dose. Too much N-9 can be toxic, as demonstrated by the Today sponge, which contained 1000 mg of N-9. In Kenya prostitutes using it frequently experienced 3 times as many genital lesions as those using a placebo. A study of Advantage 24 by a Miami laboratory involved 250 women, 22-45 years old, who had had prior tubal ligations. When the gel was applied 15-30 minutes before intercourse the efficacy rate was 98%; it was 91% for those applying it 12 hours before; and it was 86% when the gel was applied 24 hours ahead of time. FDA compliance officers are intrigued about the claim that the gel lasts 24 hours. However, if the claim is held up by research data, women will have an easily available, portable, efficient, aesthetic, and highly effective contraceptive.

  12. Great war, ethics of Vidovdan, memory

    Directory of Open Access Journals (Sweden)

    Šijaković Bogoljub

    2015-01-01

    Full Text Available Beginning with a characterization of contemporaneity (dominance of the financial sector and high technology, politicization of economy, ideological use of culture and control of the capacity for thought and a brief analysis of expansionism (political, economic, cultural on the eve of the Great War, the author embarks on a more detailed description of the spiritual situation in the wake of the Great War: in philosophy, literature, art, as well as the national-political programmatic texts and war propaganda publications of German intellectuals of the time. The continuity of the Austro-Hungarian colonial policy towards the Balkans and Serbia culminates in instigating a preventive war against Serbia by the elites in Berlin and Vienna, which is of importance with regard to the question of responsibility for the war, guided by concrete aims of war in which causes for war are reflected. These war elites wanted to declare the assassination in Sarajevo as the cause of war, which in fact was a political assassination and tyrannicide. The freedom movement of democratic youth, Mlada Bosna (Young Bosnia, needs to be viewed in the European context as inspired by the Serbian tradition of the cult of Kosovo and the ethics of Vidovdan (St Vitus' Day which speaks both about the victim's sacrifice as sublimation of history and about just suffering as elements of identity. Historical memory suggests that historical responsibility is transgenerational. The epic proportions of Serbian suffering in the Great War have additionally encouraged the positing of the theme of St Vitus' Day Temple (Vidovdanski Hram as envisaged by Ivan Meštrović. The foundations of this idea were shaken by Miloš Crnjanski who, in his 'Lyrics of Ithaca', succeeds in returning to Vidovdan (St Vitus' Day the inexhaustible national power of validity. Because of enormous Serbian military and civilian casualties in recent history, the need to establish a Victim's Sacrifice Memorial, in our day

  13. The Great Recession, unemployment and suicide.

    Science.gov (United States)

    Norström, Thor; Grönqvist, Hans

    2015-02-01

    How have suicide rates responded to the marked increase in unemployment spurred by the Great Recession? Our paper puts this issue into a wider perspective by assessing (1) whether the unemployment-suicide link is modified by the degree of unemployment protection, and (2) whether the effect on suicide of the present crisis differs from the effects of previous economic downturns. We analysed the unemployment-suicide link using time-series data for 30 countries spanning the period 1960-2012. Separate fixed-effects models were estimated for each of five welfare state regimes with different levels of unemployment protection (Eastern, Southern, Anglo-Saxon, Bismarckian and Scandinavian). We included an interaction term to capture the possible excess effect of unemployment during the Great Recession. The largest unemployment increases occurred in the welfare state regimes with the least generous unemployment protection. The unemployment effect on male suicides was statistically significant in all welfare regimes, except the Scandinavian one. The effect on female suicides was significant only in the eastern European country group. There was a significant gradient in the effects, being stronger the less generous the unemployment protection. The interaction term capturing the possible excess effect of unemployment during the financial crisis was not significant. Our findings suggest that the more generous the unemployment protection the weaker the detrimental impact on suicide of the increasing unemployment during the Great Recession. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  14. Managing authenticity: the paradox of great leadership.

    Science.gov (United States)

    Goffee, Rob; Jones, Gareth

    2005-12-01

    Leaders and followers both associate authenticity with sincerity, honesty, and integrity. It's the real thing--the attribute that uniquely defines great managers. But while the expression of a genuine self is necessary for great leadership, the concept of authenticity is often misunderstood, not least by leaders themselves. They often assume that authenticity is an innate quality--that a person is either genuine or not. In fact, the authors say, authenticity is largely defined by what other people see in you and, as such, can to a great extent be controlled by you. In this article, the authors explore the qualities of authentic leadership. To illustrate their points, they recount the experiences of some of the authentic leaders they have known and studied, including the BBC's Greg Dyke, Nestlé's Peter Brabeck-Letmathe, and Marks & Spencer's Jean Tomlin. Establishing your authenticity as a leader is a two-part challenge. You have to consistently match your words and deeds; otherwise, followers will never accept you as authentic. But it is not enough just to practice what you preach. To get people to follow you, you also have to get them to relate to you. This means presenting different faces to different audiences--a requirement that many people find hard to square with authenticity. But authenticity is not the product of manipulation. It accurately reflects aspects of the leader's inner self, so it can't be an act. Authentic leaders seem to know which personality traits they should reveal to whom, and when. Highly attuned to their environments, authentic leaders rely on an intuition born of formative, sometimes harsh experiences to understand the expectations and concerns of the people they seek to influence. They retain their distinctiveness as individuals, yet they know how to win acceptance in strong corporate and social cultures and how to use elements of those cultures as a basis for radical change.

  15. Electricity - a great asset for Canada

    International Nuclear Information System (INIS)

    Chretien, Jean.

    1983-06-01

    Canada has a great national asset in its ability to generate electricity economically from its abundant hydro, coal, and uranium resources. Its nuclear industry has an excellent product. Despite lack of orders for now, the CANDU will be a competitive force when the reactor market recovers. Canada has a proven record of reliability for electricity trade with the United States. There appear to be some opportunities for plants in Canada dedicated to the export of electric power. The federal government is prepared to work closely with the provinces to develop projects which will be attractive to customers in the United States

  16. Great deal achieved at Cape's nuclear island

    International Nuclear Information System (INIS)

    Anon.

    1979-01-01

    Since the civil engineering contract commenced a great deal has been achieved at Escom's Koeberg nuclear power station north of Cape Town. About 50 percent of the civil work has now been done and the entire project remains on schedule for a January 1982 start-up on nuclear reactor unit number one and a January 1983 start-up on unit two. Final handover is scheduled for January 1984. Completion of the civil works is scheduled for December 1981. The construction of the Koeberg nuclear power station is discussed, as well as the contractors for the civil engineering work

  17. Dipole vortices in the Great Australian Bight

    DEFF Research Database (Denmark)

    Cresswell, George R.; Lund-Hansen, Lars C.; Nielsen, Morten Holtegaard

    2015-01-01

    Shipboard measurements from late 2006 made by the Danish Galathea 3 Expedition and satellite sea surface temperature images revealed a chain of cool and warm mushroom' dipole vortices that mixed warm, salty, oxygen-poor waters on and near the continental shelf of the Great Australian Bight (GAB...... denser than the cooler offshore waters. The field of dipoles evolved and distorted, but appeared to drift westwards at 5km day-1 over two weeks, and one new mushroom carried GAB water southwards at 7km day(-1). Other features encountered between Cape Leeuwin and Tasmania included the Leeuwin Current...

  18. The great fear of the nuclear

    International Nuclear Information System (INIS)

    Labbe, M.H.

    2000-09-01

    The public opinion always kept complex relations with the atom, done of fascination and repulsion. Is it then correct to speak of ''great fear of nuclear''? To answer this question the author presents, in five chapters, an analysis of the relations between the public and the nuclear. The two first chapters are devoted to historical aspects with respectively a presentation of the atomic episodes and the ground traumatisms. The chapters three and four presents the fears of the nuclear policy and the civil nuclear. The last chapter deals with the the fear of the military nuclear. (A.L.B.)

  19. Commentary. The diseases of Alexander the Great.

    Science.gov (United States)

    York, George K; Steinberg, David A

    2004-06-01

    The accompanying articles that speculate that Alexander the Great had a traumatic carotid dissection or congenital cervical scoliosis demonstrate the difficulties in retrospective diagnosis as a historical enterprise. The extant primary sources were written centuries after Alexander's death and are ambiguous in their original languages, and even more so in translation. Thus we cannot be certain what illness Alexander actually had. Furthermore, anachronistic diagnosis removes Alexander from the medical context of this time, telling us little of historical significance about him. Such investigations also illustrate the more general limits that the absence of context imposes on the study of ancient history.

  20. Small Molecules, Diversity and Great Expectations

    Indian Academy of Sciences (India)

    Small Molecules, Diversity and Great Expectations · PowerPoint Presentation · Slide 3 · Slide 4 · Slide 5 · Slide 6 · Slide 7 · Slide 8 · Slide 9 · Slide 10 · Slide 11 · Slide 12 · Slide 13 · Slide 14 · Slide 15 · Slide 16 · Slide 17 · Slide 18 · Slide 19 · Slide 20 · Slide 21 · Slide 22 · Slide 23 · Slide 24 · Slide 25 · Slide 26 · Slide 27.

  1. The great battles of the energy

    International Nuclear Information System (INIS)

    Chevalier, J.M.

    2004-10-01

    This book presents an introduction to the great world energy challenges. The first part of this book, is devoted to the energy sources history with a special interest for the petroleum. The advantages and disadvantages of the energy sources as the natural gas, the coal, the nuclear power and the renewable energies, are also discussed. Two chapters are devoted to the analysis of the energy sectors deregulation in Europe, in particular the electric power market. The last part proposes to discuss on the twenty century challenge: how to reconcile the energy demand, the environment protection and the developing countries economic development? (A.L.B.)

  2. Comprehensive Assessments of RNA-seq by the SEQC Consortium: FDA-Led Efforts Advance Precision Medicine

    Directory of Open Access Journals (Sweden)

    Joshua Xu

    2016-03-01

    Full Text Available Studies on gene expression in response to therapy have led to the discovery of pharmacogenomics biomarkers and advances in precision medicine. Whole transcriptome sequencing (RNA-seq is an emerging tool for profiling gene expression and has received wide adoption in the biomedical research community. However, its value in regulatory decision making requires rigorous assessment and consensus between various stakeholders, including the research community, regulatory agencies, and industry. The FDA-led SEquencing Quality Control (SEQC consortium has made considerable progress in this direction, and is the subject of this review. Specifically, three RNA-seq platforms (Illumina HiSeq, Life Technologies SOLiD, and Roche 454 were extensively evaluated at multiple sites to assess cross-site and cross-platform reproducibility. The results demonstrated that relative gene expression measurements were consistently comparable across labs and platforms, but not so for the measurement of absolute expression levels. As part of the quality evaluation several studies were included to evaluate the utility of RNA-seq in clinical settings and safety assessment. The neuroblastoma study profiled tumor samples from 498 pediatric neuroblastoma patients by both microarray and RNA-seq. RNA-seq offers more utilities than microarray in determining the transcriptomic characteristics of cancer. However, RNA-seq and microarray-based models were comparable in clinical endpoint prediction, even when including additional features unique to RNA-seq beyond gene expression. The toxicogenomics study compared microarray and RNA-seq profiles of the liver samples from rats exposed to 27 different chemicals representing multiple toxicity modes of action. Cross-platform concordance was dependent on chemical treatment and transcript abundance. Though both RNA-seq and microarray are suitable for developing gene expression based predictive models with comparable prediction performance, RNA

  3. Acute renal failure with sodium-glucose-cotransporter-2 inhibitors: Analysis of the FDA adverse event report system database.

    Science.gov (United States)

    Perlman, A; Heyman, S N; Matok, I; Stokar, J; Muszkat, M; Szalat, A

    2017-12-01

    Sodium-glucose-cotransporter-2 (SGLT2) inhibitors have recently been approved for the treatment of type II diabetes mellitus (T2DM). It has been proposed that these agents could induce acute renal failure (ARF) under certain conditions. This study aimed to evaluate the association between SGLT2-inhibitors and ARF in the FDA adverse event report system (FAERS) database. We analyzed adverse event cases submitted to FAERS between January 2013 and September 2016. ARF cases were identified using a structured medical query. Medications were identified using both brand and generic names. During the period evaluated, 18,915 reports (out of a total of 3,832,015 registered in FAERS) involved the use of SGLT2-inhibitors. SGLT2-inhibitors were reportedly associated with ARF in 1224 of these cases (6.4%), and were defined as the "primary" or "secondary" cause of the adverse event in 96.8% of these cases. The proportion of reports with ARF among reports with SGLT2 inhibitor was almost three-fold higher compared to reports without these drugs (ROR 2.88, 95% CI 2.71-3.05, p SGLT2-inhibitors was significantly greater than the proportion of ARF among cases with T2DM without SGLT2-inhibitors (ROR 1.68, 95% CI 1.57-1.8, p SGLT2-inhibitors, canagliflozin was associated with a higher proportion of reports of renal failure (7.3%), compared to empagliflozin and dapagliflozin (4.7% and 4.8% respectively, p SGLT2-inhibitors are associated with an increase in the proportion of reports of ARF compared to other medications. SGLT2-inhibitor agents may differ from one another in their respective risk for ARF. Copyright © 2017 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.

  4. Multilaboratory particle image velocimetry analysis of the FDA benchmark nozzle model to support validation of computational fluid dynamics simulations.

    Science.gov (United States)

    Hariharan, Prasanna; Giarra, Matthew; Reddy, Varun; Day, Steven W; Manning, Keefe B; Deutsch, Steven; Stewart, Sandy F C; Myers, Matthew R; Berman, Michael R; Burgreen, Greg W; Paterson, Eric G; Malinauskas, Richard A

    2011-04-01

    This study is part of a FDA-sponsored project to evaluate the use and limitations of computational fluid dynamics (CFD) in assessing blood flow parameters related to medical device safety. In an interlaboratory study, fluid velocities and pressures were measured in a nozzle model to provide experimental validation for a companion round-robin CFD study. The simple benchmark nozzle model, which mimicked the flow fields in several medical devices, consisted of a gradual flow constriction, a narrow throat region, and a sudden expansion region where a fluid jet exited the center of the nozzle with recirculation zones near the model walls. Measurements of mean velocity and turbulent flow quantities were made in the benchmark device at three independent laboratories using particle image velocimetry (PIV). Flow measurements were performed over a range of nozzle throat Reynolds numbers (Re(throat)) from 500 to 6500, covering the laminar, transitional, and turbulent flow regimes. A standard operating procedure was developed for performing experiments under controlled temperature and flow conditions and for minimizing systematic errors during PIV image acquisition and processing. For laminar (Re(throat)=500) and turbulent flow conditions (Re(throat)≥3500), the velocities measured by the three laboratories were similar with an interlaboratory uncertainty of ∼10% at most of the locations. However, for the transitional flow case (Re(throat)=2000), the uncertainty in the size and the velocity of the jet at the nozzle exit increased to ∼60% and was very sensitive to the flow conditions. An error analysis showed that by minimizing the variability in the experimental parameters such as flow rate and fluid viscosity to less than 5% and by matching the inlet turbulence level between the laboratories, the uncertainties in the velocities of the transitional flow case could be reduced to ∼15%. The experimental procedure and flow results from this interlaboratory study (available

  5. The survival of the great financial journalism

    Directory of Open Access Journals (Sweden)

    Elvira CALVO GUTIÉRREZ

    2014-07-01

    Full Text Available Traditionally, the economic international journalism has had in the Anglo-Saxon groups Dow Jones (USA and Pearson (Great Britain, publishers of The Wall Street and Financial Times respectively, his big world models. Nevertheless, the new century has brought enormous convulsions to the sector, to the newspapaers of elite and big agencies specialized in economic information as Reuters, Thomson or Bloomberg. To the battle in Internet, there add the expansion of the informative economic power and the changes of mentality of the companies and of the audiences. All this has derived in a fierce war led by the big leaders who, with more than one century of tradition someones, have been object of sales or mergers, financial indispensable operations to be able to adapt to the new times. The aim of this article is to analyze the path of the great economic journalism, with special dedication to two fronts: one, to know how these neswspapers of elite are positioned in the network; other one, the dilemma between continuing being a journalism of quality, rigorous, cosmopolitan and expensive of supporting, or to change towards an ideological, gruesome journalism or amarillista that, since in other specialities, also has spread between the financial journalism

  6. Financialisation, oil and the Great Recession

    International Nuclear Information System (INIS)

    Gkanoutas-Leventis, Angelos; Nesvetailova, Anastasia

    2015-01-01

    This article addresses the role of world oil price hike of 2007–08 in serving to transform the financial and banking crisis into what is commonly referred to the Great Recession. Existing literature on the global crisis of 2007–09 tends to view it as a financial or banking phenomenon, with analyses focusing mainly on state policies, governance mechanisms and market dynamics in transforming the banking crisis of 2007–08 into the economic recession of 2008-12/13 Although often attributing the global meltdown to wider phenomenon of financialisation, rarely do existing perspectives delve into the role of the commodity sector in the global credit crunch. In this paper, we aim to fill this gap, by inquiring into the role played by oil as a financial asset class in the political economy of the global crisis. - Highlights: • We study the oil price and its effects on the Great Recession. • We approach oil as a financial asset class. • We observe the transformation of oil through deregulation.

  7. Great War legacies in Serbian culture

    Directory of Open Access Journals (Sweden)

    Milojković-Đurić Jelena

    2015-01-01

    Full Text Available In the aftermath of the Great War, Ivo Andrić published a number of poems, essays and short stories describing the hard-won victorious outcome as transient to the dire reality of the inordinate loss of human lives and suffering. Yet, personal experiences, although perceived as ephemeral, helped to define the historical discourse capturing man’s resolve to persist in his chosen mission. Over time, Serbian literature and fine arts sustained an unfinished dialogue of the past and the present, merging the individual voices with the collective voices to construct the national narrative. The young writer Miloš Crnjanski observed the sights of destruction and despair that seemed to pale in new literary works pertaining to the war. His novel A Diary about Čarnojević was closely related to his own perilous wartime journey as a conscript in the Austrian army. The vastness of Pannonian plains and Galician woods must have invoked a comparison of sorts with another historic chapter recorded in the collective consciousness of his nation: the Great Migration of Serbs led by Patriarch Arsenije III Čarnojević (Crnojević in 1690. The very title of the novel contained a powerful reference to the migration, and its illustrious historic leader which has not been discussed or explored before.

  8. How to write a great business plan.

    Science.gov (United States)

    Sahlman, W A

    1997-01-01

    Every seasoned investor knows that detailed financial projections for a new company are an act of imagination. Nevertheless, most business plans pour far too much ink on the numbers - and far too little on the information that really matters. Why? William Sahlman suggests that a great business plan is one that focuses on a series of questions. These questions relate to the four factors critical to the success of every new venture: the people, the opportunity, the context, and the possibilities for both risk and reward. The questions about people revolve around three issues: What do they know? Whom do they know? and How well are they known? As for opportunity, the plan should focus on two questions: Is the market for the venture's product or service large or rapidly growing (or preferably both)? and Is the industry structurally attractive? Then, in addition to demonstrating an understanding of the context in which their venture will operate, entrepreneurs should make clear how they will respond when that context inevitably changes. Finally, the plan should look unflinchingly at the risks the new venture faces, giving would-be backers a realistic idea of what magnitude of reward they can expect and when they can expect it. A great business plan is not easy to compose, Sahlman acknowledges, largely because most entrepreneurs are wild-eyed optimists. But one that asks the right questions is a powerful tool. A better deal, not to mention a better shot at success, awaits entrepreneurs who use it.

  9. China in space the great leap forward

    CERN Document Server

    Harvey, Brian

    2013-01-01

    The 21st century has seen the emergence, after the Soviet Union and the United States, of the third great space superpower: China. Here, in China in Space - The Great Leap Forward, Brian Harvey takes a contemporary look at the new Chinese space program. China has already launched its first space station, Tiangong; has sent its first spacecraft to the Moon, the Chang e; and has plans to send spaceships to Mars and further afield. China's annual launch rate has already overtaken those of both Europe and the United States. Huge new production plants and launch centers are under construction, to build and launch the new family of Long March 5, 6, and 7 rockets. In Roadmap 2050, the Academy of Sciences indicates that China intends to be the leading spacefaring nation by mid-century, with bases on the Moon and Mars. This book gives an informed, fully up-to-date commentary on all aspects of the Chinese space program, including its history, development, technology, missions, and the personalities involved. It lists a...

  10. Considering the Future of Pharmaceutical Promotions in Social Media Comment on "Trouble Spots in Online Direct-to-Consumer Prescription Drug Promotion: A Content Analysis of FDA Warning Letters".

    Science.gov (United States)

    Carpentier, Francesca Renee Dillman

    2016-02-09

    This commentary explores the implications of increased social media marketing by drug manufacturers, based on findings in Hyosun Kim's article of the major themes in recent Food and Drug Administration (FDA) warning letters and notices of violation regarding online direct-to-consumer promotions of pharmaceuticals. Kim's rigorous analysis of FDA letters over a 10-year span highlights a relative abundance of regulatory action toward marketer-controlled websites and sponsored advertisements, compared to branded and unbranded social media messaging. However, social media marketing efforts are increasing, as is FDA attention to these efforts. This commentary explores recent developments and continuing challenges in the FDA's attempts to provide guidance and define pharmaceutical company accountability in marketer-controlled and -uncontrolled claims disseminated through social media. © 2016 by Kerman University of Medical Sciences.

  11. Intimate Partner Violence in the Great Recession.

    Science.gov (United States)

    Schneider, Daniel; Harknett, Kristen; McLanahan, Sara

    2016-04-01

    In the United States, the Great Recession was marked by severe negative shocks to labor market conditions. In this study, we combine longitudinal data from the Fragile Families and Child Wellbeing Study with U.S. Bureau of Labor Statistics data on local area unemployment rates to examine the relationship between adverse labor market conditions and mothers' experiences of abusive behavior between 2001 and 2010. Unemployment and economic hardship at the household level were positively related to abusive behavior. Further, rapid increases in the unemployment rate increased men's controlling behavior toward romantic partners even after we adjust for unemployment and economic distress at the household level. We interpret these findings as demonstrating that the uncertainty and anticipatory anxiety that go along with sudden macroeconomic downturns have negative effects on relationship quality, above and beyond the effects of job loss and material hardship.

  12. The Great Recession and Workers' Health Benefits.

    Science.gov (United States)

    Koh, Kanghyock

    2018-03-01

    During a recession, cost-sharing of employer-sponsored health benefits could increase to reduce labor costs in the U.S. Using a variation in the severity of recession shocks across industries, I find evidence that the enrollment rate of high deductible health plans (HDHPs) among workers covered by employer-sponsored health benefits increased more among firms in industries that experienced severe recession shocks. As potential mechanisms, I study employer-side and worker-side mechanisms. I find that employers changed health benefit offerings to force or incentivize workers to enroll in HDHPs. But I find little evidence of an increase in workers' demand for HDHPs due to a reduction in income. These results suggest that the HDHP enrollment rate increased during the Great Recession, as employers tried to save costs of offering health benefits. Copyright © 2018 Elsevier B.V. All rights reserved.

  13. Leiomyosarcoma of the great saphenous vein

    Directory of Open Access Journals (Sweden)

    Alexandre Campos Moraes Amato

    2015-06-01

    Full Text Available A 56-year-old male patient presented with a complaint of two painful, hard, palpable nodules in the right lower limb. A Doppler ultrasound scan revealed the presence of nodules, likely to be neoplastic. Computed angiography showed two solid hypervascular nodules in the right great saphenous vein, fed by branches of the posterior tibial artery. Embolization of the nodules using surgical cyanoacrylate was performed, followed by an excisional biopsy. Anatomical pathology and immunohistochemical analysis identified the nodule as a high-grade leiomyosarcoma, characterized by ten mitotic figures per ten high-power fields, necrosis and cell pleomorphism. Immunohistochemical analysis results were positive for caldesmon and desmin labeling. A second surgical procedure was performed to enlarge the free margins.

  14. The Great Game and the copyright villain

    Directory of Open Access Journals (Sweden)

    Betsy Rosenblatt

    2017-03-01

    Full Text Available This essay explores the reactions of Sherlock Holmes fans and enthusiasts to assertions of intellectual property ownership and infringement by putative rights holders in two eras of Sherlockian history. In both the 1946–47 and 2013–15 eras, Sherlock Holmes devotees villainized the entities claiming ownership of intellectual property in Holmes, distancing those entities from Sir Arthur Conan Doyle and casting them as greedy and morally bankrupt. Throughout each era, Sherlockians did not shy away from creating transformative works based on the Holmes canon over the objections of putative rights holders. This complicates the usual expectation that copyright assertions against fans are likely to chill fan production. The essay explores possible reasons why Sherlockian fandom might differ from other fandoms in this respect, including the role of the Great Game form of Sherlockian fandom in shaping fan attitudes toward their subject.

  15. The Great White Guppy: Top Predator

    Science.gov (United States)

    Michalski, G. M.

    2011-12-01

    Nitrogen isotopes are often used to trace the trophic level of members of an ecosystem. As part of a stable isotope biogeochemistry and forensics course at Purdue University, students are introduced to this concept by analyzing nitrogen isotopes in sea food purchased from local grocery stores. There is a systematic increase in 15N/14N ratios going from kelp to clams/shrimp, to sardines, to tuna and finally to shark. These enrichments demonstrate how nitrogen is enriched in biomass as predators consume prey. Some of the highest nitrogen isotope enrichments observed, however, are in the common guppy. We investigated a number of aquarium fish foods and find they typically have high nitrogen isotope ratios because they are made form fish meal that is produced primarily from the remains of predator fish such as tuna. From, a isotope perspective, the guppy is the top of the food chain, more ferocious than even the Great White shark.

  16. A wonderful laboratory and a great researcher

    Science.gov (United States)

    Sheikh, N. M.

    2004-05-01

    It was great to be associated with Prof. Dr. Karl Rawer. He devoted his life to make use of the wonderful laboratory of Nature, the Ionosphere. Through acquisition of the experimental data from AEROS satellites and embedding it with data from ground stations, it was possible to achieve a better empirical model, the International Reference Ionosphere. Prof. Dr. Karl Rawer has been as dynamic as the Ionosphere. His vision about the ionospheric data is exceptional and has helped the scientific and engineering community to make use of his vision in advancing the dimensions of empirical modelling. As a human being, Prof. Dr. Karl Rawer has all the traits of an angel from Heaven. In short he developed a large team of researchers forming a blooming tree from the parent node. Ionosphere still plays an important role in over the horizon HF Radar and GPs satellite data reduction.

  17. Hummingbirds have a greatly enlarged hippocampal formation.

    Science.gov (United States)

    Ward, Brian J; Day, Lainy B; Wilkening, Steven R; Wylie, Douglas R; Saucier, Deborah M; Iwaniuk, Andrew N

    2012-08-23

    Both field and laboratory studies demonstrate that hummingbirds (Apodiformes, Trochilidae) have exceptional spatial memory. The complexity of spatial-temporal information that hummingbirds must retain and use daily is probably subserved by the hippocampal formation (HF), and therefore, hummingbirds should have a greatly expanded HF. Here, we compare the relative size of the HF in several hummingbird species with that of other birds. Our analyses reveal that the HF in hummingbirds is significantly larger, relative to telencephalic volume, than any bird examined to date. When expressed as a percentage of telencephalic volume, the hummingbird HF is two to five times larger than that of caching and non-caching songbirds, seabirds and woodpeckers. This HF expansion in hummingbirds probably underlies their ability to remember the location, distribution and nectar content of flowers, but more detailed analyses are required to determine the extent to which this arises from an expansion of HF or a decrease in size of other brain regions.

  18. Great Lakes Regional Biomass Energy Program

    International Nuclear Information System (INIS)

    Kuzel, F.

    1993-01-01

    The Great Lakes Regional Biomass Energy Program (GLRBEP) was initiated September, 1983, with a grant from the Office of Energy Efficiency and Renewable Energy of the US Department of Energy (DOE). The program provides resources to public and private organizations in the Great Lakes region to increase the utilization and production of biomass fuels. The objectives of the GLRBEP are to: (1) improve the capabilities and effectiveness of biomass energy programs in the state energy offices; (2) assess the availability of biomass resources for energy in light of other competing needs and uses; (3) encourage private sector investments in biomass energy technologies; (4) transfer the results of government-sponsored biomass research and development to the private sector; (5) eliminate or reduce barriers to private sector use of biomass fuels and technology; (6) prevent or substantially mitigate adverse environmental impacts of biomass energy use. The Program Director is responsible for the day-to-day activities of the GLRBEP and for implementing program mandates. A 40 member Technical Advisory Committee (TAC) sets priorities and recommends projects. The governor of each state in the region appoints a member to the Steering Council, which acts on recommendations of the TAC and sets basic program guidelines. The GLRBEP is divided into three separate operational elements. The State Grants component provides funds and direction to the seven state energy offices in the region to increase their capabilities in biomass energy. State-specific activities and interagency programs are emphasized. The Subcontractor component involves the issuance of solicitations to undertake projects that address regional needs, identified by the Technical Advisory Committee. The Technology Transfer component includes the development of nontechnical biomass energy publications and reports by Council staff and contractors, and the dissemination of information at conferences, workshops and other events

  19. Great Ellipse Route Planning Based on Space Vector

    Directory of Open Access Journals (Sweden)

    LIU Wenchao

    2015-07-01

    Full Text Available Aiming at the problem of navigation error caused by unified earth model in great circle route planning using sphere model and modern navigation equipment using ellipsoid mode, a method of great ellipse route planning based on space vector is studied. By using space vector algebra method, the vertex of great ellipse is solved directly, and description of great ellipse based on major-axis vector and minor-axis vector is presented. Then calculation formulas of great ellipse azimuth and distance are deduced using two basic vectors. Finally, algorithms of great ellipse route planning are studied, especially equal distance route planning algorithm based on Newton-Raphson(N-R method. Comparative examples show that the difference of route planning between great circle and great ellipse is significant, using algorithms of great ellipse route planning can eliminate the navigation error caused by the great circle route planning, and effectively improve the accuracy of navigation calculation.

  20. Issues regarding the U.S. F.D.A. Protective Action Guidelines and derived response levels for human food and animal feed

    International Nuclear Information System (INIS)

    Denney, Bruce

    1989-01-01

    Full text: A review of the Food and Drug Administration's (FDA) rationale and methods for determining protective action guidelines (PAGs) and derived response levels (DRLs) (FDAa82, FDAb82) for human food and animal feed reveals the presence of ambiguous and contradictory information that should be clarified in order to improve the usefulness of the guidance. The differences in the criteria used to determine the Preventative and Emergency PAGs and DRLs, for example, are striking. The Preventative PAGs (and DRLs) are based on accepted health physics principles, e.g. risk factors, avoidance of fetal health effects, agricultural models, etc. The Emergency PAGs (and DRLs), however, are based solely on a traditional safety factor of ten. This difference in rationale becomes more conspicuous when the protective actions for these PAGs are compared: preventative protective actions involve low impact actions, e.g. removal of cattle from pasture, storage to allow for radioactive decay, etc., while emergency protective actions involve high impact actions e.g. isolating and condemning food products. These differences result in a contradiction: high impact actions, which may cause considerable problems and loss of income for farmers and food processors, are based on non-technical premises ('tradition'), while the low impact actions, which may only result in minor inconveniences to farmers and food processors, are based on solid scientific principles. Justifying or explaining these differences to farmers or to the media may be very difficult. Clearly there exists a need to review the basis and rationale upon which the Emergency PAGs and DRLs were derived in order to provide a more scientific explanation for their choice and use. In the FDA guidance (FDAa82), references are also made to ALARA and to the use of low-impact actions at doses lower than the PAGs. Although the FDA accepts and endorses the concept of keeping doses as low as reasonably achievable, the FDA does not

  1. The "high solubility" definition of the current FDA Guidance on Biopharmaceutical Classification System may be too strict for acidic drugs.

    Science.gov (United States)

    Yazdanian, Mehran; Briggs, Katherine; Jankovsky, Corinne; Hawi, Amale

    2004-02-01

    The purpose of this study was to assess if the definition of high solubility as proposed in the FDA Guidance on Biopharmaceutical Classification System (BCS) is too strict for highly permeable acidic drugs. The solubility and permeability values of 20 (18 acidic and 2 non-acidic) nonsteroidal anti-inflammatory drugs (NSAID) were determined. The NSAIDs were grouped into three different sets having acetic acid, propionic acid, or other acidic moieties such as fenamate, oxicam, and salicylate. Two nonacidic NSAIDs (celecoxib and rofecoxib) were also included for comparison purposes. Equilibrium solubility values were determined at pH 1.2, 5.0, 7.4, and in biorelevant media simulating fed intestinal fluid at pH 5.0. For a select number of acids, we also measured solubility values in media simulating gastric and fasted intestinal fluids. Permeability classification was established relative to that of reference drugs in the Caco-2 cell permeability model. Permeability coefficients for all drugs were measured at concentrations corresponding to the lowest and highest marketed dose strengths dissolved in 250 ml volume, and their potential interaction with cellular efflux pumps was investigated. All NSAIDs with different acidic functional groups were classified as highly permeable based on their Caco-2 cell permeability. Only ketorolac appeared to have a potential for interaction with cellular efflux pumps. Solubility classification was based on comparison of equilibrium solubility at pH 1.2, 5.0. and 7.4 relative to marketed dose strengths in 250 ml. The pKa values for the acidic NSAIDs studied were between 3.5 and 5.1. and, as expected, their solubility increased dramatically at pH 7.4 compared to pH 1.2. Only three NSAIDs, ketorolac, ketoprofen. and acetyl salicylic acid, meet the current criteria for high solubility over the entire pH range. However, with the exception of ibuprofen, oxaprozin, and mefenamic acid, the remaining compounds can be classified as Class I drugs

  2. Comparison of Data on Serious Adverse Events and Mortality in ClinicalTrials.gov, Corresponding Journal Articles, and FDA Medical Reviews: Cross-Sectional Analysis.

    Science.gov (United States)

    Pradhan, Richeek; Singh, Sonal

    2018-04-11

    Inconsistencies in data on serious adverse events (SAEs) and mortality in ClinicalTrials.gov and corresponding journal articles pose a challenge to research transparency. The objective of this study was to compare data on SAEs and mortality from clinical trials reported in ClinicalTrials.gov and corresponding journal articles with US Food and Drug Administration (FDA) medical reviews. We conducted a cross-sectional study of a randomly selected sample of new molecular entities approved during the study period 1 January 2013 to 31 December 2015. We extracted data on SAEs and mortality from 15 pivotal trials from ClinicalTrials.gov and corresponding journal articles (the two index resources), and FDA medical reviews (reference standard). We estimated the magnitude of deviations in rates of SAEs and mortality between the index resources and the reference standard. We found deviations in rates of SAEs (30% in ClinicalTrials.gov and 30% in corresponding journal articles) and mortality (72% in ClinicalTrials.gov and 53% in corresponding journal articles) when compared with the reference standard. The intra-class correlation coefficient between the three resources was 0.99 (95% confidence interval [CI] 0.98-0.99) for SAE rates and 0.99 (95% CI 0.97-0.99) for mortality rates. There are differences in data on rates of SAEs and mortality in randomized clinical trials in both ClinicalTrials.gov and journal articles compared with FDA reviews. Further efforts should focus on decreasing existing discrepancies to enhance the transparency and reproducibility of data reporting in clinical trials.

  3. Analysis of the Risks and Benefits of New Chemical Entities Approved by the US Food and Drug Administration (FDA) and Subsequently Withdrawn From the US Market.

    Science.gov (United States)

    Patriarca, Peter A; Van Auken, R Michael; Kebschull, Scott A

    2018-01-01

    Benefit-risk evaluations of drugs have been conducted since the introduction of modern regulatory systems more than 50 years ago. Such judgments are typically made on the basis of qualitative or semiquantitative approaches, often without the aid of quantitative assessment methods, the latter having often been applied asymmetrically to place emphasis on benefit more so than harm. In an effort to preliminarily evaluate the utility of lives lost or saved, or quality-adjusted life-years (QALY) lost and gained as a means of quantitatively assessing the potential benefits and risks of a new chemical entity, we focused our attention on the unique scenario in which a drug was initially approved based on one set of data, but later withdrawn from the market based on a second set of data. In this analysis, a dimensionless risk to benefit ratio was calculated in each instance, based on the risk and benefit quantified in similar units. The results indicated that FDA decisions to approve the drug corresponded to risk to benefit ratios less than or equal to 0.136, and that decisions to withdraw the drug from the US market corresponded to risk to benefit ratios greater than or equal to 0.092. The probability of FDA approval was then estimated using logistic regression analysis. The results of this analysis indicated that there was a 50% probability of FDA approval if the risk to benefit ratio was 0.121, and that the probability approaches 100% for values much less than 0.121, and the probability approaches 0% for values much greater than 0.121. The large uncertainty in these estimates due to the small sample size and overlapping data may be addressed in the future by applying the methodology to other drugs.

  4. Columbia Classification Algorithm of Suicide Assessment (C-CASA): classification of suicidal events in the FDA's pediatric suicidal risk analysis of antidepressants.

    Science.gov (United States)

    Posner, Kelly; Oquendo, Maria A; Gould, Madelyn; Stanley, Barbara; Davies, Mark

    2007-07-01

    To evaluate the link between antidepressants and suicidal behavior and ideation (suicidality) in youth, adverse events from pediatric clinical trials were classified in order to identify suicidal events. The authors describe the Columbia Classification Algorithm for Suicide Assessment (C-CASA), a standardized suicidal rating system that provided data for the pediatric suicidal risk analysis of antidepressants conducted by the Food and Drug Administration (FDA). Adverse events (N=427) from 25 pediatric antidepressant clinical trials were systematically identified by pharmaceutical companies. Randomly assigned adverse events were evaluated by three of nine independent expert suicidologists using the Columbia classification algorithm. Reliability of the C-CASA ratings and agreement with pharmaceutical company classification were estimated. Twenty-six new, possibly suicidal events (behavior and ideation) that were not originally identified by pharmaceutical companies were identified in the C-CASA, and 12 events originally labeled as suicidal by pharmaceutical companies were eliminated, which resulted in a total of 38 discrepant ratings. For the specific label of "suicide attempt," a relatively low level of agreement was observed between the C-CASA and pharmaceutical company ratings, with the C-CASA reporting a 50% reduction in ratings. Thus, although the C-CASA resulted in the identification of more suicidal events overall, fewer events were classified as suicide attempts. Additionally, the C-CASA ratings were highly reliable (intraclass correlation coefficient [ICC]=0.89). Utilizing a methodical, anchored approach to categorizing suicidality provides an accurate and comprehensive identification of suicidal events. The FDA's audit of the C-CASA demonstrated excellent transportability of this approach. The Columbia algorithm was used to classify suicidal adverse events in the recent FDA adult antidepressant safety analyses and has also been mandated to be applied to all

  5. Constructing the informatics and information technology foundations of a medical device evaluation system: a report from the FDA unique device identifier demonstration.

    Science.gov (United States)

    Drozda, Joseph P; Roach, James; Forsyth, Thomas; Helmering, Paul; Dummitt, Benjamin; Tcheng, James E

    2018-02-01

    The US Food and Drug Administration (FDA) has recognized the need to improve the tracking of medical device safety and performance, with implementation of Unique Device Identifiers (UDIs) in electronic health information as a key strategy. The FDA funded a demonstration by Mercy Health wherein prototype UDIs were incorporated into its electronic information systems. This report describes the demonstration's informatics architecture. Prototype UDIs for coronary stents were created and implemented across a series of information systems, resulting in UDI-associated data flow from manufacture through point of use to long-term follow-up, with barcode scanning linking clinical data with UDI-associated device attributes. A reference database containing device attributes and the UDI Research and Surveillance Database (UDIR) containing the linked clinical and device information were created, enabling longitudinal assessment of device performance. The demonstration included many stakeholders: multiple Mercy departments, manufacturers, health system partners, the FDA, professional societies, the National Cardiovascular Data Registry, and information system vendors. The resulting system of systems is described in detail, including entities, functions, linkage between the UDIR and proprietary systems using UDIs as the index key, data flow, roles and responsibilities of actors, and the UDIR data model. The demonstration provided proof of concept that UDIs can be incorporated into provider and enterprise electronic information systems and used as the index key to combine device and clinical data in a database useful for device evaluation. Keys to success and challenges to achieving this goal were identified. Fundamental informatics principles were central to accomplishing the system of systems model. © The Author 2017. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For Permissions, please email: journals.permissions@oup.com

  6. 33 CFR 100.124 - Maggie Fischer Memorial Great South Bay Cross Bay Swim, Great South Bay, New York.

    Science.gov (United States)

    2010-07-01

    ... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Maggie Fischer Memorial Great South Bay Cross Bay Swim, Great South Bay, New York. 100.124 Section 100.124 Navigation and Navigable... NAVIGABLE WATERS § 100.124 Maggie Fischer Memorial Great South Bay Cross Bay Swim, Great South Bay, New York...

  7. Could the FDA-approved anti-HIV PR inhibitors be promising anticancer agents? An answer from enhanced docking approach and molecular dynamics analyses

    Directory of Open Access Journals (Sweden)

    Arodola OA

    2015-11-01

    Full Text Available Olayide A Arodola, Mahmoud ES SolimanMolecular Modelling and Drug Design Lab, School of Health Sciences, Westville Campus, University of KwaZulu-Natal, Durban, South AfricaAbstract: Based on experimental data, the anticancer activity of nelfinavir (NFV, a US Food and Drug Administration (FDA-approved HIV-1 protease inhibitor (PI, was reported. Nevertheless, the mechanism of action of NFV is yet to be verified. It was hypothesized that the anticancer activity of NFV is due to its inhibitory effect on heat shock protein 90 (Hsp90, a promising target for anticancer therapy. Such findings prompted us to investigate the potential anticancer activity of all other FDA-approved HIV-1 PIs against human Hsp90. To accomplish this, “loop docking” – an enhanced in-house developed molecular docking approach – followed by molecular dynamic simulations and postdynamic analyses were performed to elaborate on the binding mechanism and relative binding affinities of nine FDA-approved HIV-1 PIs against human Hsp90. Due to the lack of the X-ray crystal structure of human Hsp90, homology modeling was performed to create its 3D structure for subsequent simulations. Results showed that NFV has better binding affinity (ΔG =−9.2 kcal/mol when compared with other PIs: this is in a reasonable accordance with the experimental data (IC50 3.1 µM. Indinavir, saquinavir, and ritonavir have close binding affinity to NFV (ΔG =−9.0, −8.6, and −8.5 kcal/mol, respectively. Per-residue interaction energy decomposition analysis showed that hydrophobic interaction (most importantly with Val534 and Met602 played the most predominant role in drug binding. To further validate the docking outcome, 5 ns molecular dynamic simulations were performed in order to assess the stability of the docked complexes. To our knowledge, this is the first account of detailed computational investigations aimed to investigate the potential anticancer activity and the binding

  8. FDA (Food and Drug Administration) compliance program guidance manual and updates (FY 86). Section 4. Medical and radiological devices. Irregular report

    International Nuclear Information System (INIS)

    1986-01-01

    The FDA Compliance Program Guidance Manual provides a system for issuing and filing program plans and instructions directed to Food and Drug Administration Field operations for project implementation. Section IV provides those chapters of the Compliance Program Guidance Manual which pertain to the areas of medical and radiological devices. Some of the areas of coverage include laser and sunlamp standards inspections, compliance testing of various radiation-emitting products such as television receivers and microwave ovens, emergency response planning and policy, premarket approval and device manufacturers inspections, device problem reporting, sterilization of devices, and consumer education programs on medical and radiological devices

  9. A GREAT search for Deuterium in Comets

    Science.gov (United States)

    Mumma, Michael

    2013-10-01

    Comets are understood to be the most pristine bodies in the Solar System. Their compositions reflect the chemical state of materials at the very earliest evolutionary stages of the protosolar nebula and, as such, they provide detailed insight into the physical and chemical processes operating in planet-forming disks. Isotopic fractionation ratios of the molecular ices in the nucleus are regarded as signatures of formation processes. These ratios provide unique information on the natal heritage of those ices, and can also test the proposal that Earth's water and other volatiles were delivered by cometary bombardment. Measurement of deuterium fractionation ratios is thus a major goal in contemporary cometary science and the D/H ratio of water - the dominant volatile in comets - holds great promise for testing the formation history of cometary matter. The D/H ratio in cometary water has been measured in only eight comets. Seven were from the Oort Cloud reservoir and the D/H ratio was about twice that of the Earth's oceans. However, the recent Herschel measurement of HDO/H2O in 103P/Hartley-2 (the first from the Kuiper Belt) was consistent with exogenous delivery of Earth's water by comets. Outstanding questions remain: are cometary HDO/H2O ratios consistent with current theories of nebular chemical evolution or with an interstellar origin? Does the HDO/H2O ratio vary substantially among comet populations? Hartley-2 is the only Kuiper Belt comet with measured HDO/H2O, are there comets with similar ratios in the Oort cloud? These questions can only be addressed by measuring HDO/H2O ratios in many more suitable bright comets. We therefore propose to measure the D/H ratio in water in a suitable target-of-opportunity comet by performing observations of HDO and OH with the GREAT spectrometer on SOFIA. A multi-wavelength, ground-based observing campaign will also be conducted in support of the airborne observations.

  10. Great Plains Wind Energy Transmission Development Project

    Energy Technology Data Exchange (ETDEWEB)

    Brad G. Stevens, P.E.; Troy K. Simonsen; Kerryanne M. Leroux

    2012-06-09

    In fiscal year 2005, the Energy & Environmental Research Center (EERC) received funding from the U.S. Department of Energy (DOE) to undertake a broad array of tasks to either directly or indirectly address the barriers that faced much of the Great Plains states and their efforts to produce and transmit wind energy at the time. This program, entitled Great Plains Wind Energy Transmission Development Project, was focused on the central goal of stimulating wind energy development through expansion of new transmission capacity or development of new wind energy capacity through alternative market development. The original task structure was as follows: Task 1 - Regional Renewable Credit Tracking System (later rescoped to Small Wind Turbine Training Center); Task 2 - Multistate Transmission Collaborative; Task 3 - Wind Energy Forecasting System; and Task 4 - Analysis of the Long-Term Role of Hydrogen in the Region. As carried out, Task 1 involved the creation of the Small Wind Turbine Training Center (SWTTC). The SWTTC, located Grand Forks, North Dakota, consists of a single wind turbine, the Endurance S-250, on a 105-foot tilt-up guyed tower. The S-250 is connected to the electrical grid on the 'load side' of the electric meter, and the power produced by the wind turbine is consumed locally on the property. Establishment of the SWTTC will allow EERC personnel to provide educational opportunities to a wide range of participants, including grade school through college-level students and the general public. In addition, the facility will allow the EERC to provide technical training workshops related to the installation, operation, and maintenance of small wind turbines. In addition, under Task 1, the EERC hosted two small wind turbine workshops on May 18, 2010, and March 8, 2011, at the EERC in Grand Forks, North Dakota. Task 2 involved the EERC cosponsoring and aiding in the planning of three transmission workshops in the midwest and western regions. Under Task

  11. Utilization of a Marketing Strategy at Naval Regional Medical Center Great Lakes, Great Lakes, Illinois

    Science.gov (United States)

    1983-06-01

    22 Analysis of the Mare.....................22 Development of the Marketing Mix .. .......... 29 A Marketing Mix --Recommendations...problem. Marketing strategy, marketing mix and ultimately the marketing orientation will allow hospitals to persevere and possibly thrive in a somewhat...market are currently being met at Naval Regional Medical Center Great Lakes. The fourth objective is to demonstrate an appropriate marketing mix for

  12. Great Basin Factsheet Series 2016 - Information and tools to restore and conserve Great Basin ecosystems

    Science.gov (United States)

    Jeanne C. Chambers

    2016-01-01

    Land managers are responsible for developing effective strategies for conserving and restoring Great Basin ecosystems in the face of invasive species, conifer expansion, and altered fire regimes. A warming climate is magnifying the effects of these threats and adding urgency to implementation of management practices that will maintain or improve ecosystem...

  13. Critical metals in the great transformation

    International Nuclear Information System (INIS)

    Exner, Andreas; Held, Martin; Kuemmerer, Klaus

    2016-01-01

    The book broadens the view on the short-term availability of critical metals to the fundamental question: critical for whom? The authors take all stakeholders into consideration and deal with geological, chemical, technical, economic and social aspects as well as questions of recycling. They also address questions of good life and mining from the perspective of countries of the South, questions of resource policy and justice. A further topic is the UN deep-sea mining regime and its perspectives on how unconventional ore from the deep-sea can be won in the future. Critical metals are classified into the overlapping context of the upcoming Great Transformation. The book examines in particular the fundamental importance of the material prerequisites of the energy transition and the energetic prerequisites of the material turnaround as well as the digitization. This shows that not only rare earths are critical, but also industrial metals such as copper. Resource policy aims, among other things, to secure primary supplies of technology metals, resource efficiency, recycling and substitution of critical substances. Despite the first successes, the dynamics are still unbroken in the direction of an increasing dissipation of valuable critical metals. What is needed is a rapid reversal with the aim of no longer consuming critical metals on a grand scale, but of using them wisely. [de

  14. Natural Selection in the Great Apes.

    Science.gov (United States)

    Cagan, Alexander; Theunert, Christoph; Laayouni, Hafid; Santpere, Gabriel; Pybus, Marc; Casals, Ferran; Prüfer, Kay; Navarro, Arcadi; Marques-Bonet, Tomas; Bertranpetit, Jaume; Andrés, Aida M

    2016-12-01

    Natural selection is crucial for the adaptation of populations to their environments. Here, we present the first global study of natural selection in the Hominidae (humans and great apes) based on genome-wide information from population samples representing all extant species (including most subspecies). Combining several neutrality tests we create a multi-species map of signatures of natural selection covering all major types of natural selection. We find that the estimated efficiency of both purifying and positive selection varies between species and is significantly correlated with their long-term effective population size. Thus, even the modest differences in population size among the closely related Hominidae lineages have resulted in differences in their ability to remove deleterious alleles and to adapt to changing environments. Most signatures of balancing and positive selection are species-specific, with signatures of balancing selection more often being shared among species. We also identify loci with evidence of positive selection across several lineages. Notably, we detect signatures of positive selection in several genes related to brain function, anatomy, diet and immune processes. Our results contribute to a better understanding of human evolution by putting the evidence of natural selection in humans within its larger evolutionary context. The global map of natural selection in our closest living relatives is available as an interactive browser at http://tinyurl.com/nf8qmzh. © The Author 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  15. Incidental oligotrophication of North American Great Lakes.

    Science.gov (United States)

    Evans, Mary Anne; Fahnenstiel, Gary; Scavia, Donald

    2011-04-15

    Phytoplankton production is an important factor in determining both ecosystem stability and the provision of ecosystem goods and services. The expansive and economically important North American Great Lakes are subjected to multiple stressors and understanding their responses to those stresses is important for understanding system-wide ecological controls. Here we show gradual increases in spring silica concentration (an indicator of decreasing growth of the dominant diatoms) in all basins of Lakes Michigan and Huron (USA and Canadian waters) between 1983 and 2008. These changes indicate the lakes have undergone gradual oligotrophication coincident with and anticipated by nutrient management implementation. Slow declines in seasonal drawdown of silica (proxy for seasonal phytoplankton production) also occurred, until recent years, when lake-wide responses were punctuated by abrupt decreases, putting them in the range of oligotrophic Lake Superior. The timing of these dramatic production drops is coincident with expansion of populations of invasive dreissenid mussels, particularly quagga mussels, in each basin. The combined effect of nutrient mitigation and invasive species expansion demonstrates the challenges facing large-scale ecosystems and suggest the need for new management regimes for large ecosystems.

  16. What makes CERN’s research great

    CERN Multimedia

    2016-01-01

    As a newcomer to CERN, I find myself both honoured and humbled to have had the role of Research Director confided in me for five years.    My career has taken me from Hamburg to Stanford and Heidelberg and back to Hamburg, and although this is the first time I have been based at CERN, it is not my first involvement with the Laboratory. I was a member of the OPAL collaboration in the late 1980s, and chaired the LHCC from 2011 to 2014. In addition, over the past ten years I have enjoyed contacts with many colleagues at CERN, via joint European programmes and particularly in discussions on linear colliders. In this, my first message to personnel, I’d like to set out my view of what makes CERN’s research great, and where I’d like to see things when I step down at the end of 2020. First and foremost, I have to refer to the many excellent experts at CERN and to the thousands of users of our facilities. Their ideas are the backbone of all...

  17. [One year after the Great Tohoku Disaster].

    Science.gov (United States)

    Aoki, Masashi

    2012-01-01

    After the great earthquake of March 11, 2011, at least seven hospitals with 723 beds along the Miyagi Prefecture northern coastline were so devastated they could no longer function, leaving only several available hospitals. The two crucial issues thus became maintaining communications and regional transport. Phones and wireless were knocked out in most hospitals and areas. Many of the severe cases had to be brought to the Tohoku University Hospital at Sendai from the above the hospitals. Tohoku University Hospital and other medical facilities in the Tohoku district were in a terrible crisis of electricity shortage. It was a critical situation, particularly for patients with amyotrophic lateral sclerosis requiring artificial ventilation. We should hurry to submit a guideline for medical transportation for patients with neuromuscular diseases requiring artificial ventilation. We also should research the disaster medicine in the field of neurology, and prevent the neurological disease progressing after the earthquake. A large number of hospitals in coastal areas suffered devastating damage. We do not think it is feasible or even reasonable to restore such hospitals to what they were before the disaster. We started Tohoku Medical Megabank Organization as a disaster recovery model for revitalizing the areas reported to have scarce medical services. The project provides supports to local medical services, constructs a community coalition for medical information, sets up a biobank based on large-scale cohort studies, and provides educational training to produce highly specialized medical practitioners.

  18. Material Stock Demographics: Cars in Great Britain.

    Science.gov (United States)

    Cabrera Serrenho, André; Allwood, Julian M

    2016-03-15

    Recent literature on material flow analysis has been focused on quantitative characterization of past material flows. Fewer analyses exist on past and prospective quantification of stocks of materials in-use. Some of these analyses explore the composition of products' stocks, but a focus on the characterization of material stocks and its relation with service delivery is often neglected. We propose the use of the methods of human demography to characterize material stocks, defined herein as stock demographics, exploring the insights that this approach could provide for the sustainable management of materials. We exemplify an application of stock demographics by characterizing the composition and service delivery of iron, steel, and aluminum stocks of cars in Great Britain, 2002-2012. The results show that in this period the stock has become heavier, it is traveling less, and it is idle for more time. The visualization of material stocks' dynamics demonstrates the pace of product replacement as a function of its usefulness and enables the formulation of policy interventions and the exploration of future trends.

  19. Regional Personality Differences in Great Britain

    Science.gov (United States)

    Rentfrow, Peter J.; Jokela, Markus; Lamb, Michael E.

    2015-01-01

    Recent investigations indicate that personality traits are unevenly distributed geographically, with some traits being more prevalent in certain places than in others. The geographical distributions of personality traits are associated with a range of important political, economic, social, and health outcomes. The majority of research on this subject has focused on the geographical distributions and macro-level correlates of personality across nations or regions of the United States. The aim of the present investigation was to replicate and extend that past work by examining regional personality differences in Great Britain. Using a sample of nearly 400,000 British residents, we mapped the geographical distributions of the Big Five Personality traits across 380 Local Authority Districts and examined the associations with important political, economic, social, and health outcomes. The results revealed distinct geographical clusters, with neighboring regions displaying similar personality characteristics, and robust associations with the macro-level outcome variables. Overall, the patterns of results were similar to findings from past research. PMID:25803819

  20. A psychoanalytic study of Alexander the Great.

    Science.gov (United States)

    Thomas, K R

    1995-12-01

    The purpose of this paper was to demonstrate how Freudian concepts such as the Oedipus complex, castration anxiety, fear of loss of love, the psychosexual stages of development, and the tripartite structure of personality can be used to understand the life and achievements of Alexander the Great. To accomplish this purpose, specific incidents, myths, and relationships in Alexander's life were analyzed from a Freudian psychoanalytic perspective. Green (1991), in his recent biography of Alexander, has questioned the merit of using Freudian concepts to understand Alexander's character. In fact, he stated specifically: If he (Alexander) had any kind of Oedipus complex it came in a poor second to the burning dynastic ambition which Olympias so sedulously fostered in him; those who insist on his psychological motivation would do better to take Adler as their mentor than Freud (p.56). Later, in the concluding section of his book, Green (1991, pp. 486-487) discounted Freudian interpretations of Alexander's distaste for sex, the rumors of his homosexual liaisons, his partiality for middle-aged or elderly ladies, and the systematic domination of his early years by Olympias as little more than the projected fears and desires of the interpreters. And again, an Adlerian power-complex paradigm was suggested as the preferable theoretical framework to use. Green's argument was based primarily on an exchange, reported originally by Plutarch, which took place between Alexander and Philip prior to Alexander's tutorship with Aristotle. Purportedly, Philip enjoined his son to study hard and pay close attention to all Aristotle said "so that you may not do a great many things of the sort that I am sorry I have done." At this point, Alexander "somewhat pertly" took Philip to task "because he was having children by other women besides his wife." Philip's reply was: "Well then, if you have many competitors for the kingdom, prove yourself honorable and good, so that you may obtain the

  1. Climate change and the Great Barrier Reef

    International Nuclear Information System (INIS)

    Johnson, Johanna; Marshall, Paul

    2007-01-01

    Full text: Full text: Climate change is now recognised as the greatest long-term threat to the Great Barrier Reef (GBR). Managers face a future in which the impacts of climate change on tropical marine ecosystems are becoming increasingly frequent and severe. Further degradation is inevitable as the climate continues to change but the extent of the decline will depend on the rate and magnitude of climate change and the resilience of the ecosystem. Changes to the ecosystem have implications for the industries and regional communities that depend on the GBR. Climate projections for the GBR region include increasing air and sea temperatures, ocean acidification, nutrient enrichment (via changes in rainfall), altered light levels, more extreme weather events, changes to ocean circulation and sea level rise. Impacts have already been observed, with severe coral bleaching events in 1998 and 2002, and mass mortalities of seabirds linked to anomalously warm summer conditions. Climate change also poses significant threats to the industries and communities that depend on the GBR ecosystem, both directly and indirectly through loss of natural resources; industries such as recreational and commercial fishing, and tourism, which contributes to a regional tourism industry worth $6.1 billion (Access Economics 2005). A vulnerability assessment undertaken by leading experts in climate and marine science identified climate sensitivities for GBR species, habitats, key processes, GBR industries and communities (Johnson and Marshall 2007). This information has been used to develop a Climate Change Action Plan for the GBR. The Action Plan is a five-year program aimed at facilitating targeted science, building a resilient ecosystem, assisting adaptation of industries and communities, and reducing climate footprints. The Action Plan identifies strategies to review current management arrangements and raise awareness of the issue in order to work towards a resilient ecosystem. Integral to

  2. Natural and artificial radioactivity in Great Bratislava

    International Nuclear Information System (INIS)

    Lanc, J.

    1997-01-01

    The results of the aviation measurement of the gamma-radiation are presented in the form of the maps of iso-lines of the concentration of the natural radioactive elements (potassium, uranium, thorium) and artificial radionuclides (cesium-137, cesium-134). From the obtained dates the maps of dose rate of the gamma-radiation in the air are calculated, of the dose equivalent rate and the map of the fraction of the dose equivalent rate from the natural elements potassium, uranium, thorium. The natural radioactivity of the minerals in the Great Bratislava region, especially for the extreme low values of the contain of the thorium, does not amount the average values of the radioactivity of the Earth crust. The area activity of cesium-137 are in the range 2 - 10 kBq.m -2 and cesium-134 is 1 - 2.5 kBq.m -2 . From the point of view of the summary level of the external irradiation from the Earth surface the measured zone as relative even is evaluated, in the range 10-100 nSv.h -1 . The total average level of the dose rate of the external irradiation of man (inclusively from the cosmic radiation 40-50 nSv.h -1 ) in the conditions of Bratislava is 100 nSv.h -1 . The contribution of external component of the irradiation is 40-100 nSv.h -1 (0.1-0.3 mSv.y -1 ). The dose equivalent commitment of internal component from the cesium-137 is for the all age category of the population under the level negligible risk 0.01 mSv.y -1 [sk

  3. Abdominal pain endpoints currently recommended by the FDA and EMA for adult patients with irritable bowel syndrome may not be reliable in children.

    Science.gov (United States)

    Saps, M; Lavigne, J V

    2015-06-01

    The Food and Drug Administration (FDA) recommended ≥30% decrease on patient-reported outcomes for pain be considered clinically significant in clinical trials for adults with irritable bowel syndrome. This percent change approach may not be appropriate for children. We compared three alternate approaches to determining clinically significant reductions in pain among children. 80 children with functional abdominal pain participated in a study of the efficacy of amitriptyline. Endpoints included patient-reported estimates of feeling better, and pain Visual Analog Scale (VAS). The minimum clinically important difference in pain report was calculated as (i) mean change in VAS score for children reporting being 'better'; (ii) percent changes in pain (≥30% and ≥50%) on the VAS; and (iii) statistically reliable changes on the VAS for 68% and 95% confidence intervals. There was poor agreement between the three approaches. 43.6% of the children who met the FDA ≥30% criterion for clinically significant change did not achieve a reliable level of improvement (95% confidence interval). Children's self-reported ratings of being better may not be statistically reliable. A combined approach in which children must report improvement as better and achieve a statistically significant change may be more appropriate for outcomes in clinical trials. © 2015 John Wiley & Sons Ltd.

  4. Investigation of the binding free energies of FDA approved drugs against subtype B and C-SA HIV PR: ONIOM approach.

    Science.gov (United States)

    Sanusi, Z K; Govender, T; Maguire, G E M; Maseko, S B; Lin, J; Kruger, H G; Honarparvar, B

    2017-09-01

    Human immune virus subtype C is the most widely spread HIV subtype in Sub-Sahara Africa and South Africa. A profound structural insight on finding potential lead compounds is therefore necessary for drug discovery. The focus of this study is to rationalize the nine Food and Drugs Administration (FDA) HIV antiviral drugs complexed to subtype B and C-SA PR using ONIOM approach. To achieve this, an integrated two-layered ONIOM model was used to optimize the geometrics of the FDA approved HIV-1 PR inhibitors for subtype B. In our hybrid ONIOM model, the HIV-1 PR inhibitors as well as the ASP 25/25' catalytic active residues were treated at high level quantum mechanics (QM) theory using B3LYP/6-31G(d), and the remaining HIV PR residues were considered using the AMBER force field. The experimental binding energies of the PR inhibitors were compared to the ONIOM calculated results. The theoretical binding free energies (?G bind ) for subtype B follow a similar trend to the experimental results, with one exemption. The computational model was less suitable for C-SA PR. Analysis of the results provided valuable information about the shortcomings of this approach. Future studies will focus on the improvement of the computational model by considering explicit water molecules in the active pocket. We believe that this approach has the potential to provide much improved binding energies for complex enzyme drug interactions. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. The use of the United States FDA programs as a strategy to advance the development of drug products for neglected tropical diseases.

    Science.gov (United States)

    Sachs-Barrable, Kristina; Conway, Jocelyn; Gershkovich, Pavel; Ibrahim, Fady; Wasan, Kishor M

    2014-11-01

    Neglected tropical diseases (NTDs) are infections which are endemic in poor populations in lower- and middle-income countries (LMIC). Approximately one billion people have now or are at risk of getting an NTD and yet less than 5% of research dollars are focused on providing treatments and prevention of these highly debilitating and deadly conditions. The United States Food and Drug Administration (FDA) Orphan Drug Designation program (ODDP) provides orphan status to drugs and biologics, defined as those intended for the safe and effective treatment, diagnosis or prevention of rare diseases and/or disorders that affect fewer than 200 000 people in the United States, or that affect more than 200 000 persons but are not expected to recover the costs of developing and marketing a treatment drug. These regulations have led to the translation of rare disease knowledge into innovative rare disease therapies. The FDA Guidance for Industry on developing drugs for the treatment and prevention of NTDs describes the following regulatory strategies: Orphan Product Designation, Fast Track Designation, Priority Review Designation, Accelerated Approval and Tropical Disease Priority Review Voucher. This paper will discuss how these regulations and especially the ODDP can improve the clinical development and accessibility of drug products for NTDs.

  6. Zika antiviral chemotherapy: identification of drugs and promising starting points for drug discovery from an FDA-approved library [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Bruno S. Pascoalino

    2016-10-01

    Full Text Available Background The recent epidemics of Zika virus (ZIKV implicated it as the cause of serious and potentially lethal congenital conditions such microcephaly and other central nervous system defects, as well as the development of the Guillain-Barré syndrome in otherwise healthy patients. Recent findings showed that anti-Dengue antibodies are capable of amplifying ZIKV infection by a mechanism similar to antibody-dependent enhancement, increasing the severity of the disease. This scenario becomes potentially catastrophic when the global burden of Dengue and the advent of the newly approved anti-Dengue vaccines in the near future are taken into account. Thus, antiviral chemotherapy should be pursued as a priority strategy to control the spread of the virus and prevent the complications associated with Zika. Methods Here we describe a fast and reliable cell-based, high-content screening assay for discovery of anti-ZIKV compounds. This methodology has been used to screen the National Institute of Health Clinical Collection compound library, a small collection of FDA-approved drugs. Results and conclusion From 725 FDA-approved compounds triaged, 29 (4% were found to have anti-Zika virus activity, of which 22 had confirmed (76% of confirmation by dose-response curves. Five candidates presented selective activity against ZIKV infection and replication in a human cell line. These hits have abroad spectrum of chemotypes and therapeutic uses, offering valuable opportunities for selection of leads for antiviral drug discovery.

  7. Features of Jupiter's Great Red Spot

    Science.gov (United States)

    1996-01-01

    This montage features activity in the turbulent region of Jupiter's Great Red Spot (GRS). Four sets of images of the GRS were taken through various filters of the Galileo imaging system over an 11.5 hour period on 26 June, 1996 Universal Time. The sequence was designed to reveal cloud motions. The top and bottom frames on the left are of the same area, northeast of the GRS, viewed through the methane (732 nm) filter but about 70 minutes apart. The top left and top middle frames are of the same area and at the same time, but the top middle frame is taken at a wavelength (886 nm) where methane absorbs more strongly. (Only high clouds can reflect sunlight in this wavelength.) Brightness differences are caused by the different depths of features in the two images. The bottom middle frame shows reflected light at a wavelength (757 nm) where there are essentially no absorbers in the Jovian atmosphere. The white spot is to the northwest of the GRS; its appearance at different wavelengths suggests that the brightest elements are 30 km higher than the surrounding clouds. The top and bottom frames on the right, taken nine hours apart and in the violet (415 nm) filter, show the time evolution of an atmospheric wave northeast of the GRS. Visible crests in the top right frame are much less apparent 9 hours later in the bottom right frame. The misalignment of the north-south wave crests with the observed northwestward local wind may indicate a shift in wind direction (wind shear) with height. The areas within the dark lines are 'truth windows' or sections of the images which were transmitted to Earth using less data compression. Each of the six squares covers 4.8 degrees of latitude and longitude (about 6000 square kilometers). North is at the top of each frame.Launched in October 1989, Galileo entered orbit around Jupiter on December 7, 1995. The spacecraft's mission is to conduct detailed studies of the giant planet, its largest moons and the Jovian magnetic environment. The

  8. Ernst Chain: a great man of science.

    Science.gov (United States)

    Kardos, Nelson; Demain, Arnold L

    2013-08-01

    resources were scarce in postwar Britain, the British government declined the project. Chain then took a post in 1948 at Rome's Instituto Superiore di Sanitá, establishing a new biochemistry department with a pilot plant. During that period, his department developed important new antibiotics (including the first semisynthetic antibiotics) as well as improved technological processes to produce a wide variety of important microbial metabolites that are still in wide use today. Chain was also responsible for helping several countries to start up a modern penicillin industry following World War II, including the Soviet Union and the People's Republic of China. In 1964, Chain returned to England to establish a new biochemistry department and industrial scale fermentation pilot plant at Imperial College in London. Imperial College became the preeminent biochemical department in Europe. Chain was also a pioneer in changing the relationship between government, private universities, and private industry for collaboration and funding to support medical research. Ernst Chain has left a lasting impact as a great scientist and internationalist.

  9. An insight to the molecular interactions of the FDA approved HIV PR drugs against L38L↑N↑L PR mutant

    Science.gov (United States)

    Sanusi, Zainab K.; Govender, Thavendran; Maguire, Glenn E. M.; Maseko, Sibusiso B.; Lin, Johnson; Kruger, Hendrik G.; Honarparvar, Bahareh

    2018-03-01

    The aspartate protease of the human immune deficiency type-1 virus (HIV-1) has become a crucial antiviral target in which many useful antiretroviral inhibitors have been developed. However, it seems the emergence of new HIV-1 PR mutations enhances drug resistance, hence, the available FDA approved drugs show less activity towards the protease. A mutation and insertion designated L38L↑N↑L PR was recently reported from subtype of C-SA HIV-1. An integrated two-layered ONIOM (QM:MM) method was employed in this study to examine the binding affinities of the nine HIV PR inhibitors against this mutant. The computed binding free energies as well as experimental data revealed a reduced inhibitory activity towards the L38L↑N↑L PR in comparison with subtype C-SA HIV-1 PR. This observation suggests that the insertion and mutations significantly affect the binding affinities or characteristics of the HIV PIs and/or parent PR. The same trend for the computational binding free energies was observed for eight of the nine inhibitors with respect to the experimental binding free energies. The outcome of this study shows that ONIOM method can be used as a reliable computational approach to rationalize lead compounds against specific targets. The nature of the intermolecular interactions in terms of the host-guest hydrogen bond interactions is discussed using the atoms in molecules (AIM) analysis. Natural bond orbital analysis was also used to determine the extent of charge transfer between the QM region of the L38L↑N↑L PR enzyme and FDA approved drugs. AIM analysis showed that the interaction between the QM region of the L38L↑N↑L PR and FDA approved drugs are electrostatic dominant, the bond stability computed from the NBO analysis supports the results from the AIM application. Future studies will focus on the improvement of the computational model by considering explicit water molecules in the active pocket. We believe that this approach has the potential to provide

  10. An insight to the molecular interactions of the FDA approved HIV PR drugs against L38L↑N↑L PR mutant.

    Science.gov (United States)

    Sanusi, Zainab K; Govender, Thavendran; Maguire, Glenn E M; Maseko, Sibusiso B; Lin, Johnson; Kruger, Hendrik G; Honarparvar, Bahareh

    2018-03-01

    The aspartate protease of the human immune deficiency type-1 virus (HIV-1) has become a crucial antiviral target in which many useful antiretroviral inhibitors have been developed. However, it seems the emergence of new HIV-1 PR mutations enhances drug resistance, hence, the available FDA approved drugs show less activity towards the protease. A mutation and insertion designated L38L↑N↑L PR was recently reported from subtype of C-SA HIV-1. An integrated two-layered ONIOM (QM:MM) method was employed in this study to examine the binding affinities of the nine HIV PR inhibitors against this mutant. The computed binding free energies as well as experimental data revealed a reduced inhibitory activity towards the L38L↑N↑L PR in comparison with subtype C-SA HIV-1 PR. This observation suggests that the insertion and mutations significantly affect the binding affinities or characteristics of the HIV PIs and/or parent PR. The same trend for the computational binding free energies was observed for eight of the nine inhibitors with respect to the experimental binding free energies. The outcome of this study shows that ONIOM method can be used as a reliable computational approach to rationalize lead compounds against specific targets. The nature of the intermolecular interactions in terms of the host-guest hydrogen bond interactions is discussed using the atoms in molecules (AIM) analysis. Natural bond orbital analysis was also used to determine the extent of charge transfer between the QM region of the L38L↑N↑L PR enzyme and FDA approved drugs. AIM analysis showed that the interaction between the QM region of the L38L↑N↑L PR and FDA approved drugs are electrostatic dominant, the bond stability computed from the NBO analysis supports the results from the AIM application. Future studies will focus on the improvement of the computational model by considering explicit water molecules in the active pocket. We believe that this approach has the potential to

  11. Lessons learned from a great master!

    Directory of Open Access Journals (Sweden)

    Wagner Seixas da Silva

    2015-06-01

    critical thinking as early as the their first semester was something revolutionary and very attractive. This teaching strategy was so well accepted that was common to find either students who had already approved the course of Biochemistry or students attending advanced semesters returning to attend the class and to see the beloved teacher once again! In class it was possible to both discuss biochemistry and learn history! To have the classroom invaded by "actors" playing the judgment and beheading of Antoine-Laurent Lavoisier over 100 years after his death while discussing his experiments caused a whirlwind of emotions in the students. This was important to sensitize them to the challenges experienced by renowned scientists who paid with their lives to defend their ideas. Thus, students became protagonists of story and the biochemistry classes more interesting and challenging. This challenge was shared by the "actors", who actually were students of the Biological Chemistry program sharing the classroom with the great master. For these graduate students, it was an experience where they raised awareness of the importance of dedication to the teaching of Sciences.Prof. de Meis’ speech where he stated no one owns the truth or all knowledge was another point closing the relationship with the undergraduate students. In the modern world it is nearly impossible to keep yourself up to date, so we ended up specializing in something. De Meis used to cause some perplexity among the students by showing a picture with all copies of a single reputable scientific journal in the biochemistry field published over a year. Surprisingly, this stack of magazines was 1.5 meters tall! Could you imagine that all recent knowledge in biochemistry is compiled in few pages of a textbook? de Meis, then, revealed that we do not know everything, but we do need to learn how to interpret new facts, a new experiment, a new concept, a new technique, a new discovery. We need to develop critical thinking to

  12. Considering the Future of Pharmaceutical Promotions in Social Media; Comment on “Trouble Spots in Online Direct-to-Consumer Prescription Drug Promotion: A Content Analysis of FDA Warning Letters”

    Directory of Open Access Journals (Sweden)

    Francesca Renee Dillman Carpentier

    2016-04-01

    Full Text Available This commentary explores the implications of increased social media marketing by drug manufacturers, based on findings in Hyosun Kim’s article of the major themes in recent Food and Drug Administration (FDA warning letters and notices of violation regarding online direct-to-consumer promotions of pharmaceuticals. Kim’s rigorous analysis of FDA letters over a 10-year span highlights a relative abundance of regulatory action toward marketer-controlled websites and sponsored advertisements, compared to branded and unbranded social media messaging. However, social media marketing efforts are increasing, as is FDA attention to these efforts. This commentary explores recent developments and continuing challenges in the FDA’s attempts to provide guidance and define pharmaceutical company accountability in marketer-controlled and -uncontrolled claims disseminated through social media.

  13. Statin-associated muscular and renal adverse events: data mining of the public version of the FDA adverse event reporting system.

    Directory of Open Access Journals (Sweden)

    Toshiyuki Sakaeda

    Full Text Available OBJECTIVE: Adverse event reports (AERs submitted to the US Food and Drug Administration (FDA were reviewed to assess the muscular and renal adverse events induced by the administration of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA reductase inhibitors (statins and to attempt to determine the rank-order of the association. METHODS: After a revision of arbitrary drug names and the deletion of duplicated submissions, AERs involving pravastatin, simvastatin, atorvastatin, or rosuvastatin were analyzed. Authorized pharmacovigilance tools were used for quantitative detection of signals, i.e., drug-associated adverse events, including the proportional reporting ratio, the reporting odds ratio, the information component given by a Bayesian confidence propagation neural network, and the empirical Bayes geometric mean. Myalgia, rhabdomyolysis and an increase in creatine phosphokinase level were focused on as the muscular adverse events, and acute renal failure, non-acute renal failure, and an increase in blood creatinine level as the renal adverse events. RESULTS: Based on 1,644,220 AERs from 2004 to 2009, signals were detected for 4 statins with respect to myalgia, rhabdomyolysis, and an increase in creatine phosphokinase level, but these signals were stronger for rosuvastatin than pravastatin and atorvastatin. Signals were also detected for acute renal failure, though in the case of atorvastatin, the association was marginal, and furthermore, a signal was not detected for non-acute renal failure or for an increase in blood creatinine level. CONCLUSIONS: Data mining of the FDA's adverse event reporting system, AERS, is useful for examining statin-associated muscular and renal adverse events. The data strongly suggest the necessity of well-organized clinical studies with respect to statin-associated adverse events.

  14. Intra-articular Autologous Conditioned Plasma Injections Provide Safe and Efficacious Treatment for Knee Osteoarthritis: An FDA-Sanctioned, Randomized, Double-blind, Placebo-controlled Clinical Trial.

    Science.gov (United States)

    Smith, Patrick A

    2016-04-01

    Platelet-rich plasma (PRP) injections have become an intriguing treatment option for osteoarthritis (OA), particularly OA of the knee. Despite the plethora of PRP-related citations, there is a paucity of high-level evidence that is comparable, cohort specific, dose controlled, injection protocol controlled, and double-blinded. To determine the safety and efficacy of leukocyte-poor PRP autologous conditioned plasma (ACP) for knee OA treatment through a feasibility trial regulated by the US Food and Drug Administration (FDA). Randomized controlled trial; Level of evidence, 1. In accordance with FDA protocol, patient selection was based on strict inclusion/exclusion criteria; 114 patients were screened, and 30 were ultimately included in the study. These patients were randomized to receive either ACP (n = 15) or saline placebo (n = 15) for a series of 3 weekly injections. Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores served as the primary efficacy outcome measure. Patients were followed for 1 year. No adverse events were reported for ACP administration. Furthermore, the results demonstrated no statistically significant difference in baseline WOMAC scores between the 2 groups. However, in the ACP group, WOMAC scores at 1 week were significantly decreased compared with baseline scores, and the scores for this group remained significantly lower throughout the study duration. At the study conclusion (12 months), subjects in the ACP group had improved their overall WOMAC scores by 78% from their baseline score, compared with 7% for the placebo group. ACP is safe and provides quantifiable benefits for pain relief and functional improvement with regard to knee OA. No adverse events were reported for ACP administration. After 1 year, WOMAC scores for the ACP subjects had improved by 78% from their baseline score, whereas scores for the placebo control group had improved by only 7%. Other joints affected with OA may also benefit from this

  15. Statin-associated muscular and renal adverse events: data mining of the public version of the FDA adverse event reporting system.

    Science.gov (United States)

    Sakaeda, Toshiyuki; Kadoyama, Kaori; Okuno, Yasushi

    2011-01-01

    Adverse event reports (AERs) submitted to the US Food and Drug Administration (FDA) were reviewed to assess the muscular and renal adverse events induced by the administration of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) and to attempt to determine the rank-order of the association. After a revision of arbitrary drug names and the deletion of duplicated submissions, AERs involving pravastatin, simvastatin, atorvastatin, or rosuvastatin were analyzed. Authorized pharmacovigilance tools were used for quantitative detection of signals, i.e., drug-associated adverse events, including the proportional reporting ratio, the reporting odds ratio, the information component given by a Bayesian confidence propagation neural network, and the empirical Bayes geometric mean. Myalgia, rhabdomyolysis and an increase in creatine phosphokinase level were focused on as the muscular adverse events, and acute renal failure, non-acute renal failure, and an increase in blood creatinine level as the renal adverse events. Based on 1,644,220 AERs from 2004 to 2009, signals were detected for 4 statins with respect to myalgia, rhabdomyolysis, and an increase in creatine phosphokinase level, but these signals were stronger for rosuvastatin than pravastatin and atorvastatin. Signals were also detected for acute renal failure, though in the case of atorvastatin, the association was marginal, and furthermore, a signal was not detected for non-acute renal failure or for an increase in blood creatinine level. Data mining of the FDA's adverse event reporting system, AERS, is useful for examining statin-associated muscular and renal adverse events. The data strongly suggest the necessity of well-organized clinical studies with respect to statin-associated adverse events.

  16. Antipsychotics, glycemic disorders, and life-threatening diabetic events: a Bayesian data-mining analysis of the FDA adverse event reporting system (1968-2004).

    Science.gov (United States)

    DuMouchel, William; Fram, David; Yang, Xionghu; Mahmoud, Ramy A; Grogg, Amy L; Engelhart, Luella; Ramaswamy, Krishnan

    2008-01-01

    This analysis compared diabetes-related adverse events associated with use of different antipsychotic agents. A disproportionality analysis of the US Food and Drug Administration (FDA) Adverse Event Reporting System (AERS) was performed. Data from the FDA postmarketing AERS database (1968 through first quarter 2004) were evaluated. Drugs studied included aripiprazole, clozapine, haloperidol, olanzapine, quetiapine, risperidone, and ziprasidone. Fourteen Medical Dictionary for Regulatory Activities (MedDRA) Primary Terms (MPTs) were chosen to identify diabetes-related adverse events; 3 groupings into higher-level descriptive categories were also studied. Three methods of measuring drug-event associations were used: proportional reporting ratio, the empirical Bayes data-mining algorithm known as the Multi-Item Gamma Poisson Shrinker, and logistic regression (LR) analysis. Quantitative measures of association strength, with corresponding confidence intervals, between drugs and specified adverse events were computed and graphed. Some of the LR analyses were repeated separately for reports from patients under and over 45 years of age. Differences in association strength were declared statistically significant if the corresponding 90% confidence intervals did not overlap. Association with various glycemic events differed for different drugs. On average, the rankings of association strength agreed with the following ordering: low association, ziprasidone, aripiprazole, haloperidol, and risperidone; medium association, quetiapine; and strong association, clozapine and olanzapine. The median rank correlation between the above ordering and the 17 sets of LR coefficients (1 set for each glycemic event) was 93%. Many of the disproportionality measures were significantly different across drugs, and ratios of disproportionality factors of 5 or more were frequently observed. There are consistent and substantial differences between atypical antipsychotic drugs in the

  17. State Government Revenue Recovery from the Great Recession

    OpenAIRE

    James Alm; David L. Sjoquist

    2014-01-01

    The "Great Recession" lasted from December 2007 to June 2009, and it wreaked havoc on the revenues of state (and local) governments. While the U.S. economy has improved since the end of the Great Recession, state government revenues have in most cases still not completely recovered. We use various indicators to measure how different states have -- or have not -- recovered in the aftermath of the Great Recession, and we also attempt to explain why these different patterns of recovery have emer...

  18. Child Poverty and the Great Recession in the United States

    OpenAIRE

    Marianne Bitler; Hilary Hoynes; Elira Kuka

    2014-01-01

    In the midst of the Great Recession, median real household income fell from $61,597 in 2007 to $57,025 in 2010 and $51,007 in 2012. Given that the effects of the Great Recession on unemployment were greater for less skilled workers the authors expect the effects of the Great Recession on household incomes to be larger in relative terms for individuals in the lower end of the income distribution. To explore this issue, in this paper, they comprehensively examine the effects of the Great Recess...

  19. GREAT: a web portal for Genome Regulatory Architecture Tools.

    Science.gov (United States)

    Bouyioukos, Costas; Bucchini, François; Elati, Mohamed; Képès, François

    2016-07-08

    GREAT (Genome REgulatory Architecture Tools) is a novel web portal for tools designed to generate user-friendly and biologically useful analysis of genome architecture and regulation. The online tools of GREAT are freely accessible and compatible with essentially any operating system which runs a modern browser. GREAT is based on the analysis of genome layout -defined as the respective positioning of co-functional genes- and its relation with chromosome architecture and gene expression. GREAT tools allow users to systematically detect regular patterns along co-functional genomic features in an automatic way consisting of three individual steps and respective interactive visualizations. In addition to the complete analysis of regularities, GREAT tools enable the use of periodicity and position information for improving the prediction of transcription factor binding sites using a multi-view machine learning approach. The outcome of this integrative approach features a multivariate analysis of the interplay between the location of a gene and its regulatory sequence. GREAT results are plotted in web interactive graphs and are available for download either as individual plots, self-contained interactive pages or as machine readable tables for downstream analysis. The GREAT portal can be reached at the following URL https://absynth.issb.genopole.fr/GREAT and each individual GREAT tool is available for downloading. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

  20. Unemployment of Non-western Immigrants in the Great Recession

    NARCIS (Netherlands)

    Cervený, J.; van Ours, J.C.

    2013-01-01

    Abstract: This paper examines whether unemployment of non-western immigrant workers in the Netherlands was disproportionally affected by the Great Recession. We analyze unemployment data covering the period November 2007 to February 2013 finding that the Great Recession affected unemployment rates

  1. Unemployment of non-western immigrants in the Great Recession

    NARCIS (Netherlands)

    Cervený, J.; van Ours, J.C.

    2013-01-01

    This paper examines whether unemployment of non-western immigrant workers in the Netherlands was disproportionally affected by the Great Recession. We analyze unemployment data covering the period November 2007–February 2013 finding that the Great Recession affected unemployment rates of non-western

  2. 78 FR 5474 - Great Lakes Pilotage Advisory Committee

    Science.gov (United States)

    2013-01-25

    ... DEPARTMENT OF HOMELAND SECURITY Coast Guard [USCG-2013-0029] Great Lakes Pilotage Advisory... Meeting. SUMMARY: The Great Lakes Pilotage Advisory Committee (GLPAC) will meet on February 11, 2013, in..., 2013, after the committee completes its work on the agenda given under SUPPLEMENTARY INFORMATION...

  3. Wildlife in the Upper Great Lakes Region: a community profile.

    Science.gov (United States)

    Janine M. Benyus; Richard R. Buech; Mark D. Nelson

    1992-01-01

    Wildlife habitat data from seven Great Lakes National Forests were combined into a wildlife-habitat matrix named NORTHWOODS. The composite NORTHWOODS data base is summarized. Multiple queries of NORTHWOODS were used to profile the wildlife community of the Upper Great Lakes region.

  4. Revisiting the Seeming Unanimous Verdict on the Great Debate on ...

    African Journals Online (AJOL)

    The great debate on African Philosophy refers to the debate as to whether African Philosophy does exist or not. The debate aroused great interest among Philosophy scholars who were predominantly polarized into two opposing positions - those who denied the existence of African Philosophy and those who insisted on the ...

  5. Figuring Somepin 'bout the Great Depression. Learning Page Lesson Plan.

    Science.gov (United States)

    McElroy, Amy; Pietsch, Chris

    These 10th and 11th grade lessons plans related to the Great Depression and the novel "The Grapes of Wrath" help students to: develop research skills and strategies, such as keyword searches, for finding information; recognize and use the different voices of migrants; and understand the politics of migration and the Great Depression. By…

  6. Ambient Response Analysis of the Great Belt Bridge

    DEFF Research Database (Denmark)

    Brincker, Rune; Frandsen, Jeanette B.; Andersen, Palle

    2000-01-01

    In this paper an ambient response analysis of the Great Belt Bridge is presented. The Great Belt Bridge is one of the largest suspension bridges in the world, and the analysis was carried out in order to investigate the possibilities of estimating reliable damping values from the ambient response...

  7. Pyometra in a Great Dane: A Clinical Case Report

    Directory of Open Access Journals (Sweden)

    Malik Abu Rafee

    2015-04-01

    Full Text Available A 4-year-old Great Dane was admitted with continuous sanguino-purulent vaginal discharge, distended abdomen, and cachexia. The dog was clinically diagnosed with pyometra and successfully cured by ovario-hysterectomy. This is the first case report of pyometra seen in as Great Dane in Bareilly, India.

  8. The Social Construction of the Great Belt Fixed Link

    DEFF Research Database (Denmark)

    Munch, Birgitte

    1994-01-01

    Working paper in Technology Management. Actor Network theory (ANT) used upon the process of negotiating legislation and constructing the Great Belt fixed link.......Working paper in Technology Management. Actor Network theory (ANT) used upon the process of negotiating legislation and constructing the Great Belt fixed link....

  9. Soil salinity and alkalinity in the Great Konya Basin, Turkey

    NARCIS (Netherlands)

    Driessen, P.M.

    1970-01-01

    In the summers of 1964 to 1968 a study was made of soil salinity and alkalinity in the Great Konya Basin, under the auspices of the Konya Project, a research and training programme of the Department of Tropical Soil Science of the Agricultural University, Wageningen.

    The Great

  10. The Great Depression: An ERIC/ChESS Sample.

    Science.gov (United States)

    Kulczak, Carrie

    2001-01-01

    Provides citations with abstracts from the ERIC database focusing on the Great Depression. Includes both background information and teaching materials on such topics as an overview of the New Deal, the arts and the Great Depression, and information on the Civilian Conservation Corps. Offers directions for accessing the materials. (CMK)

  11. Using Music to Teach about the Great Depression

    Science.gov (United States)

    Stevens, Robert L.; Fogel, Jared A.

    2007-01-01

    The Great Depression is typically taught through history textbooks, but the music of this time allows students to learn about this era through different perspectives. The Great Depression witnessed many musical styles--from the light heartedness of popular music to the sadness of the blues, gospel, which offered inspiration, to the tension between…

  12. FDA Consumer Nutrition Knowledge Survey. Report II, 1975. A Nationwide Study of Food Shopper's Knowledge, Beliefs, Attitudes and Reported Behavior Regarding Food and Nutrition. Factors Related to Nutrition Labeling.

    Science.gov (United States)

    Abelson, Herbert; And Others

    During 1973, a nationwide study for the Food and Drug Administration (FDA) was conducted which provided information on nutrition knowledge, beliefs about nutrition, and first reactions to nutrition labeling among food shoppers. This initial research provided a baseline measurement of nutrition knowledge and attitudes among consumers, and in 1975…

  13. Effects of hydroxyl-functionalization and sub-Tg thermal annealing on high pressure pure- and mixed-gas CO2/CH4 separation by polyimide membranes based on 6FDA and triptycene-containing dianhydrides

    KAUST Repository

    Swaidan, Raja; Ghanem, Bader; Litwiller, Eric; Pinnau, Ingo

    2015-01-01

    -structure engaged in inter-chain charge transfer complexes (CTCs), similar to that of low-free-volume 6FDA-APAF polyimide. The isosteric heat of adsorption of CO2 as well as CO2/CH4 solubility selectivities varied negligibly upon replacement of OH with CH3 but CTC

  14. The Great Depression and the Great Recession: A Comparative Analysis of their Analogies

    Directory of Open Access Journals (Sweden)

    Cristina Peicuti

    2014-06-01

    Full Text Available The decades preceding the Great Depression and the U.S. subprime mortgage crisis have close similarities. Both decades were characterized by rapid growth without major contractions, by an increase in liquidity, a lack of inflation, and a generalized decrease in risk premiums. Additional similarities included significant changes in the financing of real estate by commercial banks along with a consolidation of the banking sector and high hopes that the efficiency of monetary policy would prevent financial crises. These decades were also characterized by the consolidation of the powers of young central banks (the Federal Reserve System in the 1920s and the European Central Bank in the 2000s, by unsuccessful attempts to control market speculation, by their international dimensions, and by the eruption of crises after the failure of a major American financial institution that could have been avoided. Understanding these analogies help us better identify the causes of the subprime mortgage crisis and prevent history from repeating itself to the extentof such large-scale devastating consequences.

  15. THE GREAT SILK ROAD BECOMES THE GREAT OIL AND GAS ROAD

    Directory of Open Access Journals (Sweden)

    I. S. Zonn

    2015-01-01

    Full Text Available The Great Silk Road (GSR called so in the late 19th century by German geographer Ferdinand von Richthofen started shaping in the 2nd century B.C. In the minds of peoples the Silk Road is a generalized symbol of trade caravan routes crossing Central Asia, connecting until the 16th century the Far East, in particular Japan, China, with Middle Asia. Appearance in the early 21st century of new independent states in Central Asia along the GSR route was a powerful impetus for revival of the ancient trade route. In September 2013 Xi Jinping, President of the People's Republic of China, during his visit to the Central Asian countries offered the strategic concept of joint construction of the “economic corridor along the Silk Road” based on innovative cooperation in order to revive and consolidate the economic contacts among the Eurasian countries. Establishment of the modern analog of GSR, a powerful transport and pipeline corridor includes the integrated system of railroads and automobile roads, oil and gas pipelines, airlines, and sea lines.

  16. Comparison of Unlicensed and Off-Label Use of Antipsychotics Prescribed to Child and Adolescent Psychiatric Outpatients for Treatment of Mental and Behavioral Disorders with Different Guidelines: The China Food and Drug Administration Versus the FDA.

    Science.gov (United States)

    Zhu, Xiuqing; Hu, Jinqing; Sun, Bin; Deng, Shuhua; Wen, Yuguan; Chen, Weijia; Qiu, Chang; Shang, Dewei; Zhang, Ming

    2018-04-01

    This study aims to compare the prevalence of unlicensed and off-label use of antipsychotics among child and adolescent psychiatric outpatients with guidelines proposed by the China Food and Drug Administration (CFDA) and the U.S. Food and Drug Administration (FDA), and to identify factors associated with inconsistencies between the two regulations. A retrospective analysis of 29,326 drug prescriptions for child and adolescent outpatients from the Affiliated Brain Hospital of Guangzhou Medical University was conducted. Antipsychotics were classified as "unlicensed" or "off-label use" according to the latest pediatric license information registered by the CFDA and the FDA or the package inserts of antipsychotics authorized by the CFDA or the FDA for the treatment of pediatric mental and behavioral disorders, respectively. Binary logistic regression analysis was performed to assess factors associated with inconsistencies between the two regulations. The total unlicensed use, according to the CFDA analysis, was higher than that found in the FDA analysis (74.14% vs. 22.04%, p according to the FDA analysis, was higher than that found in the CFDA analysis (46.53% vs. 15.77%, p gender, diagnosis of schizophrenia and schizotypal and delusional disorders, diagnosis of mood [affective] disorders, diagnosis of mental retardation, and diagnosis of psychological development disorders were associated with inconsistent off-label use. The difference in prevalence of total unlicensed and off-label use of antipsychotics between the two regulations was statistically significant. This inconsistency could be partly attributed to differences in pediatric license information and package inserts of antipsychotics. The results indicate a need for further clinical pediatric studies and better harmonization between agencies regarding antipsychotic used in pediatrics.

  17. Why greatness cannot be planned the myth of the objective

    CERN Document Server

    Stanley, Kenneth O

    2015-01-01

    Why does modern life revolve around objectives? From how science is funded, to improving how children are educated -- and nearly everything in-between -- our society has become obsessed with a seductive illusion: that greatness results from doggedly measuring improvement in the relentless pursuit of an ambitious goal. In Why Greatness Cannot Be Planned, Stanley and Lehman begin with a surprising scientific discovery in artificial intelligence that leads ultimately to the conclusion that the objective obsession has gone too far. They make the case that great achievement can't be bottled up int

  18. "Most brilliant in judgment": Alexander the Great and Aristotle.

    Science.gov (United States)

    Lainas, Panagiotis; Panutsopulos, Dimitrios; Skandalakis, Panagiotis N; Zoras, Odysseas; Skandalakis, John E

    2005-03-01

    From historical sources, it is evident that Alexander the Great was indebted to one of his teachers, Aristotle of Stagira. It was the teaching of Aristotle that evoked all the nascent talents of young Alexander and turned him into a great man. Alexander was extremely interested in the secrets of medicine and considered it an art. The medical knowledge he acquired from Aristotle may have saved his life and the lives of his troops on many occasions. If Alexander did not possess medical knowledge and if his everyday life had not been so greatly influenced by medicine, he might never have been able to create his empire.

  19. Accurate identification of ALK positive lung carcinoma patients: novel FDA-cleared automated fluorescence in situ hybridization scanning system and ultrasensitive immunohistochemistry.

    Directory of Open Access Journals (Sweden)

    Esther Conde

    Full Text Available BACKGROUND: Based on the excellent results of the clinical trials with ALK-inhibitors, the importance of accurately identifying ALK positive lung cancer has never been greater. However, there are increasing number of recent publications addressing discordances between FISH and IHC. The controversy is further fuelled by the different regulatory approvals. This situation prompted us to investigate two ALK IHC antibodies (using a novel ultrasensitive detection-amplification kit and an automated ALK FISH scanning system (FDA-cleared in a series of non-small cell lung cancer tumor samples. METHODS: Forty-seven ALK FISH-positive and 56 ALK FISH-negative NSCLC samples were studied. All specimens were screened for ALK expression by two IHC antibodies (clone 5A4 from Novocastra and clone D5F3 from Ventana and for ALK rearrangement by FISH (Vysis ALK FISH break-apart kit, which was automatically captured and scored by using Bioview's automated scanning system. RESULTS: All positive cases with the IHC antibodies were FISH-positive. There was only one IHC-negative case with both antibodies which showed a FISH-positive result. The overall sensitivity and specificity of the IHC in comparison with FISH were 98% and 100%, respectively. CONCLUSIONS: The specificity of these ultrasensitive IHC assays may obviate the need for FISH confirmation in positive IHC cases. However, the likelihood of false negative IHC results strengthens the case for FISH testing, at least in some situations.

  20. Ultra High Performance Liquid Chromatography Method for the Determination of Two Recently FDA Approved TKIs in Human Plasma Using Diode Array Detection

    Directory of Open Access Journals (Sweden)

    Marwa Fouad

    2015-01-01

    Full Text Available Generally, tyrosine kinase inhibitors have narrow therapeutic window and large interpatient variability compared to intrapatient variability. In order to support its therapeutic drug monitoring, two fast and accurate methods were developed for the determination of recently FDA approved anticancer tyrosine kinase inhibitors, afatinib and ibrutinib, in human plasma using ultra high performance liquid chromatography coupled to PDA detection. Diclofenac sodium was used as internal standard. The chromatographic separation was achieved on an Acquity UPLC BEH C18 analytical column using a mobile phase combining ammonium formate buffer and acetonitrile at a constant flow rate of 0.4 mL/min using gradient elution mode. A µSPE (solid phase extraction procedure, using Oasis MCX µElution plates, was processed and it gave satisfying and reproducible results in terms of extraction yields. Additionally, the methods were successfully validated using the accuracy profiles approach (β = 95% and acceptance limits = ±15% over the ranges 5–250 ng/mL for afatinib and from 5 to 400 ng/mL for ibrutinib in human plasma.