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Sample records for final core fda

  1. Final Report - BRER Core Support

    International Nuclear Information System (INIS)

    Evan B. Douple

    2007-01-01

    This contract provided core support for activities of the advisory committee of experts comprising the Board on Radiation Effects Research (BRER), in The National Academies Division on Earth and Life Studies. That committee met two times during the funding period. The committee members provided oversight and advice regarding ongoing BRER projects and also assisted in the identification of potential committee members for new studies and the development of proposals for projects in the radiation sciences worthy for future study. In addition, funding provided support for the planning, advertisement, and invited speakers travel-expense reimbursement for the Third and Fourth Gilbert W. Beebe Symposia held at The National Academies on December 1, 2004 and on November 30, 2005, respectively

  2. FDA gives final approval to Depo amid concerns over safety, cost and coercion.

    Science.gov (United States)

    1992-11-12

    In October 1992, the US Food and Drug Administration (FDA) approved Depo-Provera for contraceptive use thus increasing the number of available contraceptives to women. Yet USAID has distributed it through its family planning programs in developing countries for many years. It has been available in the US since 1969 for noncontraceptive purposes such as endometrial cancer treatment. More than 30 million women around the world have used it to prevent conception. Today about 9 million women in 90 countries use it. A reason FDA did not approve Depo-Provera is that some studies revealed a link between it and breast tumors and cervical cancer in animals. More recent research conducted by WHO shows no connection with cervical cancer or ovarian cancer. In fact, it demonstrates Depo-Provera may protect against endometrial cancer. Yet it does indicate an insignificant increased risk of breast cancer in younger women. Some research suggests Depo-Provera may decrease bone density leading to osteoporosis and may increase the risk of having a low birth weight infant if the child is conceived before an injection. Evidence exists that it may lead to longer delays in becoming pregnant than other forms of contraception. Still 70% do conceive within 12 months after the last injection. Each Depo-Provera injection delivers a progestin in a water-based solution over 12 weeks resulting in suppressed ovulation. Its failure rate is .5%/year, so Depo-Provera is one of the most effective reversible contraceptive available. The most common side effects are menstrual changes and weight gain (5-15 lbs.). Some contraindications include pregnancy, heart or liver disease, and breast cancer. As of November 1992, the FDA had not announced the cost or whether there would be a reduced price for family planning and public health clinics. Women's health and rights advocates plan on monitoring introduction of Depo-Provera to make sure that women have received comprehensive information and were not

  3. Schedules of Controlled Substances: Placement of FDA-Approved Products of Oral Solutions Containing Dronabinol [(-)-delta-9-trans- tetrahydrocannabinol (delta-9-THC)] in Schedule II. Final rule.

    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.

  4. Implications and challenges for implementation of the FDA's final deeming rule for waterpipe tobacco.

    Science.gov (United States)

    Sutfin, Erin L; Soule, Eric K; McKelvey, Karma; Jenson, Desmond

    2017-06-30

    For the first time, the Food and Drug Administration's (FDAs) Center for Tobacco Products now has regulatory authority over all tobacco products, including waterpipe tobacco. In the rule expanding its authority to cover all tobacco products, the FDA uses largely a one-size-fits-all approach. However, several aspects of waterpipe tobacco smoking make it unique from other tobacco products, which may require more specific, tailored rules. This paper describes the distinct features of waterpipe tobacco products and accessories, and identifies unique challenges to the current regulation posed by this form of tobacco use. Additionally, we highlight the need for further research-generated evidence to support additional rulemaking. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  5. Review of Final Draft Core Standards

    Directory of Open Access Journals (Sweden)

    R. James Milgram

    2013-04-01

    Full Text Available What follows are my comments on the nal draft of the CCSSI Core Mathematics Standards. There are a number of standards including, but not limited to 1-OA(6, 2-OA(2, 2-NBT(5, 3-OA(7, 3-NBT(2, 4-OA(4, 4-OA(6, 4-NF(1, 4-NF(2, 5-OA(3, 8-G(2, 8-G(4, F-LQE(5, G-SRT(4 that are completely unique to this document, andmost of them seem problematic to me. I have repeatedly asked for references justifying the insertions of these or similar standards in previous drafts, but references have not been provided. Consequently, to my knowledge, there is no real research base for including any of these standards in the document.

  6. 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 ...

  7. 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...

  8. 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

  9. SBIR Final Report. Liquid Core Optical Scintillating Fibers

    Energy Technology Data Exchange (ETDEWEB)

    Beetz, C.P.; Steinbeck, J.; Buerstler, R.

    2000-05-16

    This Phase I SBIR project focused on developing flexible scintillating liquid core optical fibers, with potential uses in high-energy calorimetry, tracking, preradiators, active targets or other fast detectors. Progress on the six tasks of the project is summarized. The technical developments involve three technology components: (1) highly flexible capillaries or tubes of relatively low n (index of refraction) to serve as cladding and liquid core containment; (2) scintillator (and clear) fluids of relatively high n to serve as a core-- these fluids must have a high light transmission and, for some applications, radiation hardness; (3) optical end plugs, plug insertion, and plug-cladding tube sealing technology to contain the core fluids in the tubes, and to transmit the light.

  10. Cordilleran metamorphic core complexes and their uranium favorability. Final report

    International Nuclear Information System (INIS)

    Coney, P.J.; Reynolds, S.J.

    1980-11-01

    The objective of this report is to provide a descriptive body of knowledge on Cordilleran metamorphic core complexes including their lithologic and structural characteristics, their distribution within the Cordillera, and their evolutionary history and tectonic setting. The occurrence of uranium in the context of possibility for uranium concentration is also examined. Chapter 1 is an overview of Cordilleran metamorphic core complexes which describes their physical characteristics, tectonic setting and geologic history. This overview is accompanied by a tectonic map. Chapter 2 is a discussion of the mantled gneiss dome concept. The purpose of including this work is to provide a basic history of this concept and to describe the characteristics and distribution of gneiss domes throughout the world to enable one to compare and contrast them with the metamorphic core complexes as discussed in this report. Some gneiss domes are known producers of uranium (as are also some core complexes). Chapter 3 is an examination of the effects of the core complex process on adjacent sedimentary and volcanic cover terranes. Also included is a discussion of the kinematic significance of these cover terranes as they are related to process within the cores of the complexes. Some of the cover terranes have uranium prospects in them. Chapter 4 is a detailed discussion of uranium in Cordilleran metamorphic core complexes and includes the conceptual basis for the various types of occurrences and the processes that might favor concentration of uranium. The report is supported by a 5-part Appendix. The majority of the core complexes discussed in this report either do not appear or are not recognizable on existing published geologic maps

  11. 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

  12. Schedules of Controlled Substances: Placement of FDA-Approved Products of Oral Solutions Containing Dronabinol [(-)-delta-9-transtetrahydrocannabinol (delta-9-THC)] in Schedule II. Interim final rule, with request for comments.

    Science.gov (United States)

    2017-03-23

    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. Thereafter, the Department of Health and Human Services (HHS) provided the Drug Enforcement Administration (DEA) with a scheduling recommendation that would result in Syndros (and other oral solutions containing dronabinol) being placed in schedule II of the Controlled Substances Act (CSA). In accordance with the CSA, as revised by the Improving Regulatory Transparency for New Medical Therapies Act, DEA is hereby issuing an interim final rule placing FDA-approved products of oral solutions containing dronabinol in schedule II of the CSA.

  13. 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...

  14. 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...

  15. Tank 241-BY-109, cores 201 and 203, analytical results for the final report

    International Nuclear Information System (INIS)

    Esch, R.A.

    1997-01-01

    This document is the final laboratory report for tank 241-BY-109 push mode core segments collected between June 6, 1997 and June 17, 1997. The segments were subsampled and analyzed in accordance with the Tank Push Mode Core Sampling and Analysis Plan (Bell, 1997), the Tank Safety Screening Data Quality Objective (Dukelow, et al, 1995). The analytical results are included

  16. Irradiation-Accelerated Corrosion of Reactor Core Materials. Final Report

    International Nuclear Information System (INIS)

    Jiao, Zhujie; Was, Gary; Bartels, David

    2015-01-01

    This project aims to understand how radiation accelerates corrosion of reactor core materials. The combination of high temperature, chemically aggressive coolants, a high radiation flux and mechanical stress poses a major challenge for the life extension of current light water reactors, as well as the success of most all GenIV concepts. Of these four drivers, the combination of radiation and corrosion places the most severe demands on materials, for which an understanding of the fundamental science is simply absent. Only a few experiments have been conducted to understand how corrosion occurs under irradiation, yet the limited data indicates that the effect is large; irradiation causes order of magnitude increases in corrosion rates. Without a firm understanding of the mechanisms by which radiation and corrosion interact in film formation, growth, breakdown and repair, the extension of the current LWR fleet beyond 60 years and the success of advanced nuclear energy systems are questionable. The proposed work will address the process of irradiation-accelerated corrosion that is important to all current and advanced reactor designs, but remains very poorly understood. An improved understanding of the role of irradiation in the corrosion process will provide the community with the tools to develop predictive models for in-reactor corrosion, and to address specific, important forms of corrosion such as irradiation assisted stress corrosion cracking.

  17. Irradiation-Accelerated Corrosion of Reactor Core Materials. Final Report

    Energy Technology Data Exchange (ETDEWEB)

    Jiao, Zhujie [Univ. of Michigan, Ann Arbor, MI (United States); Was, Gary [Univ. of Michigan, Ann Arbor, MI (United States); Bartels, David [Univ. of Notre Dame, IN (United States)

    2015-04-02

    This project aims to understand how radiation accelerates corrosion of reactor core materials. The combination of high temperature, chemically aggressive coolants, a high radiation flux and mechanical stress poses a major challenge for the life extension of current light water reactors, as well as the success of most all GenIV concepts. Of these four drivers, the combination of radiation and corrosion places the most severe demands on materials, for which an understanding of the fundamental science is simply absent. Only a few experiments have been conducted to understand how corrosion occurs under irradiation, yet the limited data indicates that the effect is large; irradiation causes order of magnitude increases in corrosion rates. Without a firm understanding of the mechanisms by which radiation and corrosion interact in film formation, growth, breakdown and repair, the extension of the current LWR fleet beyond 60 years and the success of advanced nuclear energy systems are questionable. The proposed work will address the process of irradiation-accelerated corrosion that is important to all current and advanced reactor designs, but remains very poorly understood. An improved understanding of the role of irradiation in the corrosion process will provide the community with the tools to develop predictive models for in-reactor corrosion, and to address specific, important forms of corrosion such as irradiation assisted stress corrosion cracking.

  18. FDA Approval for Imiquimod

    Science.gov (United States)

    On July 15, 2004, the U.S. Food and Drug Administration (FDA) announced the approval of a new indication for Aldara® (imiquimod) topical cream for the treatment of superficial basal cell carcinoma (sBCC), a type of skin cancer.

  19. 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

  20. Is It Really FDA Approved?

    Science.gov (United States)

    ... Preventive Controls for Animal Food rule, a new regulation mandated by the FDA Food Safety Modernization Act (FSMA), requires food companies to take ... is on the market, FDA evaluates the product’s safety through research and ... But FDA regulations require nutrition information to appear on most foods, ...

  1. Tank 241-AP-105, cores 208, 209 and 210, analytical results for the final report

    Energy Technology Data Exchange (ETDEWEB)

    Nuzum, J.L.

    1997-10-24

    This document is the final laboratory report for Tank 241-AP-105. Push mode core segments were removed from Risers 24 and 28 between July 2, 1997, and July 14, 1997. Segments were received and extruded at 222-S Laboratory. Analyses were performed in accordance with Tank 241-AP-105 Push Mode Core Sampling and Analysis Plan (TSAP) (Hu, 1997) and Tank Safety Screening Data Quality Objective (DQO) (Dukelow, et al., 1995). None of the subsamples submitted for total alpha activity (AT), differential scanning calorimetry (DSC) analysis, or total organic carbon (TOC) analysis exceeded the notification limits as stated in TSAP and DQO. The statistical results of the 95% confidence interval on the mean calculations are provided by the Tank Waste Remediation Systems Technical Basis Group, and are not considered in this report. Appearance and Sample Handling Two cores, each consisting of four segments, were expected from Tank 241-AP-105. Three cores were sampled, and complete cores were not obtained. TSAP states core samples should be transported to the laboratory within three calendar days from the time each segment is removed from the tank. This requirement was not met for all cores. Attachment 1 illustrates subsamples generated in the laboratory for analysis and identifies their sources. This reference also relates tank farm identification numbers to their corresponding 222-S Laboratory sample numbers.

  2. Final report for tank 241-BX-104 push mode core 126 and 127

    International Nuclear Information System (INIS)

    Hu, T.A.

    1996-01-01

    This is the final sample analysis report for tank 241-BX-104 (BX-104), cores 126 and 127. Two segments from each core yielded a total of 11 samples which were analyzed. The data quality objectives (DQOs) applicable to this sampling event were the Safety Screening DQO (Dukelow et al. 1995) and the Organic Safety DQO (Turner et al. 1995). The samples were received, extruded and analyzed at PNNL 325 Analytical Chemistry Laboratory (ACL). The analyses were performed in accordance with the Sample Analysis Plan (Gretsinger 1996) and indicated that the tank is safe with respect to the criteria in the Safety Screening and Organic DQO. Detailed analytical results were described in the analytical laboratory 45-day Report (Attachment 1, WHC-SD-WM-DP-171, REV. 0) and final report (Attachment 2, PNL-BX-104 REV.1) prepared by PNNL, 325 Laboratory. Corrections and/or exceptions to the PNNL final report are provided

  3. Development of the FDA Tobacco Credibility Scale (FDA-TCS).

    Science.gov (United States)

    Schmidt, Allison M; Ranney, Leah M; Noar, Seth M; Goldstein, Adam O

    2017-01-01

    Messages from organizations with high, compared to low, credibility may be more persuasive. Whereas the tobacco industry has long recognized the importance of credibility in promoting its messages and public image, the source credibility of key tobacco control organizations has gone largely unmeasured. To assess credibility of a key tobacco regulator, we developed a scale of the US Food and Drug Administration (FDA) tobacco-related credibility. We developed and tested 30 items reflective of the dimensions of source credibility (trust, expertise, and public interest) and FDA's tobacco regulatory roles in a sample of 1353 US adults and assessed reliability and validity. Factor analysis identified 3 dimensions of the FDA Tobacco Credibility Scale (FDA-TCS): public interest, trust, and expertise. The 3 subscales showed evidence of reliability and convergent validity; all subscales were correlated with general FDA credibility and trust in government. Those who knew that the FDA regulates tobacco scored higher on the trust and expertise subscales. The subscales were also associated with support for potential regulations, suggesting criterion-related validity. The FDA-TCS allows for an understanding of the impact of credibility on responses to the FDA's tobacco control communications and regulatory efforts.

  4. Tank 241-T-201, core 192 analytical results for the final report

    Energy Technology Data Exchange (ETDEWEB)

    Nuzum, J.L.

    1997-08-07

    This document is the final laboratory report for Tank 241-T-201. Push mode core segments were removed from Riser 3 between April 24, 1997, and April 25, 1997. Segments were received and extruded at 222-S Laboratory. Analyses were performed in accordance with Tank 241-T-201 Push Mode Core Sampling and Analysis Plan (TSAP) (Hu, 1997), Letter of Instruction for Core Sample Analysis of Tanks 241-T-201, 241-T-202, 241-T-203, and 241-T-204 (LOI) (Bell, 1997), Additional Core Composite Sample from Drainable Liquid Samples for Tank 241-T-2 01 (ACC) (Hall, 1997), and Safety Screening Data Quality Objective (DQO) (Dukelow, et al., 1995). None of the subsamples submitted for total alpha activity (AT) or differential scanning calorimetry (DSC) analyses exceeded the notification limits stated in DQO. The statistical results of the 95% confidence interval on the mean calculations are provided by the Tank Waste Remediation Systems Technical Basis Group, and are not considered in this report.

  5. Tank 241-T-105, cores 205 and 207 analytical results for the final report

    International Nuclear Information System (INIS)

    Esch, R.A.

    1997-01-01

    This document is the final laboratory report for tank 241-T-105 push mode core segments collected between June 24, 1997 and June 30, 1997. The segments were subsampled and analyzed in accordance with the Tank Push Mode Core Sampling and Analysis Plan (TSAP) (Field,1997), the Tank Safety Screening Data Quality Objective (Safety DQO) (Dukelow, et al., 1995) and Tank 241-T-105 Sample Analysis (memo) (Field, 1997a). The analytical results are included in Table 1. None of the subsamples submitted for the differential scanning calorimetry (DSC) analysis or total alpha activity (AT) exceeded the notification limits as stated in the TSAP (Field, 1997). The statistical results of the 95% confidence interval on the mean calculations are provided by the Tank Waste Remediation Systems (TWRS) Technical Basis Group in accordance with the Memorandum of Understanding (Schreiber, 1997) and not considered in this report

  6. Thermal and hydraulic behaviour of CANDU cores under severe accident conditions - final report. Vol. 1

    International Nuclear Information System (INIS)

    Rogers, J.T.

    1984-06-01

    This report gives the results of a study of the thermo-hydraulic aspects of severe accident sequences in CANDU reactors. The accident sequences considered are the loss of the moderator cooling system and the loss of the moderator heat sink, each following a large loss-of-coolant accident accompanied by loss of emergency coolant injection. Factors considered include expulsion and boil-off of the moderator, uncovery, overheating and disintegration of the fuel channels, quenching of channel debris, re-heating of channel debris following complete moderator expulsion, formation and possible boiling of a molten pool of core debris and the effectiveness of the cooling of the calandria wall by the shield tank water during the accident sequences. The effects of these accident sequences on the reactor containment are also considered. Results show that there would be no gross melting of fuel during moderator expulsion from the calandria, and for a considerable time thereafter, as quenched core debris re-heats. Core melting would not begin until about 135 minutes after accident initiation in a loss of the moderator cooling system and until about 30 minutes in a loss of the moderator heat sink. Eventually, a pool of molten material would form in the bottom of the calandria, which may or may not boil, depending on property values. In all cases, the molten core would be contained within the calandria, as long as the shield tank water cooling system remains operational. Finally, in the period from 8 to 50 hours after the initiation of the accident, the molten core would re-solidify within the calandria. There would be no consequent damage to containment resulting from these accident sequences, nor would there be a significant increase in fission product releases from containment above those that would otherwise occur in a dual failure LOCA plus LOECI

  7. Development of the FDA Tobacco Credibility Scale (FDA-TCS)

    Science.gov (United States)

    Schmidt, Allison M.; Ranney, Leah M.; Noar, Seth M.; Goldstein, Adam O.

    2016-01-01

    Objectives Messages from organizations with high, compared to low, credibility may be more persuasive. Whereas the tobacco industry has long recognized the importance of credibility in promoting its messages and public image, the source credibility of key tobacco control organizations has gone largely unmeasured. To assess credibility of a key tobacco regulator, we developed a scale of the US Food and Drug Administration (FDA) tobacco-related credibility. Methods We developed and tested 30 items reflective of the dimensions of source credibility (trust, expertise, and public interest) and FDA’s tobacco regulatory roles in a sample of 1353 US adults and assessed reliability and validity. Results Factor analysis identified 3 dimensions of the FDA Tobacco Credibility Scale (FDA-TCS): public interest, trust, and expertise. The 3 subscales showed evidence of reliability and convergent validity; all subscales were correlated with general FDA credibility and trust in government. Those who knew that the FDA regulates tobacco scored higher on the trust and expertise subscales. The subscales were also associated with support for potential regulations, suggesting criterion-related validity. Conclusions The FDA-TCS allows for an understanding of the impact of credibility on responses to the FDA’s tobacco control communications and regulatory efforts. PMID:28638857

  8. 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.

  9. Hardware concepts for a large low-energetics LMFBR core. Final report

    International Nuclear Information System (INIS)

    Hutter, E.; Batch, R.V.

    1980-12-01

    A design study was made to identify a practical set of hardware configurations that would embody the requirements developed in the numerical study of a low-energetics core and blanket for a prototype large breeder reactor. Dimensioned drawings are presented for fuel, blanket, reflector/shield, and control rod subassemblies. A horizontal cross section drawing shows how these subassemblies are arranged in the total core/blanket assembly. A core support is illustrated showing a dual plenums arrangement

  10. FDA Warns About Stem Cell Therapies

    Science.gov (United States)

    ... the FDA published a perspective article in the New England Journal of Medicine . The FDA will continue to help with the development and licensing of new stem cell therapies where the scientific evidence supports ...

  11. 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...

  12. CORE

    DEFF Research Database (Denmark)

    Krigslund, Jeppe; Hansen, Jonas; Hundebøll, Martin

    2013-01-01

    State-of-the-art in network coding for wireless, meshed networks typically considers two problems separately. First, the problem of providing reliability for a single session. Second, the problem of opportunistic combination of flows by using minimalistic coding, i.e., by XORing packets from...... different flows. Instead of maintaining these approaches separate, we propose a protocol (CORE) that brings together these coding mechanisms. Our protocol uses random linear network coding (RLNC) for intra- session coding but allows nodes in the network to setup inter- session coding regions where flows...

  13. Final Report for Project "Framework Application for Core-Edge Transport Simulations (FACETS)"

    Energy Technology Data Exchange (ETDEWEB)

    Estep, Donald [Colorado State Univ., Fort Collins, CO (United States)

    2014-01-17

    This is the final report for the Colorado State University Component of the FACETS Project. FACETS was focused on the development of a multiphysics, parallel framework application that could provide the capability to enable whole-device fusion reactor modeling and, in the process, the development of the modeling infrastructure and computational understanding needed for ITER. It was intended that FACETS be highly flexible, through the use of modern computational methods, including component technology and object oriented design, to facilitate switching from one model to another for a given aspect of the physics, and making it possible to use simplified models for rapid turnaround or high-fidelity models that will take advantage of the largest supercomputer hardware. FACETS was designed in a heterogeneous parallel context, where different parts of the application can take advantage through parallelism based on task farming, domain decomposition, and/or pipelining as needed and applicable. As with all fusion simulations, an integral part of the FACETS project was treatment of the coupling of different physical processes at different scales interacting closely. A primary example for the FACETS project is the coupling of existing core and edge simulations, with the transport and wall interactions described by reduced models. However, core and edge simulations themselves involve significant coupling of different processes with large scale differences. Numerical treatment of coupling is impacted by a number of factors including, scale differences, form of information transferred between processes, implementation of solvers for different codes, and high performance computing concerns. Operator decomposition involving the computation of the individual processes individually using appropriate simulation codes and then linking/synchronizing the component simulations at regular points in space and time, is the defacto approach to high performance simulation of multiphysics

  14. Final Report for the "Fusion Application for Core-Edge Transport Simulations (FACETS)"

    Energy Technology Data Exchange (ETDEWEB)

    Cary, John R; Kruger, Scott

    2014-10-02

    The FACETS project over its lifetime developed the first self-consistent core-edge coupled capabilities, a new transport solver for modeling core transport in tokamak cores, developed a new code for modeling wall physics over long time scales, and significantly improved the capabilities and performance of legacy components, UEDGE, NUBEAM, GLF23, GYRO, and BOUT++. These improved capabilities leveraged the team’s expertise in applied mathematics (solvers and algorithms) and computer science (performance improvements and language interoperability). The project pioneered new methods for tackling the complexity of simulating the concomitant complexity of tokamak experiments.

  15. Tank 241-TX-104, cores 230 and 231 analytical results for the final report

    International Nuclear Information System (INIS)

    Diaz, L.A.

    1998-01-01

    This document is the analytical laboratory report for tank 241-TX-104 push mode core segments collected between February 18, 1998 and February 23, 1998. The segments were subsampled and analyzed in accordance with the Tank 241-TX-104 Push Mode Core Sampling and Analysis Plan (TSAP) (McCain, 1997), the Data Quality Objective to Support Resolution of the Organic Complexant Safety Issue (Organic DQO) (Turner, et al., 1995) and the Safety Screening Data Quality Objective (DQO) (Dukelow, et.al., 1995). The analytical results are included in the data summary table. None of the samples submitted for Differential Scanning Calorimetry (DSC) and Total Alpha Activity (AT) exceeded notification limits as stated in the TSAP. The statistical results of the 95% confidence interval on the mean calculations are provided by the Tank Waste Remediation Systems Technical Basis Group in accordance with the Memorandum of Understanding (Schreiber, 1997) and are not considered in this report. Appearance and Sample Handling Attachment 1 is a cross reference to relate the tank farm identification numbers to the 222-S Laboratory LabCore/LIMS sample numbers. The subsamples generated in the laboratory for analyses are identified in these diagrams with their sources shown. Core 230: Three push mode core segments were removed from tank 241-TX-104 riser 9A on February 18, 1998. Segments were received by the 222-S Laboratory on February 19, 1998. Two segments were expected for this core. However, due to poor sample recovery, an additional segment was taken and identified as 2A. Core 231: Four push mode core segments were removed from tank 241-TX-104 riser 13A between February 19, 1998 and February 23, 1998. Segments were received by the 222-S Laboratory on February 24, 1998. Two segments were expected for this core. However, due to poor sample recovery, additional segments were taken and identified as 2A and 2B. The TSAP states the core samples should be transported to the laboratory within three

  16. Tank 241-TX-104, cores 230 and 231 analytical results for the final report

    Energy Technology Data Exchange (ETDEWEB)

    Diaz, L.A.

    1998-07-07

    This document is the analytical laboratory report for tank 241-TX-104 push mode core segments collected between February 18, 1998 and February 23, 1998. The segments were subsampled and analyzed in accordance with the Tank 241-TX-104 Push Mode Core Sampling and Analysis Plan (TSAP) (McCain, 1997), the Data Quality Objective to Support Resolution of the Organic Complexant Safety Issue (Organic DQO) (Turner, et al., 1995) and the Safety Screening Data Quality Objective (DQO) (Dukelow, et.al., 1995). The analytical results are included in the data summary table. None of the samples submitted for Differential Scanning Calorimetry (DSC) and Total Alpha Activity (AT) exceeded notification limits as stated in the TSAP. The statistical results of the 95% confidence interval on the mean calculations are provided by the Tank Waste Remediation Systems Technical Basis Group in accordance with the Memorandum of Understanding (Schreiber, 1997) and are not considered in this report. Appearance and Sample Handling Attachment 1 is a cross reference to relate the tank farm identification numbers to the 222-S Laboratory LabCore/LIMS sample numbers. The subsamples generated in the laboratory for analyses are identified in these diagrams with their sources shown. Core 230: Three push mode core segments were removed from tank 241-TX-104 riser 9A on February 18, 1998. Segments were received by the 222-S Laboratory on February 19, 1998. Two segments were expected for this core. However, due to poor sample recovery, an additional segment was taken and identified as 2A. Core 231: Four push mode core segments were removed from tank 241-TX-104 riser 13A between February 19, 1998 and February 23, 1998. Segments were received by the 222-S Laboratory on February 24, 1998. Two segments were expected for this core. However, due to poor sample recovery, additional segments were taken and identified as 2A and 2B. The TSAP states the core samples should be transported to the laboratory within three

  17. The FDA may not regulate tobacco products as "drugs" or as "medical devices".

    Science.gov (United States)

    Merrill, R A

    1998-04-01

    Professor Richard Merrill contends that the Federal Food, Drug, and Cosmetic Act does not grant the FDA regulatory authority over cigarettes and smokeless tobacco products. The fact that Congress did not expressly deny the FDA regulatory authority over tobacco cannot, Professor Merrill argues, be used to infer such authority. This inference is particularly inappropriate in the case of tobacco regulation, he maintains, because there is compelling evidence that Congress had no intention of delegating this authority to the FDA. He is unpersuaded that presidential approval legally sanctions the FDA's claim of authority by granting it a superficial political legitimacy. Finally, he reminds us of the FDA's own repeated denials of jurisdiction over tobacco products, and he recalls the numerous times that Congress passed legislation directed at tobacco without granting the FDA any role in its regulation. Professor Merrill's Essay, like the other pieces in this volume, was written after the United States District Court for the Middle District of North Carolina decided Coyne Beahm v. FDA, but before a three judge panel of the United States Court of Appeals for the Fourth Circuit reversed that decision in Brown & Williamson Tobacco Corp. v. FDA. In Coyne Beahm, the District Court held that the Federal Food, Drug, and Cosmetic Act authorized the FDA to regulate tobacco products, but not tobacco advertising. The Fourth Circuit rejected the District Court's jurisdictional ruling and invalidated the FDA's regulations in their entirety. The Clinton Administration has since requested an en banc rehearing before the Fourth Circuit.

  18. Thermal and hydraulic behaviour of CANDU cores under severe accident conditions - final report

    International Nuclear Information System (INIS)

    Rogers, J.T.

    1984-06-01

    This volume of appendices presents listings and sample runs of the computer codes used in the study of the thermalhydraulic behaviour of CANDU reactor cores during severe loss of coolant accidents. The codes, written in standard FORTRAN, are MODBOIL, to calculate moderator temperatures, pressures and water levels; DEBRIS, to calculate the transient temperature distribution in the debris of calandria and pressure tubes and fuel pellets; MOLTENPOOL, to calculate the temperature history in a pool of molten debris; CONFILM, to calculate the behaviour of a condensing film of vaporized core debris on the calandria wall, and BLDG, to calculate the pressurization of the containment during the expulsion of moderator through pressure relief ducts. In addition there are discussions of the average condensation heat transfer coefficient for vaporized core material on the calandria wall, and of vapor explosions

  19. Use of Solid Hydride Fuel for Improved long-Life LWR Core Designs. Final summary report

    International Nuclear Information System (INIS)

    Greenspan, E

    2006-01-01

    The primary objective of this project was to assess the feasibility of improving the performance of PWR and BWR cores by using solid hydride fuels instead of the commonly used oxide fuel. The primary measure of performance considered is the bus-bar cost of electricity (COE). Additional performance measures considered are safety, fuel bundle design simplicity in particular for BWR's, and plutonium incineration capability. It was found that hydride fuel can safely operate in PWR's and BWR's without restricting the linear heat generation rate of these reactors relative to that attainable with oxide fuel. A couple of promising applications of hydride fuel in PWR's and BWR's were identified: (1) Eliminating dedicated water moderator volumes in BWR cores thus enabling to significantly increase the cooled fuel rods surface area as well as the coolant flow cross section area in a given volume fuel bundle while significantly reducing the heterogeneity of BWR fuel bundles thus achieving flatter pin-by-pin power distribution. The net result is a possibility to significantly increase the core power density ? on the order of 30% and, possibly, more, while greatly simplifying the fuel bundle design. Implementation of the above modifications is, though, not straightforward; it requires a design of completely different control system that could probably be implemented only in newly designed plants. It also requires increasing the coolant pressure drop across the core. (2) Recycling plutonium in PWR's more effectively than is possible with oxide fuel by virtue of a couple of unique features of hydride fuel reduced inventory of U-238 and increased inventory of hydrogen. As a result, the hydride fueled core achieves nearly double the average discharge burnup and the fraction of the loaded Pu it incinerates in one pass is double that of the MOX fuel. The fissile fraction of the Pu in the discharged hydride fuel is only ∼2/3 that of the MOX fuel and the discharged hydride fuel is

  20. Identification of a Core Curriculum in Gerontology for Allied Health Professionals. Final Report.

    Science.gov (United States)

    Hedl, John J.; And Others

    The overall goal of this project was to identify a core curriculum in gerontology for seven allied health professions (radiologic technologist, radiation therapist, respiratory therapist, dental hygienist, dental assistant, physical therapy assistant, and occupational therapy assistant). The project also identified the current state of gerontology…

  1. Tank 241-AZ-102 Privatization Push Mode Core Sampling and Analysis Plan; FINAL

    International Nuclear Information System (INIS)

    TEMPLETON, A.M.

    1999-01-01

    This sampling and analysis plan (SAP) identifies characterization objectives pertaining to sample collection, laboratory analytical evaluation, and reporting requirements for samples obtained from tank 241-AZ-102. The purpose of this sampling event is to obtain information about the characteristics of the contents of 241-AZ-102. Push mode core samples will be obtained from risers 15C and 24A to provide sufficient material for the chemical analyses and tests required to satisfy these data quality objectives. The 222-S Laboratory will extrude core samples, composite the liquids and solids, perform chemical analyses, and provide subsamples to the Process Chemistry Laboratory. The Process Chemistry Laboratory will prepare test plans and perform process tests to evaluate the behavior of the 241-AZ-102 waste undergoing the retrieval and treatment scenarios defined in the applicable DQOs. Requirements for analyses of samples originating in the process tests will be documented in the corresponding test plan

  2. Tank 241-AN-104, cores 163 and 164 analytical results for the final report

    International Nuclear Information System (INIS)

    Steen, F.H.

    1997-01-01

    This document is the analytical laboratory report for tank 241-AN-104 push mode core segments collected between August 8, 1996 and September 12, 1996. The segments were subsampled and analyzed in accordance with the Tank 241-AAr-1 04 Push Mode Core Sampling and Analysis Plan (TSAP) (Winkelman, 1996), the Safety Screening Data Quality Objective (DQO) (Dukelow, et at., 1995) and the Flammable Gas Data Quality Objective (DQO) (Benar, 1995). The analytical results are included in a data summary table. None of the samples submitted for Differential Scanning Calorimetry (DSC), Total Alpha Activity (AT), Total Organic Carbon (TOC) and Plutonium analyses (239,240 Pu) exceeded notification limits as stated in the TSAP. The statistical results of the 95% confidence interval on the mean calculations are provided by the Tank Waste Remediation Systems Technical Basis Group in accordance with the Memorandum of Understanding (Schreiber, 1997) and not considered in this report

  3. LDRD final report : a lightweight operating system for multi-core capability class supercomputers.

    Energy Technology Data Exchange (ETDEWEB)

    Kelly, Suzanne Marie; Hudson, Trammell B. (OS Research); Ferreira, Kurt Brian; Bridges, Patrick G. (University of New Mexico); Pedretti, Kevin Thomas Tauke; Levenhagen, Michael J.; Brightwell, Ronald Brian

    2010-09-01

    The two primary objectives of this LDRD project were to create a lightweight kernel (LWK) operating system(OS) designed to take maximum advantage of multi-core processors, and to leverage the virtualization capabilities in modern multi-core processors to create a more flexible and adaptable LWK environment. The most significant technical accomplishments of this project were the development of the Kitten lightweight kernel, the co-development of the SMARTMAP intra-node memory mapping technique, and the development and demonstration of a scalable virtualization environment for HPC. Each of these topics is presented in this report by the inclusion of a published or submitted research paper. The results of this project are being leveraged by several ongoing and new research projects.

  4. Tank 241-AX-103, cores 212 and 214 analytical results for the final report

    Energy Technology Data Exchange (ETDEWEB)

    Steen, F.H.

    1998-02-05

    This document is the analytical laboratory report for tank 241-AX-103 push mode core segments collected between July 30, 1997 and August 11, 1997. The segments were subsampled and analyzed in accordance with the Tank 241-AX-103 Push Mode Core Sampling and Analysis Plan (TSAP) (Comer, 1997), the Safety Screening Data Quality Objective (DQO) (Dukelow, et al., 1995) and the Data Quality Objective to Support Resolution of the Organic Complexant Safety Issue (Organic DQO) (Turner, et al., 1995). The analytical results are included in the data summary table (Table 1). None of the samples submitted for Differential Scanning Calorimetry (DSC), Total Alpha Activity (AT), plutonium 239 (Pu239), and Total Organic Carbon (TOC) exceeded notification limits as stated in the TSAP (Conner, 1997). The statistical results of the 95% confidence interval on the mean calculations are provided by the Tank Waste Remediation Systems Technical Basis Group in accordance with the Memorandum of Understanding (Schreiber, 1997) and not considered in this report.

  5. Tank 241-T-203, core 190 analytical results for the final report

    International Nuclear Information System (INIS)

    Steen, F.H.

    1997-01-01

    This document is the analytical laboratory report for tank 241-T-203 push mode core segments collected on April 17, 1997 and April 18, 1997. The segments were subsainpled and analyzed in accordance with the Tank 241-T-203 Push Mode Core Sampling andanalysis Plan (TSAP) (Schreiber, 1997a), the Safety Screening Data Quality Objective (DQO)(Dukelow, et al., 1995) and Leffer oflnstructionfor Core Sample Analysis of Tanks 241-T-201, 241-T-202, 241-T-203, and 241-T-204 (LOI)(Hall, 1997). The analytical results are included in the data summary report (Table 1). None of the samples submitted for Differential Scanning Calorimetry (DSC), Total Alpha Activity (AT) and Total Organic Carbon (TOC) exceeded notification limits as stated in the TSAP (Schreiber, 1997a). The statistical results of the 95% confidence interval on the mean calculations are provided by the Tank Waste Remediation Systems (TWRS) Technical Basis Group in accordance with the Memorandum of Understanding (Schreiber, 1997b) and not considered in this report

  6. Tank 241-TX-118, core 236 analytical results for the final report

    International Nuclear Information System (INIS)

    ESCH, R.A.

    1998-01-01

    This document is the analytical laboratory report for tank 241-TX-118 push mode core segments collected between April 1, 1998 and April 13, 1998. The segments were subsampled and analyzed in accordance with the Tank 241-TX-118 Push Mode Core sampling and Analysis Plan (TSAP) (Benar, 1997), the Safety Screening Data Quality Objective (DQO) (Dukelow, et al., 1995), the Data Quality Objective to Support Resolution of the Organic Complexant Safety Issue (Organic DQO) (Turner, et al, 1995) and the Historical Model Evaluation Data Requirements (Historical DQO) (Sipson, et al., 1995). The analytical results are included in the data summary table (Table 1). None of the samples submitted for Differential Scanning Calorimetry (DSC) and Total Organic Carbon (TOC) exceeded notification limits as stated in the TSAP (Benar, 1997). One sample exceeded the Total Alpha Activity (AT) analysis notification limit of 38.4microCi/g (based on a bulk density of 1.6), core 236 segment 1 lower half solids (S98T001524). Appropriate notifications were made. Plutonium 239/240 analysis was requested as a secondary analysis. The statistical results of the 95% confidence interval on the mean calculations are provided by the Tank Waste Remediation Systems Technical Basis Group in accordance with the Memorandum of Understanding (Schreiber, 1997) and are not considered in this report

  7. Tank 241-TX-118, core 236 analytical results for the final report

    Energy Technology Data Exchange (ETDEWEB)

    ESCH, R.A.

    1998-11-19

    This document is the analytical laboratory report for tank 241-TX-118 push mode core segments collected between April 1, 1998 and April 13, 1998. The segments were subsampled and analyzed in accordance with the Tank 241-TX-118 Push Mode Core sampling and Analysis Plan (TSAP) (Benar, 1997), the Safety Screening Data Quality Objective (DQO) (Dukelow, et al., 1995), the Data Quality Objective to Support Resolution of the Organic Complexant Safety Issue (Organic DQO) (Turner, et al, 1995) and the Historical Model Evaluation Data Requirements (Historical DQO) (Sipson, et al., 1995). The analytical results are included in the data summary table (Table 1). None of the samples submitted for Differential Scanning Calorimetry (DSC) and Total Organic Carbon (TOC) exceeded notification limits as stated in the TSAP (Benar, 1997). One sample exceeded the Total Alpha Activity (AT) analysis notification limit of 38.4{micro}Ci/g (based on a bulk density of 1.6), core 236 segment 1 lower half solids (S98T001524). Appropriate notifications were made. Plutonium 239/240 analysis was requested as a secondary analysis. The statistical results of the 95% confidence interval on the mean calculations are provided by the Tank Waste Remediation Systems Technical Basis Group in accordance with the Memorandum of Understanding (Schreiber, 1997) and are not considered in this report.

  8. Final Report, Nuclear Energy Research Initiative (NERI) Project: An Innovative Reactor Analysis Methodology Based on a Quasidiffusion Nodal Core Model

    International Nuclear Information System (INIS)

    Anistratov, Dmitriy Y.; Adams, Marvin L.; Palmer, Todd S.; Smith, Kord S.; Clarno, Kevin; Hikaru Hiruta; Razvan Nes

    2003-01-01

    OAK (B204) Final Report, NERI Project: ''An Innovative Reactor Analysis Methodology Based on a Quasidiffusion Nodal Core Model'' The present generation of reactor analysis methods uses few-group nodal diffusion approximations to calculate full-core eigenvalues and power distributions. The cross sections, diffusion coefficients, and discontinuity factors (collectively called ''group constants'') in the nodal diffusion equations are parameterized as functions of many variables, ranging from the obvious (temperature, boron concentration, etc.) to the more obscure (spectral index, moderator temperature history, etc.). These group constants, and their variations as functions of the many variables, are calculated by assembly-level transport codes. The current methodology has two main weaknesses that this project addressed. The first weakness is the diffusion approximation in the full-core calculation; this can be significantly inaccurate at interfaces between different assemblies. This project used the nodal diffusion framework to implement nodal quasidiffusion equations, which can capture transport effects to an arbitrary degree of accuracy. The second weakness is in the parameterization of the group constants; current models do not always perform well, especially at interfaces between unlike assemblies. The project developed a theoretical foundation for parameterization and homogenization models and used that theory to devise improved models. The new models were extended to tabulate information that the nodal quasidiffusion equations can use to capture transport effects in full-core calculations

  9. The engineering and final assembly of S-1 Spheromak Flux Core

    International Nuclear Information System (INIS)

    Helmich, R.C.; Dahlgren, F.; Mullaney, D.; Reilly, B.; Snook, P.

    1983-01-01

    The Flux Core of the S-1 Spheromak (Figure 1) is a torus with a major radius of 1m and a minor radius of 19 cm. The primary elements within it are the PF and TF (Poloidal and Toroidal) windings which are a water cooled copper cable, two turns of EF (equilibrium Field) coils, and an epoxy-glass mandrel to support them. Surrounding these are an aluminum shell, potting material, and a thin, highly resistive Inconel liner which is a vacuum boundary. After the winding of the TF cables (see previous report for 9th Symposium), a built-up layer of dry interwoven fiberglass tape was wound around the entire flux core. The fiberglass, when vacuum impregnated, provides structural support. Next, the four piece aluminum shell which also served as an enclosure for vacuum impregnation was applied. The epoxy used in this operation was cured at low temperature to insure integrity of the PF/TF polyethylene insulation. After impregnation, a wet layup of fiberglass/air cure epoxy was wound over the aluminum shell for further structural support. The Inconel liner, which had been spun, ground, and chem-milled to a 0.254 mm thickness, was welded in position about the circumference at the midplane. A midplane band of 2.286mm thickness was left for this purpose along with elements to provide for closure welding of vacuum feedthru assemblies. The annulus between the liner and fiberglass/ epoxy structural wrapping was then pressure potted with urethane. This material was chosen because it would bond to the Inconel and fiberglass yet would allow for thermal expansion. The completed flux core was then installed between the domes of the S-1 vacuum vessel. Initial testing of S-1 indicates that the fabrication techniques have proven successful. A detailed description of the fabrication, installation, and testing will follow

  10. Tank 241-S-102, Core 232 analytical results for the final report

    Energy Technology Data Exchange (ETDEWEB)

    STEEN, F.H.

    1998-11-04

    This document is the analytical laboratory report for tank 241-S-102 push mode core segments collected between March 5, 1998 and April 2, 1998. The segments were subsampled and analyzed in accordance with the Tank 241-S-102 Retained Gas Sampler System Sampling and Analysis Plan (TSAP) (McCain, 1998), Letter of Instruction for Compatibility Analysis of Samples from Tank 241-S-102 (LOI) (Thompson, 1998) and the Data Quality Objectives for Tank Farms Waste Compatibility Program (DQO) (Mulkey and Miller, 1998). The analytical results are included in the data summary table (Table 1).

  11. Evaluation of improved light water reactor core designs. Final progress report, September 1979. LWRCD-20

    International Nuclear Information System (INIS)

    1979-01-01

    The work conducted under this research project has developed information which supports in all respects the U.S. position evolved under the NASAP/INFCE programs with respect to the near and intermediate term potential for ore conservation in LWRs on the once-through fuel cycle. Moreover, in the even longer term, it has been confirmed that contention by Edlund and others that tight-pitch Pu/UO 2 PWR cores can achieve conversion ratios which may allow these reactors to provide a competitive energy source far into the ore-scarce post-2000 era

  12. Evaluation of improved light water reactor core designs. Final progress report, September 1979. LWRCD-20

    Energy Technology Data Exchange (ETDEWEB)

    1979-10-31

    The work conducted under this research project has developed information which supports in all respects the U.S. position evolved under the NASAP/INFCE programs with respect to the near and intermediate term potential for ore conservation in LWRs on the once-through fuel cycle. Moreover, in the even longer term, it has been confirmed that contention by Edlund and others that tight-pitch Pu/UO/sub 2/ PWR cores can achieve conversion ratios which may allow these reactors to provide a competitive energy source far into the ore-scarce post-2000 era.

  13. Tank 241-S-102, Core 232 analytical results for the final report

    International Nuclear Information System (INIS)

    STEEN, F.H.

    1998-01-01

    This document is the analytical laboratory report for tank 241-S-102 push mode core segments collected between March 5, 1998 and April 2, 1998. The segments were subsampled and analyzed in accordance with the Tank 241-S-102 Retained Gas Sampler System Sampling and Analysis Plan (TSAP) (McCain, 1998), Letter of Instruction for Compatibility Analysis of Samples from Tank 241-S-102 (LOI) (Thompson, 1998) and the Data Quality Objectives for Tank Farms Waste Compatibility Program (DQO) (Mulkey and Miller, 1998). The analytical results are included in the data summary table (Table 1)

  14. Three-dimensional NDE of VHTR core components via simulation-based testing. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Guzina, Bojan [Univ. of Minnesota, Minneapolis, MN (United States); Kunerth, Dennis [Idaho National Lab. (INL), Idaho Falls, ID (United States)

    2014-09-30

    A next generation, simulation-driven-and-enabled testing platform is developed for the 3D detection and characterization of defects and damage in nuclear graphite and composite structures in Very High Temperature Reactors (VHTRs). The proposed work addresses the critical need for the development of high-fidelity Non-Destructive Examination (NDE) technologies for as-manufactured and replaceable in-service VHTR components. Centered around the novel use of elastic (sonic and ultrasonic) waves, this project deploys a robust, non-iterative inverse solution for the 3D defect reconstruction together with a non-contact, laser-based approach to the measurement of experimental waveforms in VHTR core components. In particular, this research (1) deploys three-dimensional Scanning Laser Doppler Vibrometry (3D SLDV) as a means to accurately and remotely measure 3D displacement waveforms over the accessible surface of a VHTR core component excited by mechanical vibratory source; (2) implements a powerful new inverse technique, based on the concept of Topological Sensitivity (TS), for non-iterative elastic waveform tomography of internal defects - that permits robust 3D detection, reconstruction and characterization of discrete damage (e.g. holes and fractures) in nuclear graphite from limited-aperture NDE measurements; (3) implements state-of-the art computational (finite element) model that caters for accurately simulating elastic wave propagation in 3D blocks of nuclear graphite; (4) integrates the SLDV testing methodology with the TS imaging algorithm into a non-contact, high-fidelity NDE platform for the 3D reconstruction and characterization of defects and damage in VHTR core components; and (5) applies the proposed methodology to VHTR core component samples (both two- and three-dimensional) with a priori induced, discrete damage in the form of holes and fractures. Overall, the newly established SLDV-TS testing platform represents a next-generation NDE tool that surpasses

  15. Three-dimensional NDE of VHTR core components via simulation-based testing. Final report

    International Nuclear Information System (INIS)

    Guzina, Bojan; Kunerth, Dennis

    2014-01-01

    A next generation, simulation-driven-and-enabled testing platform is developed for the 3D detection and characterization of defects and damage in nuclear graphite and composite structures in Very High Temperature Reactors (VHTRs). The proposed work addresses the critical need for the development of high-fidelity Non-Destructive Examination (NDE) technologies for as-manufactured and replaceable in-service VHTR components. Centered around the novel use of elastic (sonic and ultrasonic) waves, this project deploys a robust, non-iterative inverse solution for the 3D defect reconstruction together with a non-contact, laser-based approach to the measurement of experimental waveforms in VHTR core components. In particular, this research (1) deploys three-dimensional Scanning Laser Doppler Vibrometry (3D SLDV) as a means to accurately and remotely measure 3D displacement waveforms over the accessible surface of a VHTR core component excited by mechanical vibratory source; (2) implements a powerful new inverse technique, based on the concept of Topological Sensitivity (TS), for non-iterative elastic waveform tomography of internal defects - that permits robust 3D detection, reconstruction and characterization of discrete damage (e.g. holes and fractures) in nuclear graphite from limited-aperture NDE measurements; (3) implements state-of-the art computational (finite element) model that caters for accurately simulating elastic wave propagation in 3D blocks of nuclear graphite; (4) integrates the SLDV testing methodology with the TS imaging algorithm into a non-contact, high-fidelity NDE platform for the 3D reconstruction and characterization of defects and damage in VHTR core components; and (5) applies the proposed methodology to VHTR core component samples (both two- and three-dimensional) with a priori induced, discrete damage in the form of holes and fractures. Overall, the newly established SLDV-TS testing platform represents a next-generation NDE tool that surpasses

  16. Utterance-final particles in Taiwan Mandarin : contact, context and core functions

    NARCIS (Netherlands)

    Lin, Chin-hui

    2014-01-01

    The use of utterance-final particles (UFPs) is a salient feature of Taiwan Mandarin, a Mandarin variety spoken in Taiwan. Despite their widespread use, Taiwan Mandarin UFPs have not attracted much attention in previous research. One reason for this neglect is that previous studies focus on UFPs that

  17. FDA Approves Lutathera for Neuroendocrine Tumors

    Science.gov (United States)

    FDA has approved Lutathera® for some people with neuroendocrine tumors (NETs) that affect the digestive tract. On January 29, FDA approved Lutathera® for adult patients with advanced NETs that affect the pancreas or gastrointestinal tract, known as GEP-NETs.

  18. Production circulator fabrication and testing for core flow test loop. Final report, Phase III

    International Nuclear Information System (INIS)

    1981-05-01

    The performance testing of two production helium circulators utilizing gas film lubrication is described. These two centrifugal-type circulators plus an identical circulator prototype will be arranged in series to provide the helium flow requirements for the Core Flow Test Loop which is part of the Gas-Cooled Fast Breeder Reactor Program (GCFR) at the Oak Ridge National Laboratory. This report presents the results of the Phase III performance and supplemental tests, which were carried out by MTI during the period of December 18, 1980 through March 19, 1981. Specific test procedures are outlined and described, as are individual tests for measuring the performance of the circulators. Test data and run descriptions are presented

  19. Production circulator fabrication and testing for core flow test loop. Final report, Phase III

    Energy Technology Data Exchange (ETDEWEB)

    1981-05-01

    The performance testing of two production helium circulators utilizing gas film lubrication is described. These two centrifugal-type circulators plus an identical circulator prototype will be arranged in series to provide the helium flow requirements for the Core Flow Test Loop which is part of the Gas-Cooled Fast Breeder Reactor Program (GCFR) at the Oak Ridge National Laboratory. This report presents the results of the Phase III performance and supplemental tests, which were carried out by MTI during the period of December 18, 1980 through March 19, 1981. Specific test procedures are outlined and described, as are individual tests for measuring the performance of the circulators. Test data and run descriptions are presented.

  20. How the FDA and the ADA affect development of prescription drugs for oral care.

    Science.gov (United States)

    Cooley, W E

    1992-01-01

    The patient-consumer, the health professional, and the producer are all essential in the world of prescription drugs for oral care. Also essential are the Food and Drug Administration (FDA) and the American Dental Association (ADA). The FDA is charged with reviewing new-drug applications in the United States and approving those drugs that are proved safe and effective. The FDA also controls prescription-drug advertising and promotion. The ADA applies professional standards in judging all submitted dental drugs. Those drugs accepted by ADA's Council on Dental Therapeutics may display the ADA seal in labeling and advertising. All advertising for accepted products must be cleared by the ADA. An example of a prescription drug approved by the FDA and accepted by the ADA is 0.12 percent chlorhexidine gluconate oral rinse (Peridex). This drug followed the FDA's investigational-drug (IND) regulations before final approval as a treatment for gingivitis.

  1. Use of X-ray computed tomography in core analysis of tight North Sea Chalk. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Mogensen, K.; Stenby, E.H.

    1997-12-01

    This EFP-95 final report summarizes work performed at the Engineering Research Center (IVC-SEP) on the use of CT scanning in core analysis of tight core material from the North Sea. In this work, CT scanning has been applied to chalk material from Danish North Sea oil reservoirs. Results indicate that CT is fast and reliable for prediction of porosity. Typical errors lie within 2-3%. Calculation of fluid saturations requires considerable care from the experimentalists. Saturating a core ought to be performed by pulling vacuum to avoid trapped air bubbles. These bubbles may be produced after subsequent water and gas flooding, thereby ruining the mass balance calculations. Results performed at Stanford University show that if these simple precautions are taken, fluid saturations calculated from CT scanning are generally very accurate. Moreover, it appears that contrast agents need not be added to either phase. Regarding three-phase measurements the results are somewhat disappointing. Previous work using the dual-energy technique has indicated that the accuracy is less than satisfactory, due to an increased noise level at the low-energy setting. More work needs to be done in the future to develop the necessary expertise. The image analysis of the residual oil saturation after a gas flood can be simplified if water is assumed to be immobile during the injection. In that case, the resulting prediction of residual oil saturation is in excellent agreement with measured values. The general conclusion is that CT scanning holds a great potential as an assisting tool in modern core analysis, despite its limitations and the numerous implementation-related problems encountered during this work. (au) EFP-95. 57 refs.

  2. Technical specification improvements to containment heat removal and emergency core cooling systems: Final report

    International Nuclear Information System (INIS)

    Sullivan, W.P.; Ha, C.; Pentzien, D.C.; Visweswaran, S.

    1988-07-01

    This report presents the results of an analysis for technical specification improvements to the emergency core cooling systems (ECCS) and containment heat removal systems (EPRI Research Project 2142-3). The objective of this project is to further develop a reliability- and risk-based methodology to provide improvements by considering groups of surveillance test intervals and allowed out-of-service times jointly. This was done for the technical specifications for the ECCS, containment heat removal equipment, and supporting systems of a boiling water reactor plant. The project (1) developed a methodology for optimizing groups of surveillance test intervals and allowed out-of-service times jointly, (2) applied the methodology in a case study of a specific operating plant, Hatch-2, and (3) evaluated benefits of the application. The results of the case study demonstrate that beneficial technical specification improvements can be realized with application of the methodology. By tightening a small group of sensitive surveillance test intervals (STIs) and allowed out-of-service times (AOTs), a larger group of less sensitive STIs and AOTs can be extended resulting in an overall plant operating cost improvement without reducing the plant safety. The reliability- and risk-based methodology and results from this project can be effectively applied for technical specification improvements at other operating plants

  3. An evaluation of the FDA's analysis of the costs and benefits of the graphic warning label regulation

    OpenAIRE

    Chaloupka, Frank J; Warner, Kenneth E; Acemoğlu, Daron; Gruber, Jonathan; Laux, Fritz; Max, Wendy; Newhouse, Joseph; Schelling, Thomas; Sindelar, Jody

    2015-01-01

    The Family Smoking Prevention and Tobacco Control Act of 2009 gave the Food and Drug Administration (FDA) regulatory authority over cigarettes and smokeless tobacco products and authorised it to assert jurisdiction over other tobacco products. As with other Federal agencies, FDA is required to assess the costs and benefits of its significant regulatory actions. To date, FDA has issued economic impact analyses of one proposed and one final rule requiring graphic warning labels (GWLs) on cigare...

  4. FDA Regulation of Health and Fitness Equipment

    OpenAIRE

    Moss, Nicole J.

    2000-01-01

    As new "quasi-medical" devices continue to push the bounds of the FDCA definition of a medical device and with growing popular support for using the FDA to regulate previously off-limit products such as tobacco, the FDA may very well broaden its regulatory scope into the health and fitness industry. By focusing on the specific example of the scuba industry, this paper will examine first, whether the FDA has the authority to regulate athletic equipment as medical devices. Part two will explore...

  5. Final design of an air core, compulsator driven, 0.60 caliber railgun system

    International Nuclear Information System (INIS)

    Kitzmiller, J.R.; Faidley, R.W.; Fuller, R.L.; Headifen, G.R.; Pratap, S.B.; Spann, M.L.; Thelen, R.F.

    1991-01-01

    The Center for Electromechanics at The University of Texas at Austin (CEM-UT), is currently in the manufacturing phase of a laboratory based small caliber electromagnetic (EM) launcher and compulsator power supply. The objective of the 29-month program is to develop a compact, lightweight test bed capable of accelerating 32-g masses to 2 km/s at a rate of 10 Hz. Both the power supply and launcher feature significant component design advances which will allow the system to operate at considerably higher energy and power densities than previously demonstrated. The 750-kg compulsator will generate 2.2 kV and the Silicon- controlled rectifier (SCR) switch will commutate 386-kA pulses into the 1.6-m long, 0.60 caliber augmented solid armature railgun. This paper describes the final design and predicted operating characteristics of the compulsator system. Overall system performance parameters are reported, including results from the optimization code used to aid in the design of the compulsator system. A system design overview is presented with emphasis on new materials and state-of-the-art machine components to be used for the first time in a compulsator

  6. FDA Approves Apalutamide for Prostate Cancer

    Science.gov (United States)

    Apalutamide (Erleada) is a hormone therapy that counteracts resistance to androgen deprivation therapy. Learn more about the FDA approval of apalutamide for men with castration-resistant nonmetastatic prostate cancer in this Cancer Currents blog post.

  7. 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.

  8. 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...

  9. Effects of cooking method and final core-temperature on cooking loss, lipid oxidation, nucleotide-related compounds and aroma volatiles of Hanwoo brisket

    Directory of Open Access Journals (Sweden)

    Dicky Tri Utama

    2018-02-01

    Full Text Available Objective This study observed the effects of cooking method and final core temperature on cooking loss, lipid oxidation, aroma volatiles, nucleotide-related compounds and aroma volatiles of Hanwoo brisket (deep pectoralis. Methods Deep pectoralis muscles (8.65% of crude fat were obtained from three Hanwoo steer carcasses with 1+ quality grade. Samples were either oven-roasted at 180°C (dry heat or cooked in boiling water (moist heat to final core temperature of 70°C (medium or 77°C (well-done. Results Boiling method reduced more fat but retained more moisture than did the oven roasting method (p<0.001, thus no significant differences were found on cooking loss. However, samples lost more weight as final core temperature increased (p<0.01. Further, total saturated fatty acid increased (p = 0.02 while total monounsaturated fatty acid decreased (p = 0.03 as final core temperature increased. Regardless the method used for cooking, malondialdehyde (p<0.01 and free iron contents (p<0.001 were observed higher in samples cooked to 77°C. Oven roasting retained more inosinic acid, inosine and hypoxanthine in samples than did the boiling method (p<0.001, of which the concentration decreased as final core temperature increased except for hypoxanthine. Samples cooked to 77°C using oven roasting method released more intense aroma than did the others and the aroma pattern was discriminated based on the intensity. Most of aldehydes and pyrazines were more abundant in oven-roasted samples than in boiled samples. Among identified volatiles, hexanal had the highest area unit in both boiled and oven-roasted samples, of which the abundance increased as the final core temperature increased. Conclusion The boiling method extracted inosinic acid and rendered fat from beef brisket, whereas oven roasting intensified aroma derived from aldehydes and pyrazines and prevented the extreme loss of inosinic acid.

  10. 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...

  11. FDA Expands Abiraterone Approval for Prostate Cancer

    Science.gov (United States)

    The FDA has expanded the approval of abiraterone (Zytiga) to treat men with metastatic prostate cancer. The agency approved abiraterone, in combination with prednisone, for men whose cancer that is responsive to hormone-blocking treatments (also known as castration-sensitive) and is at high risk of progressing.

  12. 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

  13. Final PANTHER solution to the NEA-NSC3-DPWR core transient benchmark. Uncontrolled withdrawal of control rods at zero power

    International Nuclear Information System (INIS)

    Kuijper, J.C.

    1996-10-01

    This report contains the final results of PANTHER calculations for the 'NEA-NSC 3-D PWR Core Transient Benchmark: Uncontrolled Withdrawal of Control Rods at Zero Power'. PANTHER was able to model the benchmark problems without modifications to the code. All the calculations were performed in 3-D. (orig.)

  14. Evidentiary Support in Public Comments to the FDA's Center for Tobacco Products.

    Science.gov (United States)

    Hemmerich, Natalie; Klein, Elizabeth G; Berman, Micah

    2017-08-01

    Electronic Nicotine Delivery Systems (ENDS) were introduced into the US market in 2007, and until recently these devices were unregulated at the federal level. In 2014, the US Food and Drug Administration (FDA) published a Notice of Proposed Rulemaking asserting its intention to regulate ENDS and requesting public comments on numerous related issues, including potential limits on the sale of flavored ENDS. This article analyzes key comments submitted to the FDA on the issue of flavor regulation in ENDS and examines the weight and credibility of the evidence presented by both supporters and opponents of regulation. It also describes the final deeming rule, published in May 2016, and the FDA's response to the evidence submitted. This is the first study to examine public comments submitted to the FDA's Center for Tobacco Products, and it concludes that opponents of regulation were more likely to rely on sources that were not peer reviewed and that were affected by conflicts of interest. In light of these findings, the FDA and the research community should develop processes to carefully and critically analyze public comments submitted to the FDA on issues of tobacco regulation. Copyright © 2017 by Duke University Press.

  15. 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.

  16. 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.

  17. Vitamin D discovery outpaces FDA decision making.

    Science.gov (United States)

    Marshall, Trevor G

    2008-02-01

    The US FDA currently encourages the addition of vitamin D to milk and cereals, with the aim of reducing rickets in children and osteoporosis in adults. However, vitamin D not only regulates the expression of genes associated with calcium homeostasis, but also genes associated with cancers, autoimmune disease, and infection. It does this by controlling the activation of the vitamin D receptor (VDR), a type 1 nuclear receptor and DNA transcription factor. Molecular biology is rapidly coming to an understanding of the multiplicity of roles played by the VDR, but clinical medicine is having difficulty keeping up with the pace of change. For example, the FDA recently proposed a rule change that will encourage high levels of vitamin D to be added to even more foods, so that the manufacturers can claim those foods "reduce the risk of osteoporosis". The FDA docket does not review one single paper detailing the transcriptional activity of vitamin D, even though, on average, one new paper a day is being published on that topic. Nor do they review whether widespread supplementation with vitamin D, an immunomodulatory secosteroid, might predispose the population to immune dysfunction. This BioEssay explores how lifelong supplementation of the food chain with vitamin D might well be contributing to the current epidemics of obesity and chronic disease. (c) 2008 Wiley Periodicals, Inc.

  18. 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 …

  19. 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...

  20. 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...

  1. An evaluation of the FDA's analysis of the costs and benefits of the graphic warning label regulation

    Science.gov (United States)

    Chaloupka, Frank J; Warner, Kenneth E; Acemoğlu, Daron; Gruber, Jonathan; Laux, Fritz; Max, Wendy; Newhouse, Joseph; Schelling, Thomas; Sindelar, Jody

    2015-01-01

    The Family Smoking Prevention and Tobacco Control Act of 2009 gave the Food and Drug Administration (FDA) regulatory authority over cigarettes and smokeless tobacco products and authorised it to assert jurisdiction over other tobacco products. As with other Federal agencies, FDA is required to assess the costs and benefits of its significant regulatory actions. To date, FDA has issued economic impact analyses of one proposed and one final rule requiring graphic warning labels (GWLs) on cigarette packaging and, most recently, of a proposed rule that would assert FDA’s authority over tobacco products other than cigarettes and smokeless tobacco. Given the controversy over the FDA's approach to assessing net economic benefits in its proposed and final rules on GWLs and the importance of having economic impact analyses prepared in accordance with sound economic analysis, a group of prominent economists met in early 2014 to review that approach and, where indicated, to offer suggestions for an improved analysis. We concluded that the analysis of the impact of GWLs on smoking substantially underestimated the benefits and overestimated the costs, leading the FDA to substantially underestimate the net benefits of the GWLs. We hope that the FDA will find our evaluation useful in subsequent analyses, not only of GWLs but also of other regulations regarding tobacco products. Most of what we discuss applies to all instances of evaluating the costs and benefits of tobacco product regulation and, we believe, should be considered in FDA's future analyses of proposed rules. PMID:25550419

  2. Effects of cooking method and final core-temperature on cooking loss, lipid oxidation, nucleotide-related compounds and aroma volatiles of Hanwoo brisket.

    Science.gov (United States)

    Utama, Dicky Tri; Baek, Ki Ho; Jeong, Hae Seong; Yoon, Seok Ki; Joo, Seon-Tea; Lee, Sung Ki

    2018-02-01

    This study observed the effects of cooking method and final core temperature on cooking loss, lipid oxidation, aroma volatiles, nucleotide-related compounds and aroma volatiles of Hanwoo brisket ( deep pectoralis ). Deep pectoralis muscles (8.65% of crude fat) were obtained from three Hanwoo steer carcasses with 1 + quality grade. Samples were either oven-roasted at 180°C (dry heat) or cooked in boiling water (moist heat) to final core temperature of 70°C (medium) or 77°C (well-done). Boiling method reduced more fat but retained more moisture than did the oven roasting method (pcore temperature increased (pcore temperature increased. Regardless the method used for cooking, malondialdehyde (pcore temperature increased except for hypoxanthine. Samples cooked to 77°C using oven roasting method released more intense aroma than did the others and the aroma pattern was discriminated based on the intensity. Most of aldehydes and pyrazines were more abundant in oven-roasted samples than in boiled samples. Among identified volatiles, hexanal had the highest area unit in both boiled and oven-roasted samples, of which the abundance increased as the final core temperature increased. The boiling method extracted inosinic acid and rendered fat from beef brisket, whereas oven roasting intensified aroma derived from aldehydes and pyrazines and prevented the extreme loss of inosinic acid.

  3. Evaluation of final vapor pressures in the loss of flow accident in an irradiation device of a pool reactor core

    International Nuclear Information System (INIS)

    Verri, A.

    1987-01-01

    The reliability feature, are described for a device containing samples, at a temperatures of 300 grade centigrades, in a reactor core for a long time. After an examination of the maximum accident event, the maximum vapour pressure originated by the inlet of reactor cooling water into the experimental device, is evaluated

  4. ["The hard core". Science between politics and philosophy by Carl Friedrich von Weizsäcker and in the finalization theory].

    Science.gov (United States)

    Krohn, Wolfgang

    2014-01-01

    In the Starnberg Max-Planck Institute one of the working groups was concerned with science as the formative condition--or "hard core"--of societal modernity, and with science as potential resource for solving social problems and addressing future goals. More precisely, the group intended to differentiate between phases in which scientific disciplines predominantly care for their own paradigmatic completion and those allowing their theoretical potential resonate with external needs. The conceptual model was coined "finalization in science". It soon provoked a heated controversy on the dangers of social control of science. The paper analyses Carl Friedrich von Weizsäcker's views on the relation between philosophy and policy of science including his interpretation of Thomas Kuhn and reconstructs the impact of his ideas on the finalization model. It finally reflects on the relationship between science development and change of consciousness in the context of scientific responsibility for (the use of) research outcomes.

  5. 78 FR 14309 - Implementation of the FDA Food Safety Modernization Act Provision Requiring FDA To Establish...

    Science.gov (United States)

    2013-03-05

    ... tracing of foods along the supply chain from source to points of service; 6. Demonstrate the tracking and.... The report recommends that each member of the food supply chain should be required to develop..., entitled ``Pilot Projects for Improving Product Tracing along the Food Supply System.'' FDA is announcing...

  6. Advanced computational methods for the assessment of reactor core behaviour during reactivity initiated accidents. Final report; Fortschrittliche Rechenmethoden zum Kernverhalten bei Reaktivitaetsstoerfaellen. Abschlussbericht

    Energy Technology Data Exchange (ETDEWEB)

    Pautz, A.; Perin, Y.; Pasichnyk, I.; Velkov, K.; Zwermann, W.; Seubert, A.; Klein, M.; Gallner, L.; Krzycacz-Hausmann, B.

    2012-05-15

    The document at hand serves as the final report for the reactor safety research project RS1183 ''Advanced Computational Methods for the Assessment of Reactor Core Behavior During Reactivity-Initiated Accidents''. The work performed in the framework of this project was dedicated to the development, validation and application of advanced computational methods for the simulation of transients and accidents of nuclear installations. These simulation tools describe in particular the behavior of the reactor core (with respect to neutronics, thermal-hydraulics and thermal mechanics) at a very high level of detail. The overall goal of this project was the deployment of a modern nuclear computational chain which provides, besides advanced 3D tools for coupled neutronics/ thermal-hydraulics full core calculations, also appropriate tools for the generation of multi-group cross sections and Monte Carlo models for the verification of the individual calculational steps. This computational chain shall primarily be deployed for light water reactors (LWR), but should beyond that also be applicable for innovative reactor concepts. Thus, validation on computational benchmarks and critical experiments was of paramount importance. Finally, appropriate methods for uncertainty and sensitivity analysis were to be integrated into the computational framework, in order to assess and quantify the uncertainties due to insufficient knowledge of data, as well as due to methodological aspects.

  7. Constant-atomic-final-state filtering of dissociative states in the O1s-->sigma* core excitation in O2.

    Science.gov (United States)

    Hjelte, I; Björneholm, O; Carravetta, V; Angeli, C; Cimiraglia, R; Wiesner, K; Svensson, S; Piancastelli, M N

    2005-08-08

    The below-threshold region in core-excited O2 is very complex, consisting of a multitude of exchange-split states with mixed molecular orbital-Rydberg character. We have investigated the nature of these intermediate states by resonant Auger spectroscopy. In particular, we have obtained constant-atomic-final-state yield curves for several atomic peaks in the electron decay spectra which are stemming from ultrafast dissociation. The relative intensity of Auger decay leading to atomic final states is considered a signature of the relative weight of the sigma* character. This method allows one to "filter out" intermediate states with dissociative character. Extensive calculations have been performed by multi-reference configuration interaction at different interatomic distances in order to evaluate the potential curves of the core-excited states and propose a qualitative description of the dissociative molecular dynamics. The calculations show that the core-excited states have a relevant admixture of excitations to orbitals with Rydberg character and excitations to the sigma* orbital with different spin couplings. A diabatization of the adiabatic potential curves shows that the coupling between Rydberg and sigma* diabatic states is very different at the different crossing points and ultrafast dissociation occurs more easily on the lowest sigma* diabatic potential curve. As a consequence, the observation of atomic peaks only in the lower-energy region of the absorption curve is well justified.

  8. Final report on the sampling and analysis of sediment cores from the L-Area oil and chemical basin

    Energy Technology Data Exchange (ETDEWEB)

    1985-08-01

    Nine vibracores were collected in the L-Area oil and chemical basin (904-83G) during late March and early April 1985. These cores were collected for analysis of the sludge on the basin floor and the underlying sediment. Several different field and laboratory analyses were performed on each three inch segment of all the cores. These included: (1) Sediment characterization; (2) Percent moisture; (3) Dry weight; (4) Spectral gamma analysis; (5) Gross alpha and beta analysis. Detailed chemical analysis were measured on selected intervals of 2 cores (LBC-5 and 6) for complete chemical characterization of the sediments. This sampling program was conducted to provide information so that a closure plan for the basin could be developed. This report describes the methods employed during the project and provide a hard copy of the analytical results from the sample analyses. Included in the appendices are copies of all field and laboratory notes taken during the project and copies of the gas chromatograms for the petroleum hydrocarbon analysis. All chemical results were also submitted on a 5-inch floppy disk.

  9. FDA advierte sobre cardiotoxicidad de cisaprida

    Directory of Open Access Journals (Sweden)

    Carlos Bustamante Rojas

    1998-07-01

    Full Text Available La FDA y Janssen Phamaceuticals -el fabricante de cisaprida- han advertido mediante cartas a los prescriptores que el fármaco no deberá ser utilizado simultáneamente junto con macrólidos antifúngicos, algunos antidepresivos e inhibidores de las proteasas, ya que puede aparecer prolongación del intervalo QT y severos trastornos del ritmo cardiaco. Adicionalmente, el fármaco está contraindicado en los pacientes con EPOC, ICC, cáncer avanzado y en pacientes can alteraciones del equilibrio hidroelectrolítico como hipomagnesemia o hipokalemia. Igualmente, su uso debe hacerse con bastantes precauciones en los pacientes que reciben insulina y aquellos que presentan náuseas, vómito, diarrea o deshidratación.

  10. Conceptual design analysis of an MHD power conversion system for droplet-vapor core reactors. Final report

    International Nuclear Information System (INIS)

    Anghaie, S.; Saraph, G.

    1995-01-01

    A nuclear driven magnetohydrodynamic (MHD) generator system is proposed for the space nuclear applications of few hundreds of megawatts. The MHD generator is coupled to a vapor-droplet core reactor that delivers partially ionized fissioning plasma at temperatures in range of 3,000 to 4,000 K. A detailed MHD model is developed to analyze the basic electrodynamics phenomena and to perform the design analysis of the nuclear driven MHD generator. An incompressible quasi one dimensional model is also developed to perform parametric analyses

  11. Fuel efficient hydrodynamic containment for gas core fission reactor rocket propulsion. Final report, September 30, 1992--May 31, 1995

    International Nuclear Information System (INIS)

    Sforza, P.M.; Cresci, R.J.

    1997-01-01

    Gas core reactors can form the basis for advanced nuclear thermal propulsion (NTP) systems capable of providing specific impulse levels of more than 2,000 sec., but containment of the hot uranium plasma is a major problem. The initial phase of an experimental study of hydrodynamic confinement of the fuel cloud in a gas core fission reactor by means of an innovative application of a base injection stabilized recirculation bubble is presented. The development of the experimental facility, a simulated thrust chamber approximately 0.4 m in diameter and 1 m long, is described. The flow rate of propellant simulant (air) can be varied up to about 2 kg/sec and that of fuel simulant (air, air-sulfur hexafluoride) up to about 0.2 kg/sec. This scale leads to chamber Reynolds numbers on the same order of magnitude as those anticipated in a full-scale nuclear rocket engine. The experimental program introduced here is focused on determining the size, geometry, and stability of the recirculation region as a function of the bleed ratio, i.e. the ratio of the injected mass flux to the free stream mass flux. A concurrent CFD study is being carried out to aid in demonstrating that the proposed technique is practical

  12. Compendium of ECCS [Emergency Core Cooling Systems] research for realistic LOCA [loss-of-coolant accidents] analysis: Final report

    International Nuclear Information System (INIS)

    1988-12-01

    In the United States, Emergency Core Cooling Systems (ECCS) are required for light water reactors (LWRs) to provide cooling of the reactor core in the event of a break or leak in the reactor piping or an inadvertent opening of a valve. These accidents are called loss-of-coolant accidents (LOCA), and they range from small leaks up to a postulated full break of the largest pipe in the reactor cooling system. Federal government regulations provide that LOCA analysis be performed to show that the ECCS will maintain fuel rod cladding temperatures, cladding oxidation, and hydrogen production within certain limits. The NRC and others have completed a large body of research which investigated fuel rod behavior and LOCA/ECCS performance. It is now possible to make a realistic estimate of the ECCS performance during a LOCA and to quantify the uncertainty of this calculation. The purpose of this report is to summarize this research and to serve as a general reference for the extensive research effort that has been performed. The report: (1) summarizes the understanding of LOCA phenomena in 1974; (2) reviews experimental and analytical programs developed to address the phenomena; (3) describes the best-estimate computer codes developed by the NRC; (4) discusses the salient technical aspects of the physical phenomena and our current understanding of them; (5) discusses probabilistic risk assessment results and perspectives, and (6) evaluates the impact of research results on the ECCS regulations. 736 refs., 412 figs., 66 tabs

  13. The FDA's program for monitoring radionuclides in food

    International Nuclear Information System (INIS)

    Baratta, E.J.

    1992-01-01

    The US Food and Drug Administration (FDA) modified its food-monitoring program in 1973 to include radioactive isotopes. There was concern at this time about the possibility of food contamination by effluents from nuclear power plants, some above-ground weapons testing by nonsignatory powers, and increased use of medical and commercial radioactive materials. The FDA decided, therefore, that a radioanalytical capability must be maintained to detect any upward trend of radioactive contamination in food. This capability would also allow the FDA to respond to any incidents that might occur in order to protect the US food supply. This program is located at the FDA's Winchester Engineering and Analytical Center, Winchester, Massachusetts

  14. 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

    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......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...

  15. An evaluation of the FDA's analysis of the costs and benefits of the graphic warning label regulation.

    Science.gov (United States)

    Chaloupka, Frank J; Warner, Kenneth E; Acemoğlu, Daron; Gruber, Jonathan; Laux, Fritz; Max, Wendy; Newhouse, Joseph; Schelling, Thomas; Sindelar, Jody

    2015-03-01

    The Family Smoking Prevention and Tobacco Control Act of 2009 gave the Food and Drug Administration (FDA) regulatory authority over cigarettes and smokeless tobacco products and authorised it to assert jurisdiction over other tobacco products. As with other Federal agencies, FDA is required to assess the costs and benefits of its significant regulatory actions. To date, FDA has issued economic impact analyses of one proposed and one final rule requiring graphic warning labels (GWLs) on cigarette packaging and, most recently, of a proposed rule that would assert FDA's authority over tobacco products other than cigarettes and smokeless tobacco. Given the controversy over the FDA's approach to assessing net economic benefits in its proposed and final rules on GWLs and the importance of having economic impact analyses prepared in accordance with sound economic analysis, a group of prominent economists met in early 2014 to review that approach and, where indicated, to offer suggestions for an improved analysis. We concluded that the analysis of the impact of GWLs on smoking substantially underestimated the benefits and overestimated the costs, leading the FDA to substantially underestimate the net benefits of the GWLs. We hope that the FDA will find our evaluation useful in subsequent analyses, not only of GWLs but also of other regulations regarding tobacco products. Most of what we discuss applies to all instances of evaluating the costs and benefits of tobacco product regulation and, we believe, should be considered in FDA's future analyses of proposed rules. 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.

  16. A High Temperature-Tolerant and Radiation-Resistant In-Core Neutron Sensor for Advanced Reactors. Final report

    International Nuclear Information System (INIS)

    Cao, Lei; Miller, Don

    2015-01-01

    The objectives of this project are to develop a small and reliable gallium nitride (GaN) neutron sensor that is capable of withstanding high neutron fluence and high temperature, isolating gamma background, and operating in a wide dynamic range. The first objective will be the understanding of the fundamental materials properties and electronic response of a GaN semiconductor materials and device in an environment of high temperature and intense neutron field. To achieve such goal, an in-situ study of electronic properties of GaN device such as I-V, leakage current, and charge collection efficiency (CCE) in high temperature using an external neutron beam will be designed and implemented. We will also perform in-core irradiation of GaN up to the highest yet fast neutron fluence and an off-line performance evaluation.

  17. A High Temperature-Tolerant and Radiation-Resistant In-Core Neutron Sensor for Advanced Reactors. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Cao, Lei [The Ohio State Univ., Columbus, OH (United States); Miller, Don [The Ohio State Univ., Columbus, OH (United States)

    2015-01-23

    The objectives of this project are to develop a small and reliable gallium nitride (GaN) neutron sensor that is capable of withstanding high neutron fluence and high temperature, isolating gamma background, and operating in a wide dynamic range. The first objective will be the understanding of the fundamental materials properties and electronic response of a GaN semiconductor materials and device in an environment of high temperature and intense neutron field. To achieve such goal, an in-situ study of electronic properties of GaN device such as I-V, leakage current, and charge collection efficiency (CCE) in high temperature using an external neutron beam will be designed and implemented. We will also perform in-core irradiation of GaN up to the highest yet fast neutron fluence and an off-line performance evaluation.

  18. Draft guidance for industry; exports and imports under the FDA Export Reform and Enhancement Act of 1996--FDA. Notice.

    Science.gov (United States)

    1998-06-12

    The Food and Drug Administration (FDA) is announcing the availability of a draft guidance document entitled, "FDA Draft Guidance for Industry on: Exports and Imports Under the FDA Export Reform and Enhancement Act of 1996." The draft guidance document addresses issues pertaining to the exportation of human drugs, animal drugs, biologics, food additives, and devices as well as the importation of components, parts, accessories, or other articles for incorporation or further processing into articles intended for export.

  19. An analysis of the proposed MITR-III core to establish thermal-hydraulic limits at 10 MW. Final report

    International Nuclear Information System (INIS)

    Harling, O.K.; Lanning, D.D.; Bernard, J.A.; Meyer, J.E.; Henry, A.F.

    1997-01-01

    The 5 MW Massachusetts Institute of Technology Research Reactor (MITR-II) is expected to operate under a new license beginning in 1999. Among the options being considered is an upgrade in the heat removal system to allow operation at 10 MW. The purpose of this study is to predict the Limiting Safety System Settings and Safety Limits for the upgraded reactor (MITR-III). The MITR Multi-Channel Analysis Code was written to analyze the response of the MITR system to a series of anticipated transients in order to determine the Limiting Safety System Settings and Safety Limits under various operating conditions. The MIT Multi-Channel Analysis Code models the primary and secondary systems, with special emphasis placed on analyzing the thermal-hydraulic conditions in the core. The code models each MITR fuel element explicitly in order to predict the behavior of the system during flow instabilities. The results of the code are compared to experimental data from MITR-II and other sources. New definitions are suggested for the Limiting Safety System Settings and Safety Limits. MITR Limit Diagrams are included for three different heat removal system configurations. It is concluded that safe, year-round operating at 10 MW is possible, given that the primary and secondary flow rates are both increased by approximately 40%

  20. Editorial Commentary: Core Muscle Injuries or Athletic Pubalgia-Finally the Real Sausage, Not Just the Same Ole Baloney.

    Science.gov (United States)

    Meyers, William C

    2017-05-01

    In their paper "Prevalence of Surgical Repair for Athletic Pubalgia and Impact on Performance in Football Athletes Participating in the National Football League Combine," Knapik et al. cut through the baloney in the literature on "sports hernia" and apply new eyes to the impact of the results of core muscle surgery on young elite athletes trying out for the National Football League (NFL). They found that the players who had surgery did just as well as all the others in and following NFL Combines. Even the players with presumptively residual, MRI findings did well. The paper is superb and identifies, in subtle ways, the importance of magnetic resonance imaging, as well as the role of experience in diagnosing and handling these injuries. The paper is a case control series that extracts tremendous beneficial information for sports physicians, athletic trainers, management, agents, players, and all of us Sunday afternoon, TV-watching football experts. Copyright © 2017 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

  1. 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...

  2. FDA licensure of and ACIP recommendations for vaccines.

    Science.gov (United States)

    Pickering, Larry K; Orenstein, Walter A; Sun, Wellington; Baker, Carol J

    2017-09-05

    Many healthcare providers are not familiar with the Food and Drug Administration (FDA) vaccine licensure process, the Advisory Committee on Immunization Practices (ACIP) vaccine recommendation process, and how FDA vaccine licensure and ACIP recommendations are related. Vaccines for use in the United States military and civilian populations are licensed by the FDA by several potential pathways but use of licensed vaccines in the civilian population should be based on recommendations made by the ACIP. In performing these distinct activities, FDA and ACIP function under different mandates. In this article, we discuss whether the FDA licensure pathways used to approve a vaccine impacts ACIP recommendation categories for vaccines licensed from 2006 to 2016. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. 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....

  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. Regulatory administrative databases in FDA's Center for Biologics Evaluation and Research: convergence toward a unified database.

    Science.gov (United States)

    Smith, Jeffrey K

    2013-04-01

    Regulatory administrative database systems within the Food and Drug Administration's (FDA) Center for Biologics Evaluation and Research (CBER) are essential to supporting its core mission, as a regulatory agency. Such systems are used within FDA to manage information and processes surrounding the processing, review, and tracking of investigational and marketed product submissions. This is an area of increasing interest in the pharmaceutical industry and has been a topic at trade association conferences (Buckley 2012). Such databases in CBER are complex, not for the type or relevance of the data to any particular scientific discipline but because of the variety of regulatory submission types and processes the systems support using the data. Commonalities among different data domains of CBER's regulatory administrative databases are discussed. These commonalities have evolved enough to constitute real database convergence and provide a valuable asset for business process intelligence. Balancing review workload across staff, exploring areas of risk in review capacity, process improvement, and presenting a clear and comprehensive landscape of review obligations are just some of the opportunities of such intelligence. This convergence has been occurring in the presence of usual forces that tend to drive information technology (IT) systems development toward separate stovepipes and data silos. CBER has achieved a significant level of convergence through a gradual process, using a clear goal, agreed upon development practices, and transparency of database objects, rather than through a single, discrete project or IT vendor solution. This approach offers a path forward for FDA systems toward a unified database.

  6. Effect of the final-state interaction on the initial core-hole lifetime: the case of the 4s-hole lifetime of Sn metal

    International Nuclear Information System (INIS)

    Ohno, Masahide

    2003-01-01

    The first theoretical study of the effect of the final-state interaction on the initial core-hole lifetime is presented. The 4s-hole lifetime width of Sn metal is calculated by an ab-initio atomic many-body theory (Green's function method). When the final-state interaction in the 4p4d two-hole state, created by the 4s -1 -4p -1 4d -1 εf super Coster-Kronig (CK) transition of the initial 4s hole, is explicitly taken into account, the ab-initio atomic many-body calculation of the 4s-hole X-ray photoelectron spectroscopy (XPS) spectrum of Sn atom can provide excellent agreement with experiment in both the 4s-hole energy and the 4s-hole lifetime width. Otherwise, the many-body calculation underestimates considerably the 4s-hole lifetime width. The 4p4d two-hole state interacts strongly with the 4d triple-hole state by the 4p -1 4d -1 -4d -3 εf super CK transition. The interaction affects greatly the initial 4s-hole lifetime width

  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. Tobacco products, exemptions from substantial equivalence requirements. Final rule.

    Science.gov (United States)

    2011-07-05

    The Food and Drug Administration (FDA) is issuing this final rule to establish procedures for requesting an exemption from the substantial equivalence requirements of the Family Smoking Prevention and Tobacco Control Act (Tobacco Control Act). The final rule describes the process and statutory criteria for requesting an exemption and explains how FDA reviews requests for exemptions. This regulation satisfies the requirement in the Tobacco Control Act that FDA issue regulations implementing the exemption provision.

  9. 75 FR 76992 - Guidance for the Public, FDA Advisory Committee Members, and FDA Staff: The Open Public Hearing...

    Science.gov (United States)

    2010-12-10

    ... CFR 14.29. FDA encourages participation from all public stakeholders in our decisionmaking processes... speak at an OPH session, logistical procedures, and disclosure of financial relationships relevant to...

  10. Frenchay dysarthria assessment (FDA-2) in Parkinson's disease: cross-cultural adaptation and psychometric properties of the European Portuguese version.

    Science.gov (United States)

    Cardoso, Rita; Guimarães, Isabel; Santos, Helena; Loureiro, Rita; Domingos, Josefa; de Abreu, Daisy; Gonçalves, Nilza; Pinto, Serge; Ferreira, Joaquim

    2017-01-01

    Hypokinetic dysarthria is a common symptom in those with Parkinson's disease (PD); there is currently no standardized or validated tool for assessing speech in this population. To translate into European Portuguese (EP) the FDA-2 and perform a cultural adaptation followed by an evaluation of its psychometric properties in PD in a sample of people with PD in different stages of disease progression. Translation, back-translation, experts' analysis, pre-test and final version test were performed. The EP version of the FDA-2 was administered to 80 people with PD (PwP) with dysarthria, feasibility and acceptability, reliability (internal consistency and inter-rater reliability) and validity (face and convergent) were measured. Overall, the EP-FDA-2 proved to be similar to the original demonstrating the same conceptual meanings, semantics, idiomatic and score equivalences. It has good feasibility (missing data dysarthria in PD in clinical practice as in the research field.

  11. Biosimilars: the need, the challenge, the future: the FDA perspective.

    Science.gov (United States)

    Epstein, Michael S; Ehrenpreis, Eli D; Kulkarni, Prasad M

    2014-12-01

    This article summarizes the brief history of the biosimilars industry, the FDA's regulations and guidance for biosimilars development, and the issues and challenges facing developers and regulators in bringing biosimilars to market. Current literature, regulations, and FDA guidance documents were summarized and interpreted to define biosimilars and to present their financial and clinical implications. Some biologic agents that will lose patent protection during the next few years may be replaced with lower cost follow-on biologics. However, unlike generic drugs, biosimilars may be structurally and functionally different from the reference product they are designed to resemble. The FDA has yet to approve any agent via the abbreviated licensure pathway for biosimilars that was passed as part of the Affordable Care Act. The FDA has issued new guidance describing processes by which manufacturers may demonstrate either biosimilarity or interchangeability with an FDA-approved biologic agent, which is required for abbreviated licensure. Biosimilars approved in Europe consist of relatively small molecules; complex large-molecule biosimilars could be subjected to a rigorous and prolonged FDA approval process, which would defeat attempts to develop lower-cost versions of biologic drugs. Biosimilar development is a consequence of the financial success of biologic therapies and their eventual patent expiration. The pharmaceutical industry must now develop complex biosimilars that resemble FDA-approved biologic agents and invent analytical tools and end points to demonstrate similarity to regulatory authorities. Already in development is a new wave of "biobetter" or "biosuperior" drugs that mimic but also improve upon a biologic drug's chemistry, formulation, or delivery.

  12. Attitudes Toward FDA Regulation of Newly Deemed Tobacco Products.

    Science.gov (United States)

    Kowitt, Sarah D; Goldstein, Adam O; Schmidt, Allison M; Hall, Marissa G; Brewer, Noel T

    2017-10-01

    To examine how smokers perceive FDA oversight of e-cigarettes, hookah, and cigars. Current US smokers (N = 1,520) participating in a randomized clinical trial of pictorial cigarette pack warnings completed a survey that included questions about attitudes toward new FDA regulations covering newly deemed tobacco products (ie, regulation of e-cigarettes, nicotine gels or liquids used in e-cigarettes, hookah, and cigars). Between 47% and 56% of current smokers viewed these new FDA regulations favorably and between 17% - 24% opposed them. Favorable attitudes toward the regulations were more common among smokers with higher quit intentions (adjusted odds ratio (aOR): 1.17, 95% CI: 1.02, 1.33) and more negative beliefs about smokers (aOR: 1.18, 95% CI: 1.05, 1.33). Participants with higher education, higher income, and previous exposure to e-cigarette advertisements had higher odds of expressing positive attitudes toward the new FDA regulations (p FDA regulation of newly deemed tobacco products favorably. Local and state policy-makers and tobacco control advocates can build on this support to enact and strengthen tobacco control provisions for e-cigarettes, cigars, and hookah.

  13. 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.

  14. 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... Transparency Initiative: Draft Proposals for Public Comment Regarding Disclosure Policies of the U.S. Food and... relates to FDA's policies on disclosure of information to the public about FDA activities. FDA is...

  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

    ... accountability for domestic and foreign food and animal feed firms in the supply chain from farm to U.S. table... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket Nos. FDA-2011-N-0134, FDA-2011-N-0143, FDA-2011-N-0144, FDA- 2011-N-0145, and FDA-2011-N-0146] FDA Food Safety Modernization...

  16. 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.

  17. 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...

  18. 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

  19. FDA Expands Approval of Brentuximab for Hodgkin Lymphoma

    Science.gov (United States)

    The FDA has expanded the approved uses of brentuximab (Adcetris) in people with Hodgkin lymphoma. As this Cancer Currents post explains, it can now be used in combination with three chemotherapy drugs as an initial treatment in patients with advanced disease.

  20. FDA Drug Safety Podcasts: resources for drug information.

    Science.gov (United States)

    Wu, Kimberly; Shepherd, Jennifer; Jackson, Steven; Chew, Catherine

    2013-01-01

    To describe a Web-based drug information service provided by the Food and Drug Administration (FDA) to increase the reach of Drug Safety Communications to pharmacists and other health professionals. The Division of Drug Information (DDI) within the FDA Center for Drug Evaluation and Research (CDER), Office of Communications, Silver Spring, MD, between January 2010 and April 2012. DDI provides drug information services regarding human drug products and expert advice and guidance on all aspects of CDER activities. Customers include consumers, health professionals, regulated industry, insurance companies, academia, law enforcement, and other government agencies (national and international). Use of audio podcasts to disseminate timely drug safety information targeted toward pharmacists and other health professionals. RESULTS Since 2010, DDI has recorded and published 119 FDA Drug Safety Podcasts that have reached more than 620,000 individuals. FDA Drug Safety Podcasts serve as portable and convenient options for pharmacists to stay current on the latest drug safety information. Pharmacists are encouraged to explore incorporating Web-based technologies, such as audio podcasts, into their practices.

  1. 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...

  2. 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.

  3. Paleo-Climate and Glaciological Reconstruction in Central Asia through the Collection and Analysis of Ice Cores and Instrumental Data from the Tien Shan; FINAL

    International Nuclear Information System (INIS)

    Vladimir Aizen; Donald Bren; Karl Kreutz; Cameron Wake

    2001-01-01

    While the majority of ice core investigations have been undertaken in the polar regions, a few ice cores recovered from carefully selected high altitude/mid-to-low latitude glaciers have also provided valuable records of climate variability in these regions. A regional array of high resolution, multi-parameter ice core records developed from temperate and tropical regions of the globe can be used to document regional climate and environmental change in the latitudes which are home to the vase majority of the Earth's human population. In addition, these records can be directly compared with ice core records available from the polar regions and can therefore expand our understanding of inter-hemispheric dynamics of past climate changes. The main objectives of our paleoclimate research in the Tien Shan mountains of middle Asia combine the development of detailed paleoenvironmental records via the physical and chemical analysis of ice cores with the analysis of modern meteorological and hydrological data. The first step in this research was the collection of ice cores from the accumulation zone of the Inylchek Glacier and the collection of meteorological data from a variety of stations throughout the Tien Shan. The research effort described in this report was part of a collaborative effort with the United State Geological Survey's (USGS) Global Environmental Research Program which began studying radionuclide deposition in mid-latitude glaciers in 1995

  4. The Gestalt of functioning in autism spectrum disorder: Results of the international conference to develop final consensus International Classification of Functioning, Disability and Health core sets.

    Science.gov (United States)

    Bölte, Sven; Mahdi, Soheil; de Vries, Petrus J; Granlund, Mats; Robison, John E; Shulman, Cory; Swedo, Susan; Tonge, Bruce; Wong, Virginia; Zwaigenbaum, Lonnie; Segerer, Wolfgang; Selb, Melissa

    2018-01-01

    Autism spectrum disorder is associated with diverse social, educational, and occupational challenges. To date, no standardized, internationally accepted tools exist to assess autism spectrum disorder-related functioning. World Health Organization's International Classification of Functioning, Disability and Health can serve as foundation for developing such tools. This study aimed to identify a comprehensive, a common brief, and three age-appropriate brief autism spectrum disorder Core Sets. Four international preparatory studies yielded in total 164 second-level International Classification of Functioning, Disability and Health candidate categories. Based on this evidence, 20 international autism spectrum disorder experts applied an established iterative decision-making consensus process to select from the candidate categories the most relevant ones to constitute the autism spectrum disorder Core Sets. The consensus process generated 111 second-level International Classification of Functioning, Disability and Health categories in the Comprehensive Core Set for autism spectrum disorder-one body structure, 20 body functions, 59 activities and participation categories, and 31 environmental factors. The Common Brief Core Set comprised 60 categories, while the age-appropriate core sets included 73 categories in the preschool version (0- to 5-year-old children), 81 in the school-age version (6- to 16-year-old children and adolescents), and 79 in the older adolescent and adult version (⩾17-year-old individuals). The autism spectrum disorder Core Sets mark a milestone toward the standardized assessment of autism spectrum disorder-related functioning in educational, administrative, clinical, and research settings.

  5. The FDA "Deeming Rule" and Tobacco Regulatory Research.

    Science.gov (United States)

    Backinger, Cathy L; Meissner, Helen I; Ashley, David L

    2016-07-01

    In May 2016, the Food and Drug Administration extended its tobacco regulatory authorities to other products meeting the definition of a tobacco product (Deeming Rule). This authority now includes, but is not limited to, electronic nicotine delivery systems (ENDS), such as electronic cigarettes, as well as all cigars, pipes, and hookahs (waterpipes). The FDA's Center for Tobacco Products has been able to fund research projects addressing these newly deemed tobacco products through a variety of mechanisms, including partnership with the Tobacco Regulatory Science Program, National Institutes of Health. In building the evidence base to inform the regulation of and communications about new and emerging tobacco products, it is important for investigators to be mindful of the goals of tobacco regulatory science, ie, scientific inquiry specifically to inform potential regulatory decisions and actions to protect the public's health. Having solid scientific evidence will allow the FDA to make the most appropriate regulatory decisions regarding newly deemed products.

  6. 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.

  7. Advancing women's health via FDA Critical Path Initiative.

    Science.gov (United States)

    Parekh, A; Sanhai, W; Marts, S; Uhl, K

    2007-01-01

    Studying sex and gender differences is critical to understanding diseases that affect women solely, disproportionately or differently from men. Although inclusion of both sexes is essential in clinical research, advanced technology and analysis methods offer tools to define complex biological and physicochemical differences and improve prevention, diagnosis and treatments for diseases in women and men. This paper identifies the potential for biomarker development, pharmacogenetics and bioinformatics in research under the FDA Critical Path Initiative.: � 2007 Elsevier Ltd . All rights reserved.

  8. 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.

  9. The role of the FDA in the effort against AIDS.

    Science.gov (United States)

    Young, F E

    1988-01-01

    The Food and Drug Administration has instituted several pro-active measures to expedite the review of treatments, diagnostics, and vaccines for AIDS and related conditions. In particular, the agency has established a special designation--1-AA--for a potential AIDS product which gives top priority to its review. This special expedited review process for AIDS products has provided for greater cooperation between their sponsors and FDA's reviewers. AIDS products also receive prompt consideration for orphan product status--a status providing financial incentives to the developers of treatments for certain rare and complex diseases. FDA's special procedures for AIDS drugs have resulted in several major advances in available AIDS treatments. Foremost among these was the FDA's review and approval of zidovudine (commonly known as AZT) as the first effective palliative for AIDS within 107 days--an agency record. Similarly, the agency quickly evaluated and approved ELISA and Western blot diagnostic kits for detecting the presence of HIV antibody. These test kits have made an important contribution to safeguarding the nation's blood supply. The agency has also instituted new "treatment" investigational new drug regulations to allow earlier pre-approval distribution of promising experimental treatments to patients with immediately life-threatening conditions, including persons with AIDS. Under this system and its earlier prototype, eligible AIDS patients were able to receive pre-approval treatment with zidovudine and trimetrexate (an experimental drug for the treatment of AIDS patients with Pneumocystis carinii pneumonia who have experienced severe adverse reactions using standard approved therapies). The agency has made institutional reforms to effectively streamline the review of candidate AIDS treatments and vaccines. Two new centers within the agency have been established for the processing of drug and biologics. In addition,reviewing divisions have been created within

  10. 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

  11. 76 FR 38666 - Food and Drug Administration (FDA) and Marine Environmental Sciences Consortium/Dauphin Island...

    Science.gov (United States)

    2011-07-01

    ..., FDA must stay abreast of the latest developments in research and also communicate with stakeholders... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-N-0012] Food and Drug Administration (FDA) and Marine Environmental Sciences Consortium/Dauphin Island Sea Lab...

  12. 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

    adults. Finally, several warnings were made about statins. Routine periodic monitoring of liver enzymes does not appear to be effective in detecting or preventing serious liver injury from statin use; thus, liver enzymes are no longer recommended to be routinely monitored. Statin-induced cognitive changes are rare, and insufficient evidence is currently available to establish causality. Statins appear to moderately increase the risk of developing diabetes (versus placebo), and regular screening for diabetes should be considered, especially for patients taking high-dose statins and patients with multiple risk factors for diabetes. FDA drug safety communications incorporate complex methodologies that investigate the risks (and relative benefits) of medication therapy. Clinicians caring for older adults need to be aware of the most current evidence behind these drug risks to effectively communicate with and care for their patients. Copyright © 2012 Elsevier HS Journals, Inc. All rights reserved.

  13. Summary final report: Contract between the Japan atomic power company and the U.S. Department of Energy Improvement of core safety - study on GEM (III)

    Energy Technology Data Exchange (ETDEWEB)

    Burke, T.M.; Lucoff, D.M.

    1997-03-18

    This report provides a summary of activities associated with the technical exchange between representatives of the Japan Atomic Power Company (JAPC) and the United States Department of Energy (DOE) regarding the development and testing of Gas Expansion Modules (GEM) at the Fast Flux Test Facility (FFTF). Issuance of this report completes the scope of work defined in the original contract between JAPC and DOE titled ''Study on Improvement of Core Safety - Study on GEM (III).'' Negotiations related to potential modification of the contract are in progress. Under the proposed contract modification, DOE would provide an additional report documenting FFTF pump start tests with GEMs and answer additional JAPC questions related to core safety with and without GEMs.

  14. Summary final report: Contract between the Japan atomic power company and the U.S. Department of Energy Improvement of core safety - study on GEM (III)

    International Nuclear Information System (INIS)

    Burke, T.M.; Lucoff, D.M.

    1997-01-01

    This report provides a summary of activities associated with the technical exchange between representatives of the Japan Atomic Power Company (JAPC) and the United States Department of Energy (DOE) regarding the development and testing of Gas Expansion Modules (GEM) at the Fast Flux Test Facility (FFTF). Issuance of this report completes the scope of work defined in the original contract between JAPC and DOE titled ''Study on Improvement of Core Safety - Study on GEM (III).'' Negotiations related to potential modification of the contract are in progress. Under the proposed contract modification, DOE would provide an additional report documenting FFTF pump start tests with GEMs and answer additional JAPC questions related to core safety with and without GEMs

  15. FDA's expanding postmarket authority to monitor and publicize food and consumer health product risks: the need for procedural safeguards to reduce "transparency" policy harms in the post-9/11 regulatory environment.

    Science.gov (United States)

    Roller, Sarah Taylor; Pippins, Raqiyyah R; Ngai, Jennifer W

    2009-01-01

    This article provides a summary of the expansion of FDA's discretionary authority in the post-9/11 period, particularly with respect to FDA's authority to monitor and publicize potential health risks linked to food, dietary supplements, nonprescription drugs, and other consumer health products. In addition, this article evaluates the need for FDA to establish procedural safeguards to reduce the significant risks of unintended and undue harm to people and regulated companies that can result from adverse publicity in the more "transparent" post 9/11 FDA regulatory environment. Specifically, Part I summarizes the amendments to the FDCA enacted during the post-9/11 period that have expanded FDA's postmarket authority to monitor, evaluate, and publicize potential health risks linked to food, dietary supplements, nonprescription drugs and other consumer health products marketed in the United States, in conjunction with FDA's Sentinel Initiative, Reportable Food Registry, and other adverse event reporting requirements. Part II discusses the convergence of FDA's expanded postmarket authority to publicize product-related risks with President Obama's transparency initiative aimed at fostering "open government" through increased public access to government information. In addition, Part II considers the nature of the procedural safeguards needed in the post-9/11 FDA regulatory environment, in view of FDA's historical record and illustrative cases that help expose how adverse "transparency" surrounding FDA warning letters, recalls and safety alerts concerning products in the marketplace can have undue and unintended prejudicial and harmful effects for the people and companies that are legally responsible for such products. Finally, based on these analysis, this article concludes with some observations concerning the nature of the procedural safeguards needed to reduce the significant risks of "transparency" policy harms in the pos-9/11 regulatory environment.

  16. Public opinion about FDA regulation of menthol and nicotine.

    Science.gov (United States)

    Bolcic-Jankovic, Dragana; Biener, Lois

    2015-12-01

    Regulations that reduce nicotine and eliminate menthol in cigarettes have been proposed to the US Food and Drug Administration (FDA) as product alterations that could reduce smoking prevalence in the USA. This study sought to assess the public response to either action. A mail survey of a representative sample of 1074 adults was conducted in two major metropolitan areas to determine the level of support for immediate, gradual or no reduction of menthol and nicotine in cigarettes. There was more support for reducing nicotine (79%) than for reducing or removing menthol (59.5%). Most smokers (59.2%; 95% CI 50.7 to 67.2) and 36% of non-smokers (95% CI 31.7 to 40.8) opposed eliminating menthol, but few smokers (23.8%) or non-smokers (20.3%) were opposed to reducing nicotine. Logistic regression showed no significant effect of smoking status on support for reductions in nicotine, but that smokers were significantly less supportive than non-smokers of FDA action on menthol (OR=0.32, 95% CI 0.21 to 0.49). A significant race by smoking status interaction showed that African-American smokers were more supportive of removing menthol than non-African-American smokers. The greater smoker support for reductions in nicotine than menthol could be due to inaccurate beliefs about the disease risk associated with the two substances (ie, a belief that nicotine is more harmful than menthol), or to greater awareness of the sensory role that menthol plays in smokers' satisfaction. In any case, if FDA goes ahead with regulations to remove menthol, it will be important to develop strategies to reduce smoker resistance. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  17. Outcomes of LASIK for myopia with FDA-approved lasers.

    Science.gov (United States)

    Bailey, Melissa D; Zadnik, Karla

    2007-04-01

    To report expected outcomes of laser in situ keratomileusis (LASIK) for myopia and myopic astigmatism from existing US Food and Drug Administration (FDA) data. Data from Summaries of Safety and Effectiveness for each of the 12 lasers approved by the FDA for LASIK for myopia or myopic astigmatism between 1998 and 2004 were recorded from the FDA Web site. The Cochran-Armitage test for trend was used to determine whether improvements in outcomes occurred with laser technology changes. For all patients, there was a statistically significant trend toward improvement with improved laser technology in the proportion of patients with uncorrected visual acuity (UCVA) of 20/20 or better, UCVA of 20/40 or better, results within +/-0.50 D of intended correction, results within +/-1.00 D of the intended correction, and night vision symptoms (all P myopia, low to moderate myopia, spherical myopia, and myopic astigmatism) for visual acuity and refractive error outcomes were similar to results for analyses for all groups combined. Conversely, there was no difference across laser types in the proportion of patients who experienced dry eye symptoms or for the proportion of patients with low to moderate myopia who experienced night vision symptoms that were worse or significantly worse than before LASIK. LASIK provides excellent visual acuity and refractive error outcomes. Night vision and dryness symptoms still occur in a significant proportion of patients. Future studies should seek to determine whether additional changes in technology, patient selection criteria, or postoperative treatment could reduce or eliminate these symptoms.

  18. 2014 in review: FDA approval of new drugs.

    Science.gov (United States)

    Kinch, Michael S

    2017-04-01

    The year 2014 witnessed the approval by the US Food and Drug Administration (FDA) of 42 new molecular entities (NMEs), which is well above recent averages. These molecules targeted a range of molecular pathways and clinical indications, although the latter was skewed toward hepatitis C virus (HCV) infection and diabetes. By contrast, a single drug was approved for cardiovascular diseases and none for neurological indications (excepting sleeping disorders). Of note is a continued trend toward consolidation because the net number of biotechnology companies has reached its lowest point in over 25 years, raising questions about sustainability. Copyright © 2015 Elsevier Ltd. All rights reserved.

  19. Three-dimensional gyrokinetic particle-in-cell simulation of plasmas on a massively parallel computer: Final report on LDRD Core Competency Project, FY 1991--FY 1993

    International Nuclear Information System (INIS)

    Byers, J.A.; Williams, T.J.; Cohen, B.I.; Dimits, A.M.

    1994-01-01

    One of the programs of the Magnetic fusion Energy (MFE) Theory and computations Program is studying the anomalous transport of thermal energy across the field lines in the core of a tokamak. We use the method of gyrokinetic particle-in-cell simulation in this study. For this LDRD project we employed massively parallel processing, new algorithms, and new algorithms, and new formal techniques to improve this research. Specifically, we sought to take steps toward: researching experimentally-relevant parameters in our simulations, learning parallel computing to have as a resource for our group, and achieving a 100 x speedup over our starting-point Cray2 simulation code's performance

  20. 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.

  1. 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.

  2. FDA finds emergency postcoital contraception safe and effective.

    Science.gov (United States)

    1996-07-12

    During a 1996 hearing, the US Food and Drug Administration (FDA) Reproductive Health Drugs Advisory Committee reached the unanimous conclusion that certain oral contraceptives (OCs) are safe and effective for use in an emergency postcoital regimen. Because such a regimen reduces the risk of unintended pregnancies by about 75%, widespread access to emergency contraception in the US could prevent as many as 1.7 million pregnancies and 1 million abortions each year. The six brands of OCs manufactured in the US which contain the necessary chemical compound are Ovral, Lo/Ovral, Nordette, Triphasil, Levlen, and Tri-Levlen. For Ovral, the regimen involves taking two pills within 72 hours of unprotected intercourse followed 12 hours later by another two pills. The other OCs require a dosage of four pills each time. When using Levlen and Tri-Levlen, the yellow pills are the only ones which are effective. Publication of the FDA's support should spur pharmaceutical companies to petition the agency for virtually automatic approval of this use of OCs. Drug manufacturers have failed to take this action to date because of the fear of the opposition of antiabortion groups and of product liability suits. Detailed information on various types of emergency contraception and on physicians who provide this service can be obtained from the Reproductive Health Technologies Project hotline (1-800-584-9911).

  3. Proteomics Core

    Data.gov (United States)

    Federal Laboratory Consortium — Proteomics Core is the central resource for mass spectrometry based proteomics within the NHLBI. The Core staff help collaborators design proteomics experiments in a...

  4. Public Knowledge and Credibility Perceptions of the FDA as a Tobacco Regulator.

    Science.gov (United States)

    Schmidt, Allison M; Jarman, Kristen; Ranney, Leah M; Queen, Tara; Noar, Seth M; Ruel, Laura; Agans, Robert; Hannan, Anika; Goldstein, Adam O

    2017-09-26

    Since the US Food and Drug Administration (FDA) was granted regulatory authority over tobacco products in 2009, few studies have examined perceived credibility of the FDA in this role. The current study assessed knowledge and credibility of the FDA as a regulator of tobacco products. In a nationally representative survey of US adults (N=4,758), we assessed knowledge that the FDA regulates the manufacture, distribution, and marketing of cigarettes, and credibility of the FDA as a tobacco regulator. We examined demographic differences in knowledge and credibility, and associations of knowledge and trust in government with credibility perceptions. Less than half of respondents reported knowing the FDA regulates how cigarettes are sold (46.8%) and advertised (49.7%), and only 36.0% knew the FDA regulates how cigarettes are made, with few demographic differences. Respondents reported that the FDA was moderately credible in regulating tobacco. Knowledge of the FDA as a tobacco regulator and trust in government were the strongest predictors of credibility. Being of younger age, being White (compared to African American), and being male were associated with higher credibility ratings of the FDA. Much of the public still does not know that the FDA regulates tobacco products, and credibility perceptions are moderate. Greater knowledge of the FDA's regulatory role was associated with higher credibility; efforts that increase the public's understanding of the FDA's role as a tobacco regulator may positively impact views of the agency's credibility. This may in turn improve public reception to the FDA's messages and regulations. This study is the first to show nationally representative estimates of both knowledge and credibility of the FDA as a tobacco regulator. Our research shows further that knowledge of the FDA's tobacco regulatory roles is likely to be an important factor related to perceived credibility of the FDA. Increasing the public's knowledge of the FDA's roles may

  5. Amendments to general regulations of the Food and Drug Administration. Direct final rule.

    Science.gov (United States)

    2010-11-30

    The Food and Drug Administration (FDA) is amending certain of its general regulations to include tobacco products, where appropriate, in light of FDA's authority to regulate these products under the Family Smoking Prevention and Tobacco Control Act (Tobacco Control Act). With these amendments, tobacco products will be subject to the same general requirements that apply to other FDA-regulated products. Elsewhere in this issue of the Federal Register, we are publishing a companion proposed rule under FDA's usual procedures for notice and comment to provide a procedural framework to finalize the rule in the event we receive significant adverse comment and withdraw this direct final rule.

  6. Steady-State Gyrokinetics Transport Code (SSGKT), A Scientific Application Partnership with the Framework Application for Core-Edge Transport Simulations, Final Report

    Energy Technology Data Exchange (ETDEWEB)

    Fahey, Mark R. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Candy, Jeff [General Atomics, San Diego, CA (United States)

    2013-11-07

    This project initiated the development of TGYRO - a steady-state Gyrokinetic transport code (SSGKT) that integrates micro-scale GYRO turbulence simulations into a framework for practical multi-scale simulation of conventional tokamaks as well as future reactors. Using a lightweight master transport code, multiple independent (each massively parallel) gyrokinetic simulations are coordinated. The capability to evolve profiles using the TGLF model was also added to TGYRO and represents a more typical use-case for TGYRO. The goal of the project was to develop a steady-state Gyrokinetic transport code (SSGKT) that integrates micro-scale gyrokinetic turbulence simulations into a framework for practical multi-scale simulation of a burning plasma core ? the International Thermonuclear Experimental Reactor (ITER) in particular. This multi-scale simulation capability will be used to predict the performance (the fusion energy gain, Q) given the H-mode pedestal temperature and density. At present, projections of this type rely on transport models like GLF23, which are based on rather approximate fits to the results of linear and nonlinear simulations. Our goal is to make these performance projections with precise nonlinear gyrokinetic simulations. The method of approach is to use a lightweight master transport code to coordinate multiple independent (each massively parallel) gyrokinetic simulations using the GYRO code. This project targets the practical multi-scale simulation of a reactor core plasma in order to predict the core temperature and density profiles given the H-mode pedestal temperature and density. A master transport code will provide feedback to O(16) independent gyrokinetic simulations (each massively parallel). A successful feedback scheme offers a novel approach to predictive modeling of an important national and international problem. Success in this area of fusion simulations will allow US scientists to direct the research path of ITER over the next two

  7. The FDA “Deeming Rule” and Tobacco Regulatory Research

    Science.gov (United States)

    Backinger, Cathy L.; Meissner, Helen I.; Ashley, David L.

    2016-01-01

    In May 2016, the Food and Drug Administration extended its tobacco regulatory authorities to other products meeting the definition of a tobacco product (Deeming Rule). This authority now includes, but is not limited to, electronic nicotine delivery systems (ENDS), such as electronic cigarettes, as well as all cigars, pipes, and hookahs (waterpipes). The FDA’s Center for Tobacco Products has been able to fund research projects addressing these newly deemed tobacco products through a variety of mechanisms, including partnership with the Tobacco Regulatory Science Program, National Institutes of Health. In building the evidence base to inform the regulation of and communications about new and emerging tobacco products, it is important for investigators to be mindful of the goals of tobacco regulatory science, ie, scientific inquiry specifically to inform potential regulatory decisions and actions to protect the public’s health. Having solid scientific evidence will allow the FDA to make the most appropriate regulatory decisions regarding newly deemed products. PMID:29423429

  8. Repurposing FDA-approved drugs for anti-aging therapies.

    Science.gov (United States)

    Snell, Terry W; Johnston, Rachel K; Srinivasan, Bharath; Zhou, Hongyi; Gao, Mu; Skolnick, Jeffrey

    2016-11-01

    There is great interest in drugs that are capable of modulating multiple aging pathways, thereby delaying the onset and progression of aging. Effective strategies for drug development include the repurposing of existing drugs already approved by the FDA for human therapy. FDA approved drugs have known mechanisms of action and have been thoroughly screened for safety. Although there has been extensive scientific activity in repurposing drugs for disease therapy, there has been little testing of these drugs for their effects on aging. The pool of FDA approved drugs therefore represents a large reservoir of drug candidates with substantial potential for anti-aging therapy. In this paper we employ FINDSITE comb , a powerful ligand homology modeling program, to identify binding partners for proteins produced by temperature sensing genes that have been implicated in aging. This list of drugs with potential to modulate aging rates was then tested experimentally for lifespan and healthspan extension using a small invertebrate model. Three protein targets of the rotifer Brachionus manjavacas corresponding to products of the transient receptor potential gene 7, ribosomal protein S6 polypeptide 2 gene, or forkhead box C gene, were screened against a compound library consisting of DrugBank drugs including 1347 FDA approved, non-nutraceutical molecules. Twenty nine drugs ranked in the top 1 % for binding to each target were subsequently included in our experimental analysis. Continuous exposure of rotifers to 1 µM naproxen significantly extended rotifer mean lifespan by 14 %. We used three endpoints to estimate rotifer health: swimming speed (mobility proxy), reproduction (overall vitality), and mitochondria activity (cellular senescence proxy). The natural decline in swimming speed with aging was more gradual when rotifers were exposed to three drugs, so that on day 6, mean swimming speed of females was 1.19 mm/s for naproxen (P = 0.038), 1.20 for fludarabine (P = 0

  9. FDA quality assurance for radioactivity in foods and radiopharmaceuticals

    International Nuclear Information System (INIS)

    Baratta, E.J.

    1993-01-01

    The Food and Drug Administration (FDA) has regulatory responsibility for radionuclides in foods and radiopharmaceuticals and must maintain an ongoing Quality Assurance Program. These Quality Control Programs involve the U.S. Environmental Protection Agency (EPA) and the National Institute of Standards and Technology (NIST), who supply the necessary reference materials and standards to ensure that the measurements are accurate and reproduceable. Data from EPA (1987 to 1991) and from a NIST 'Blind' Source study (1985 to 1991) show the results are accurate with an average variation from NIST values of 1.8%. The use of standard materials with the same matrices as the samples being analyzed provides credibility to the measurements. (orig.)

  10. 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

  11. Acrylamide in Food – EU versus FDA Approaches

    Directory of Open Access Journals (Sweden)

    Gabriel Mustăţea

    2015-11-01

    Full Text Available Acrylamide is a versatile organic compound that finds its way into many products in our everyday life. The presence of acrylamide in foods dates from 2002, when a series of studies published in Sweden, confirmed its presence in high temperatures processed foods. At EU level, first adopted measure was Commission Recommendation on the monitoring of acrylamide levels in food, on May 2007, extended then by Commission Recommendation 2010/307/EU. European Food Safety Authority (EFSA then, collected and compiled data, each year (2007-2010, and published an annual report. On January 2011 was adopted the Recommendation on the investigations into the levels of acrylamide in food and then, on November 2013 was adopted Commission Recommendation 2013/647/EU on investigation into levels of acrylamide in food. Based on these, EFSA had published, in June 2015 a comprehensive risk assessment on acrylamide in food. The FDA first published a draft regarding Detection and Quantitation of Acrylamide in Foods, in 2003 followed in 2004 by the Action Plan for Acrylamide in Food. In 2006 FDA published Survey Data on Acrylamide in food then in 2009, in August (updated in November a Federal Register Notice entitled: Acrylamide in food: Request for comments and for scientific data and information. Their findings have been materialized, in November 2013, into a powerful tool for industry: Draft Guidance for industry: Acrylamide in Foods. Despite research implications that exposure to acrylamide from food is safe, some consumers may choose to take measures to further reduce their acrylamide exposure. 

  12. Development of hybrid fog detection algorithm (FDA) using satellite and ground observation data for nighttime

    Science.gov (United States)

    Kim, So-Hyeong; Han, Ji-Hae; Suh, Myoung-Seok

    2017-04-01

    In this study, we developed a hybrid fog detection algorithm (FDA) using AHI/Himawari-8 satellite and ground observation data for nighttime. In order to detect fog at nighttime, Dual Channel Difference (DCD) method based on the emissivity difference between SWIR and IR1 is most widely used. DCD is good at discriminating fog from other things (middle/high clouds, clear sea and land). However, it is difficult to distinguish fog from low clouds. In order to separate the low clouds from the pixels that satisfy the thresholds of fog in the DCD test, we conducted supplementary tests such as normalized local standard derivation (NLSD) of BT11 and the difference of fog top temperature (BT11) and air temperature (Ta) from NWP data (SST from OSTIA data). These tests are based on the larger homogeneity of fog top than low cloud tops and the similarity of fog top temperature and Ta (SST). Threshold values for the three tests were optimized through ROC analysis for the selected fog cases. In addition, considering the spatial continuity of fog, post-processing was performed to detect the missed pixels, in particular, at edge of fog or sub-pixel size fog. The final fog detection results are presented by fog probability (0 100 %). Validation was conducted by comparing fog detection probability with the ground observed visibility data from KMA. The validation results showed that POD and FAR are ranged from 0.70 0.94 and 0.45 0.72, respectively. The quantitative validation and visual inspection indicate that current FDA has a tendency to over-detect the fog. So, more works which reducing the FAR is needed. In the future, we will also validate sea fog using CALIPSO data.

  13. 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

  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. 21 CFR 1271.27 - Will FDA assign me a registration number?

    Science.gov (United States)

    2010-04-01

    ..., TISSUES, AND CELLULAR AND TISSUE-BASED PRODUCTS Procedures for Registration and Listing § 1271.27 Will FDA...) FDA acceptance of an establishment registration and HCT/P listing form does not constitute a determination that an establishment is in compliance with applicable rules and regulations or that the HCT/P is...

  16. OARSI-FDA initiative: defining the disease state of osteoarthritis.

    Science.gov (United States)

    Lane, N E; Brandt, K; Hawker, G; Peeva, E; Schreyer, E; Tsuji, W; Hochberg, M C

    2011-05-01

    To respond to a pre-specified set of questions posed by the United States Food and Drug Administration (FDA) on defining the disease state to inform the clinical development of drugs, biological products, and medical devices for the prevention and treatment of osteoarthritis (OA). An Osteoarthritis Research Society International (OARSI) Disease State working group was established, comprised of representatives from academia and industry. The Working Group met in person and by teleconference on several occasions from the Spring of 2008 through the Autumn of 2009 to develop consensus-based, evidence-informed responses to these questions. A report was presented at a public forum in December 2009 and accepted by the OARSI Board of Directors in the Summer of 2010. An operational definition of OA was developed incorporating current understanding of the condition. The structural changes that characterize OA at the joint level were distinguished from the patients' experience of OA as the 'disease' and 'illness', respectively. Recommendations were made regarding the evaluation of both in future OA clinical trials. The current poor understanding of the phenotypes that characterize OA was identified as an important area for future research. The design and conduct of clinical trials for new OA treatments should address the heterogeneity of the disease, treatment-associated structural changes in target joints and patient-reported outcomes. Copyright © 2011 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

  17. 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...

  18. 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.

  19. 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

  20. Food labeling: health claims; D-tagatose and dental caries. Final rule.

    Science.gov (United States)

    2003-07-03

    The Food and Drug Administration (FDA) is adopting as a final rule, without change, the provisions of the interim final rule that amended the regulation authorizing a health claim on sugar alcohols and dental caries, i.e., tooth decay, to include the sugar D-tagatose as a substance eligible for the dental caries health claim. FDA is taking this action to complete the rulemaking initiated with the interim final rule.

  1. PWR degraded core analysis

    International Nuclear Information System (INIS)

    Gittus, J.H.

    1982-04-01

    A review is presented of the various phenomena involved in degraded core accidents and the ensuing transport of fission products from the fuel to the primary circuit and the containment. The dominant accident sequences found in the PWR risk studies published to date are briefly described. Then chapters deal with the following topics: the condition and behaviour of water reactor fuel during normal operation and at the commencement of degraded core accidents; the generation of hydrogen from the Zircaloy-steam and the steel-steam reactions; the way in which the core deforms and finally melts following loss of coolant; debris relocation analysis; containment integrity; fission product behaviour during a degraded core accident. (U.K.)

  2. Beliefs about FDA tobacco regulation, modifiability of cancer risk, and tobacco product comparative harm perceptions: Findings from the HINTS-FDA 2015.

    Science.gov (United States)

    Nguyen, Anh B; Henrie, James; Slavit, Wendy I; Kaufman, Annette R

    2018-05-01

    Smokers who inaccurately believe that FDA evaluates cigarettes for safety hold lower harm perceptions of cigarettes compared to those who do not hold this belief. However, not much is known about associations between beliefs about FDA tobacco regulatory authority and comparative harm perceptions of tobacco products. Data were analyzed from the Health Information National Trends Survey, HINTS-FDA 2015 (N = 3738), which is a cross-sectional, probability-based, nationally representative survey of U.S. non-institutionalized civilian adults aged 18 years or older. Weighted multinomial and logistic regression analyses regressed comparative harm perceptions on sociodemographic factors, beliefs about FDA regulatory authority, perceptions of FDA credibility, and beliefs about modifiability of cancer risk (behavioral cancer causal beliefs and cancer fatalism). Findings indicate that, compared to non-users, current tobacco users are more likely to report believing that e-cigarettes are less harmful than cigarettes, to report believing that some cigarette types may be less harmful than others, and to report believing that tobacco products are safer now than they were five years ago. Awareness of FDA regulatory authority was associated with reporting the belief that tobacco products are safer now than five years ago, that e-cigarettes are less harmful than cigarettes, and that some cigarette types are less harmful than other cigarette types. Believing behavior as a cause of cancer and endorsing cancer fatalism were associated with uncertainty of comparative harm perceptions. Communication efforts can help target inaccurate beliefs by raising awareness about regulation of tobacco products as well as the risks of tobacco products. Published by Elsevier Inc.

  3. Transformer core

    NARCIS (Netherlands)

    Mehendale, A.; Hagedoorn, Wouter; Lötters, Joost Conrad

    2010-01-01

    A transformer core includes a stack of a plurality of planar core plates of a magnetically permeable material, which plates each consist of a first and a second sub-part that together enclose at least one opening. The sub-parts can be fitted together via contact faces that are located on either side

  4. Transformer core

    NARCIS (Netherlands)

    Mehendale, A.; Hagedoorn, Wouter; Lötters, Joost Conrad

    2008-01-01

    A transformer core includes a stack of a plurality of planar core plates of a magnetically permeable material, which plates each consist of a first and a second sub-part that together enclose at least one opening. The sub-parts can be fitted together via contact faces that are located on either side

  5. A systematic approach to biomarker discovery; Preamble to "the iSBTc-FDA taskforce on immunotherapy biomarkers"

    Directory of Open Access Journals (Sweden)

    Schendel Dolores

    2008-12-01

    Full Text Available Abstract The International Society for the Biological Therapy of Cancer (iSBTc has initiated in collaboration with the United States Food and Drug Administration (FDA a programmatic look at innovative avenues for the identification of relevant parameters to assist clinical and basic scientists who study the natural course of host/tumor interactions or their response to immune manipulation. The task force has two primary goals: 1 identify best practices of standardized and validated immune monitoring procedures and assays to promote inter-trial comparisons and 2 develop strategies for the identification of novel biomarkers that may enhance our understating of principles governing human cancer immune biology and, consequently, implement their clinical application. Two working groups were created that will report the developed best practices at an NCI/FDA/iSBTc sponsored workshop tied to the annual meeting of the iSBTc to be held in Washington DC in the Fall of 2009. This foreword provides an overview of the task force and invites feedback from readers that might be incorporated in the discussions and in the final document.

  6. 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.

  7. 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.

  8. 76 FR 20588 - FDA Food Safety Modernization Act: Focus on Preventive Controls for Facilities; Public Meeting

    Science.gov (United States)

    2011-04-13

    ...://www.blsmeetings.net/FDAPreventiveControls by April 15, 2011. FDA is holding the public meeting on.... FDAPreventiveCont presentation rols. should be submitted in Microsoft PowerPoint, Microsoft Word, or Adobe...

  9. FDA Response to the Fukushima Dai-ichi Nuclear Power Facility Incident

    Science.gov (United States)

    ... is wholesome, safe to eat, and produced under sanitary conditions. FDA has a team of more than ... shipment. United States Customs and Border Protection (CBP) agents routinely use radiation detection equipment to screen food ...

  10. 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 ...

  11. Economic Welfare Effects of the FDA Regulation of Tobacco Products on Tobacco Growers

    OpenAIRE

    Tiller, Kelly; Feleke, Shiferaw T.; Starnes, Jane H.

    2011-01-01

    The Family Smoking Prevention and Tobacco Control Act of 2009 (FSPTCA) became federal law on June 22, 2009, authorizing the U.S. Food and Drug Administration (FDA) to regulate the manufacturing and marketing of tobacco products in the country. This study examines the potential economic welfare implications for tobacco farms using the Equilibrium Displacement Model. Results suggest that the FDA regulation of tobacco products could induce a significant fall in domestic cigarette sales, leading ...

  12. A Retrospective Review of FDA v. Brown Williamson Tobacco Corporation and the Issue of Congressional Intent

    OpenAIRE

    Brooks, Angela

    2004-01-01

    Contrary to a tradition of the FDA (Federal Food and Drug Administration) consistently maintaining that it could not assert jurisdiction over tobacco products, the agency issued a determination of jurisdiction over cigarettes and smokeless tobacco and proposed a set of regulations in 1996 in an effort to combat the public health problems caused by tobacco products. Rather than a complete ban, the FDA proposed regulations aimed solely at younger Americans due to its conclusion that such an app...

  13. [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.

  14. U.S. Tobacco Growers’ Concern about the Impact of the FDA Regulation of Tobacco Products

    OpenAIRE

    Feleke, Shiferaw T.; Starnes, Jane H.; Tiller, Kelly

    2012-01-01

    The objective of the paper is to establish an empirical relationship between household characteristics and tobacco growers’ perception of the impact of the FDA regulation. A logistic model is applied on primary data that came from the Center for Tobacco Grower Research’s (CTGR’s) 2011 mail survey of tobacco producers. Results indicate that over 80 percent of the sample tobacco growers are concerned about the impact of the FDA regulation. The profiles of growers who reported to be concerned ab...

  15. 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.

  16. 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

  17. 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.

  18. FDA's misplaced priorities: premarket review under the Family Smoking Prevention and Tobacco Control Act.

    Science.gov (United States)

    Jenson, Desmond; Lester, Joelle; Berman, Micah L

    2016-05-01

    Among other key objectives, the 2009 Family Smoking Prevention and Tobacco Control Act was designed to end an era of constant product manipulation by the tobacco industry that had led to more addictive and attractive products. The law requires new tobacco products to undergo premarket review by the US Food and Drug Administration (FDA) before they can be sold. To assess FDA's implementation of its premarket review authorities, we reviewed FDA actions on new product applications, publicly available data on industry applications to market new products, and related FDA guidance documents and public statements. We conclude that FDA has not implemented the premarket review process in a manner that prioritises the protection of public health. In particular, FDA has (1) prioritised the review of premarket applications that allow for the introduction of new tobacco products over the review of potentially non-compliant products that are already on the market; (2) misallocated resources by accommodating the industry's repeated submissions of deficient premarket applications and (3) weakened the premarket review process by allowing the tobacco industry to market new and modified products that have not completed the required review process. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  19. ADVERTISING, THE FDA, AND THE TOBACCO SETTLEMENT: AS HOPES FOR SETTLEMENT DIM, CHALLENGES OF FDA AUTHORITY AND FIRST AMENDMENT CONCERNS ARE REKINDLED

    OpenAIRE

    Liu, Levi

    1998-01-01

    This discussion will attempt to explore the controversy and dynamics of FDA authority over tobacco advertising and the constitutionality of the existing (although unapproved) restrictions on tobacco advertising, the two major obstacles to the firm establishment of government limitations on the tobacco industry's commercial speech.

  20. Ice Cores

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Records of past temperature, precipitation, atmospheric trace gases, and other aspects of climate and environment derived from ice cores drilled on glaciers and ice...

  1. Core BPEL

    DEFF Research Database (Denmark)

    Hallwyl, Tim; Højsgaard, Espen

    extensions. Combined with the fact that the language definition does not provide a formal semantics, it is an arduous task to work formally with the language (e.g. to give an implementation). In this paper we identify a core subset of the language, called Core BPEL, which has fewer and simpler constructs......, does not allow omissions, and does not contain ignorable elements. We do so by identifying syntactic sugar, including default values, and ignorable elements in WS-BPEL. The analysis results in a translation from the full language to the core subset. Thus, we reduce the effort needed for working...... formally with WS-BPEL, as one, without loss of generality, need only consider the much simpler Core BPEL. This report may also be viewed as an addendum to the WS-BPEL standard specification, which clarifies the WS-BPEL syntax and presents the essential elements of the language in a more concise way...

  2. 77 FR 10535 - Final Guidances for Industry Describing Product-Specific Bioequivalence Recommendations...

    Science.gov (United States)

    2012-02-22

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2007-D-0369] Final Guidances for Industry Describing Product-Specific Bioequivalence Recommendations; Availability... drug products containing the following active ingredients: A Acetaminophen; Caffeine; Dihydrocodeine...

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. Coring apparatus

    Energy Technology Data Exchange (ETDEWEB)

    Mount, W.W.

    1967-11-14

    This invention relates to coring equipment and has special reference to such as are intended to be driven or otherwise inserted into sand or other loose formations to obtain a true sample of the formation. The device includes a plurality of elongated angular members positioned to form an elongated core receptacle between them. A plurality of links are each pivotally mounted at each end on an adjacent member to hold the members in spaced-apart relation in one position. The receptable is driven into the sand, and the members are moved toward one another when they are longitudinally moved with respect to one another to close the receptable. (3 claims)

  8. Credible deterrence: FDA and the Park Doctrine in the 21st century.

    Science.gov (United States)

    O'Leary, Patrick

    2013-01-01

    One of FDA's most powerful enforcement tools is strict liability criminal prosecution of corporate officers under the Park Doctrine. Recent comments by high-ranking FDA officials about using this power more aggressively and recent cases apparently making good on this promise have spurred commentators to call for the doctrine's demise. Critics argue that strict liability for corporate officers violates fundamental notions of fairness and the appropriate relationship between guilt and liability in criminal law. As a response to these critics, this article argues that the Park Doctrine continues to serve a valuable purpose in deterring conduct that endangers the public health and that structural, political, and practical limitations on FDA's use of Park prosecutions have been, and will continue to be, effective protections against the abuses critics fear. This article proposes a model for understanding why and how FDA uses its prosecutorial powers and assesses a sample of recent high-profile prosecutions under this model to argue that the modern "escalation" of Park prosecutions is in fact a continuation of FDA's historical policy.

  9. 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.

  10. The FDA's role in medical device clinical studies of human subjects

    Science.gov (United States)

    Saviola, James

    2005-03-01

    This paper provides an overview of the United States Food and Drug Administration's (FDA) role as a regulatory agency in medical device clinical studies involving human subjects. The FDA's regulations and responsibilities are explained and the device application process discussed. The specific medical device regulatory authorities are described as they apply to the development and clinical study of retinal visual prosthetic devices. The FDA medical device regulations regarding clinical studies of human subjects are intended to safeguard the rights and safety of subjects. The data gathered in pre-approval clinical studies provide a basis of valid scientific evidence in order to demonstrate the safety and effectiveness of a medical device. The importance of a working understanding of applicable medical device regulations from the beginning of the device development project is emphasized particularly for novel, complex products such as implantable visual prosthetic devices.

  11. FDA Experience with Medical Countermeasures under the Animal Rule

    Directory of Open Access Journals (Sweden)

    Paul Aebersold

    2012-01-01

    Full Text Available The Food and Drug Administration issued a final rule in May 2002 to permit the Agency to approve drugs or license biological products on the basis of animal efficacy studies for use in ameliorating or preventing serious or life-threatening conditions caused by exposure to lethal or permanently disabling toxic biological, chemical, radiological, or nuclear substances. Only two drugs were approved in the first nine years of the “Animal Rule” despite massive investment by the federal government since 2001 to stimulate development of medical countermeasures to biological threats. This article therefore examines the Food and Drug Administration reviews made public after approval of those two drugs and the public discussion at the Agency's Anti-Infective Drugs Advisory Committee of one biological product under development under the Animal Rule. Despite the paucity of approved drugs or licensed biological products as medical countermeasures, several investigational drugs have been placed in the National Strategic Stockpile for use as medical countermeasures, if needed.

  12. 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...

  13. Levelling the Playing Field: the FDA's Regulation of Nicotine Dependence Products

    OpenAIRE

    Szubin, Adam J.

    1999-01-01

    There is a great need for the increased development and use of nicotine dependence products (NDPs) in this country. A creative regulatory approach, such as the FDA brought to tobacco regulation, could do an enormous amount of good. In the field of NDPs, as in every area of drug regulation, a new regulatory approach will bring with it costs and benefits. As our knowledge advances, the FDA should not be slow to adopt the same aggressive yet flexible approach to NDPs that it has adopted towards ...

  14. 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 partnership with NIST and the FDA, NCL has laid a solid, scientific foundation for using the power of nanotechnology to increase the potency and target the delivery

  15. 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.

  16. 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

  17. 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... contract is an advisory committee subject to the Federal Advisory Committee Act and this subpart depends...

  18. 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...

  19. 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...

  20. 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...

  1. 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...

  2. Existing FDA pathways have potential to ensure early access to, and appropriate use of, specialty drugs.

    Science.gov (United States)

    Kesselheim, Aaron S; Tan, Yongtian Tina; Darrow, Jonathan J; Avorn, Jerry

    2014-10-01

    Specialty drugs are notable among prescription drugs in that they offer the possibility of substantial clinical improvement, come with important risks of adverse events and mortality, can be complex to manufacture or administer, and are usually extremely costly. The Food and Drug Administration (FDA) plays a critical role in ensuring that patients who could benefit from specialty drugs have access to them in a timely fashion. In this article we review the different strategies that the FDA can use to approve and influence the post-approval prescribing of specialty drugs. When specialty drugs show promise in early clinical trials, the FDA can expedite the drugs' availability to patients through expanded access programs and expedited approval pathways that speed regulatory authorization. After approval, to ensure that specialty drugs are directed to the patients who are most likely to benefit from them, the FDA can limit the scope of the drugs' indications, encourage the development of companion diagnostic tests to indicate which patients should receive the drugs, or require that manufacturers subject them to Risk Evaluation and Mitigation Strategies to ensure that their use is appropriately limited to a restricted population that is aware of the drugs' risks and benefits. Implementing these existing regulatory approaches can promote timely patient access to specialty drugs while preventing expensive and potentially inappropriate overuse. Project HOPE—The People-to-People Health Foundation, Inc.

  3. 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...

  4. 76 FR 30175 - Draft Guidance for Clinical Investigators, Industry, and FDA Staff: Financial Disclosure by...

    Science.gov (United States)

    2011-05-24

    ... Investigators.'' This draft guidance is intended to assist clinical investigators, industry, and FDA staff in... Dockets Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane, rm. 1061, Rockville, MD...-7100). Send one self-addressed adhesive label to assist the office in processing your requests. Submit...

  5. 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

  6. 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

  7. 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.

  8. The Pharmaceutical Industry in 2017. An Analysis of FDA Drug Approvals from the Perspective of Molecules.

    Science.gov (United States)

    de la Torre, Beatriz G; Albericio, Fernando

    2018-02-27

    This is an analysis from a chemical point of view of the 46 drugs (34 New Chemical Entities and 12 Biologics) approved by the FDA during 2017. The drugs included in the 2017 "harvest" have been classified on the basis of their chemical structure: biologics (antibodies and proteins); peptides; amino acids and natural products; drug combinations; and small molecules.

  9. 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.

  10. 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.

  11. 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.

  12. Advancing pharmaceutical quality: An overview of science and research in the U.S. FDA's Office of Pharmaceutical Quality.

    Science.gov (United States)

    Fisher, Adam C; Lee, Sau L; Harris, Daniel P; Buhse, Lucinda; Kozlowski, Steven; Yu, Lawrence; Kopcha, Michael; Woodcock, Janet

    2016-12-30

    Failures surrounding pharmaceutical quality, particularly with respect to product manufacturing issues and facility remediation, account for the majority of drug shortages and product recalls in the United States. Major scientific advancements pressure established regulatory paradigms, especially in the areas of biosimilars, precision medicine, combination products, emerging manufacturing technologies, and the use of real-world data. Pharmaceutical manufacturing is increasingly globalized, prompting the need for more efficient surveillance systems for monitoring product quality. Furthermore, increasing scrutiny and accelerated approval pathways provide a driving force to be even more efficient with limited regulatory resources. To address these regulatory challenges, the Office of Pharmaceutical Quality (OPQ) in the Center for Drug Evaluation and Research (CDER) at the U.S. Food and Drug Administration (FDA) harbors a rigorous science and research program in core areas that support drug quality review, inspection, surveillance, standards, and policy development. Science and research is the foundation of risk-based quality assessment of new drugs, generic drugs, over-the-counter drugs, and biotechnology products including biosimilars. This is an overview of the science and research activities in OPQ that support the mission of ensuring that safe, effective, and high-quality drugs are available to the American public. Published by Elsevier B.V.

  13. 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

  14. 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

  15. 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."

  16. 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.

  17. OpenVigil FDA - Inspection of U.S. American Adverse Drug Events Pharmacovigilance Data and Novel Clinical Applications.

    Science.gov (United States)

    Böhm, Ruwen; von Hehn, Leocadie; Herdegen, Thomas; Klein, Hans-Joachim; Bruhn, Oliver; Petri, Holger; Höcker, Jan

    2016-01-01

    Pharmacovigilance contributes to health care. However, direct access to the underlying data for academic institutions and individual physicians or pharmacists is intricate, and easily employable analysis modes for everyday clinical situations are missing. This underlines the need for a tool to bring pharmacovigilance to the clinics. To address these issues, we have developed OpenVigil FDA, a novel web-based pharmacovigilance analysis tool which uses the openFDA online interface of the Food and Drug Administration (FDA) to access U.S. American and international pharmacovigilance data from the Adverse Event Reporting System (AERS). OpenVigil FDA provides disproportionality analyses to (i) identify the drug most likely evoking a new adverse event, (ii) compare two drugs concerning their safety profile, (iii) check arbitrary combinations of two drugs for unknown drug-drug interactions and (iv) enhance the relevance of results by identifying confounding factors and eliminating them using background correction. We present examples for these applications and discuss the promises and limits of pharmacovigilance, openFDA and OpenVigil FDA. OpenVigil FDA is the first public available tool to apply pharmacovigilance findings directly to real-life clinical problems. OpenVigil FDA does not require special licenses or statistical programs.

  18. 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

  19. 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

  20. 76 FR 41506 - Draft Guidance for Industry and FDA Staff on In Vitro Companion Diagnostic Devices; Availability

    Science.gov (United States)

    2011-07-14

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-D-0215...: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA) is... guidance is intended to assist sponsors planning to develop a therapeutic product that depends on the use...

  1. 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...

  2. Dandruff, seborrheic dermatitis, and psoriasis drug products containing coal tar and menthol for over-the-counter human use; amendment to the monograph. Final rule

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2006-03-15

    The Food and Drug Administration (FDA) is issuing a final rule amending the final monograph (FM) for over-the-counter (OTC) dandruff, seborrheic dermatitis, and psoriasis drug products to include the combination of 1.8 percent coal tar solution and 1.5 percent menthol in a shampoo drug product to control dandruff. FDA did not receive any comments or data in response to its previously proposed rule to include this combination. This final rule is part of FDA's ongoing review of OTC drug products.

  3. Multi-core Microprocessors

    Indian Academy of Sciences (India)

    core processors. Abstract. Multi-core microprocessor is an interconnected set of independentprocessors called cores integrated on a single siliconchip. These processing cores communicate and cooperatewith one another to execute one or more ...

  4. FDA Adverse Event Reporting System: Recruiting Doctors to Make Surveillance a Little Less Passive.

    Science.gov (United States)

    Mann, Justin M

    2015-01-01

    Within the last few decades, a shift has taken place in FDA's approach to drug development, with greater emphasis put on postmarketing data collection and less on the traditional premarketing scheme. The FDA Adverse Event Reporting System (FAERS) is the primary system for collecting Adverse Events, but has been criticized for years for the low reporting rate into the system and the poor quality of the information submitted. This paper argues that physicians need to be required to submit adverse event reports to FAERS, because such a requirement (1) would produce a greater number of the high quality reports necessary to better determine causality; (2) is merely an extension of physicians' ethical obligations; and (3) aligns with the approach in the Vaccine Adverse Event Reporting System (VAERS). Furthermore, advances in electronic health records can aid in reporting efficiency.

  5. Data Sets Representative of the Structures and Experimental Properties of FDA-Approved Drugs.

    Science.gov (United States)

    Douguet, Dominique

    2018-03-08

    Presented here are several data sets that gather information collected from the labels of the FDA approved drugs: their molecular structures and those of the described active metabolites, their associated pharmacokinetics and pharmacodynamics data, and the history of their marketing authorization by the FDA. To date, 1852 chemical structures have been identified with a molecular weight less than 2000 of which 492 are or have active metabolites. To promote the sharing of data, the original web server was upgraded for browsing the database and downloading the data sets (http://chemoinfo.ipmc.cnrs.fr/edrug3d). It is believed that the multidimensional chemistry-oriented collections are an essential resource for a thorough analysis of the current drug chemical space. The data sets are envisioned as being used in a wide range of endeavors that include drug repurposing, drug design, privileged structures analyses, structure-activity relationship studies, and improving of absorption, distribution, metabolism, and elimination predictive models.

  6. Large-scale combining signals from both biomedical literature and the FDA Adverse Event Reporting System (FAERS) to improve post-marketing drug safety signal detection.

    Science.gov (United States)

    Xu, Rong; Wang, QuanQiu

    2014-01-15

    Independent data sources can be used to augment post-marketing drug safety signal detection. The vast amount of publicly available biomedical literature contains rich side effect information for drugs at all clinical stages. In this study, we present a large-scale signal boosting approach that combines over 4 million records in the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) and over 21 million biomedical articles. The datasets are comprised of 4,285,097 records from FAERS and 21,354,075 MEDLINE articles. We first extracted all drug-side effect (SE) pairs from FAERS. Our study implemented a total of seven signal ranking algorithms. We then compared these different ranking algorithms before and after they were boosted with signals from MEDLINE sentences or abstracts. Finally, we manually curated all drug-cardiovascular (CV) pairs that appeared in both data sources and investigated whether our approach can detect many true signals that have not been included in FDA drug labels. We extracted a total of 2,787,797 drug-SE pairs from FAERS with a low initial precision of 0.025. The ranking algorithm combined signals from both FAERS and MEDLINE, significantly improving the precision from 0.025 to 0.371 for top-ranked pairs, representing a 13.8 fold elevation in precision. We showed by manual curation that drug-SE pairs that appeared in both data sources were highly enriched with true signals, many of which have not yet been included in FDA drug labels. We have developed an efficient and effective drug safety signal ranking and strengthening approach We demonstrate that large-scale combining information from FAERS and biomedical literature can significantly contribute to drug safety surveillance.

  7. FDA Approves Two HPV Vaccines: Cervarix for Girls, Gardasil for Boys | Division of Cancer Prevention

    Science.gov (United States)

    The FDA has approved a second vaccine to prevent cervical cancer and cervical precancers, the vaccine’s manufacturer, GlaxoSmithKline (GSK), announced last week. The approval is based on data from a large clinical trial showing that the vaccine, Cervarix, prevented precancerous lesions in 93 percent of those who received the full vaccine sequence of three injections over 6 months. |

  8. Participatory surveillance of diabetes device safety: a social media-based complement to traditional FDA reporting.

    Science.gov (United States)

    Mandl, Kenneth D; McNabb, Marion; Marks, Norman; Weitzman, Elissa R; Kelemen, Skyler; Eggleston, Emma M; Quinn, Maryanne

    2014-01-01

    Malfunctions or poor usability of devices measuring glucose or delivering insulin are reportable to the FDA. Manufacturers submit 99.9% of these reports. We test online social networks as a complementary source to traditional FDA reporting of device-related adverse events. Participatory surveillance of members of a non-profit online social network, TuDiabetes.org, from October 2011 to September 2012. Subjects were volunteers from a group within TuDiabetes, actively engaged online in participatory surveillance. They used the free TuAnalyze app, a privacy-preserving method to report detailed clinical information, available through the network. Network members were polled about finger-stick blood glucose monitors, continuous glucose monitors, and insulin delivery devices, including insulin pumps and insulin pens. Of 549 participants, 75 reported device-related adverse events, nearly half (48.0%) requiring intervention from another person to manage the event. Only three (4.0%) of these were reported by participants to the FDA. All TuAnalyze reports contained outcome information compared with 22% of reports to the FDA. Hypoglycemia and hyperglycemia were experienced by 48.0% and 49.3% of participants, respectively. Members of an online community readily engaged in participatory surveillance. While polling distributed online populations does not yield generalizable, denominator-based rates, this approach can characterize risk within online communities using a bidirectional communication channel that enables reach-back and intervention. Engagement of distributed communities in social networks is a viable complementary approach to traditional public health surveillance for adverse events related to medical devices. 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.

  9. Biomarkers of Potential Harm: Summary of an FDA-Sponsored Public Workshop.

    Science.gov (United States)

    Chang, Cindy M; Cheng, Yu-Ching; Cho, Matthew; Mishina, Elena; Del Valle-Pinero, Arseima Y; van Bemmel, Dana; Hatsukami, Dorothy K

    2017-12-14

    Since 2009, the United States (U.S.) Food and Drug Administration (FDA) Center for Tobacco Products (CTP) has had the authority to regulate the manufacture, distribution, and marketing of tobacco products in order to reduce the death and disease caused by tobacco use. Biomarkers could play an important role across a number of FDA regulatory activities, including assessing new and modified risk tobacco products and identifying and evaluating potential product standards. On April 4-5, 2016, FDA/CTP hosted a public workshop focused on biomarkers of potential harm (BOPH) with participants from government, industry, academia, and other organizations. The workshop was divided into five sessions focused on: 1) overview of BOPH; 2) cardiovascular disease (CVD); 3) chronic obstructive pulmonary disease (COPD); 4) cancer; and 5) new areas of research. The deliberations from the workshop noted some promising BOPH but also highlighted the lack of systematic effort to identify BOPH that would have utility and validity for evaluating tobacco products. Research areas that could further strengthen the applicability of BOPH to tobacco regulatory science include the exploration of composite biomarkers as predictors of disease risk, "omics" biomarkers, and examining biomarkers using existing cohorts, surveys and experimental studies. This paper synthesizes the main findings from the 2016 FDA-sponsored workshop focused on biomarkers of potential harm (BOPH) and highlights research areas that could further strengthen the science around BOPH and their applicability to tobacco regulatory science. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco 2017. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  10. 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...

  11. 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

  12. Warnings without guidance: patient responses to an FDA warning about ezetimibe.

    Science.gov (United States)

    Shrank, William H; Choudhry, Niteesh K; Tong, Angela; Myers, Jessica; Fischer, Michael A; Swanton, Kellie; Slezak, Julie; Brennan, Troyen A; Liberman, Joshua N; Moffit, Susan; Avorn, Jerry; Carpenter, Daniel

    2012-06-01

    In January 2008, the Food and Drug Administration (FDA) communicated concerns about the efficacy of ezetimibe, but did not provide clear clinical guidance, and substantial media attention ensued. We investigated the proportion of patients who discontinued therapy and switched to a clinically appropriate alternative after the FDA communication. Using claims data from a national pharmacy benefits manager, we created a rolling cohort of new users of ezetimibe between January 2006 and August 2008 and created a supply diary for each patient in the year after cohort entry. A patient was identified as nonpersistent if a gap of 90 days was seen in the diary. Using segmented linear regression, we compared rates of nonpersistence before and after the FDA communication and assessed patient-level characteristics associated with discontinuation. Among nonpersistent patients, we determined whether a patient made a clinically appropriate switch in the subsequent 90 days by adding a new cholesterol-lowering medication or by increasing the dose of an existing one. We used a weighted t test to compare the rates of appropriate switching before and after the communication. Among 867,027 new ezetimibe users, 407,006 (46.9%) were nonpersistent in the first year. After the FDA communication, the monthly level of ezetimibe nonpersistence increased by 5.7 percentage points (Pcommunication regarding its efficacy and following associated media attention, and a small proportion of patients made a clinically appropriate switch after discontinuation. Further consideration is needed to deliver messages that promote appropriate use of chronic therapy rather than simply reduce use.

  13. 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

  14. 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

  15. Medical devices; exception from general requirements for informed consent. Final rule.

    Science.gov (United States)

    2011-06-24

    The Food and Drug Administration (FDA) is issuing a final regulation to confirm, with one change, the interim final rule (IFR) entitled "Medical Devices; Exception From General Requirements for Informed Consent." This final rule confirms the IFR's establishment of a new exception from the general requirements for informed consent to permit the use of investigational in vitro diagnostic devices to identify chemical, biological, radiological, or nuclear agents without informed consent in certain circumstances. FDA has created this exception to help ensure that individuals who may have been exposed to a chemical, biological, radiological, or nuclear agent are able to benefit from the timely use of the most appropriate diagnostic devices, including those that are investigational. This final rule adds a requirement that the investigator submit the required documentation to FDA, in addition to submitting it to the reviewing Institutional Review Board (IRB).

  16. Biomarkers of Tobacco Exposure: Summary of an FDA-Sponsored Public Workshop.

    Science.gov (United States)

    Chang, Cindy M; Edwards, Selvin H; Arab, Aarthi; Del Valle-Pinero, Arseima Y; Yang, Ling; Hatsukami, Dorothy K

    2017-03-01

    Since 2009, the FDA Center for Tobacco Products (CTP) has had the authority to regulate the manufacturing, distribution, and marketing of tobacco products in order to reduce the death and disease caused by tobacco use. Biomarkers of exposure pertain to actual human exposure to chemicals arising from tobacco use and could play an important role across a number of FDA regulatory activities, including assessing new and modified-risk tobacco products and identifying and evaluating potential product standards. On August 3-4, 2015, FDA/CTP hosted a public workshop focused on biomarkers of exposure with participants from government, industry, academia, and other organizations. The workshop was divided into four sessions focused on: (i) approaches to evaluating and selecting biomarkers; (ii) biomarkers of exposure and relationship to disease risk; (iii) currently used biomarkers of exposure and biomarkers in development; and (iv) biomarkers of exposure and the assessment of smokeless tobacco and electronic nicotine delivery systems. This article synthesizes the main findings from the workshop and highlights research areas that could further strengthen the science around biomarkers of exposure and help determine their application in tobacco product regulation. Cancer Epidemiol Biomarkers Prev; 26(3); 291-302. ©2016 AACR . ©2016 American Association for Cancer Research.

  17. New and incremental FDA black box warnings from 2008 to 2015.

    Science.gov (United States)

    Solotke, Michael T; Dhruva, Sanket S; Downing, Nicholas S; Shah, Nilay D; Ross, Joseph S

    2018-02-01

    The boxed warning (also known as 'black box warning [BBW]') is one of the strongest drug safety actions that the U.S. Food & Drug Administration (FDA) can implement, and often warns of serious risks. The objective of this study was to comprehensively characterize BBWs issued for drugs after FDA approval. We identified all post-marketing BBWs from January 2008 through June 2015 listed on FDA's MedWatch and Drug Safety Communications websites. We used each drug's prescribing information to classify its BBW as new, major update to a preexisting BBW, or minor update. We then characterized these BBWs with respect to pre-specified BBW-specific and drug-specific features. There were 111 BBWs issued to drugs on the US market, of which 29% (n = 32) were new BBWs, 32% (n = 35) were major updates, and 40% (n = 44) were minor updates. New BBWs and major updates were most commonly issued for death (51%) and cardiovascular risk (27%). The new BBWs and major updates impacted 200 drug formulations over the study period, of which 64% were expected to be used chronically and 58% had available alternatives without a BBW. New BBWs and incremental updates to existing BBWs are frequently added to drug labels after regulatory approval.

  18. Impact of the US FDA "Biopharmaceutics Classification System" (BCS) Guidance on Global Drug Development.

    Science.gov (United States)

    Mehta, Mehul U; Uppoor, Ramana S; Conner, Dale P; Seo, Paul; Vaidyanathan, Jayabharathi; Volpe, Donna A; Stier, Ethan; Chilukuri, Dakshina; Dorantes, Angelica; Ghosh, Tapash; Mandula, Haritha; Raines, Kimberly; Dhanormchitphong, Pariban; Woodcock, Janet; Yu, Lawrence X

    2017-12-04

    The FDA guidance on application of the biopharmaceutics classification system (BCS) for waiver of in vivo bioequivalence (BE) studies was issued in August 2000. Since then, this guidance has created worldwide interest among biopharmaceutical scientists in regulatory agencies, academia, and industry toward its implementation and further expansion. This article describes how the review implementation of this guidance was undertaken at the FDA and results of these efforts over last dozen years or so across the new, and the generic, drug domains are provided. Results show that greater than 160 applications were approved, or tentatively approved, based on the BCS approach across multiple therapeutic areas; an additional significant finding was that at least 50% of these approvals were in the central nervous system (CNS) area. These findings indicate a robust utilization of the BCS approach toward reducing unnecessary in vivo BE studies and speeding up availability of high quality pharmaceutical products. The article concludes with a look at the adoption of this framework by regulatory and health policy organizations across the globe, and FDA's current thinking on areas of improvement of this guidance.

  19. An Improved Adaptive Received Beamforming for Nested Frequency Offset and Nested Array FDA-MIMO Radar

    Directory of Open Access Journals (Sweden)

    Sibei Cheng

    2018-02-01

    Full Text Available For the conventional FDA-MIMO (frequency diversity array multiple-input-multiple-output Radar with uniform frequency offset and uniform linear array, the DOFs (degrees of freedom of the adaptive beamformer are limited by the number of elements. A better performance—for example, a better suppression for strong interferences and a more desirable trade-off between the main lobe and side lobe—can be achieved with a greater number of DOFs. In order to obtain larger DOFs, this paper researches the signal model of the FDA-MIMO Radar with nested frequency offset and nested array, then proposes an improved adaptive beamforming method that uses the augmented matrix instead of the covariance matrix to calculate the optimum weight vectors and can be used to improve the output performances of FDA-MIMO Radar with the same element number or reduce the element number while maintain the approximate output performances such as the received beampattern, the main lobe width, side lobe depths and the output SINR (signal-to-interference-noise ratio. The effectiveness of the proposed scheme is verified by simulations.

  20. Effects of FDA advisories on the pharmacologic treatment of ADHD, 2004-2008.

    Science.gov (United States)

    Kornfield, Rachel; Watson, Sydeaka; Higashi, Ashley S; Conti, Rena M; Dusetzina, Stacie B; Garfield, Craig F; Dorsey, E Ray; Huskamp, Haiden A; Alexander, G Caleb

    2013-04-01

    This study assessed the effect of public health advisories issued between 2005 and 2007 by the U.S. Food and Drug Administration (FDA) on treatments of attention-deficit hyperactivity disorder (ADHD) and physician prescribing practices. Data obtained from the IMS Health National Disease and Therapeutic Index, a nationally representative audit of ambulatory physicians, were used to examine trends in office visits by children and adolescents (under age 18) during which ADHD was treated with Adderall, other psychostimulants, or atomoxetine. Segmented time series regressions were conducted to determine changes in use associated with three advisories issued between 2005 and 2007. In 2004, before the first FDA advisory, Adderall accounted for 36% of ADHD pharmacotherapy treatment visits. Other stimulants accounted for 46%, and atomoxetine accounted for 19%. Overall pharmacotherapy treatment rates were stable over the study period, but by 2008 the treatment visits accounted for by Adderall (that is, market share) declined to 24%, and the market share for atomoxetine declined to 8%. The market share for substitute therapies-clonidine, guanfacine, and bupropion-was stable over this period, ranging from 5% to 7%. Despite the declines in the use of Adderall and atomoxetine over the study period, results from the regression models suggest that the advisories did not have a statistically significant effect on ADHD medication prescribing. FDA advisories regarding potential cardiovascular and other risks of ADHD medications had little discernible incremental effect on the use of these medicines in this nationally representative ambulatory audit.

  1. Effects of FDA Advisories on the Pharmacologic Treatment of ADHD, 2004–2008

    Science.gov (United States)

    Kornfield, Rachel; Watson, Sydeaka; Higashi, Ashley S.; Conti, Rena M.; Dusetzina, Stacie B.; Garfield, Craig F.; Dorsey, E. Ray; Huskamp, Haiden A.; Alexander, G. Caleb

    2014-01-01

    Objective This study assessed the effect of public health advisories issued between 2005 and 2007 by the U.S. Food and Drug Administration (FDA) on treatments of attention-deficit hyperactivity disorder (ADHD) and physician prescribing practices. Methods Data obtained from the IMS Health National Disease and Therapeutic Index, a nationally representative audit of ambulatory physicians, were used to examine trends in office visits by children and adolescents (under age 18) during which ADHD was treated with Adderall, other psychostimulants, or atomoxetine. Segmented time series regressions were conducted to determine changes in use associated with three advisories issued between 2005 and 2007. Results In 2004, before the first FDA advisory, Adderall accounted for 36% of ADHD pharmacotherapy treatment visits. Other stimulants accounted for 46%, and atomoxetine accounted for 19%. Overall pharmacotherapy treatment rates were stable over the study period, but by 2008 the treatment visits accounted for by Adderall (that is, market share) declined to 24%, and the market share for atomoxetine declined to 8%. The market share for substitute therapies—clonidine, guanfacine, and bupropion—was stable over this period, ranging from 5% to 7%. Despite the declines in the use of Adderall and atomoxetine over the study period, results from the regression models suggest that the advisories did not have a statistically significant effect on ADHD medication prescribing. Conclusions FDA advisories regarding potential cardiovascular and other risks of ADHD medications had little discernible incremental effect on the use of these medicines in this nationally representative ambulatory audit. PMID:23318985

  2. FDA Approval of PARP Inhibitors and the Impact on Genetic Counseling and Genetic Testing Practices.

    Science.gov (United States)

    Buchtel, Kathryn M; Vogel Postula, Kristen J; Weiss, Shelly; Williams, Carmen; Pineda, Mario; Weissman, Scott M

    2018-02-01

    In December 2014, the FDA approved olaparib, a poly(ADP-ribose) polymerase inhibitor (PARPi) for ovarian cancer patients who have failed three or more lines of chemotherapy and have a germline BRCA1/2 mutation identified through a companion diagnostic test (BRACAnalysis CDx™ (CDx™)) offered exclusively by Myriad Genetic Laboratories. This study explored the impact of PARPi/CDx™ on genetic counselors' (GCs) counseling and testing practices. One hundred twenty three GCs responded to an online survey regarding pre- and post-FDA approval referral patterns, testing strategies/influences, and anecdotal experiences with insurance coverage of PARPi for BRCA1/2 positive patients through a non-CDx™ platform. Following PARPi approval, 40% of respondents reported an increase in overall referrals of ovarian cancer patients and 20% had an increase in post-test counseling only referrals. The majority (61.9%) of respondents reported no change in genetic testing strategy, and there was no change in factors influencing choice of testing laboratory. Nearly all (98.1%) respondents who had experience with insurance covering PARPi indicated approval with mutations identified via non-CDx™ testing. Respondents indicated an increase in referral volume following FDA approval of PARPi/CDx™, but did not report changes in testing practices. Respondents were not aware of PARPi insurance coverage denial in the absence of CDx™.

  3. HOW STARLESS ARE STARLESS CORES?

    International Nuclear Information System (INIS)

    Schnee, Scott; Friesen, Rachel; Di Francesco, James; Johnstone, Doug; Enoch, Melissa; Sadavoy, Sarah

    2012-01-01

    In this paper, we present the results of Combined Array for Research in Millimeter-wave Astronomy continuum and spectral line observations of the dense core Per-Bolo 45. Although this core has previously been classified as starless, we find evidence for an outflow and conclude that Per-Bolo 45 is actually an embedded, low-luminosity protostar. We discuss the impact of newly discovered, low-luminosity, embedded objects in the Perseus molecular cloud on starless core and protostar lifetimes. We estimate that the starless core lifetime has been overestimated by 4%-18% and the Class 0/I protostellar lifetime has been underestimated by 5%-20%. Given the relatively large systematic uncertainties involved in these calculations, variations on the order of 10% do not significantly change either core lifetimes or the expected protostellar luminosity function. Finally, we suggest that high-resolution (sub)millimeter surveys of known cores lacking near-infrared and mid-infrared emission are necessary to make an accurate census of starless cores.

  4. FDA MAUDE data on complications with lasers, light sources, and energy-based devices.

    Science.gov (United States)

    Tremaine, Anne Marie; Avram, Mathew M

    2015-02-01

    It is essential for physicians to be fully informed regarding adverse events and malfunctions associated with medical devices that occur in routine practice. There is limited information on this important issue in the medical literature, and it is mostly based on initial studies and case reports. More advanced knowledge regarding device adverse events is necessary to guide physicians towards providing safe treatments. The FDA requires that manufacturers and device users submit medical device reports (MDRs) for suspected injuries from device use or malfunction. The database of MDRs, entitled Manufacturer and User Facility Device Experience (MAUDE) enables the FDA to monitor device performance and identify potential safety issues. We employed the following search strategy to identify reported adverse events. We searched the MAUDE electronic database on the FDA website in December 2013: http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfmaude/search.cfm We collected all reported cases between 1991 and December 2013. The search terms utilized included a comprehensive list of device manufacturers, specific product names, and the wavelengths/technology of the devices used in the field of dermatology. Our search yielded 1257 MDRs. Forty-five MDRs were excluded due to insufficient data. The data is broken down into the adverse events observed, such as, but not limited to: blistering, burns, scarring, dyschromia, fat loss, and nerve palsy. The MDRs describe the adverse event and attempt to determine if it was related to device malfunction versus operator error. Radiofrequency devices, diode lasers, and intense pulsed light devices were the most commonly reported devices related to injuries. 1257 MDRs, from a myriad of devices used in dermatology, have been reported to the FDA as of December 2013. Despite the underreporting of adverse events, the MAUDE database is an untapped resource of post-market surveillance of medical devices. The database can offer additional

  5. 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

    support its use 'under emergency conditions'. In another part of the guidance, however, the FDA describes the concentrations at which the cost of implementing a protective action equals the risk avoided by (i.e., benefit of) the action. These concentrations are fractions of the DRLs, which suggests, as the guidance itself states, that it may be 'appropriate to implement low-impact protective actions at projected radiation doses less than those specified in the guides'. The resulting implication is that ALARA principles may indeed play an important role in ingestion pathway planning. The FDA should, therefore, re-evaluate its position on ALARA and should estimate the concentrations of radionuclides in human food and animal feed below which protective actions are unnecessary based on ALARA principles and cost/benefit evaluations. Finally, to determine if the PAGs for milk are being exceeded when mixtures of radionuclides are present, DRLs must be derived fbr radionuclides other than those currently in the guidance (i.e., I-131, Cs-134, Cs-137, Sr-89, Sr-90). Such data already exists for more than thirty other radionuclides for water, produce, and leafy foodstuffs in the Federal Emergency Management Agency document entitled 'Guidance on Offsite Emergency Radiation Measurement Systems, Phase 3, Water and Non-Dairy Food Pathway' (FEMA88). In conclusion, the basis and principles upon which the protective action guides and derived response levels for the ingestion pathway were created need to be re-evaluated to ensure that the guidance is technically valid and practical to implement. In addition, efforts should be made to improve the applicability of the guidance by including DRLs for other radionuclides which may be present in milk. (author)

  6. Experimental Constraints on Core Composition

    Science.gov (United States)

    Li, J.; Fei, Y.

    2003-12-01

    composition. The discussion of the role of nickel will be brief, as the number of experimental studies of nickel is limited. A large portion of the chapter will be devoted to constraints on the light element composition of the core, a highly controversial subject, with direct implications for diverse topics concerned with the origin, evolution, and current state of the Earth. Finally, we summarize the latest experimental results on potassium, niobium, rhenium, and osmium, some of the interesting minor and trace elements in the core.

  7. 76 FR 69333 - Derivatives Clearing Organization General Provisions and Core Principles

    Science.gov (United States)

    2011-11-08

    ... Parts 1, 21, 39 et al. Derivatives Clearing Organization General Provisions and Core Principles; Final... Derivatives Clearing Organization General Provisions and Core Principles AGENCY: Commodity Futures Trading... with DCO Core Principles A (Compliance), B (Financial Resources), C (Participant and Product...

  8. 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...

  9. The FDA and the US direct-to-consumer marketplace for stem cell interventions: a temporal analysis.

    Science.gov (United States)

    Knoepfler, Paul S; Turner, Leigh G

    2018-01-01

    Hundreds of businesses in the US currently advertise a wide range of non-US FDA-approved stem cell interventions. Here we present a novel systematic temporal analysis of US companies engaged in direct-to-consumer marketing of putative stem cell treatments. Between 2009 and 2014, the number of new US stem cell businesses with websites grew rapidly, at least doubling on average every year. From 2014 to 2016, approximately 90-100 new stem cell business websites appeared per year. In contrast, from 2012 to the present, regulatory activity in the form of FDA warning letters has been limited. These data point to a problematic disconnect between a rapidly expanding US direct-to-consumer stem cell industry and limited FDA oversight of this marketplace. More consistent, timely and effective FDA actions are urgently needed.

  10. Comparison and analysis of FDA reported visual outcomes of the three latest platforms for LASIK: wavefront guided Visx iDesign, topography guided WaveLight Allegro Contoura, and topography guided Nidek EC-5000 CATz.

    Science.gov (United States)

    Moshirfar, Majid; Shah, Tirth J; Skanchy, David Franklin; Linn, Steven H; Kang, Paul; Durrie, Daniel S

    2017-01-01

    To compare and analyze the differences in visual outcomes between Visx iDesign Advanced WaveScan Studio™ System, Alcon Wavelight Allegro Topolyzer and Nidek EC-5000 using Final Fit™ Custom Ablation Treatment Software from the submitted summary of safety and effectiveness of the US Food and Drug Administration (FDA) data. In this retrospective comparative study, 334 eyes from Visx iDesign, 212 eyes from Alcon Contour, and 135 eyes from Nidek CATz platforms were analyzed for primary and secondary visual outcomes. These outcomes were compared via side-by-side graphical and tabular representation of the FDA data. Statistical significance was calculated when appropriate to assess differences. A P -value LASIK surgery.

  11. LMFBR Ultra Long Life Cores

    International Nuclear Information System (INIS)

    Schmidt, J.E.; Doncals, R.A.; Porter, C.A.; Gundy, L.M.

    1986-01-01

    The Ultra Long Life Core is an attractive and innovative design approach with several extremely beneficial attributes. Long Life cores are applicable to the full range of LMR plant sizes resulting in lifetimes up to 30 years. Core life is somewhat limited for smaller plant sizes, however significant benefits of this approach still exist for all plant sizes. The union of long life cores and the complementary inherent safety technology offer a means of utilizing the well-proven oxide fuel in a system with unsurpassed safety capability. A further benefit is that the uranium fuel cycle can be used in long life cores, especially for initial LMR plant deployment, thereby eliminating the need for reprocessing prior to starting LMR plant construction in the U.S. Finally the long life core significantly reduces power costs. With inherent safety capability designed into an LMR and with the ULLC fuel cycle, power costs competitive with light water plants are achievable while offering improved operational flexibility derived through extending refueling intervals

  12. Has the tobacco industry evaded the FDA's ban on 'Light' cigarette descriptors?

    Science.gov (United States)

    Connolly, Gregory N; Alpert, Hillel R

    2014-03-01

    Under the Family Smoking Prevention and Tobacco Control Act (FSPTCA), the Food and Drug Administration (FDA) banned the use of "Lights" descriptors or similar terms on tobacco products that convey messages of reduced risk. Manufacturers eliminated terms explicitly stated and substituted colour name descriptors corresponding to the banned terms. This paper examines whether the tobacco industry complied with or circumvented the law and potential FDA regulatory actions. Philip Morris retailer manuals, manufacturers' annual reports filed with the Massachusetts Department of Public Health, a national public opinion survey, and market-wide cigarette sales data were examined. Manufacturers substituted "Gold" for "Light" and "Silver" for "Ultra-light" in the names of Marlboro sub-brands, and "Blue", "Gold", and "Silver" for banned descriptors in sub-brand names. Percent filter ventilation levels, used to generate the smoke yield ranges associated with "Lights" categories, appear to have been reassigned to the new colour brand name descriptors. Following the ban, 92% of smokers reported they could easily identify their usual brands, and 68% correctly named the package colour associated with their usual brand, while sales for "Lights" cigarettes remained unchanged. Tobacco manufacturers appear to have evaded a critical element of the FSPTCA, the ban on misleading descriptors that convey reduced health risk messages. The FPSTCA provides regulatory mechanisms, including banning these products as adulterated (Section 902). Manufacturers could then apply for pre-market approval as new products and produce evidence for FDA evaluation and determination whether or not sales of these products are in the public health interest.

  13. 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.

  14. BCS Biowaivers: Similarities and Differences Among EMA, FDA, and WHO Requirements.

    Science.gov (United States)

    Davit, Barbara M; Kanfer, Isadore; Tsang, Yu Chung; Cardot, Jean-Michel

    2016-05-01

    The Biopharmaceutics Classification System (BCS), based on aqueous solubility and intestinal permeability, has enjoyed wide use since 1995 as a mechanism for waiving in vivo bioavailability and bioequivalence studies. In 2000, the US-FDA was the first regulatory agency to publish guidance for industry describing how to meet criteria for requesting a waiver of in vivo bioavailability and bioequivalence studies for highly soluble, highly permeable (BCS Class I) drugs. Subsequently, the World Health Organization (WHO) and European Medicines Agency (EMA) published guidelines recommending how to obtain BCS biowaivers for BCS Class III drugs (high solubility, low permeability), in addition to Class I drugs. In 2015, the US-FDA became better harmonized with the EMA and WHO following publication of two guidances for industry outlining criteria for obtaining BCS biowaivers for both Class I and Class III drugs. A detailed review and comparison of the BCS Class I and Class III criteria currently recommended by the US-FDA, EMA, and WHO revealed good convergence of the three agencies with respect to BCS biowaiver criteria. The comparison also suggested that, by applying the most conservative of the three jurisdictional approaches, it should be possible for a sponsor to design the same set of BCS biowaiver studies in preparing a submission for worldwide filing to satisfy US, European, and emerging market regulators. It is hoped that the availability of BCS Class I and Class III biowaivers in multiple jurisdictions will encourage more sponsors to request waivers of in vivo bioavailability/bioequivalence testing using the BCS approach.

  15. 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

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

    Directory of Open Access Journals (Sweden)

    Xu Xiaowei

    2011-10-01

    Full Text Available Abstract 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 Conclusions The successful application of topic modeling on the FDA drug labeling demonstrates its potential utility as a hypothesis generation means to infer hidden relationships of concepts such as, in this study, drug safety and therapeutic use

  17. Consortium on Methods Evaluating Tobacco: Research Tools to Inform FDA Regulation of Snus.

    Science.gov (United States)

    Berman, Micah L; Bickel, Warren K; Harris, Andrew C; LeSage, Mark G; O'Connor, Richard J; Stepanov, Irina; Shields, Peter G; Hatsukami, Dorothy K

    2017-10-04

    The U.S. Food and Drug Administration (FDA) has purview over tobacco products. To set policy, the FDA must rely on sound science, yet most existing tobacco research methods have not been designed to specifically inform regulation. The NCI and FDA-funded Consortium on Methods Evaluating Tobacco (COMET) was established to develop and assess valid and reliable methods for tobacco product evaluation. The goal of this paper is to describe these assessment methods using a U.S. manufactured "snus" as the test product. In designing studies that could inform FDA regulation, COMET has taken a multidisciplinary approach that includes experimental animal models and a range of human studies that examine tobacco product appeal, addictiveness, and toxicity. This paper integrates COMET's findings over the last 4 years. Consistency in results was observed across the various studies, lending validity to our methods. Studies showed low abuse liability for snus and low levels of consumer demand. Toxicity was less than cigarettes on some biomarkers but higher than medicinal nicotine. Using our study methods and the convergence of results, the snus that we tested as a potential modified risk tobacco product is likely to neither result in substantial public health harm nor benefit. This review describes methods that were used to assess the appeal, abuse liability, and toxicity of snus. These methods included animal, behavioral economics, and consumer perception studies, and clinical trials. Across these varied methods, study results showed low abuse-liability and appeal of the snus product we tested. In several studies, demand for snus was lower than for less toxic nicotine gum. The consistency and convergence of results across a range of multi-disciplinary studies lends validity to our methods and suggests that promotion of snus as a modified risk tobacco products is unlikely to produce substantial public health benefit or harm. © The Author 2017. Published by Oxford University Press

  18. 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.

  19. 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.

  20. Animal MRI Core

    Data.gov (United States)

    Federal Laboratory Consortium — The Animal Magnetic Resonance Imaging (MRI) Core develops and optimizes MRI methods for cardiovascular imaging of mice and rats. The Core provides imaging expertise,...

  1. Final report

    DEFF Research Database (Denmark)

    Badger, Merete; Monaco, Lucio; Fransson, Torsten

    2013-01-01

    This report represents the deliverable D1.2 of project Virtual Campus Hub. The project runs from October 2011 to September 2013. The report is the core of the project’s 2nd periodic report, which was submitted to the European Commission on November 4th, 2013.......This report represents the deliverable D1.2 of project Virtual Campus Hub. The project runs from October 2011 to September 2013. The report is the core of the project’s 2nd periodic report, which was submitted to the European Commission on November 4th, 2013....

  2. 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

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

    Science.gov (United States)

    Fix, Brian V; O'Connor, Richard J; Fong, Geoffrey T; Borland, Ron; Cummings, K M; Hyland, Andrew

    2011-12-16

    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. 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. 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. 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.

  4. 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.

  5. Safety assessment of FDA-approved (orlistat and lorcaserin) anti-obesity medications.

    Science.gov (United States)

    Halpern, Bruno; Halpern, Alfredo

    2015-02-01

    Options for treating obesity remain limited despite it being a chronic, recurrent and morbid condition. New drugs that are proposed for its treatment encounter strong reluctance by regulatory agencies and many doctors. This review will focus on the safety of an older drug, orlistat (the only one still approved in the European Union) and a newer recently FDA-approved one, lorcaserin. Both are approved as long-term monotherapy for obesity in the United States of America and they have demonstrated median weight loss of nearly 3% over placebo. Research, development and approval of new anti-obesity drugs are necessary for improved management of this chronic condition. Orlistat and lorcaserin are two FDA-approved drugs with limited overall efficacy. Nevertheless they are useful weapons for at least some obese individuals. Orlistat has a long and solid safety profile, whereas the safety of lorcaserin is still a matter of debate, mainly due to a lack of long-term data. However, lorcaserin's selective agonism on 5HT2c serotonin receptors diminishes concerns about valvulopathy associated with other serotonin agonists, such as fenfluramine.

  6. Larval zebrafish model for FDA-approved drug repositioning for tobacco dependence treatment.

    Directory of Open Access Journals (Sweden)

    Margot A Cousin

    Full Text Available Cigarette smoking remains the most preventable cause of death and excess health care costs in the United States, and is a leading cause of death among alcoholics. Long-term tobacco abstinence rates are low, and pharmacotherapeutic options are limited. Repositioning medications approved by the U.S. Food and Drug Administration (FDA may efficiently provide clinicians with new treatment options. We developed a drug-repositioning paradigm using larval zebrafish locomotion and established predictive clinical validity using FDA-approved smoking cessation therapeutics. We evaluated 39 physician-vetted medications for nicotine-induced locomotor activation blockade. We further evaluated candidate medications for altered ethanol response, as well as in combination with varenicline for nicotine-response attenuation. Six medications specifically inhibited the nicotine response. Among this set, apomorphine and topiramate blocked both nicotine and ethanol responses. Both positively interact with varenicline in the Bliss Independence test, indicating potential synergistic interactions suggesting these are candidates for translation into Phase II clinical trials for smoking cessation.

  7. 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.

  8. 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.

  9. In Vitro Tolerance of Drug-Naive Staphylococcus aureus Strain FDA209P to Vancomycin

    Science.gov (United States)

    Singh, Madhuri; Sasaki, Takashi; Morimoto, Yuh; Hishinuma, Tomomi; Hiramatsu, Keiichi

    2016-01-01

    ABSTRACT The mechanisms underlying bacterial tolerance to antibiotics are unclear. A possible adaptation strategy was explored by exposure of drug-naive methicillin-susceptible Staphylococcus aureus strain FDA209P to vancomycin in vitro. Strains surviving vancomycin treatment (vancomycin survivor strains), which appeared after 96 h of exposure, were slow-growing derivatives of the parent strain. Although the vancomycin MICs for the survivor strains were within the susceptible range, the cytokilling effects of vancomycin at 20-fold the MIC were significantly lower for the survivor strains than for the parent strain. Whole-genome sequencing demonstrated that ileS, encoding isoleucyl-tRNA synthetase (IleRS), was mutated in two of the three vancomycin survivor strains. The IleRS Y723H mutation is located close to the isoleucyl-tRNA contact site and potentially affects the affinity of IleRS binding to isoleucyl-tRNA, thereby inhibiting protein synthesis and leading to vancomycin tolerance. Introduction of the mutation encoding IleRS Y723H into FDA209P by allelic replacement successfully transferred the vancomycin tolerance phenotype. We have identified mutation of ileS to be one of the bona fide genetic events leading to the acquisition of vancomycin tolerance in S. aureus, potentially acting via inhibition of the function of IleRS. PMID:27855063

  10. Modeling and simulation in dose determination for biodefense products approved under the FDA animal rule.

    Science.gov (United States)

    Bergman, Kimberly L; Krudys, K; Seo, S K; Florian, J

    2017-04-01

    Development of effective medical countermeasures for biodefense is vital to United States biopreparedness and response in the age of terrorism, both foreign and domestic. A traditional drug development pathway toward approval is not possible for most biodefense-related indications, creating the need for alternative development pathways such as the FDA's Animal Rule. Under this unique regulatory mechanism, FDA-approval is based on adequate and well-controlled animal studies when it is neither ethical nor feasible to conduct human efficacy studies. Translation of animal efficacy findings to humans is accomplished by use of modeling and simulation techniques. Pharmacokinetic and exposure-response modeling allow effective dosing regimens in humans to be identified, which are expected to produce similar benefit to that observed in animal models of disease. In this review, the role of modeling and simulation in determining the human dose for biodefense products developed under the Food and Drug Administration's Animal Rule regulatory pathway is discussed, and case studies illustrating the utility of modeling and simulation in this area of development are presented.

  11. 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.

  12. A Retrospective Evaluation of the Use of Mass Spectrometry in FDA Biologics License Applications

    Science.gov (United States)

    Rogstad, Sarah; Faustino, Anneliese; Ruth, Ashley; Keire, David; Boyne, Michael; Park, Jun

    2017-05-01

    The characterization sections of biologics license applications (BLAs) approved by the United States Food and Drug Administration (FDA) between 2000 and 2015 were investigated to examine the extent of the use of mass spectrometry. Mass spectrometry was found to be integral to the characterization of these biotherapeutics. Of the 80 electronically submitted monoclonal antibody and protein biotherapeutic BLAs included in this study, 79 were found to use mass spectrometric workflows for protein or impurity characterization. To further examine how MS is being used in successful BLAs, the applications were filtered based on the type and number of quality attributes characterized, the mass spectrometric workflows used (peptide mapping, intact mass analysis, and cleaved glycan analysis), the methods used to introduce the proteins into the gas phase (ESI, MALDI, or LC-ESI), and the specific types of instrumentation used. Analyses were conducted over a time course based on the FDA BLA approval to determine if any trends in utilization could be observed over time. Additionally, the different classes of protein-based biotherapeutics among the approved BLAs were clustered to determine if any trends could be attributed to the specific type of biotherapeutic.

  13. Data mining of the public version of the FDA Adverse Event Reporting System.

    Science.gov (United States)

    Sakaeda, Toshiyuki; Tamon, Akiko; Kadoyama, Kaori; Okuno, Yasushi

    2013-01-01

    The US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS, formerly AERS) is a database that contains information on adverse event and medication error reports submitted to the FDA. Besides those from manufacturers, reports can be submitted from health care professionals and the public. The original system was started in 1969, but since the last major revision in 1997, reporting has markedly increased. Data mining algorithms have been developed for the quantitative detection of signals from such a large database, where a signal means a statistical association between a drug and an adverse event or a drug-associated adverse event, including the proportional reporting ratio (PRR), the reporting odds ratio (ROR), the information component (IC), and the empirical Bayes geometric mean (EBGM). A survey of our previous reports suggested that the ROR provided the highest number of signals, and the EBGM the lowest. Additionally, an analysis of warfarin-, aspirin- and clopidogrel-associated adverse events suggested that all EBGM-based signals were included in the PRR-based signals, and also in the IC- or ROR-based ones, and that the PRR- and IC-based signals were in the ROR-based ones. In this article, the latest information on this area is summarized for future pharmacoepidemiological studies and/or pharmacovigilance analyses.

  14. Update on medical and regulatory issues pertaining to compounded and FDA-approved drugs, including hormone therapy.

    Science.gov (United States)

    Pinkerton, JoAnn V; Pickar, James H

    2016-02-01

    We review the historical regulation of drug compounding, concerns about widespread use of non-Food and Drug Admiistration (FDA)-approved compounded bioidentical hormone therapies (CBHTs), which do not have proper labeling and warnings, and anticipated impact of the 2013 Drug Quality and Security Act (DQSA) on compounding. US government websites were searched for documents concerning drug compounding regulation and oversight from 1938 (passage of Federal Food, Drug, and Cosmetic Act [FDCA]) through 2014, including chronologies, Congressional testimony, FDA guidelines and enforcements, and reports. The FDCA and DQSA were reviewed. PubMed and Google were searched for articles on compounded drugs, including CBHT. Congress explicitly granted the FDA limited oversight of compounded drugs in a 1997 amendment to the FDCA, but the FDA has encountered obstacles in exercising that authority. After 64 patient deaths and 750 adversely affected patients from the 2012 meningitis outbreak due to contaminated compounded steroid injections, Congress passed the DQSA, authorizing the FDA to create a voluntary registration for facilities that manufacture and distribute sterile compounded drugs in bulk and reinforcing FDCA regulations for traditional compounding. Given history and current environment, concerns remain about CBHT product regulation and their lack of safety and efficacy data. The DQSA and its reinforcement of §503A of the FDCA solidifies FDA authority to enforce FDCA provisions against compounders of CBHT. The new law may improve compliance and accreditation by the compounding industry; support state and FDA oversight; and prevent the distribution of misbranded, adulterated, or inconsistently compounded medications, and false and misleading claims, thus reducing public health risk.

  15. 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.

  16. 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.

  17. Linking Core Competence, Innovation and Firm Performance

    Directory of Open Access Journals (Sweden)

    Öznur Gökkaya

    2015-03-01

    Full Text Available Organizational resources and capabilities realized by business practitioners and researchershave significant importanceas they support firmperformance and competitive advantage. However, what exactly core competence is not clearly understood since terms such as resource, capability and compe tence are used interchangeably by researchers. From this point forth, this article provides a framework for separating organization's core competencies from resource and capability. We propose three empirical determiners such as uniqueness,inimitability and extendibilityto the research modelfor separating organization's core competencies from resource and capability.Second, the proposed core competence framework serves as a tool for assessing the relationship between core competencies and innovation. Finally, the paper intended to help leaders and managers about how they can enhance firm performance by means of supporting core competencies and innovation.

  18. Moulds associated with contaminated ocular and injectable drugs: FDA recalls, epidemiology considerations, drug shortages, and aseptic processing.

    Science.gov (United States)

    Ahearn, Donald G; Stulting, R Doyle

    2017-10-09

    Recent (2012) grave but rare outbreaks of fungal meningitis and endophthalmitis associated with drugs contaminated with select environmental moulds (Exserohilum and Fusarium, respectively) have exacerbated mycology concerns for formulation, good laboratory practices (GLP), and use of the final drug product. Intensified investigations (2013-2015) by the Food and Drug Administration (FDA) that included added responsibilities for specialty compounding laboratories have prompted at least nine voluntary mould-related drug recalls during 2014-2015. Both primary manufactures (five recalls, two companies) and secondary-processing compound laboratories (at least eight recalls, six companies) and near 0.8 million units were involved. These constituted minor fractions of recalled drug products in an estimated 2500 recalls among other causes during this time period. Recalls of similar drugs in 2016 were indirectly related to fungi. None of the mould-related- drug-recall episodes during 2014-2016 have been identified with fungal disease outbreaks. The recalls included drugs in short supply worldwide such as injectable sodium chloride- and related saline solutions as well as ocular formulations. Insufficient environmental monitoring and GLP compliance, particularly for aseptic processing of non-preserved formulations, appeared to be underlying factors in the fungal contaminations. Observations of mould growth in drugs during their processing should be accurately recorded and investigated; cryptic listings under "particulate" designations should be avoided. Confirmed identifications for chronic contaminants are recommended. Heat-tolerant moulds with resistant morphotypes are prime concerns. © The Author 2017. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  19. 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

  20. Final Report

    Energy Technology Data Exchange (ETDEWEB)

    DeTar, Carleton [P.I.

    2012-12-10

    This document constitutes the Final Report for award DE-FC02-06ER41446 as required by the Office of Science. It summarizes accomplishments and provides copies of scientific publications with significant contribution from this award.

  1. Final Report

    Energy Technology Data Exchange (ETDEWEB)

    Gurney, Kevin R. [Arizona Univ., Mesa, AZ (United States)

    2015-01-12

    This document constitutes the final report under DOE grant DE-FG-08ER64649. The organization of this document is as follows: first, I will review the original scope of the proposed research. Second, I will present the current draft of a paper nearing submission to Nature Climate Change on the initial results of this funded effort. Finally, I will present the last phase of the research under this grant which has supported a Ph.D. student. To that end, I will present the graduate student’s proposed research, a portion of which is completed and reflected in the paper nearing submission. This final work phase will be completed in the next 12 months. This final workphase will likely result in 1-2 additional publications and we consider the results (as exemplified by the current paper) high quality. The continuing results will acknowledge the funding provided by DOE grant DE-FG-08ER64649.

  2. Reductions in Use of Colchicine after FDA Enforcement of Market Exclusivity in a Commercially Insured Population.

    Science.gov (United States)

    Kesselheim, Aaron S; Franklin, Jessica M; Kim, Seoyoung C; Seeger, John D; Solomon, Daniel H

    2015-11-01

    A brand-name version of colchicine (Colcrys) was introduced after its manufacturer conducted a clinical trial in acute gout patients, leading to higher prices for this drug. We analyzed the impact of the new single-source colchicine product on prescribing and patient health spending as well as incidence rates of potentially dangerous concomitant use of clarithromycin and cyclosporine after formal FDA approval. We conducted a retrospective cohort study of UnitedHealth-affiliated enrollees newly diagnosed with gout or FMF. Among gout and FMF patients separately, we assessed linear trends in colchicine prescriptions, prescription drug costs, and total health care costs from 2009 to September 2010 (market exclusivity announced) compared to January 2011 (market exclusivity enforced) through 2012. Next, we estimated trends in co-prescription within 15 days of clarithromycin, azithromycin (indicated on the Colcrys label for use in place of clarithromycin), and cyclosporine. Among gout patients, before Colcrys' market exclusivity, the odds of receiving colchicine within 30 days of gout diagnosis increased 1.4 %/month (OR: 1.014, 95 % CI: 1.011-1.018). Following FDA action, the odds decreased by 0.5 %/month (OR: 0.995, 95 % CI: 0.992-0.999) (p colchicine changed from an increase of 2.8 %/month to a decrease by 7.6 %/month (p = 0.01). Patients receiving colchicine experienced increases in average monthly prescription drug costs ($418 vs. $651, p colchicine/clarithromycin co-prescription before and after FDA action did not change, while co-prescription of colchicine/cyclosporine increased after introduction of Colcrys [-0.75 monthly change in patients (95 % CI: -1.07, -0.43) vs. 0.13 (95 % CI: -0.16, 0.42), p colchicine initiation and an increase in patient spending. By contrast, we did not observe any association with improvements in avoidance of potentially dangerous co-prescriptions.

  3. 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

  4. 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

  5. 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

  6. k -core covers and the core

    NARCIS (Netherlands)

    Sanchez-Rodriguez, E.; Borm, P.; Estevez Fernandez, M.A.; Fiestras-Janeiro, M.G.; Mosquera, M.A.

    2015-01-01

    This paper extends the notion of individual minimal rights for a transferable utility game (TU-game) to coalitional minimal rights using minimal balanced families of a specific type, thus defining a corresponding minimal rights game. It is shown that the core of a TU-game coincides with the core of

  7. k-core covers and the core

    NARCIS (Netherlands)

    Sanchez-Rodriguez, E.; Borm, Peter; Estevez-Fernandez, A.; Fiestras-Janeiro, G.; Mosquera, M.A.

    This paper extends the notion of individual minimal rights for a transferable utility game (TU-game) to coalitional minimal rights using minimal balanced families of a specific type, thus defining a corresponding minimal rights game. It is shown that the core of a TU-game coincides with the core of

  8. Can the FDA improve oversight of foreign clinical trials?: Closing the information gap and moving towards a globalized regulatory scheme.

    Science.gov (United States)

    Ourso, André

    2012-01-01

    Currently, pharmaceutical companies' utilization of foreign clinical trial data is a ubiquitous and indispensable aspect of gaining approval to market drugs in the United States. Cost benefits, a larger pool of ready volunteer subjects, and greater efficiency in clinical testing are some of the reasons for conducting clinical trials overseas. Despite these advantages, lack of proper oversight may have serious public health implications regarding the integrity of clinical research, ethical treatment of human subjects, and drug safety. Due to the expansive global nature of foreign clinical trials, there are concerns with the FDA's ability to monitor and regulate these trials. This article examines the FDA's oversight of foreign clinical trials and the agency's limitations regulating these trials. In addition to looking at steps the FDA is taking to address these limitations, the article examines other potential regulatory and cooperative actions that can be taken to effectively monitor foreign clinical trials and to ensure data integrity and patient safety.

  9. 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.

  10. The Role of the FDA and Regulatory Approval of New Devices for Diabetes Care.

    Science.gov (United States)

    Jazowski, Shelley A; Winn, Aaron N

    2017-06-01

    The Food and Drug Administration (FDA) is responsible for assuring the safety, effectiveness, and quality of medical devices in the USA. Extensive review times coupled with the demand for necessary treatments have prompted the policymakers to implement measures to speed medical devices to market.The purpose of this review is to summarize the evolution of the regulatory pathways through which medical devices utilized in diabetes care gain market access. Regulatory pathways, ranging from premarket notification to premarket approval, require distinct, yet necessary ("least burdensome") evidence demonstrating a device's safety and effectiveness. Collaboration between manufacturers, regulators, and patients has resulted in the development and approval of novel diabetes care devices, including the first hybrid closed-loop artificial pancreas. Policy provisions, ranging from the least burdensome approach to the "breakthrough device" expedited pathway, aim to balance innovation, access, and safety. Clinicians must be aware of the evolving regulatory landscape and play an active role in enhancing patient safety.

  11. 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.

  12. 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.

  13. Potential reduction exposure products and FDA tobacco and regulation: a CNS call to action.

    Science.gov (United States)

    Heath, Janie; Andrews, Jeannette; Balkstra, Cindy R

    2004-01-01

    A new generation of tobacco harm reduction products is stirring controversy and confusion among healthcare providers. These products, known as "potential reduction exposure products" (PREPs), can be described in terms of reported scientific evidence, as "the good, the bad, and the ugly." On the good side, there is sufficient scientific evidence to support the use of Commit, a new over-the-counter nicotine lozenge PREP, approved for smoking cessation. On the bad side, there is no scientific evidence to support the use of Ariva, another over-the-counter nicotine lozenge PREP, marketed as an alternative to cigarettes when smoking is restricted. On the ugly side, both of these PREPs are nicotine delivery systems with "candy-like" appearances; however, one (Commit) has the Food and Drug Administration (FDA) approval and the other (Ariva) does not. This article provides an overview of PREPs and strategies to help clinical nurse specialists (CNSs) address tobacco harm reduction issues.

  14. Um mundo de cores

    Directory of Open Access Journals (Sweden)

    Elis Artz

    2016-08-01

    Full Text Available A pintura de Elis Artz é feita com muita alma e transborda alegria. A vitalidade de seu trabalho transparece nas cores fortes e nos traços simples e harmoniosos. Confira o trabalho da artista nesta edição da Revista Jangada. ELIS by ELIS Descobri meu talento artístisco e criativo há uns 25 anos. Nasci no Brasil e me mudei para os EUA 10 anos atrás por puro amor. Embora seja psicóloga de formação, o meu apreço pela pintura só cresceu e, com o passar dos anos, a paixão pelas tintas me direcionou a fazer cursos com artistas brasileiros renomados. Já morando nos EUA e com essa grande paixão adormecida, durante anos, decidi me entregar para as cores que sempre me trouxeram alegria e cor para os meus dias. Embora muitas de minhas pinturas tenham ido para minha família e amigos no Brasil, vendi inúmeras outras pelo país através de exposições em galerias de arte. Em 2014, fui uma das artistas em destaque no MTD ART nos Estados Unidos. Minha obra estava dentro de cada ônibus das cidades de Champaign e Urbana e exposta em destaque na Estação de Trem. Em maio de 2015, tive o prazer de ter outro trabalho meu nos outdoors da cidade, destacando a minha tela 'Frida' o ano inteiro e de expor em conjunto com alguns artistas locais no final de outubro. Desde então, tenho pintado cada vez mais e me interessado em divulgar o meu trabalho. E, como diria um amigo meu "Elis, você me mostrou que a vida não é só preto no branco". Ele estava certo.

  15. Narrative Finality

    Directory of Open Access Journals (Sweden)

    Armine Kotin Mortimer

    1981-01-01

    Full Text Available The cloturai device of narration as salvation represents the lack of finality in three novels. In De Beauvoir's Tous les hommes sont mortels an immortal character turns his story to account, but the novel makes a mockery of the historical sense by which men define themselves. In the closing pages of Butor's La Modification , the hero plans to write a book to save himself. Through the thrice-considered portrayal of the Paris-Rome relationship, the ending shows the reader how to bring about closure, but this collective critique written by readers will always be a future book. Simon's La Bataille de Pharsale , the most radical attempt to destroy finality, is an infinite text. No new text can be written. This extreme of perversion guarantees bliss (jouissance . If the ending of De Beauvoir's novel transfers the burden of non-final world onto a new victim, Butor's non-finality lies in the deferral to a future writing, while Simon's writer is stuck in a writing loop, in which writing has become its own end and hence can have no end. The deconstructive and tragic form of contemporary novels proclaims the loss of belief in a finality inherent in the written text, to the profit of writing itself.

  16. Repurposed FDA-approved drugs targeting genes influencing aging can extend lifespan and healthspan in rotifers.

    Science.gov (United States)

    Snell, Terry W; Johnston, Rachel K; Matthews, Amelia B; Zhou, Hongyi; Gao, Mu; Skolnick, Jeffrey

    2018-04-01

    Pharmaceutical interventions can slow aging in animals, and have advantages because their dose can be tightly regulated and the timing of the intervention can be closely controlled. They also may complement environmental interventions like caloric restriction by acting additively. A fertile source for therapies slowing aging is FDA approved drugs whose safety has been investigated. Because drugs bind to several protein targets, they cause multiple effects, many of which have not been characterized. It is possible that some of the side effects of drugs prescribed for one therapy may have benefits in retarding aging. We used computationally guided drug screening for prioritizing drug targets to produce a short list of candidate compounds for in vivo testing. We applied the virtual ligand screening approach FINDSITE comb for screening potential anti-aging protein targets against FDA approved drugs listed in DrugBank. A short list of 31 promising compounds was screened using a multi-tiered approach with rotifers as an animal model of aging. Primary and secondary survival screens and cohort life table experiments identified four drugs capable of extending rotifer lifespan by 8-42%. Exposures to 1 µM erythromycin, 5 µM carglumic acid, 3 µM capecitabine, and 1 µM ivermectin, extended rotifer lifespan without significant effect on reproduction. Some drugs also extended healthspan, as estimated by mitochondria activity and mobility (swimming speed). Our most promising result is that rotifer lifespan was extended by 7-8.9% even when treatment was started in middle age.

  17. Synergy testing of FDA-approved drugs identifies potent drug combinations against Trypanosoma cruzi.

    Directory of Open Access Journals (Sweden)

    Joseph D Planer

    2014-07-01

    Full Text Available An estimated 8 million persons, mainly in Latin America, are infected with Trypanosoma cruzi, the etiologic agent of Chagas disease. Existing antiparasitic drugs for Chagas disease have significant toxicities and suboptimal effectiveness, hence new therapeutic strategies need to be devised to address this neglected tropical disease. Due to the high research and development costs of bringing new chemical entities to the clinic, we and others have investigated the strategy of repurposing existing drugs for Chagas disease. Screens of FDA-approved drugs (described in this paper have revealed a variety of chemical classes that have growth inhibitory activity against mammalian stage Trypanosoma cruzi parasites. Aside from azole antifungal drugs that have low or sub-nanomolar activity, most of the active compounds revealed in these screens have effective concentrations causing 50% inhibition (EC50's in the low micromolar or high nanomolar range. For example, we have identified an antihistamine (clemastine, EC50 of 0.4 µM, a selective serotonin reuptake inhibitor (fluoxetine, EC50 of 4.4 µM, and an antifolate drug (pyrimethamine, EC50 of 3.8 µM and others. When tested alone in the murine model of Trypanosoma cruzi infection, most compounds had insufficient efficacy to lower parasitemia thus we investigated using combinations of compounds for additive or synergistic activity. Twenty-four active compounds were screened in vitro in all possible combinations. Follow up isobologram studies showed at least 8 drug pairs to have synergistic activity on T. cruzi growth. The combination of the calcium channel blocker, amlodipine, plus the antifungal drug, posaconazole, was found to be more effective at lowering parasitemia in mice than either drug alone, as was the combination of clemastine and posaconazole. Using combinations of FDA-approved drugs is a promising strategy for developing new treatments for Chagas disease.

  18. 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.

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

    Science.gov (United States)

    Moshirfar, Majid; Desautels, Jordan D; Wallace, Ryan T; Koen, Nicholas; Hoopes, Phillip C.

    2017-01-01

    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. PMID:28944206

  20. AAPS and US FDA Crystal City VI workshop on bioanalytical method validation for biomarkers.

    Science.gov (United States)

    Lowes, Steve; Ackermann, Bradley L

    2016-02-01

    Crystal City VI Workshop on Bioanalytical Method Validation of Biomarkers, Renaissance Baltimore Harborplace Hotel, Baltimore, MD, USA, 28-29 September 2015 The Crystal City VI workshop was organized by the American Association of Pharmaceutical Scientists in association with the US FDA to continue discussion on the bioanalysis of biomarkers. An outcome of the Crystal City V workshop, convened following release of the draft FDA Guidance for Industry on Bioanalytical Methods Validation in 2013 was the need to have further discussion on biomarker methods. Biomarkers ultimately became the sole focal point for Crystal City VI, a meeting attended by approximately 200 people and composed of industry scientists and regulators from around the world. The meeting format included several panel discussions to maximize the opportunity for dialogue among participants. Following an initial session on the general topic of biomarker assays and intended use, more focused sessions were held on chromatographic (LC-MS) and ligand-binding assays. In addition to participation by the drug development community, significant representation was present from clinical testing laboratories. The experience of this latter group, collectively identified as practitioners of CLIA (Clinical Laboratory Improvement Amendments), helped shape the discussion and takeaways from the meeting. While the need to operate within the framework of the current BMV guidance was clearly acknowledged, a general understanding that biomarker methods validation cannot be adequately depicted by current PK-centric guidelines emerged as a consensus from the meeting. This report is not intended to constitute the official proceedings from Crystal City VI, which is expected to be published in early 2016.

  1. Electrosurgical injuries during robot assisted surgery: insights from the FDA MAUDE database

    Science.gov (United States)

    Fuller, Andrew; Vilos, George A.; Pautler, Stephen E.

    2012-02-01

    Introduction: The da Vinci surgical system requires the use of electrosurgical instruments. The re-use of such instruments creates the potential for stray electrical currents from capacitive coupling and/or insulation failure with subsequent injury. The morbidity of such injuries may negate many of the benefits of minimally invasive surgery. We sought to evaluate the rate and nature of electrosurgical injury (ESI) associated with this device. Methods: The Manufacturer and User Facility Device Experience (MAUDE) database is administered by the US Food and Drug Administration (FDA) and reports adverse events related to medical devices in the United States. We analyzed all incidents in the context of robotic surgery between January 2001 and June 2011 to identify those related to the use of electrosurgery. Results: In the past decade, a total of 605 reports have been submitted to the FDA with regard to adverse events related to the da Vinci robotic surgical platform. Of these, 24 (3.9%) were related to potential or actual ESI. Nine out of the 24 cases (37.5%) resulted in additional surgical intervention for repair. There were 6 bowel injuries of which only one was recognized and managed intra-operatively. The remainder required laparotomy between 5 and 8 days after the initial robotic procedure. Additionally, there were 3 skin burns. The remaining cases required conservative management or resulted in no harm. Conclusion: ESI in the context of robotic surgery is uncommon but remains under-recognized and under-reported. Surgeons performing robot assisted surgery should be aware that ESI can occur with robotic instruments and vigilance for intra- and post-operative complications is paramount.

  2. Cigarette graphic warning labels and smoking prevalence in Canada: a critical examination and reformulation of the FDA regulatory impact analysis.

    Science.gov (United States)

    Huang, Jidong; Chaloupka, Frank J; Fong, Geoffrey T

    2014-03-01

    The estimated effect of cigarette graphic warning labels (GWL) on smoking rates is a key input to the Food and Drug Administration's (FDA) regulatory impact analysis (RIA), required by law as part of its rule-making process. However, evidence on the impact of GWLs on smoking prevalence is scarce. The goal of this paper is to critically analyse FDA's approach to estimating the impact of GWLs on smoking rates in its RIA, and to suggest a path forward to estimating the impact of the adoption of GWLs in Canada on Canadian national adult smoking prevalence. A quasi-experimental methodology was employed to examine the impact of adoption of GWLs in Canada in 2000, using the USA as a control. We found a statistically significant reduction in smoking rates after the adoption of GWLs in Canada in comparison with the USA. Our analyses show that implementation of GWLs in Canada reduced smoking rates by 2.87-4.68 percentage points, a relative reduction of 12.1-19.6%; 33-53 times larger than FDA's estimates of a 0.088 percentage point reduction. We also demonstrated that FDA's estimate of the impact was flawed because it is highly sensitive to the changes in variable selection, model specification, and the time period analysed. Adopting GWLs on cigarette packages reduces smoking prevalence. Applying our analysis of the Canadian GWLs, we estimate that if the USA had adopted GWLs in 2012, the number of adult smokers in the USA would have decreased by 5.3-8.6 million in 2013. Our analysis demonstrates that FDA's approach to estimating the impact of GWLs on smoking rates is flawed. Rectifying these problems before this approach becomes the norm is critical for FDA's effective regulation of tobacco products.

  3. Utilization trends of cervical artificial disc replacement after FDA approval compared with anterior cervical fusion: adoption of new technology.

    Science.gov (United States)

    Lu, Young; McAnany, Steven J; Hecht, Andrew C; Cho, Samuel K; Qureshi, Sheeraz A

    2014-02-01

    Epidemiologic study. To compare the utilization of anterior cervical discectomy and fusion (ACDF) versus cervical disc arthroplasty (CDA) in terms of patient and hospital characteristics during the 3 years after Food and Drug Administration (FDA) approval of CDA devices in 2007. There was a surge in CDA adoption in the 3 years prior to FDA approval of CDA devices in 2007. However, utilization trends of CDA versus ACDF since the FDA approval are unknown. The Nationwide Inpatient Sample database was used to identify CDA and ACDF procedures performed in the United States in the 3 years after FDA approval of CDA devices (2008-2010). The frequencies of CDA and ACDF were estimated, stratified by patient and hospital characteristics. Average length of hospital stay and total charges and costs were estimated. Multivariable analysis was performed to identify patient and hospital characteristics associated with CDA utilization. In the 3 years after FDA approval of cervical disc devices, population-adjusted growth rates for CDA and ACDF were 4.9% and 11.8%, respectively (P = 0.6977). Female, African American and Medicaid patients were less likely to receive CDA. CDA was less likely to be performed in patients with cervical spondylotic changes and more likely to be performed in younger and healthier patients. CDA was less likely to be performed in the Midwestern United States or in public hospitals. The prevalence of CDA increased in the 3 years after FDA approval with a growth rate that is approximately twice than that for ACDF. Although there seems to be CDA adoption, CDA growth seemed to have reached a plateau and ACDF still remained the dominant surgical strategy for cervical disc disease. Possible regional, racial, and sex disparities in CDA utilization and a more strict approach in the selection of CDA over traditional ACDF may have impeded rapid adoption of CDA. 3.

  4. Final Report

    Energy Technology Data Exchange (ETDEWEB)

    Hollingsworth, Jeff

    2014-04-04

    The goal of this project was to create a community tool infrastructure for program development tools targeting Petascale class machines and beyond. This includes performance analysis, debugging, and correctness tools, as well as tuning and optimization frameworks. The infrastructure provides a comprehensive and extensible set of individual tool building components. Within this project we developed the basis for this infrastructure as well as set of core modules that allow a comprehensive performance analysis at scale. Further, we developed a methodology and workflow that allows others to add or replace modules, to integrate parts into their own tools, or to customize existing solutions.

  5. Regulatory and scientific issues regarding use of foreign data in support of new drug applications in the United States: an FDA perspective.

    Science.gov (United States)

    Khin, N A; Yang, P; Hung, H M J; Maung-U, K; Chen, Y-F; Meeker-O'Connell, A; Okwesili, P; Yasuda, S U; Ball, L K; Huang, S-M; O'Neill, R T; Temple, R

    2013-08-01

    Globalization of clinical research has led to an increase in clinical trials conducted outside of the United States that are submitted to the US Food and Drug Administration (FDA) in new drug applications. This article discusses the FDA's experience with these submissions in specific therapeutic areas, including the extent of this practice, differences between the effectiveness and safety outcomes of studies conducted inside and outside the United States, and the FDA's approach to acceptance of these trials.

  6. Reactor core fuel management

    International Nuclear Information System (INIS)

    Silvennoinen, P.

    1976-01-01

    The subject is covered in chapters, entitled: concepts of reactor physics; neutron diffusion; core heat transfer; reactivity; reactor operation; variables of core management; computer code modules; alternative reactor concepts; methods of optimization; general system aspects. (U.K.)

  7. Nuclear reactor core catcher

    International Nuclear Information System (INIS)

    1977-01-01

    A nuclear reactor core catcher is described for containing debris resulting from an accident causing core meltdown and which incorporates a method of cooling the debris by the circulation of a liquid coolant. (U.K.)

  8. Final Report

    DEFF Research Database (Denmark)

    Heiselberg, Per; Brohus, Henrik; Nielsen, Peter V.

    This final report for the Hybrid Ventilation Centre at Aalborg University describes the activities and research achievement in the project period from August 2001 to August 2006. The report summarises the work performed and the results achieved with reference to articles and reports published...

  9. Core Competence and Education.

    Science.gov (United States)

    Holmes, Gary; Hooper, Nick

    2000-01-01

    Outlines the concept of core competence and applies it to postcompulsory education in the United Kingdom. Adopts an educational perspective that suggests accreditation as the core competence of universities. This economic approach suggests that the market trend toward lifetime learning might best be met by institutions developing a core competence…

  10. 77 FR 11554 - Final Decision on Withdrawal of Breast Cancer Indication for AVASTIN (Bevacizumab) Following...

    Science.gov (United States)

    2012-02-27

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-N-0621] Final Decision on Withdrawal of Breast Cancer Indication for AVASTIN (Bevacizumab) Following Public... the breast cancer indication for AVASTIN (Bevacizumab). The Commissioner of Food and Drugs (the...

  11. 77 FR 56241 - Notice of Withdrawal of Final Design Approval; Westinghouse Electric Company; Advanced Passive 1000

    Science.gov (United States)

    2012-09-12

    ... No. ML060110467, referenced Revision 15 of the AP1000 design control document (DCD). As amended on... versions of the AP1000 design--an FDA for Revision 15 of the AP1000 DCD and a DCR for Revision 19 of the... reflect the version of the DCD approved and incorporated by reference as part of the final DC rulemaking...

  12. Processing of Activated Core Components

    Energy Technology Data Exchange (ETDEWEB)

    Friske, A.; Gestermann, G.; Finkbeiner, R.

    2003-02-26

    Used activated components from the core of a NPP like control elements, water channels from a BWR, and others like in-core measurement devices need to be processed into waste forms suitable for interim storage, and for the final waste repository. Processing of the activated materials can be undertaken by underwater cutting and packaging or by cutting and high-pressure compaction in a hot cell. A hot cell is available in Germany as a joint investment between GNS and the Karlsruhe Research Center at the latter's site. Special transport equipment is available to transport the components ''as-is'' to the hot cell. Newly designed underwater processing equipment has been designed, constructed, and operated for the special application of NPP decommissioning. This equipment integrates an underwater cutting device with an 80 ton force underwater in-drum compactor.

  13. Research priorities and infrastructure needs of the Family Smoking Prevention and Tobacco Control Act: science to inform FDA policy.

    Science.gov (United States)

    Leischow, Scott J; Zeller, Mitch; Backinger, Cathy L

    2012-01-01

    A new law in the United States gives the Food and Drug Administration (FDA) wide latitude to regulate tobacco products for the first time. Given the need for science to serve as a foundation for FDA actions, it is critical that a scientific review of the literature relevant to the proposed legislation be undertaken by experts in the field of nicotine and tobacco research in order to develop research priorities. This paper describes an initiative that was implemented to identify research opportunities under "The Family Smoking Prevention and Tobacco Control Act" and summarizes the conclusions and future directions derived from that initiative. Multiple research and surveillance needs were identified, such as characterization of biomarkers and increased analysis of risk perception. It was also recognized that science will play a critical role in policy determinations such as what constitutes "substantial equivalence" and that there will be considerable infrastructure needs (e.g., laboratories for product testing). Science must drive FDA's decision making regarding tobacco regulation. This article provides a summary of research opportunities identified through literature reviews related to various provisions of the new law. However, the science required by the law requires a transdisciplinary approach because of its complexity, so one of the challenges facing the FDA will be to connect the silos of research in recognition that the "system" of tobacco regulation is greater than the sum of its parts.

  14. 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

  15. 76 FR 24494 - Draft Guidance for Industry and FDA Staff: Processing/Reprocessing Medical Devices in Health Care...

    Science.gov (United States)

    2011-05-02

    ...] Draft Guidance for Industry and FDA Staff: Processing/ Reprocessing Medical Devices in Health Care... Devices in Health Care Settings: Validation Methods and Labeling.'' The recommendations in this guidance... Staff: Processing/Reprocessing Medical Devices in Health Care Settings: Validation Methods and Labeling...

  16. 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...

  17. 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.

  18. 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.

  19. Final Report

    Energy Technology Data Exchange (ETDEWEB)

    Stinis, Panos [Pacific Northwest National Lab. (PNNL), Richland, WA (United States)

    2016-08-07

    This is the final report for the work conducted at the University of Minnesota (during the period 12/01/12-09/18/14) by PI Panos Stinis as part of the "Collaboratory on Mathematics for Mesoscopic Modeling of Materials" (CM4). CM4 is a multi-institution DOE-funded project whose aim is to conduct basic and applied research in the emerging field of mesoscopic modeling of materials.

  20. Core stability exercise principles.

    Science.gov (United States)

    Akuthota, Venu; Ferreiro, Andrea; Moore, Tamara; Fredericson, Michael

    2008-02-01

    Core stability is essential for proper load balance within the spine, pelvis, and kinetic chain. The so-called core is the group of trunk muscles that surround the spine and abdominal viscera. Abdominal, gluteal, hip girdle, paraspinal, and other muscles work in concert to provide spinal stability. Core stability and its motor control have been shown to be imperative for initiation of functional limb movements, as needed in athletics. Sports medicine practitioners use core strengthening techniques to improve performance and prevent injury. Core strengthening, often called lumbar stabilization, also has been used as a therapeutic exercise treatment regimen for low back pain conditions. This article summarizes the anatomy of the core, the progression of core strengthening, the available evidence for its theoretical construct, and its efficacy in musculoskeletal conditions.

  1. 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

  2. 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.

  3. Experimental evaluation of the production of the poisons Xe-135 and Sm-149 of the TRIGA Mark III reactor with mixed core, configuration No. 16 (Final report of the project); Evaluacion experimental de la produccion de los venenos Xe-135 y Sm-149 del reactor TRIGA Mark III con nucleo mixto, config. No. 16 (Informe final del proyecto)

    Energy Technology Data Exchange (ETDEWEB)

    Paredes G, L.C

    1991-11-15

    It was generated the concentration curve of the Xe{sup 135} (t) during the TRIGA Mark III reactor operation cycle, for a continuous irradiation of 72 h to 1 MW of thermal power, as well as the accumulation curve of the isotope after the shutdown, for the fuel configuration No. 16 in the thermal column. The maximum negative reactivities generated by the Xe{sup 135} for operation times greater than 60 h to 1 MW and after the reactor shutdown its were of 1.968 {+-} 0.15 dollars and 2.30 {+-} 0.15 dollars respectively. When comparing these results with those theoretically calculated we find differences of the order of 3.6% and 5.34% which are understood inside the experimental error that on the average was of 7.6%. The results before mentioned have an important application during the start up process of the Reactor, when analyzing the value of the weekly reactivity excess of the core and when is choice the pattern of bars to use for experiments of but of 2 h, where is required to minimize the temporary and space interferences of the neutron flux. (Author)

  4. Conclusiones finales

    OpenAIRE

    Guerrero Gaitán, Manuel

    2016-01-01

    La investigación realizada permite extraer las siguientes conclusiones finales que serán agrupadas según los principales problemas abordados: 1. En relación a las cláusulas que impiden una adecuada transferencia de tecnología, en la presente investigación se demuestra: Primero. Que las cláusulas más frecuentes recogidas en los contratos internacionales de transferencia de tecnología son: la fijación de precios, las restricciones a la investigación y adaptación de la tecnología objeto del cont...

  5. Final Report

    Energy Technology Data Exchange (ETDEWEB)

    R Paul Drake

    2004-01-12

    OAK-B135 This is the final report from the project Hydrodynamics by High-Energy-Density Plasma Flow and Hydrodynamics and Radiation Hydrodynamics with Astrophysical Applications. This project supported a group at the University of Michigan in the invention, design, performance, and analysis of experiments using high-energy-density research facilities. The experiments explored compressible nonlinear hydrodynamics, in particular at decelerating interfaces, and the radiation hydrodynamics of strong shock waves. It has application to supernovae, astrophysical jets, shock-cloud interactions, and radiative shock waves.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. Docking of calcium-binding protein 1 of Entamoeba histolytica using FDA approved drugs

    Directory of Open Access Journals (Sweden)

    Zahid Ahmad

    2017-11-01

    Full Text Available Objective: To find out an alternative potential inhibitor of Entamoeba histolytica calciumbinding protein 1 (EhCaBP1 through in silico studies. Methods: An attempt was made to find a new FDA approved, and cost effective alternative drug for amoebiasis. Sequence of the EhCaBP1 of Entamoeba histolytica was obtained through searching the UniProt database and protein BLAST was performed. The 3D structure of EhCaBP1 was retrieved from Research Collaboratory for Structural Bioinformatics and visualized using Discovery Studio Visualizer® 3.1. A total of 100 drugs were selected and docked using Patchdock and the different sorts of interactions with the target protein were studied using GS viewer, Ligplot and Discovery Studio visualizer. Results: Among the 100 selected drugs, dolutegravir, cefazedone and ergotamine showed large number of interactions with the target protein. Conclusions: The drugs cefazedone and ergotamine showed twenty and nineteen different sorts of interactions respectively with the target protein. These interactions may lead to metabolic changes and can subsequently stop the growth and cause the death of the parasite. Further investigations and experimental analysis are required to unveil the effects of these drugs.

  14. 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.

  15. 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.

  16. 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.

  17. Implementing the Biopharmaceutics Classification System in Drug Development: Reconciling Similarities, Differences, and Shared Challenges in the EMA and US-FDA-Recommended Approaches.

    Science.gov (United States)

    Cardot, J-M; Garcia Arieta, A; Paixao, P; Tasevska, I; Davit, B

    2016-07-01

    The US-FDA recently posted a draft guideline for industry recommending procedures necessary to obtain a biowaiver for immediate-release oral dosage forms based on the Biopharmaceutics Classification System (BCS). This review compares the present FDA BCS biowaiver approach, with the existing European Medicines Agency (EMA) approach, with an emphasis on similarities, difficulties, and shared challenges. Some specifics of the current EMA BCS guideline are compared with those in the recently published draft US-FDA BCS guideline. In particular, similarities and differences in the EMA versus US-FDA approaches to establishing drug solubility, permeability, dissolution, and formulation suitability for BCS biowaiver are critically reviewed. Several case studies are presented to illustrate the (i) challenges of applying for BCS biowaivers for global registration in the face of differences in the EMA and US-FDA BCS biowaiver criteria, as well as (ii) challenges inherent in applying for BCS class I or III designation and common to both jurisdictions.

  18. Nuclear reactor core flow baffling

    International Nuclear Information System (INIS)

    Berringer, R.T.

    1979-01-01

    A flow baffling arrangement is disclosed for the core of a nuclear reactor. A plurality of core formers are aligned with the grids of the core fuel assemblies such that the high pressure drop areas in the core are at the same elevations as the high pressure drop areas about the core periphery. The arrangement minimizes core bypass flow, maintains cooling of the structure surrounding the core, and allows the utilization of alternative beneficial components such as neutron reflectors positioned near the core

  19. 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.

  20. Sediment Core Laboratory

    Data.gov (United States)

    Federal Laboratory Consortium — FUNCTION: Provides instrumentation and expertise for physical and geoacoustic characterization of marine sediments.DESCRIPTION: The multisensor core logger measures...

  1. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Jarillo-Herrero, Pablo [Massachusetts Inst. of Technology (MIT), Cambridge, MA (United States)

    2017-02-07

    This is the final report of our research program on electronic transport experiments on Topological Insulator (TI) devices, funded by the DOE Office of Basic Energy Sciences. TI-based electronic devices are attractive as platforms for spintronic applications, and for detection of emergent properties such as Majorana excitations , electron-hole condensates , and the topological magneto-electric effect . Most theoretical proposals envision geometries consisting of a planar TI device integrated with materials of distinctly different physical phases (such as ferromagnets and superconductors). Experimental realization of physics tied to the surface states is a challenge due to the ubiquitous presence of bulk carriers in most TI compounds as well as degradation during device fabrication.

  2. Final Report: "Recreating Planet Cores in the Laboratory"

    Energy Technology Data Exchange (ETDEWEB)

    Jeanloz, Raymond [Univ. of California, Berkeley, CA (United States)

    2017-06-02

    The grant supported a combination of experimental and theoretical research characterizing materials at high pressures (above 0.1-1 TPa = 1-10 million atmospheres) and modest temperatures (below 20,000-100,000 K). This is the “warm dense” (sub-nuclear) regime relevant to understanding the properties of planets, and also to characterizing the chemical bonding forces between atoms. As such, the experiments provide important validation and extensions of theoretical simulations based on quantum mechanics, and offer new insights into the nature and evolution of planets, including the thousands of recently discovered extra-solar planets. In particular, our experiments have documented that: 1) helium can separate from hydrogen at conditions existing inside Jupiter and Saturn, providing much of these planets’ internal energy hence observed luminosities; 2) water ice is likely present in a superionic state with mobile protons inside Uranus and Neptune; 3) rock (oxides) can become metallic at conditions inside “super-Earths” and other large planets, thereby contributing to their magnetic fields; and 4) the “statistical atom” regime that provides the theoretical foundation for characterizing materials at planetary and astrophysical conditions is now accessible to experimental testing.

  3. Awareness of the role of science in the FDA regulatory submission process: a survey of the TERMIS-Americas membership.

    Science.gov (United States)

    Johnson, Peter C; Bertram, Tim A; Carty, Neal R; Hellman, Kiki B; Tawil, Bill J; Van Dyke, Mark

    2014-06-01

    The Industry Committee of the Tissue Engineering Regenerative Medicine International Society, Americas Chapter (TERMIS-AM) administered a survey to its membership in 2013 to assess the awareness of science requirements in the U.S. Food and Drug Administration (FDA) regulatory process. One hundred forty-four members responded to the survey. Their occupational and geographical representation was representative of the TERMIS-AM membership as a whole. The survey elicited basic demographic information, the degree to which members were involved in tissue engineering technology development, and their plans for future involvement in such development. The survey then assessed the awareness of general FDA scientific practices as well as specific science requirements for regulatory submissions to the Center for Biologics Evaluation and Research (CBER), the Center for Drug Evaluation and Research (CDER), the Center for Devices and Radiological Health (CDRH), and the Office of Combination Projects (OCP). The FDA-specific questions in the survey were culled from guidance documents posted on the FDA web site ( www.fda.gov ). One of the answer options was an opt-out clause that enabled survey respondents to claim a lack of sufficient awareness of the topic to answer the question. This enabled the stratification of respondents on the basis of confidence in the topic. Results indicate that across all occupational groups (academic, business, and government) that are represented in the TERMIS-AM membership, the awareness of FDA science requirements varies markedly. Those who performed best were for-profit company employees, consultants, and government employees; while students, professors, and respondents from outside the USA performed least well. Confidence in question topics was associated with increased correctness in responses across all groups, though the association between confidence and the ability to answer correctly was poorest among students and professors. Though 80% of

  4. Can Psychiatric Rehabilitation Be Core to CORE?

    Science.gov (United States)

    Olney, Marjorie F.; Gill, Kenneth J.

    2016-01-01

    Purpose: In this article, we seek to determine whether psychiatric rehabilitation principles and practices have been more fully incorporated into the Council on Rehabilitation Education (CORE) standards, the extent to which they are covered in four rehabilitation counseling "foundations" textbooks, and how they are reflected in the…

  5. 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

  6. 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

  7. FDA drug prescribing warnings: is the black box half empty or half full?

    Science.gov (United States)

    Wagner, Anita K; Chan, K Arnold; Dashevsky, Inna; Raebel, Marsha A; Andrade, Susan E; Lafata, Jennifer Elston; Davis, Robert L; Gurwitz, Jerry H; Soumerai, Stephen B; Platt, Richard

    2006-06-01

    Black box warnings (BBWs) are the Food and Drug Administration's (FDA) strongest labeling requirements for high-risk medicines. It is unknown how frequently physicians prescribe BBW drugs and whether they do so in compliance with the warnings. The purpose of the present study was to assess the frequency of use of BBW medications in ambulatory care and prescribing compliance with BBW recommendations. This retrospective study used automated claims data of 929 958 enrollees in 10 geographically diverse health plans in the United States to estimate frequency of use in ambulatory care of 216 BBW drugs/drug groups between 1/1/99 and 31/6/01. We assessed dispensing compliance with the BBW requirements for selected drugs. During a 30-month period, more than 40% of enrollees received at least one medication that carried a BBW that could potentially apply to them. We found few instances of prescribing during pregnancy of BBW drugs absolutely contra-indicated in pregnancy. There was almost no co-prescribing of contra-indicated drugs with the two QT-interval-prolonging BBW drugs evaluated. Most non-compliance occurred with recommendations for baseline laboratory monitoring (49.6% of all therapy initiations that should have been accompanied by baseline laboratory monitoring were not). Many individuals receive drugs considered to carry the potential for serious risk. For some of these drugs, use is largely consistent with their BBW, while for others it is not. Since it will not be possible to avoid certain drug- associated risks, it will be important to develop effective methods to use BBWs and other methods to minimize risks.

  8. 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

  9. 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

  10. 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

  11. 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

    2015-01-01

    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

  12. 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.

  13. SUMMARY OF 2017 FDA PUBLIC WORKSHOP: ANTIBODY MEDIATED REJECTION IN KIDNEY TRANSPLANTATION.

    Science.gov (United States)

    Velidedeoglu, Ergun; Cavaillé-Coll, Marc W; Bala, Shukal; Belen, Ozlem A; Wang, Yan; Albrecht, Renata

    2018-03-20

    Despite major advances in understanding the pathophysiology of antibody mediated rejection (AMR); prevention, diagnosis and treatment remain unmet medical needs. It appears that early T-cell mediated rejection (TCMR), de novo donor specific antibody (dnDSA) formation and AMR result from patient or physician initiated suboptimal immunosuppression, and represent landmarks in an ongoing process rather than separate events. On April 12-13, 2017, the Food and Drug Administration (FDA) sponsored a public workshop on AMR in kidney transplantation to discuss new advances, importance of immunosuppressive medication nonadherence in dnDSA formation, associations between AMR, cellular rejection, changes in GFR, and challenges of clinical trial design for the prevention and treatment of AMR.Results and ConclusionsKey messages from the workshop are summarized in Table 2. Distinction between type 1 (due to preexisting DSA) and type 2 (due to dnDSA) phenotypes of AMR needs to be considered in patient management and clinical trial design. Standardization and more widespread adoption of routine posttransplant DSA monitoring may permit timely diagnosis and understanding of the natural course of type 2 and chronic AMR. Clinical trial design, especially as related to type 2 and chronic AMR, have specific challenges including the high prevalence of nonadherence in the population at risk, indolent nature of the process until the appearance of graft dysfunction and the absence of accepted surrogate endpoints (SEP). Other challenges include sample size and study duration, which could be mitigated by enrichment strategies.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

  14. Validation of reactor core protection system

    International Nuclear Information System (INIS)

    Lee, Sang-Hoon; Bae, Jong-Sik; Baeg, Seung-Yeob; Cho, Chang-Ho; Kim, Chang-Ho; Kim, Sung-Ho; Kim, Hang-Bae; In, Wang-Kee; Park, Young-Ho

    2008-01-01

    Reactor COre Protection System (RCOPS), an advanced core protection calculator system, is a digitized one which provides core protection function based on two reactor core operation parameters, Departure from Nucleate Boiling Ratio (DNBR) and Local Power Density (LPD). It generates a reactor trip signal when the core condition exceeds the DNBR or LPD design limit. It consists of four independent channels adapted a two-out-of-four trip logic. System configuration, hardware platform and an improved algorithm of the newly designed core protection calculator system are described in this paper. One channel of RCOPS was implemented as a single channel facility for this R and D project where we performed final integration software testing. To implement custom function blocks, pSET is used. Software test is performed by two methods. The first method is a 'Software Module Test' and the second method is a 'Software Unit Test'. New features include improvement of core thermal margin through a revised on-line DNBR algorithm, resolution of the latching problem of control element assembly signal and addition of the pre-trip alarm generation. The change of the on-line DNBR calculation algorithm is considered to improve the DNBR net margin by 2.5%-3.3%. (author)

  15. Making an Ice Core.

    Science.gov (United States)

    Kopaska-Merkel, David C.

    1995-01-01

    Explains an activity in which students construct a simulated ice core. Materials required include only a freezer, food coloring, a bottle, and water. This hands-on exercise demonstrates how a glacier is formed, how ice cores are studied, and the nature of precision and accuracy in measurement. Suitable for grades three through eight. (Author/PVD)

  16. Multi-core Microprocessors

    Indian Academy of Sciences (India)

    Design cost of multi-core processors is lower than the cost of designing very complex single processors. This is because in a multi-core pro- cessor a simple processor is designed and replicated. The idea of using several independent processors to work simul- taneously and cooperate to execute a single program is quite ...

  17. PWR core design calculations

    International Nuclear Information System (INIS)

    Trkov, A.; Ravnik, M.; Zeleznik, N.

    1992-01-01

    Functional description of the programme package Cord-2 for PWR core design calculations is presented. Programme package is briefly described. Use of the package and calculational procedures for typical core design problems are treated. Comparison of main results with experimental values is presented as part of the verification process. (author) [sl

  18. Multi-core Microprocessors

    Indian Academy of Sciences (India)

    using these transistors and resultant improvement in the process-. Keywords. Moore's law, evolution of multi- core processors, programming multi-core processors. ing speed. Packing more transistors in a chip also enabled de- signers to improve the architecture of microprocessors in many. RESONANCE | December 2017.

  19. Evaluating oversight of human drugs and medical devices: a case study of the FDA and implications for nanobiotechnology.

    Science.gov (United States)

    Paradise, Jordan; Tisdale, Alison W; Hall, Ralph F; Kokkoli, Efrosini

    2009-01-01

    This article evaluates the oversight of drugs and medical devices by the U.S. Food and Drug Administration (FDA) using an integration of public policy, law, and bioethics approaches and employing multiple assessment criteria, including economic, social, safety, and technological. Criteria assessment and expert elicitation are combined with existing literature, case law, and regulations in an integrative historical case studies approach. We then use our findings as a tool to explore possibilities for effective oversight and regulatory mechanisms for nanobiotechnology. Section I describes oversight mechanisms for human drugs and medical devices and presents current nanotechnology products. Section II describes the results of expert elicitation research. Section III highlights key criteria and relates them to the literature and larger debate. We conclude with broad lessons for the oversight of nanobiotechnology informed by Sections I-III in order to provide useful analysis from multiple disciplines and perspectives to guide discussions regarding appropriate FDA oversight.

  20. 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.

  1. 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.

  2. 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.

  3. Final Report

    Energy Technology Data Exchange (ETDEWEB)

    Webb, Robert C. [Texas A& M University; Kamon, Teruki [Texas A& M University; Toback, David [Texas A& M University; Safonov, Alexei [Texas A& M University; Dutta, Bhaskar [Texas A& M University; Dimitri, Nanopoulos [Texas A& M University; Pope, Christopher [Texas A& M University; White, James [Texas A& M University

    2013-11-18

    Overview The High Energy Physics Group at Texas A&M University is submitting this final report for our grant number DE-FG02-95ER40917. This grant has supported our wide range of research activities for over a decade. The reports contained here summarize the latest work done by our research team. Task A (Collider Physics Program): CMS & CDF Profs. T. Kamon, A. Safonov, and D. Toback co-lead the Texas A&M (TAMU) collider program focusing on CDF and CMS experiments. Task D: Particle Physics Theory Our particle physics theory task is the combined effort of Profs. B. Dutta, D. Nanopoulos, and C. Pope. Task E (Underground Physics): LUX & NEXT Profs. R. Webb and J. White(deceased) lead the Xenon-based underground research program consisting of two main thrusts: the first, participation in the LUX two-phase xenon dark matter search experiment and the second, detector R&D primarily aimed at developing future detectors for underground physics (e.g. NEXT and LZ).

  4. Understanding how perceptions of tobacco constituents and the FDA relate to effective and credible tobacco risk messaging: A national phone survey of U.S. adults, 2014-2015.

    Science.gov (United States)

    Boynton, Marcella H; Agans, Robert P; Bowling, J Michael; Brewer, Noel T; Sutfin, Erin L; Goldstein, Adam O; Noar, Seth M; Ribisl, Kurt M

    2016-06-23

    The passage of the 2009 Family Smoking Prevention and Tobacco Control Act has necessitated the execution of timely, innovative, and policy-relevant tobacco control research to inform Food and Drug Administration (FDA) regulatory and messaging efforts. With recent dramatic changes to tobacco product availability and patterns of use, nationally representative data on tobacco-related perceptions and behaviors are vital, especially for vulnerable populations. The UNC Center for Regulatory Research on Tobacco Communication conducted a telephone survey with a national sample of adults ages 18 and older living in the United States (U.S.). The survey assessed regulatory relevant factors such as tobacco product use, tobacco constituent perceptions, and tobacco regulatory agency credibility. The study oversampled high smoking/low income areas as well as cell phone numbers to ensure adequate representation among smokers and young adults, respectively. Coverage extended to approximately 98 % of U.S. households. The final dataset (N = 5,014) generated weighted estimates that were largely comparable to other national demographic and tobacco use estimates. Results revealed that over one quarter of U.S. adults, and over one third of smokers, reported having looked for information about tobacco constituents in cigarette smoke; however, the vast majority was unaware of what constituents might actually be present. Although only a minority of people reported trust in the federal government, two thirds felt that the FDA can effectively regulate tobacco products. As the FDA continues their regulatory and messaging activities, they should expand both the breadth and availability of constituent-related information, targeting these efforts to reach all segments of the U.S. population, especially those disproportionately vulnerable to tobacco product use and its associated negative health outcomes.

  5. Understanding how perceptions of tobacco constituents and the FDA relate to effective and credible tobacco risk messaging: A national phone survey of U.S. adults, 2014–2015

    Directory of Open Access Journals (Sweden)

    Marcella H. Boynton

    2016-06-01

    Full Text Available Abstract Background The passage of the 2009 Family Smoking Prevention and Tobacco Control Act has necessitated the execution of timely, innovative, and policy-relevant tobacco control research to inform Food and Drug Administration (FDA regulatory and messaging efforts. With recent dramatic changes to tobacco product availability and patterns of use, nationally representative data on tobacco-related perceptions and behaviors are vital, especially for vulnerable populations. Methods The UNC Center for Regulatory Research on Tobacco Communication conducted a telephone survey with a national sample of adults ages 18 and older living in the United States (U.S.. The survey assessed regulatory relevant factors such as tobacco product use, tobacco constituent perceptions, and tobacco regulatory agency credibility. The study oversampled high smoking/low income areas as well as cell phone numbers to ensure adequate representation among smokers and young adults, respectively. Coverage extended to approximately 98 % of U.S. households. Results The final dataset (N = 5,014 generated weighted estimates that were largely comparable to other national demographic and tobacco use estimates. Results revealed that over one quarter of U.S. adults, and over one third of smokers, reported having looked for information about tobacco constituents in cigarette smoke; however, the vast majority was unaware of what constituents might actually be present. Although only a minority of people reported trust in the federal government, two thirds felt that the FDA can effectively regulate tobacco products. Conclusions As the FDA continues their regulatory and messaging activities, they should expand both the breadth and availability of constituent-related information, targeting these efforts to reach all segments of the U.S. population, especially those disproportionately vulnerable to tobacco product use and its associated negative health outcomes.

  6. Mars' core and magnetism.

    Science.gov (United States)

    Stevenson, D J

    2001-07-12

    The detection of strongly magnetized ancient crust on Mars is one of the most surprising outcomes of recent Mars exploration, and provides important insight about the history and nature of the martian core. The iron-rich core probably formed during the hot accretion of Mars approximately 4.5 billion years ago and subsequently cooled at a rate dictated by the overlying mantle. A core dynamo operated much like Earth's current dynamo, but was probably limited in duration to several hundred million years. The early demise of the dynamo could have arisen through a change in the cooling rate of the mantle, or even a switch in convective style that led to mantle heating. Presently, Mars probably has a liquid, conductive outer core and might have a solid inner core like Earth.

  7. Lunar Core and Tides

    Science.gov (United States)

    Williams, J. G.; Boggs, D. H.; Ratcliff, J. T.

    2004-01-01

    Variations in rotation and orientation of the Moon are sensitive to solid-body tidal dissipation, dissipation due to relative motion at the fluid-core/solid-mantle boundary, and tidal Love number k2 [1,2]. There is weaker sensitivity to flattening of the core-mantle boundary (CMB) [2,3,4] and fluid core moment of inertia [1]. Accurate Lunar Laser Ranging (LLR) measurements of the distance from observatories on the Earth to four retroreflector arrays on the Moon are sensitive to lunar rotation and orientation variations and tidal displacements. Past solutions using the LLR data have given results for dissipation due to solid-body tides and fluid core [1] plus Love number [1-5]. Detection of CMB flattening, which in the past has been marginal but improving [3,4,5], now seems significant. Direct detection of the core moment has not yet been achieved.

  8. Physicians? Trust in the FDA?s Use of Product-Specific Pathways for Generic Drug Approval

    OpenAIRE

    Kesselheim, Aaron S.; Eddings, Wesley; Raj, Tara; Campbell, Eric G.; Franklin, Jessica M.; Ross, Kathryn M.; Fulchino, Lisa A.; Avorn, Jerry; Gagne, Joshua J.

    2016-01-01

    Background: Generic drugs are cost-effective versions of brand-name drugs approved by the Food and Drug Administration (FDA) following proof of pharmaceutical equivalence and bioequivalence. Generic drugs are widely prescribed by physicians, although there is disagreement over the clinical comparability of generic drugs to brand-name drugs within the physician community. The objective of this survey was to assess physicians' perceptions of generic drugs and the generic drug approval process....

  9. 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

  10. 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.

  11. 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.

  12. The Methodology of Clinical Studies Used by the FDA for Approval of High-Risk Orthopaedic Devices.

    Science.gov (United States)

    Barker, Jordan P; Simon, Stephen D; Dubin, Jonathan

    2017-05-03

    The purpose of this investigation was to examine the methodology of clinical trials used by the U.S. Food and Drug Administration (FDA) to determine the safety and effectiveness of high-risk orthopaedic devices approved between 2001 and 2015. Utilizing the FDA's online public database, this systematic review audited study design and methodological variables intended to minimize bias and confounding. An additional analysis of blinding as well as the Checklist to Evaluate a Report of a Nonpharmacological Trial (CLEAR NPT) was applied to the randomized controlled trials (RCTs). Of the 49 studies, 46 (94%) were prospective and 37 (76%) were randomized. Forty-seven (96%) of the studies were controlled in some form. Of 35 studies that reported it, blinding was utilized in 21 (60%), of which 8 (38%) were reported as single-blinded and 13 (62%) were reported as double-blinded. Of the 37 RCTs, outcome assessors were clearly blinded in 6 (16%), whereas 15 (41%) were deemed impossible to blind as implants could be readily discerned on imaging. When the CLEAR NPT was applied to the 37 RCTs, >70% of studies were deemed "unclear" in describing generation of allocation sequences, treatment allocation concealment, and adequate blinding of participants and outcome assessors. This study manifests the highly variable reporting and strength of clinical research methodology accepted by the FDA to approve high-risk orthopaedic devices.

  13. Pelvic organ prolapse surgical management in Portugal and FDA safety communication have an impact on vaginal mesh.

    Science.gov (United States)

    Mascarenhas, Teresa; Mascarenhas-Saraiva, Miguel; Ricon-Ferraz, Amélia; Nogueira, Paula; Lopes, Fernando; Freitas, Alberto

    2015-01-01

    Pelvic organ prolapse (POP) surgery has lately gained importance in gynecological practice. This study aims to characterize the evolution of POP surgical procedures conducted in Portugal in the last decade and the impact of an FDA 2011 safety communication on mesh POP surgeries. Trends in the surgical management of POP were assessed using the Portuguese National Medical Registry. We considered all records of women with diagnosis of genital prolapse from 1 January 2000 to 31 December 2012. Additionally, we also conducted a survey among members of the Portuguese Society of Urogynecology to evaluate current practices in the surgical management of POP. From 2000 to 2012, 46,819 diagnoses of genital prolapse were registered, with a 105 % increase during the study period (2,368 in 2000 to 4,941 in 2012). POP mesh surgery represented only 6 % of total prolapse diagnoses, but mesh use greatly increased up to 2011, when only a slight increase was registered. Among gynecologists who responded to the questionnaire, there was considerable variability on the procedures of choice to treat POP. Fifty-seven per cent of respondents performed vaginal mesh POP surgery, but only 27 % of those actually reported having changed their practice after the FDA 2011 safety communication. Surgical procedures for POP conducted in Portugal greatly increased over the last decade. The use of surgical meshes is still limited, but despite FDA safety communication it has increased over the years, with a slight increase in 2012, which illustrates the need for further analyses in the coming years.

  14. 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.

  15. Dependence of Core and Extended Flux on Core Dominance ...

    Indian Academy of Sciences (India)

    2016-01-27

    Jan 27, 2016 ... Based on two extragalactic radio source samples, the core dominance parameter is calculated, and the correlations between the core/extended flux density and core dominance parameter are investigated. When the core dominance parameter is lower than unity, it is linearly correlated with the core flux ...

  16. Earth's inner core: Innermost inner core or hemispherical variations?

    NARCIS (Netherlands)

    Lythgoe, K. H.; Deuss, A.; Rudge, J. F.; Neufeld, J. A.

    2014-01-01

    The structure of Earth's deep inner core has important implications for core evolution, since it is thought to be related to the early stages of core formation. Previous studies have suggested that there exists an innermost inner core with distinct anisotropy relative to the rest of the inner core.

  17. Dependence of Core and Extended Flux on Core Dominance ...

    Indian Academy of Sciences (India)

    Abstract. Based on two extragalactic radio source samples, the core dominance parameter is calculated, and the correlations between the core/extended flux density and core dominance parameter are investi- gated. When the core dominance parameter is lower than unity, it is linearly correlated with the core flux density, ...

  18. Alternative soaking media for the FDA procedure in the detection of salmonella from tomatoes and spinach leaf using phage magnetoelastic biosensors

    Science.gov (United States)

    Chen, I.-Hsuan; Hu, Jiajia; Wang, Fengen; Horikawa, Shin; Barbaree, James M.; Chin, Bryan A.

    2016-05-01

    Efforts were made to incorporate the phage Magnetoelastic (ME) biosensor in FDA's Spinach Soaking procedures according to FDA 2015 BAM method. Three soaking materials (Lactose broth, LB broth, and Peptone water) and various soaking times were investigated. Using merely 100 Salmonella cells spiked on the produce surfaces, the phage biosensors detected Salmonella within 5 hours when soaking tomatoes in LB broth as opposed to taking up to 24 hours. Salmonella was detected on spinach leaves within 7 hours. These phage ME biosensors provide a promising rapid detection platform using LB broth in FDA's soaking procedures while shortening the incubation period.

  19. Core shroud corner joints

    Energy Technology Data Exchange (ETDEWEB)

    Gilmore, Charles B.; Forsyth, David R.

    2013-09-10

    A core shroud is provided, which includes a number of planar members, a number of unitary corners, and a number of subassemblies each comprising a combination of the planar members and the unitary corners. Each unitary corner comprises a unitary extrusion including a first planar portion and a second planar portion disposed perpendicularly with respect to the first planar portion. At least one of the subassemblies comprises a plurality of the unitary corners disposed side-by-side in an alternating opposing relationship. A plurality of the subassemblies can be combined to form a quarter perimeter segment of the core shroud. Four quarter perimeter segments join together to form the core shroud.

  20. Core stability and bicycling.

    Science.gov (United States)

    Asplund, Chad; Ross, Michael

    2010-01-01

    Bicycling is a popular fitness activity in the United States and around the world. Because of the nature of the bicycling position, the neck and back are at risk for injury. One method to prevent these injuries is to ensure that the body's "core" is strong and stable. A strong and stable core also provides a platform to maximize power transfer, improving performance. Core exercises also may enhance recovery from intense bicycling efforts. Simple stability exercises can improve performance and may prevent injuries in bicyclists.

  1. IGCSE core mathematics

    CERN Document Server

    Wall, Terry

    2013-01-01

    Give your core level students the support and framework they require to get their best grades with this book dedicated to the core level content of the revised syllabus and written specifically to ensure a more appropriate pace. This title has been written for Core content of the revised Cambridge IGCSE Mathematics (0580) syllabus for first teaching from 2013. ? Gives students the practice they require to deepen their understanding through plenty of practice questions. ? Consolidates learning with unique digital resources on the CD, included free with every book. We are working with Cambridge

  2. 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

  3. 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

  4. Retinal Neuroprotective Effects of Flibanserin, an FDA-Approved Dual Serotonin Receptor Agonist-Antagonist.

    Directory of Open Access Journals (Sweden)

    Aaron S Coyner

    Full Text Available To assess the neuroprotective effects of flibanserin (formerly BIMT-17, a dual 5-HT1A agonist and 5-HT2A antagonist, in a light-induced retinopathy model.Albino BALB/c mice were injected intraperitoneally with either vehicle or increasing doses of flibanserin ranging from 0.75 to 15 mg/kg flibanserin. To assess 5-HT1A-mediated effects, BALB/c mice were injected with 10 mg/kg WAY 100635, a 5-HT1A antagonist, prior to 6 mg/kg flibanserin and 5-HT1A knockout mice were injected with 6 mg/kg flibanserin. Injections were administered once immediately prior to light exposure or over the course of five days. Light exposure lasted for one hour at an intensity of 10,000 lux. Retinal structure was assessed using spectral domain optical coherence tomography and retinal function was assessed using electroretinography. To investigate the mechanisms of flibanserin-mediated neuroprotection, gene expression, measured by RT-qPCR, was assessed following five days of daily 15 mg/kg flibanserin injections.A five-day treatment regimen of 3 to 15 mg/kg of flibanserin significantly preserved outer retinal structure and function in a dose-dependent manner. Additionally, a single-day treatment regimen of 6 to 15 mg/kg of flibanserin still provided significant protection. The action of flibanserin was hindered by the 5-HT1A antagonist, WAY 100635, and was not effective in 5-HT1A knockout mice. Creb, c-Jun, c-Fos, Bcl-2, Cast1, Nqo1, Sod1, and Cat were significantly increased in flibanserin-injected mice versus vehicle-injected mice.Intraperitoneal delivery of flibanserin in a light-induced retinopathy mouse model provides retinal neuroprotection. Mechanistic data suggests that this effect is mediated through 5-HT1A receptors and that flibanserin augments the expression of genes capable of reducing mitochondrial dysfunction and oxidative stress. Since flibanserin is already FDA-approved for other indications, the potential to repurpose this drug for treating retinal

  5. Core Exercises: Why You Should Strengthen Your Core Muscles

    Science.gov (United States)

    Healthy Lifestyle Fitness You know core exercises are good for you — but do you include core exercises in your fitness routine? Here's why you should. By Mayo Clinic Staff Core exercises are an important part of a ...

  6. Safety and Effectiveness of Health Care Antiseptics; Topical Antimicrobial Drug Products for Over-the-Counter Human Use. Final rule.

    Science.gov (United States)

    2017-12-20

    The Food and Drug Administration (FDA, the Agency, or we) is issuing this final rule establishing that certain active ingredients used in nonprescription (also known as over-the-counter or OTC) antiseptic products intended for use by health care professionals in a hospital setting or other health care situations outside the hospital are not generally recognized as safe and effective (GRAS/GRAE). FDA is issuing this final rule after considering the recommendations of the Nonprescription Drugs Advisory Committee (NDAC); public comments on the Agency's notices of proposed rulemaking; and all data and information on OTC health care antiseptic products that have come to the Agency's attention. This final rule finalizes the 1994 tentative final monograph (TFM) for OTC health care antiseptic drug products that published in the Federal Register of June 17, 1994 (the 1994 TFM) as amended by the proposed rule published in the Federal Register (FR) of May 1, 2015 (2015 Health Care Antiseptic Proposed Rule (PR)).

  7. Restraint system for core elements of a reactor core

    International Nuclear Information System (INIS)

    Class, G.

    1975-01-01

    In a nuclear reactor, a core element bundle formed of a plurality of side-by-side arranged core elements is surrounded by restraining elements that exert a radially inwardly directed restraining force generating friction forces between the core elements in a restraining plane that is transverse to the core element axes. The adjoining core elements are in rolling contact with one another in the restraining plane by virtue of rolling-type bearing elements supported in the core elements

  8. INTEGRAL core programme

    Science.gov (United States)

    Gehrels, N.; Schoenfelder, V.; Ubertini, P.; Winkler, C.

    1997-01-01

    The International Gamma Ray Astrophysics Laboratory (INTEGRAL) mission is described with emphasis on the INTEGRAL core program. The progress made in the planning activities for the core program is reported on. The INTEGRAL mission has a nominal lifetime of two years with a five year extension option. The observing time will be divided between the core program (between 30 and 35 percent during the first two years) and general observations. The core program consists of three main elements: the deep survey of the Galactic plane in the central radian of the Galaxy; frequent scans of the Galactic plane in the search for transient sources, and pointed observations of several selected sources. The allocation of the observation time is detailed and the sensitivities of the observations are outlined.

  9. Core Flight Software

    Data.gov (United States)

    National Aeronautics and Space Administration — The AES Core Flight Software (CFS) project purpose is to analyze applicability, and evolve and extend the reusability of the CFS system originally developed by...

  10. Organizing Core Tasks

    DEFF Research Database (Denmark)

    Boll, Karen

    Civil servants conduct the work which makes welfare states functions on an everyday bases: Police men police, school teachers teach, and tax inspectors inspect. Focus in this paper is on the core tasks of tax inspectors. The paper argues that their core task of securing the collection of revenue...... projects influence the organization of core tasks within the tax administration. The paper shows that the organizational transformations based on the use of these devices have had consequences both for the overall collection of revenue and for the employees’ feeling of “making a difference”. All in all...... has remained much the same within the last 10 years. However, how the core task has been organized has changed considerable under the influence of various “organizing devices”. The paper focusses on how organizing devices such as risk assessment, output-focus, effect orientation, and treatment...

  11. iPSC Core

    Data.gov (United States)

    Federal Laboratory Consortium — The induced Pluripotent Stem Cells (iPSC) Core was created in 2011 to accelerate stem cell research in the NHLBI by providing investigators consultation, technical...

  12. LMFBR core materials

    International Nuclear Information System (INIS)

    Roberts, J.T.A

    1981-01-01

    This paper discusses initial fuel and core designs that are conservative, emphasizing high reliability at the expense of breeding ration and doubling time. The progression in design improvements to better doubling time, plutonium inventory requirements, and power density are shown. The recent progress in advanced oxide fuel, cladding, and duct development is reported. Breeding ratios and compound system doubling times are computed for both the conventional homogeneous and alternative heterogeneous core configurations. Results are summarized and it is shown that both carbide and metal cores can achieve breeding ratios in the range of 1.5 to 1.6 versus 1.45 for oxide; the carbide and metal cores can achieve 10 year doubling times, which translate into millions of dollars savings in fuel cycle costs. Carbide fuel development is being continued at a modest level to provide backup to the mixed oxide design

  13. The Core Knowledge System

    National Research Council Canada - National Science Library

    Strat, Thomas M; Smith, Grahame B

    1987-01-01

    This document contains an in-depth description of the Core Knowledge System (CKS)-an integrative environment for the many functions that must be performed by sensor-based autonomous and semi-autonomous systems...

  14. Emergency core cooling system

    International Nuclear Information System (INIS)

    Kato, Masaru.

    1981-01-01

    Purpose: To enable quick cooling of a core by efficiently utilizing coolant supplied in an emergency. Constitution: A feedwater nozzle and a water level detector are disposed in the gap between a partition plate for supporting the top of a fuel assembly and a lattice plate for supporting the bottom of the fuel assembly. At the time of a loss of coolant accident, coolant is injected from a sprinkling nozzle toward the reactor core, and is also injected from a feedwater nozzle. When the coolant reaches a prescribed level in the reactor core, the water level is detected by the detector, the coolant is fed by a pump to the lower plenum, and the submerging speed of the reactor core is thereby accelerated. When the water level again becomes lower than the prescribed level, the coolant is again filled from the feedwater nozzle, and similar operation is thereafter repeated. Accordingly, the coolant filled in the reactor core can be efficiently utilized to cool the reactor core. (Kamimura, M.)

  15. Export of pharmaceuticals and medical devices under the federal Food, Drug & Cosmetic Act: FDA's striking change in interpretation post-Shelhigh.

    Science.gov (United States)

    Basile, Edward M; Tolomeo, Deborah; Gluck, Elizabeth

    2009-01-01

    With no communication to industry except court filings in United States v. Undetermined Quantities of Boxes of Articles of Device (Shelhigh) and a draft guidance document, the Food and Drug Administration (FDA) has articulated new policies regarding export of pharmaceutical products and medical devices. FDA's departure from its historic interpretation of the export provisions of the Federal Food, Drug, and Cosmetic Act (FDCA) significantly limits the ability of manufacturers to export misbranded drugs and medical devices that FDA deems "adulterated," contrary to the plain language and legislative intent of the FDCA. To further exacerbate the issue, FDA has begun to implement these policies without the notice-and-comment rulemaking required by the Administrative Procedures Act (APA), but rather through an enforcement proceeding brought in the United States District Court for the District of New Jersey. In a letter opinion, the District Court prevented the export of Current Good Manufacturing Practices (CGMP) --adulterated medical devices that complied with FDCA Section 801(e)(1), at least as historically interpreted by FDA. The purpose of this article is to review the history of FDA's export policies for pharmaceuticals and medical devices, particularly those aspects of the export policies that are affected by FDA's recent change in position. Three changes in FDA's interpretation of the export provisions of the FDCA will be addressed: 1) unapproved devices that a manufacturer reasonably believes are eligible for Section 510(k) clearance may no longer be exported under Section 801(e) and now must be exported under Section 802, in substantial compliance with Current CGMP; 2) adulterated devices and misbranded drugs can only be exported if the foreign purchaser's specifications cause the product to be adulterated; and 3) an article may not be exported if a like article has ever been sold or offered for sale in domestic commerce. FDA's new interpretations of FDCA

  16. Research on plasma core reactors

    International Nuclear Information System (INIS)

    Jarvis, G.A.; Barton, D.M.; Helmick, H.H.; Bernard, W.; White, R.H.

    1976-01-01

    Experiments and theoretical studies are being conducted for NASA on critical assemblies with one-meter diameter by one-meter long low-density cores surrounded by a thick beryllium reflector. These assemblies make extensive use of existing nuclear propulsion reactor components, facilities, and instrumentation. Due to excessive porosity in the reflector, the initial critical mass was 19 kg U(93.2). Addition of a 17-cm-thick by 89-cm-diameter beryllium flux trap in the cavity reduced the critical mass to 7 kg when all the uranium was in the zone just outside the flux trap. A mockup aluminum UF 6 container was placed inside the flux trap and fueled with uranium-graphite elements. Fission distributions and reactivity worths of fuel and structural materials were measured. Finally, an 85,000 cm 3 aluminum canister in the central region was fueled with UF 6 gas and fission density distributions determined. These results will be used to guide the design of a prototype plasma core reactor which will test energy removal by optical radiation

  17. The impact of FDA regulatory activities on incident dispensing of LABA-containing medication: 2005-2011.

    Science.gov (United States)

    Baker, Meghan A; Butler, Melissa G; Seymour, Sally; Zhang, Fang; Wu, Yute; Wu, Ann Chen; Levenson, Mark S; Wu, Pingsheng; Iyer, Aarthi; Toh, Sengwee; Iyasu, Solomon; Zhou, Esther H

    2017-09-14

    Evidence of safety issues associated with long-acting beta 2 -agonist (LABA) treatment has led to multiple regulatory activities by the U.S. Food and Drug Administration (FDA) on this class of medications. This study describes the impact of the regulatory activities on incident LABA-containing medication dispensing. A monthly rolling cohort of asthma patients who were eligible to initiate a LABA-containing product was created in the Mini-Sentinel Distributed Database between January 2005 and June 2011. Cohorts of individuals who initiated LABA were examined for the changes in the proportions of single-ingredient to fixed-dose inhaled corticosteroid (ICS)-LABA initiators, appropriate initiation of LABA-containing products, and use of controller medications. The impact of the 2005 and 2010 FDA regulatory activities associated with LABA-containing products was measured using interrupted time series with segmented regression. LABA-containing product initiation was declining prior to the 2005 regulatory activities and continued to decline over the study period, accompanied by increased initiation of fixed dose ICS-LABA among LABA initiators. While the 2010 regulatory activities had no immediate impact on the proportion of LABA initiation in patients with prior controller medication dispensing and/or poor asthma control, there was an increasing positive trend toward LABA initiation in the appropriate patient population after the regulatory activities. The 2005 and 2010 FDA regulatory activities likely had an impact on communicating the safety concerns of LABA products. However, the impact cannot be viewed independent of scientific publications, guidelines for asthma treatment and other regulatory activities.

  18. 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

  19. 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

  20. Disproportionality analysis of buprenorphine transdermal system and cardiac arrhythmia using FDA and WHO postmarketing reporting system data.

    Science.gov (United States)

    Sessler, Nelson E; Walker, Ekaterina; Chickballapur, Harsha; Kacholakalayil, James; Coplan, Paul M

    2017-01-01

    Positive-controlled clinical studies have shown a dose dependent effect of buprenorphine transdermal system on QTc interval prolongation. This study provides assessment of the buprenorphine transdermal system and cardiac arrhythmia using US FDA and WHO postmarketing reporting databases. Disproportionality analysis of spontaneously reported adverse events to assess whether the reporting rate of cardiac arrhythmia events was disproportionately elevated relative to expected rates of reporting in both FDA and WHO databases. Cardiac arrhythmia events were identified using the standardized Medical Dictionary for Regulatory Activities query for torsade de pointes and/or QT prolongation (TdP/QTP). The threshold for a signal of disproportionate adverse event reporting was defined as the lower 90% confidence limit ≥ 2 of the Empiric Bayes geometric mean in FDA database and as the lower 95% confidence limit of the Informational Component >0 in WHO database. There were 124 (reporting for TdP/QTP (EB05 3.26); however, buprenorphine transdermal was not (EB05 0.33). In the WHO database methadone was associated with a signal of disproportionate reporting for TdP/QTP (IC025 2.66); however, buprenorphine transdermal was not (IC025 -0.88). Similar trends were observed in sensitivity analyses by age, gender, and specific terms related to ventricular arrhythmia. The signal identified in the transdermal buprenorphine thorough QTc study, which led to a dose limitation in its US label, does not translate into a signal of increased risk for cardiac arrhythmia in real world use, as assessed by this method of analyzing post-market surveillance data.

  1. 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.

  2. Reactor core control device

    International Nuclear Information System (INIS)

    Sano, Hiroki

    1998-01-01

    The present invention provides a reactor core control device, in which switching from a manual operation to an automatic operation, and the control for the parameter of an automatic operation device are facilitated. Namely, the hysteresis of the control for the operation parameter by an manual operation input means is stored. The hysteresis of the control for the operation parameter is collected. The state of the reactor core simulated by an operation control to which the collected operation parameters are manually inputted is determined as an input of the reactor core state to the automatic input means. The record of operation upon manual operation is stored as a hysteresis of control for the operation parameter, but the hysteresis information is not only the result of manual operation of the operation parameter. This is results of operation conducted by a skilled operator who judge the state of the reactor core to be optimum. Accordingly, it involves information relevant to the reactor core state. Then, it is considered that the optimum automatic operation is not deviated greatly from the manual operation. (I.S.)

  3. [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.

  4. 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

  5. FDA (Food and Drug Administration) Compliance Program Guidance Manual (FY 85). Section 4. Medical and radiological devices

    International Nuclear Information System (INIS)

    1985-01-01

    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. 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.

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

    Science.gov (United States)

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

    2017-01-01

    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.”1 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.2 PMID:28571121

  8. Mars' Inner Core

    Science.gov (United States)

    1997-01-01

    This figure shows a cross-section of the planet Mars revealing an inner, high density core buried deep within the interior. Dipole magnetic field lines are drawn in blue, showing the global scale magnetic field that one associates with dynamo generation in the core. Mars must have one day had such a field, but today it is not evident. Perhaps the energy source that powered the early dynamo has shut down. The differentiation of the planet interior - heavy elements like iron sinking towards the center of the planet - can provide energy as can the formation of a solid core from the liquid.The Jet Propulsion Laboratory's Mars Surveyor Operations Project operates the Mars Global Surveyor spacecraft with its industrial partner, Lockheed Martin Astronautics, from facilities in Pasadena, CA and Denver, CO. JPL is an operating division of California Institute of Technology (Caltech).

  9. Core status computing system

    International Nuclear Information System (INIS)

    Yoshida, Hiroyuki.

    1982-01-01

    Purpose: To calculate power distribution, flow rate and the like in the reactor core with high accuracy in a BWR type reactor. Constitution: Total flow rate signals, traverse incore probe (TIP) signals as the neutron detector signals, thermal power signals and pressure signals are inputted into a process computer, where the power distribution and the flow rate distribution in the reactor core are calculated. A function generator connected to the process computer calculates the absolute flow rate passing through optional fuel assemblies using, as variables, flow rate signals from the introduction part for fuel assembly flow rate signals, data signals from the introduction part for the geometrical configuration data at the flow rate measuring site of fuel assemblies, total flow rate signals for the reactor core and the signals from the process computer. Numerical values thus obtained are given to the process computer as correction signals to perform correction for the experimental data. (Moriyama, K.)

  10. Superconducting tin core fiber

    Energy Technology Data Exchange (ETDEWEB)

    Homa, Daniel; Liang, Yongxuan; Hill, Cary; Kaur, Gurbinder; Pickrell, Gary [Virginia Polytechnic Institute and State University, Department of Materials Science and Engineering, Blacksburg, VA (United States)

    2014-11-13

    In this study, we demonstrated superconductivity in a fiber with a tin core and fused silica cladding. The fibers were fabricated via a modified melt-draw technique and maintained core diameters ranging from 50-300 microns and overall diameters of 125-800 microns. Superconductivity of this fiber design was validated via the traditional four-probe test method in a bath of liquid helium at temperatures on the order of 3.8 K. The synthesis route and fiber design are perquisites to ongoing research dedicated all-fiber optoelectronics and the relationships between superconductivity and the material structures, as well as corresponding fabrication techniques. (orig.)

  11. Superconducting tin core fiber

    International Nuclear Information System (INIS)

    Homa, Daniel; Liang, Yongxuan; Hill, Cary; Kaur, Gurbinder; Pickrell, Gary

    2015-01-01

    In this study, we demonstrated superconductivity in a fiber with a tin core and fused silica cladding. The fibers were fabricated via a modified melt-draw technique and maintained core diameters ranging from 50-300 microns and overall diameters of 125-800 microns. Superconductivity of this fiber design was validated via the traditional four-probe test method in a bath of liquid helium at temperatures on the order of 3.8 K. The synthesis route and fiber design are perquisites to ongoing research dedicated all-fiber optoelectronics and the relationships between superconductivity and the material structures, as well as corresponding fabrication techniques. (orig.)

  12. TMI-2 core examination

    International Nuclear Information System (INIS)

    Hobbins, R.R.; MacDonald, P.E.; Owen, D.E.

    1983-01-01

    The examination of the damaged core at the Three Mile Island Unit 2 (TMI-2) reactor is structured to address the following safety issues: fission product release, transport, and deposition; core coolability; containment integrity; and recriticality during severe accidents; as well as zircaloy cladding ballooning and oxidation during so-called design basis accidents. The numbers of TMI-2 components or samples to be examined, the priority of each examination, the safety issue addressed by each examination, the principal examination techniques to be employed, and the data to be obtained and the principal uses of the data are discussed in this paper

  13. CORE COMPONENT POT

    Energy Technology Data Exchange (ETDEWEB)

    MARTIN RL; OMBERG RP

    1975-12-19

    The core component pot is an open top vessel used to hold both new and irradiated core components for storage in the IDS and for holding the components submerged in sodium while being trasported inside CLEM. The top of the CCP is equipped with a grapple lip which is engaged by the hoisting grapples. Heat for maintaining the preheat of new components and dissipation of decay heat of irradiated fuel assemblies is conducted between the wall of the pot and the surrounding environment by thermal radiation and convection.

  14. Nuclear core catchers

    International Nuclear Information System (INIS)

    Golden, M.P.; Tilbrook, R.W.; Heylmun, N.F.

    1976-01-01

    A receptacle is described for taking the molten fragments of a nuclear reactor during a reactor core fusion accident. The receptacle is placed under the reactor. It includes at least one receptacle for the reactor core fragments, with a dome shaped part to distribute the molten fragments and at least one outside layer of alumina bricks around the dome. The characteristic of this receptacle is that the outer layer of bricks contains neutron poison rods which pass through the bricks and protrude in relation to them [fr

  15. Maximum stellar iron core mass

    Indian Academy of Sciences (India)

    An analytical method of estimating the mass of a stellar iron core, just prior to core collapse, is described in this paper. The method employed depends, in part, upon an estimate of the true relativistic mass increase experienced by electrons within a highly compressed iron core, just prior to core collapse, and is significantly ...

  16. The flawed basis for FDA post-marketing safety decisions: the example of anti-depressants and children.

    Science.gov (United States)

    Klein, Donald F

    2006-04-01

    The FDA (February 3, 2005) issued a black box warning that all antidepressants increase the risk of suicidal thinking and behavior in children and adolescents that must be cited in all advertising as well as included in the package insert. Following this, there was a sharp decrease in antidepressant prescriptions for children with uncertain public health impact. The current black box does not claim that these medications increase the risk of completed suicides, although this is the clear implication of the term 'suicidality'. The interpretation by the press is unequivocal that lethal outcomes prompted this action. This review concludes the following: (1) Since no suicide occurred in clinical trials of approximately 4400 children, the analyses relied upon 'suicidality' as a surrogate. (2) The classification of adverse events by the Columbia group necessarily relied on inferences, because the available evidence was not prospectively collected for this purpose. (3) The data analysis relied on a composite variable labeled 'suicidality', an unvalidated, inappropriate surrogate. Specific criticisms of analytic procedures and inferences are presented. The failure of the FDA's post-marketing surveillance system is reviewed. The data necessary for objective evaluations of possible post-marketing harm cannot be gathered by the current process. Proper prospective post-marketing surveillance by linked computerized medical records is a crucial issue that deserves major public and political attention and prompt action.

  17. 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.

  18. 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.

  19. 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.

  20. Bisphosphonates and Nonhealing Femoral Fractures: Analysis of the FDA Adverse Event Reporting System (FAERS) and International Safety Efforts

    Science.gov (United States)

    Edwards, Beatrice J.; Bunta, Andrew D.; Lane, Joseph; Odvina, Clarita; Rao, D. Sudhaker; Raisch, Dennis W.; McKoy, June M.; Omar, Imran; Belknap, Steven M.; Garg, Vishvas; Hahr, Allison J.; Samaras, Athena T.; Fisher, Matthew J.; West, Dennis P.; Langman, Craig B.; Stern, Paula H.

    2013-01-01

    Background: In the United States, hip fracture rates have declined by 30% coincident with bisphosphonate use. However, bisphosphonates are associated with sporadic cases of atypical femoral fracture. Atypical femoral fractures are usually atraumatic, may be bilateral, are occasionally preceded by prodromal thigh pain, and may have delayed fracture-healing. This study assessed the occurrence of bisphosphonate-associated nonhealing femoral fractures through a review of data from the U.S. FDA (Food and Drug Administration) Adverse Event Reporting System (FAERS) (1996 to 2011), published case reports, and international safety efforts. Methods: We analyzed the FAERS database with use of the proportional reporting ratio (PRR) and empiric Bayesian geometric mean (EBGM) techniques to assess whether a safety signal existed. Additionally, we conducted a systematic literature review (1990 to February 2012). Results: The analysis of the FAERS database indicated a PRR of 4.51 (95% confidence interval [CI], 3.44 to 5.92) for bisphosphonate use and nonhealing femoral fractures. Most cases (n = 317) were attributed to use of alendronate (PRR = 3.32; 95% CI, 2.71 to 4.17). In 2008, international safety agencies issued warnings and required label changes. In 2010, the FDA issued a safety notification, and the American Society for Bone and Mineral Research (ASBMR) issued recommendations about bisphosphonate-associated atypical femoral fractures. Conclusions: Nonhealing femoral fractures are unusual adverse drug reactions associated with bisphosphonate use, as up to 26% of published cases of atypical femoral fractures exhibited delayed healing or nonhealing. PMID:23426763

  1. Targeting the β-clamp in Helicobacter pylori with FDA-approved drugs reveals micromolar inhibition by diflunisal.

    Science.gov (United States)

    Pandey, Preeti; Verma, Vijay; Gautam, Gunjan; Kumari, Nilima; Dhar, Suman Kumar; Gourinath, Samudrala

    2017-08-01

    The β-clamp is the processivity-promoting factor for most of the enzymes in prokaryotic DNA replication; hence, it is a crucial drug target. In the present study, we investigated the β-clamp from Helicobacter pylori, aiming to seek potential drug molecules against this gastric-cancer-causing bacterium. An in silico screening of Food and Drug Administration (FDA) approved drugs against the H. pylori β-clamp, followed by its in vitro inhibition using a surface competition approach, yielded the drug diflunisal as a positive initial hit. Diflunisal inhibits the growth of H. pylori in the micromolar range. We determined the structure of diflunisal in complex with the β-clamp to show that the drug binds at subsite I, which is a protein-protein interaction site. Successful identification of FDA-approved molecules against H. pylori may lead to better and faster drug development. © 2017 Federation of European Biochemical Societies.

  2. Overview on Hydrate Coring, Handling and Analysis

    Energy Technology Data Exchange (ETDEWEB)

    Jon Burger; Deepak Gupta; Patrick Jacobs; John Shillinglaw

    2003-06-30

    Gas hydrates are crystalline, ice-like compounds of gas and water molecules that are formed under certain thermodynamic conditions. Hydrate deposits occur naturally within ocean sediments just below the sea floor at temperatures and pressures existing below about 500 meters water depth. Gas hydrate is also stable in conjunction with the permafrost in the Arctic. Most marine gas hydrate is formed of microbially generated gas. It binds huge amounts of methane into the sediments. Worldwide, gas hydrate is estimated to hold about 1016 kg of organic carbon in the form of methane (Kvenvolden et al., 1993). Gas hydrate is one of the fossil fuel resources that is yet untapped, but may play a major role in meeting the energy challenge of this century. In June 2002, Westport Technology Center was requested by the Department of Energy (DOE) to prepare a ''Best Practices Manual on Gas Hydrate Coring, Handling and Analysis'' under Award No. DE-FC26-02NT41327. The scope of the task was specifically targeted for coring sediments with hydrates in Alaska, the Gulf of Mexico (GOM) and from the present Ocean Drilling Program (ODP) drillship. The specific subjects under this scope were defined in 3 stages as follows: Stage 1: Collect information on coring sediments with hydrates, core handling, core preservation, sample transportation, analysis of the core, and long term preservation. Stage 2: Provide copies of the first draft to a list of experts and stakeholders designated by DOE. Stage 3: Produce a second draft of the manual with benefit of input from external review for delivery. The manual provides an overview of existing information available in the published literature and reports on coring, analysis, preservation and transport of gas hydrates for laboratory analysis as of June 2003. The manual was delivered as draft version 3 to the DOE Project Manager for distribution in July 2003. This Final Report is provided for records purposes.

  3. Core damage risk indicators

    International Nuclear Information System (INIS)

    Szikszai, T.

    1994-01-01

    The purpose of this document is to show a method for the fast recalculation of the PSA. To avoid the information loose, it is necessary to simplify the PSA models, or at least reorganize them. The method, introduced in this document, require that preparation, so we try to show, how to do that. This document is an introduction. This is the starting point of the work related to the development of the risk indicators. In the future, with the application of this method, we are going to show an everyday use of the PSA results to produce the indicators of the core damage risk. There are two different indicators of the plant safety performance, related to the core damage risk. The first is the core damage frequency indicator (CDFI), and the second is the core damage probability indicator (CDPI). Of course, we cannot describe all of the possible ways to use these indicators, rather we will try to introduce the requirements to establish such an indicator system and the calculation process

  4. The Uncommon Core

    Science.gov (United States)

    Ohler, Jason

    2013-01-01

    This author contends that the United States neglects creativity in its education system. To see this, he states, one may look at the Common Core State Standards. If one searches the English Language Arts and Literacy standards for the words "creative," "innovative," and "original"--and any associated terms, one will…

  5. Utah's New Mathematics Core

    Science.gov (United States)

    Utah State Office of Education, 2011

    2011-01-01

    Utah has adopted more rigorous mathematics standards known as the Utah Mathematics Core Standards. They are the foundation of the mathematics curriculum for the State of Utah. The standards include the skills and understanding students need to succeed in college and careers. They include rigorous content and application of knowledge and reflect…

  6. Core Obstetrics and Gynaecology*

    African Journals Online (AJOL)

    Core Obstetrics and Gynaecology*. By J. T. Nel. Pp xvii + 992. Illustrated. Durban: Butterworths. 1995. ISBN 0-409-10134-6. For some years now, I have lamented the absence of a good, home-grown, comprehensive, student-centred textbook of obstetrics and gynaecology designed specifically for South African needs.

  7. Core calculations of JMTR

    Energy Technology Data Exchange (ETDEWEB)

    Nagao, Yoshiharu [Japan Atomic Energy Research Inst., Oarai, Ibaraki (Japan). Oarai Research Establishment

    1998-03-01

    In material testing reactors like the JMTR (Japan Material Testing Reactor) of 50 MW in Japan Atomic Energy Research Institute, the neutron flux and neutron energy spectra of irradiated samples show complex distributions. It is necessary to assess the neutron flux and neutron energy spectra of an irradiation field by carrying out the nuclear calculation of the core for every operation cycle. In order to advance core calculation, in the JMTR, the application of MCNP to the assessment of core reactivity and neutron flux and spectra has been investigated. In this study, in order to reduce the time for calculation and variance, the comparison of the results of the calculations by the use of K code and fixed source and the use of Weight Window were investigated. As to the calculation method, the modeling of the total JMTR core, the conditions for calculation and the adopted variance reduction technique are explained. The results of calculation are shown. Significant difference was not observed in the results of neutron flux calculations according to the difference of the modeling of fuel region in the calculations by K code and fixed source. The method of assessing the results of neutron flux calculation is described. (K.I.)

  8. Investigation of EAS cores

    Directory of Open Access Journals (Sweden)

    Shaulov S.B.

    2017-01-01

    Full Text Available The development of nuclear-electromagnetic cascade models in air in the late forties have shown informational content of the study of cores of extensive air showers (EAS. These investigations were the main goal in different experiments which were carried out over many years by a variety of methods. Outcomes of such investigations obtained in the HADRON experiment using an X-ray emulsion chamber (XREC as a core detector are considered. The Ne spectrum of EAS associated with γ-ray families, spectra of γ-rays (hadrons in EAS cores and the Ne dependence of the muon number, ⟨Nμ⟩, in EAS with γ-ray families are obtained for the first time at energies of 1015–1017 eV with this method. A number of new effects were observed, namely, an abnormal scaling violation in hadron spectra which are fundamentally different from model predictions, an excess of muon number in EAS associated with γ-ray families, and the penetrating component in EAS cores. It is supposed that the abnormal behavior of γ-ray spectra and Ne dependence of the muon number are explained by the emergence of a penetrating component in the 1st PCR spectrum ‘knee’ range. Nuclear and astrophysical explanations of the origin of the penetrating component are discussed. The necessity of considering the contribution of a single close cosmic-ray source to explain the PCR spectrum in the knee range is noted.

  9. Looking for Core Values

    Science.gov (United States)

    Carter, Margie

    2010-01-01

    People who view themselves as leaders, not just managers or teachers, are innovators who focus on clarifying core values and aligning all aspects of the organization with these values to grow their vision. A vision for an organization can't be just one person's idea. Visions grow by involving people in activities that help them name and create…

  10. Nuclear core baffling apparatus

    International Nuclear Information System (INIS)

    Cooper, F.W. Jr.; Silverblatt, B.L.; Knight, C.B.; Berringer, R.T.

    1979-01-01

    An apparatus for baffling the flow of reactor coolant fluid into and about the core of a nuclear reactor is described. The apparatus includes a plurality of longitudinally aligned baffle plates with mating surfaces that allow longitudinal growth with temperature increases while alleviating both leakage through the aligned plates and stresses on the components supporting the plates

  11. Inflation targeting and core inflation

    OpenAIRE

    Julie Smith

    2005-01-01

    This paper examines the interaction of core inflation and inflation targeting as a monetary policy regime. Interest in core inflation has grown because of inflation targeting. Core inflation is defined in numerous ways giving rise to many potential measures; this paper defines core inflation as the best forecaster of inflation. A cross-country study finds before the start of inflation targeting, but not after, core inflation differs between non-inflation targeters and inflation targeters. Thr...

  12. 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

  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. Ice cores and palaeoclimate

    International Nuclear Information System (INIS)

    Krogh Andersen, K.; Ditlevsen, P.; Steffensen, J.P.

    2001-01-01

    Ice cores from Greenland give testimony of a highly variable climate during the last glacial period. Dramatic climate warmings of 15 to 25 deg. C for the annual average temperature in less than a human lifetime have been documented. Several questions arise: Why is the Holocene so stable? Is climatic instability only a property of glacial periods? What is the mechanism behind the sudden climate changes? Are the increased temperatures in the past century man-made? And what happens in the future? The ice core community tries to attack some of these problems. The NGRIP ice core currently being drilled is analysed in very high detail, allowing for a very precise dating of climate events. It will be possible to study some of the fast changes on a year by year basis and from this we expect to find clues to the sequence of events during rapid changes. New techniques are hoped to allow for detection of annual layers as far back as 100,000 years and thus a much improved time scale over past climate changes. It is also hoped to find ice from the Eemian period. If the Eemian layers confirm the GRIP sequence, the Eemian was actually climatically unstable just as the glacial period. This would mean that the stability of the Holocene is unique. It would also mean, that if human made global warming indeed occurs, we could jeopardize the Holocene stability and create an unstable 'Eemian situation' which ultimately could start an ice age. Currenlty mankind is changing the composition of the atmosphere. Ice cores document significant increases in greenhouse gases, and due to increased emissions of sulfuric and nitric acid from fossil fuel burning, combustion engines and agriculture, modern Greenland snow is 3 - 5 times more acidic than pre-industrial snow (Mayewski et al., 1986). However, the magnitude and abruptness of the temperature changes of the past century do not exceed the magnitude of natural variability. It is from the ice core perspective thus not possible to attribute the

  15. Birefringent hollow core fibers

    DEFF Research Database (Denmark)

    Roberts, John

    2007-01-01

    Hollow core photonic crystal fiber (HC-PCF), fabricated according to a nominally non-birefringent design, shows a degree of un-controlled birefringence or polarization mode dispersion far in excess of conventional non polarization maintaining fibers. This can degrade the output pulse in many...... applications, and places emphasis on the development of polarization maintaining (PM) HC-PCF. The polarization cross-coupling characteristics of PM HC-PCF are very different from those of conventional PM fibers. The former fibers have the advantage of suffering far less from stress-field fluctuations...... and an increased overlap between the polarization modes at the glass interfaces. The interplay between these effects leads to a wavelength for optimum polarization maintenance, lambda(PM), which is detuned from the wavelength of highest birefringence. By a suitable fiber design involving antiresonance of the core...

  16. Reactor core lower support

    International Nuclear Information System (INIS)

    1981-01-01

    This patent refers to the lower support of a nuclear reactor core, and is intended for supporting each fuel assembly of the core and for distributing the primary coolant through these assemblies. It is composed of: - A first thick plate supporting the fuel assemblies. Vertical channels are machined in this plate directly facing each assembly for the passage of the primary fluid: - A second thin plate drilled with orifices, fixed under the first plate, with no space between them, and so positioned that each orifice is directly facing one of the channels. The section of the orifices diminishes from the centre of the plate towards its periphery. The second plate can also be constituted of an assembly of juxtaposed smaller plates, each small plate being secured to the first plate independently of the neighbouring plates [fr

  17. Some core contested concepts.

    Science.gov (United States)

    Chomsky, Noam

    2015-02-01

    Core concepts of language are highly contested. In some cases this is legitimate: real empirical and conceptual issues arise. In other cases, it seems that controversies are based on misunderstanding. A number of crucial cases are reviewed, and an approach to language is outlined that appears to have strong conceptual and empirical motivation, and to lead to conclusions about a number of significant issues that differ from some conventional beliefs.

  18. Schumpeter's core works revisited

    DEFF Research Database (Denmark)

    Andersen, Esben Sloth

    2012-01-01

    This paper organises Schumpeter’s core books in three groups: the programmatic duology,the evolutionaryeconomic duology,and the socioeconomic synthesis. By analysing these groups and their interconnections from the viewpoint of modern evolutionaryeconomics,the paper summarises resolved problems...... and points at remaining challenges. Its analyses are based on distinctions between microevolution and macroevolution, between economic evolution and socioeconomic coevolution, and between Schumpeter’s three major evolutionary models (called Mark I, Mark II and Mark III)....

  19. BWR type reactor core

    International Nuclear Information System (INIS)

    Tatemichi, Shin-ichiro.

    1981-01-01

    Purpose: To eliminate the variation in the power distribution of a BWR type reactor core in the axial direction even if the flow rate is increased or decreased by providing a difference in the void coefficient between the upper part and the lower parts of the reactor core, and increasing the void coefficient at the lower part of the reactor core. Constitution: The void coefficient of the lower region from the center to the lower part along the axial direction of a nuclear fuel assembly is increased to decrease the dependence on the flow rate of the axial power distribution of the nuclear fuel assembly. That is, a water/fuel ratio is varied, the water in non-boiled region is increased or the neutron spectrum is varied so as to vary the void coefficient. In order to exemplify it, the rate of the internal pellets of the fuel rod of the nuclear fuel assembly or the shape of the channel box is varied. Accordingly, the power does not considerably vary even if the flow rate is altered since the power is varied in the power operation. (Yoshihara, H.)

  20. 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.

  1. 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

  2. Comparison and analysis of FDA reported visual outcomes of the three latest platforms for LASIK: wavefront guided Visx iDesign, topography guided WaveLight Allegro Contoura, and topography guided Nidek EC-5000 CATz

    Directory of Open Access Journals (Sweden)

    Moshirfar M

    2017-01-01

    Full Text Available Majid Moshirfar,1,2 Tirth J Shah,3 David Franklin Skanchy,4 Steven H Linn,1 Paul Kang,3 Daniel S Durrie5 1HDR Research Center, Hoopes Vision, Salt Lake City, UT, 2Department of Ophthalmology and Visual Sciences, John A Moran Eye Center, University of Utah School of Medicine, Salt Lake City, UT, 3University of Arizona College of Medicine – Phoenix, Phoenix, AZ, 4McGovern Medical School, The University of Texas Health Science Center at Houston, TX, 5Durrie Vision, Kansas City, KS, USA Purpose: To compare and analyze the differences in visual outcomes between Visx iDesign Advanced WaveScan Studio™ System, Alcon Wavelight Allegro Topolyzer and Nidek EC-5000 using Final Fit™ Custom Ablation Treatment Software from the submitted summary of safety and effectiveness of the US Food and Drug Administration (FDA data.Methods: In this retrospective comparative study, 334 eyes from Visx iDesign, 212 eyes from Alcon Contour, and 135 eyes from Nidek CATz platforms were analyzed for primary and secondary visual outcomes. These outcomes were compared via side-by-side graphical and tabular representation of the FDA data. Statistical significance was calculated when appropriate to assess differences. A P-value <0.05 was considered statistically significant. Results: The mean postoperative uncorrected distance visual acuity (UDVA at 12 months was 20/19.25±8.76, 20/16.59±5.94, and 20/19.17±4.46 for Visx iDesign, Alcon Contoura, and Nidek CATz, respectively. In at least 90% of treated eyes at 3 months and 12 months, all three lasers showed either no change or a gain of corrected distance visual acuity (CDVA. Mesopic contrast sensitivity at 6 months showed a clinically significant increase of 41.3%, 25.1%, and 10.6% for eyes using Visx iDesign, Alcon Contoura, and Nidek CATz, respectively. Photopic contrast sensitivity at 6 months showed a clinically significant increase of 19.2%, 31.9%, and 10.6% for eyes using Visx iDesign, Alcon Contoura, and Nidek CATz

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

    Science.gov (United States)

    Kim, Hyosun

    2015-01-01

    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 FDA has thus

  4. 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

  5. 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.

  6. 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.

  7. Selenium semiconductor core optical fibers

    Directory of Open Access Journals (Sweden)

    G. W. Tang

    2015-02-01

    Full Text Available Phosphate glass-clad optical fibers containing selenium (Se semiconductor core were fabricated using a molten core method. The cores were found to be amorphous as evidenced by X-ray diffraction and corroborated by Micro-Raman spectrum. Elemental analysis across the core/clad interface suggests that there is some diffusion of about 3 wt % oxygen in the core region. Phosphate glass-clad crystalline selenium core optical fibers were obtained by a postdrawing annealing process. A two-cm-long crystalline selenium semiconductor core optical fibers, electrically contacted to external circuitry through the fiber end facets, exhibit a three times change in conductivity between dark and illuminated states. Such crystalline selenium semiconductor core optical fibers have promising utility in optical switch and photoconductivity of optical fiber array.

  8. Study on core design for reduced-moderation water reactors

    Energy Technology Data Exchange (ETDEWEB)

    Okubo, Tsutomu [Japan Atomic Energy Research Inst., Tokai, Ibaraki (Japan). Tokai Research Establishment

    2002-12-01

    The Reduced-Moderation Water Reactor (RMWR) is a water-cooled reactor with the harder neutron spectrum comparing with the LWR, resulting from low neutron moderation due to reduced water volume fraction. Based on the difference from the spectrum from the LWR, the conversion from U-238 to Pu-239 is promoted and the new cores preferable to effective utilization of uranium resource can be possible Design study of the RMWR core started in 1997 and new four core concepts (three BWR cores and one PWR core) are recently evaluated in terms of control rod worths, plutonium multiple recycle, high burnup and void coefficient. Comparative evaluations show needed incorporation of control rod programming and simplified PUREX process as well as development of new fuel cans for high burnup of 100 GW-d/t. Final choice of design specifications will be made at the next step aiming at realization of the RMWR. (T. Tanaka)

  9. Investigating the impact of uneven magnetic flux density distribution on core loss estimation

    DEFF Research Database (Denmark)

    Niroumand, Farideh Javidi; Nymand, Morten; Wang, Yiren

    2017-01-01

    . The presented work in this paper has been carried out for two common excitation waveforms in power electronics applications, sinusoid and square-wave and for two different core shapes, toroid and E-cores. Results show that ±10% discrepancy should be expected in loss estimation of the core using effective...... is calculated according to an effective flux density value and the macroscopic dimensions of the cores. However, the flux distribution in the core can alter by core shapes and/or operating conditions due to nonlinear material properties. This paper studies the element-wise estimation of the loss in magnetic...... cores. FEM has been used to investigate the flux density distribution in the core and the loss has been estimated considering this distribution. Finally, comparative results are shown between the classical macroscopic core loss estimation using effective dimensions and the element-wise loss estimation...

  10. Admission CT perfusion may overestimate initial infarct core: the ghost infarct core concept.

    Science.gov (United States)

    Boned, Sandra; Padroni, Marina; Rubiera, Marta; Tomasello, Alejandro; Coscojuela, Pilar; Romero, Nicolás; Muchada, Marián; Rodríguez-Luna, David; Flores, Alan; Rodríguez, Noelia; Juega, Jesús; Pagola, Jorge; Alvarez-Sabin, José; Molina, Carlos A; Ribó, Marc

    2017-01-01

    Identifying infarct core on admission is essential to establish the amount of salvageable tissue and indicate reperfusion therapies. Infarct core is established on CT perfusion (CTP) as the severely hypoperfused area, however the correlation between hypoperfusion and infarct core may be time-dependent as it is not a direct indicator of tissue damage. This study aims to characterize those cases in which the admission core lesion on CTP does not reflect an infarct on follow-up imaging. We studied patients with cerebral large vessel occlusion who underwent CTP on admission but received endovascular thrombectomy based on a non-contrast CT Alberta Stroke Program Early CT Score (ASPECTS) >6. Admission infarct core was measured on initial cerebral blood volume (CBV) CTP and final infarct on follow-up CT. We defined ghost infarct core (GIC) as initial core minus final infarct >10 mL. 79 patients were studied. Median National Institutes of Health Stroke Scale (NIHSS) score was 17 (11-20), median time from symptoms to CTP was 215 (87-327) min, and recanalization rate (TICI 2b-3) was 77%. Thirty patients (38%) presented with a GIC >10 mL. GIC >10 mL was associated with recanalization (TICI 2b-3: 90% vs 68%; p=0.026), admission glycemia (185 min: 26%; p=0.033). An adjusted logistic regression model identified time from symptom to CTP imaging 10 mL (OR 2.89, 95% CI 1.04 to 8.09). At 24 hours, clinical improvement was more frequent in patients with GIC >10 mL (66.6% vs 39%; p=0.017). CT perfusion may overestimate final infarct core, especially in the early time window. Selecting patients for reperfusion therapies based on the CTP mismatch concept may deny treatment to patients who might still benefit from reperfusion. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  11. Hollow-Core Fiber Lamp

    Science.gov (United States)

    Yi, Lin (Inventor); Tjoelker, Robert L. (Inventor); Burt, Eric A. (Inventor); Huang, Shouhua (Inventor)

    2016-01-01

    Hollow-core capillary discharge lamps on the millimeter or sub-millimeter scale are provided. The hollow-core capillary discharge lamps achieve an increased light intensity ratio between 194 millimeters (useful) and 254 millimeters (useless) light than conventional lamps. The capillary discharge lamps may include a cone to increase light output. Hollow-core photonic crystal fiber (HCPCF) may also be used.

  12. On core stability and extendability

    OpenAIRE

    Shellshear, Evan

    2007-01-01

    This paper investigates conditions under which the core of a TU cooperative game is stable. In particular the author extends the idea of extendability to find new conditions under which the core is stable. It is also shown that these new conditions are not necessary for core stability.

  13. Core TuLiP

    NARCIS (Netherlands)

    Czenko, M.R.; Etalle, Sandro

    2007-01-01

    We propose CoreTuLiP - the core of a trust management language based on Logic Programming. CoreTuLiP is based on a subset of moded logic programming, but enjoys the features of TM languages such as RT; in particular clauses are issued by different authorities and stored in a distributed manner. We

  14. Dual-core Itanium Processor

    CERN Multimedia

    2006-01-01

    Intel’s first dual-core Itanium processor, code-named "Montecito" is a major release of Intel's Itanium 2 Processor Family, which implements the Intel Itanium architecture on a dual-core processor with two cores per die (integrated circuit). Itanium 2 is much more powerful than its predecessor. It has lower power consumption and thermal dissipation.

  15. Radiation quality factor of spherical antennas with material cores

    DEFF Research Database (Denmark)

    Hansen, Troels Vejle; Kim, Oleksiy S.; Breinbjerg, Olav

    2011-01-01

    This paper gives a description of the radiation quality factor and resonances of spherical antennas with material cores. Conditions for cavity and radiating resonances are given, and a theoretical description of the radiation quality factor, as well as simple expressions describing the relative...... increase in quality factor due to the effect of the internally stored energy are given in special cases. For the air-core antenna of vanishing size, it is shown that the dipole modes are the modes providing the lowest quality factor of all modes. Finally an investigation of the effect of the core...

  16. Stator Core Fault Diagnosis in Induction Motor Using Adaptive Observer

    Directory of Open Access Journals (Sweden)

    Hailiang HOU

    2014-09-01

    Full Text Available This document presents a method of on-line fault diagnosis for iron core of induction motor stator based on adaptive observer. Due to the equivalent resistance is directly affected by the stator core fault, while the iron loss is considered in the series iron loss model of the induction motor, so we can determine the core fault state by identifying equivalent iron consumption resistance. In this paper, Matlab LMI toolbox is employed to calculate the feedback gain matrix of adaptive observer, which can makes up the deficiency of other method such as pole assignment. Finally, the experimental results confirm the validity of the proposed approach.

  17. The TMI-2 core relocation: Heat transfer and mechanism

    International Nuclear Information System (INIS)

    Epstein, M.; Fauske, H.K.

    1987-07-01

    It is postulated that the collapse of the upper debris bed was the main cause of core failure and core material relocation during the TMI-2 accident. It is shown that this mechanism of core relocation can account for the timescale(s) and energy transfer rate inferred from plant instrumentation. Additional analysis suggests that the water in the lower half of the reactor vessel was subcooled at the onset of relocation, as subcooling serves to explain the final coolable configuration at the bottom of the TMI vessel

  18. FDA perspective on specifications for biotechnology products--from IND to PLA.

    Science.gov (United States)

    Murano, G

    1997-01-01

    Quality standards are obligatory throughout development, approval and post-marketing phases of biotechnology-derived products, thus assuring product identity, purity, and potency/strength. The process of developing and setting specifications should be based on sound science and should represent a logical progression of actions based on the use of experiential data spanning manufacturing process validation, consistency in production, and characterization of relevant product properties/attributes, by multiple analytical means. This interactive process occurs in phases, varying in rigour. It is best described as encompassing a framework which starts with the implementation of realistic/practical operational quality limits, progressing to the establishment/adoption of more stringent specifications. The historical database is generated from preclinical, toxicology and early clinical lots. This supports the clinical development programme which, as it progresses, allows for further assay method validation/refinement, adoption/addition due to relevant or newly recognized product attributes or rejection due to irrelevance. In the next phase, (licensing/approval) specifications are set through extended experience and validation of both the preparative and analytical processes, to include availability of suitable reference standards and extensive product characterization throughout its proposed dating period. Subsequent to product approval, the incremental database of test results serves as a natural continuum for further evolving/refining specifications. While there is considerable latitude in the kinds of testing modalities finally adopted to establish product quality on a routine basis, for both drugs and drug products, it is important that the selection takes into consideration relevant (significant) product characteristics that appropriately reflect on identity, purity and potency.

  19. Nuclear reactor core assembly

    International Nuclear Information System (INIS)

    Baxi, C.B.

    1978-01-01

    The object of the present invention is to provide a fast reactor core assembly design for use with a fluid coolant such as liquid sodium or carbon monoxide incorporating a method of increasing the percentage of coolant flow though the blanket elements relative to the total coolant flow through the blanket and fuel elements during shutdown conditions without using moving parts. It is claimed that deterioration due to reactor radiation or temperature conditions is avoided and ready modification or replacement is possible. (U.K.)

  20. The core and cosmopolitans

    DEFF Research Database (Denmark)

    Dahlander, Linus; Frederiksen, Lars

    2012-01-01

    Users often interact and help each other solve problems in communities, but few scholars have explored how these relationships provide opportunities to innovate. We analyze the extent to which people positioned within the core of a community as well as people that are cosmopolitans positioned...... across multiple external communities affect innovation. Using a multimethod approach, including a survey, a complete database of interactions in an online community, content coding of interactions and contributions, and 36 interviews, we specify the types of positions that have the strongest effect...

  1. Monitoring an electric cable core

    International Nuclear Information System (INIS)

    Bhattacharya, S.; Marris, A.

    1984-01-01

    A method of, and apparatus for, continuously monitoring an advancing core having a continuous covering comprises directing X-ray radiation laterally towards the advancing covered core; continuously forming an X-ray image pattern of the advancing covered core and translating the image pattern into a visible image pattern; continuously transforming the visible pattern into a digital bit pattern; and processing the digital bit pattern using a microprocessor with interfacing electronics to provide an image profile of the advancing covered core and/or to provide analogue and/or digital signals indicative of the overall diameter and eccentricity of the covered core and of the thickness of the covering. (author)

  2. Gas core reactors for coal gasification

    International Nuclear Information System (INIS)

    Weinstein, H.

    1976-01-01

    The concept of using a gas core reactor to produce hydrogen directly from coal and water is presented. It is shown that the chemical equilibrium of the process is strongly in favor of the production of H 2 and CO in the reactor cavity, indicating a 98 percent conversion of water and coal at only 1500 0 K. At lower temperatures in the moderator-reflector cooling channels the equilibrium strongly favors the conversion of CO and additional H 2 O to CO 2 and H 2 . Furthermore, it is shown the H 2 obtained per pound of carbon has 23 percent greater heating value than the carbon so that some nuclear energy is also fixed. Finally, a gas core reactor plant floating in the ocean is conceptualized which produces H 2 , fresh water and sea salts from coal

  3. Statistical core design

    International Nuclear Information System (INIS)

    Oelkers, E.; Heller, A.S.; Farnsworth, D.A.; Kearfott, K.J.

    1978-01-01

    The report describes the statistical analysis of DNBR thermal-hydraulic margin of a 3800 MWt, 205-FA core under design overpower conditions. The analysis used LYNX-generated data at predetermined values of the input variables whose uncertainties were to be statistically combined. LYNX data were used to construct an efficient response surface model in the region of interest; the statistical analysis was accomplished through the evaluation of core reliability; utilizing propagation of the uncertainty distributions of the inputs. The response surface model was implemented in both the analytical error propagation and Monte Carlo Techniques. The basic structural units relating to the acceptance criteria are fuel pins. Therefore, the statistical population of pins with minimum DNBR values smaller than specified values is determined. The specified values are designated relative to the most probable and maximum design DNBR values on the power limiting pin used in present design analysis, so that gains over the present design criteria could be assessed for specified probabilistic acceptance criteria. The results are equivalent to gains ranging from 1.2 to 4.8 percent of rated power dependent on the acceptance criterion. The corresponding acceptance criteria range from 95 percent confidence that no pin will be in DNB to 99.9 percent of the pins, which are expected to avoid DNB

  4. PMMA/PMMA core-shell particles with ellipsoidal, fluorescent cores: accessing rotational dynamics.

    Science.gov (United States)

    Klein, Matthias K; Klinkenberg, Nele; Schuetter, Stefan; Saenger, Nicolai; Pfleiderer, Patrick; Zumbusch, Andreas

    2015-03-10

    For several decades, nonaqueous dispersions of PMMA particles have played an important role in colloid research. They have found application as colloidal model systems, which are used to probe glassy dynamics or to explore crystal nucleation. To date, most research has focused on spherical particles, in which only translational motion can be investigated. Recently, however, there has been a surge of interest in analyzing also rotational dynamics. In this contribution, we introduce a new class of core-shell particles, which can be used as rotational probes. The colloids described herein are composed of shape anisotropic, fluorescent cores covered with nonfluorescent PMMA shells. The core-shell particles are built up in four steps. In a first step, we produce fluorescent and photo-cross-linkable PMMA colloids. In the second step, these particles are thermomechanically elongated and fixed in defined ellipsoidal shapes by photo-cross-linking. Subsequently, we cover the cross-linked, fluorescent core with a nonfluorescent PMMA shell. The shape of the resulting core-shell colloids is tunable between the initial anisotropic and perfect spherical shape. For shaping, we apply a simple solvent swelling procedure. As one option, this method yields perfect PMMA spheres with ellipsoidal, fluorescent centers. We also report morphological particle characterization using various fluorescence microscopy techniques. Finally, we demonstrate that the rotational dynamics of individual colloids can be tracked and analyzed.

  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. 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...

  8. A review of the progress and pitfalls of FDA policy process: Planning a pathway for pharmaceutical interventions for hearing loss development.

    Science.gov (United States)

    Hammill, Tanisha L

    2017-06-01

    The Federal Food and Drug Administration, or FDA is generally considered a powerful gatekeeper, able to deliver or withhold life-saving cures and create or destroy economic windfalls. As the decades go by, and technologies, diseases, public health demands, and politics evolve, we can identify patterns of change, action and inter-action among some of these traditional stakeholders in the FDA's policy sphere. A careful examination of this agency's colorful history can shed light on central features of the agency's policy process, which has been quite receptive to its stakeholders and adaptive to change over the decades and, in turn, show the way for development in lanes which do not fit neatly into the current paradigms offered by the agency. This paper will explore the history of FDA policy process, through examination of seminal moments in FDA history, the prominent actors and focusing events within them, and the outcomes of those events, in an attempt to illuminate a pattern of behavior or processes by which a struggling field of pharmaceutical development such as interventions for hearing loss can advance. Copyright © 2016 Elsevier B.V. All rights reserved.

  9. A dual track system to give more-rapid access to new drugs: applying a systems mindset to the US food and drug administration (FDA).

    Science.gov (United States)

    Madden, Bartley J

    2009-02-01

    A widely applicable lesson learned from systems analysis is that a proposed change should always be studied in terms of value to the customer and not a gain in efficiency of any particular component of the system. A systems mindset reveals invalid assumptions that have caused the FDA to substitute its own needs for the needs of its customers (patients). Further, the key constraint to overall system improvement is the lack of consumer choice and competition due to FDA's monopoly over access to drugs. Therefore, we need legislation to implement a proposed dual track system for access to drugs that have successfully passed Phase I safety trials. On one track, an experimental drug would continue with conventional FDA clinical trials. On a new, free-to-choose track, patients, advised by their doctors, would make informed decisions about immediate access to not-yet-approved drugs. Internet access to a government-operated tradeoff evaluation database would provide patients and doctors with up-to-date information on all drug treatment outcomes for both tracks. Dual tracking is a dynamic process that overcomes the limitations of a static FDA regulatory process that ignores individual risk preferences.

  10. In vessel core melt progression phenomena

    International Nuclear Information System (INIS)

    Courtaud, M.

    1993-01-01

    For all light water reactor (LWR) accidents, including the so called severe accidents where core melt down can occur, it is necessary to determine the amount and characteristics of fission products released to the environment. For existing reactors this knowledge is used to evaluate the consequences and eventual emergency plans. But for future reactors safety authorities demand decrease risks and reactors designed in such a way that fission products are retained inside the containment, the last protective barrier. This requires improved understanding and knowledge of all accident sequences. In particular it is necessary to be able to describe the very complex phenomena occurring during in vessel core melt progression because they will determine the thermal and mechanical loads on the primary circuit and the timing of its rupture as well as the fission product source term. On the other hand, in case of vessel failure, knowledge of the physical and chemical state of the core melt will provide the initial conditions for analysis of ex-vessel core melt progression and phenomena threatening the containment. Finally a good understanding of in vessel phenomena will help to improve accident management procedures like Emergency Core Cooling System water injection, blowdown and flooding of the vessel well, with their possible adverse effects. Research and Development work on this subject was initiated a long time ago and is still in progress but now it must be intensified in order to meet the safety requirements of the next generation of reactors. Experiments, limited in scale, analysis of the TMI 2 accident which is a unique source of global information and engineering judgment are used to establish and assess physical models that can be implemented in computer codes for reactor accident analysis

  11. Core catcher for nuclear reactor core meltdown containment

    International Nuclear Information System (INIS)

    Driscoll, M.J.; Bowman, F.L.

    1978-01-01

    A bed of graphite particles is placed beneath a nuclear reactor core outside the pressure vessel but within the containment building to catch the core debris in the event of failure of the emergency core cooling system. Spray cooling of the debris and graphite particles together with draining and flooding of coolant fluid of the graphite bed is provided to prevent debris slump-through to the bottom of the bed

  12. Understanding core conductor fabrics

    International Nuclear Information System (INIS)

    Swenson, D E

    2011-01-01

    ESD Association standard test method ANSI/ESD STM2.1 - Garments (STM2.1), provides electrical resistance test procedures that are applicable for materials and garments that have surface conductive or surface dissipative properties. As has been reported in other papers over the past several years 1 fabrics are now used in many industries for electrostatic control purposes that do not have surface conductive properties and therefore cannot be evaluated using the procedures in STM2.1 2 . A study was conducted to compare surface conductive fabrics with samples of core conductor fibre based fabrics in order to determine differences and similarities with regards to various electrostatic properties. This work will be used to establish a new work item proposal within WG-2, Garments, in the ESD Association Standards Committee in the USA.

  13. Adult educators' core competences

    DEFF Research Database (Denmark)

    Wahlgren, Bjarne

    2016-01-01

    Abstract Which competences do professional adult educators need? This research note discusses the topic from a comparative perspective, finding that adult educators’ required competences are wide-ranging, heterogeneous and complex. They are subject to context in terms of national and cultural...... environment as well as the kind of adult education concerned (e.g. basic education, work-related education etc.). However, it seems that it is possible to identify certain competence requirements which transcend national, cultural and functional boundaries. This research note summarises these common or “core......” requirements, organising them into four thematic subcategories: (1) communicating subject knowledge; (2) taking students’ prior learning into account; (3) supporting a learning environment; and (4) the adult educator’s reflection on his or her own performance. At the end of his analysis of different competence...

  14. CORE annual report 2006

    International Nuclear Information System (INIS)

    Gut, A.

    2007-04-01

    This annual report for the Swiss Federal Office of Energy (SFOE) summarises the activities of the Swiss Federal Commission on Energy Research CORE in 2006. The six main areas of work during the period 2004 - 2007 are examined, including a review of the SFOE's energy research programme, a road-map for the way towards the realisation of a 2000-watt society, the formulation of an energy research concept for 2008 - 2011, international co-operation, the dissemination of information and the assessment of existing and new instruments. International activities and Switzerland's involvement in energy research within the framework of the International Energy Agency IEA are discussed. New and existing projects are listed and the work done at the Competence Centre for Energy and Mobility noted. The Swiss Technology Award 2007 is presented. Information supplied to interested bodies to help improve knowledge on research work being done and to help make discussions on future energy supply more objective is discussed

  15. In core system mapping reactor power distribution

    International Nuclear Information System (INIS)

    Yoriyaz, H.; Moreira, J.M.L.

    1989-01-01

    Based on the signals of SPND'S (Self Powered Neutron Detectors) distributed inside of a core, the spatial power distribution is obtained using the MAP program, developed in this work. The methodology applied in MAP program uses a least mean square technique to calculate expansion coefficients that depend on the SPND'S signals. The final power or neutron flux distribution is obtained by a combination of certains functions or expansion modes that are provided from diffusion calculation with the CITATION code. The MAP program is written in PASCAL language and will be used in IEA-R1 reactor for assisting its operation. (author) [pt

  16. Growth outside the core.

    Science.gov (United States)

    Zook, Chris; Allen, James

    2003-12-01

    Growth in an adjacent market is tougher than it looks; three-quarters of the time, the effort fails. But companies can change those odds dramatically. Results from a five-year study of corporate growth conducted by Bain & Company reveal that adjacency expansion succeeds only when built around strong core businesses that have the potential to become market leaders. And the best place to look for adjacency opportunities is inside a company's strongest customers. The study also found that the most successful companies were able to consistently, profitably outgrow their rivals by developing a formula for pushing out the boundaries of their core businesses in predictable, repeatable ways. Companies use their repeatability formulas to expand into any number of adjacencies. Some companies make repeated geographic moves, as Vodafone has done in expanding from one geographic market to another over the past 13 years, building revenues from $1 billion in 1990 to $48 billion in 2003. Others apply a superior business model to new segments. Dell, for example, has repeatedly adapted its direct-to-customer model to new customer segments and new product categories. In other cases, companies develop hybrid approaches. Nike executed a series of different types of adjacency moves: it expanded into adjacent customer segments, introduced new products, developed new distribution channels, and then moved into adjacent geographic markets. The successful repeaters in the study had two common characteristics. First, they were extraordinarily disciplined, applying rigorous screens before they made an adjacency move. This discipline paid off in the form of learning curve benefits, increased speed, and lower complexity. And second, in almost all cases, they developed their repeatable formulas by studying their customers and their customers' economics very, very carefully.

  17. 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

  18. Evaluation of Facebook and Twitter Monitoring to Detect Safety Signals for Medical Products: An Analysis of Recent FDA Safety Alerts.

    Science.gov (United States)

    Pierce, Carrie E; Bouri, Khaled; Pamer, Carol; Proestel, Scott; Rodriguez, Harold W; Van Le, Hoa; Freifeld, Clark C; Brownstein, John S; Walderhaug, Mark; Edwards, I Ralph; Dasgupta, Nabarun

    2017-04-01

    The rapid expansion of the Internet and computing power in recent years has opened up the possibility of using social media for pharmacovigilance. While this general concept has been proposed by many, central questions remain as to whether social media can provide earlier warnings for rare and serious events than traditional signal detection from spontaneous report data. Our objective was to examine whether specific product-adverse event pairs were reported via social media before being reported to the US FDA Adverse Event Reporting System (FAERS). A retrospective analysis of public Facebook and Twitter data was conducted for 10 recent FDA postmarketing safety signals at the drug-event pair level with six negative controls. Social media data corresponding to two years prior to signal detection of each product-event pair were compiled. Automated classifiers were used to identify each 'post with resemblance to an adverse event' (Proto-AE), among English language posts. A custom dictionary was used to translate Internet vernacular into Medical Dictionary for Regulatory Activities (MedDRA ® ) Preferred Terms. Drug safety physicians conducted a manual review to determine causality using World Health Organization-Uppsala Monitoring Centre (WHO-UMC) assessment criteria. Cases were also compared with those reported in FAERS. A total of 935,246 posts were harvested from Facebook and Twitter, from March 2009 through October 2014. The automated classifier identified 98,252 Proto-AEs. Of these, 13 posts were selected for causality assessment of product-event pairs. Clinical assessment revealed that posts had sufficient information to warrant further investigation for two possible product-event associations: dronedarone-vasculitis and Banana Boat Sunscreen--skin burns. No product-event associations were found among the negative controls. In one of the positive cases, the first report occurred in social media prior to signal detection from FAERS, whereas the other case

  19. Use of field-portable XRF analyzers for rapid screening of toxic elements in FDA-regulated products.

    Science.gov (United States)

    Palmer, Peter T; Jacobs, Richard; Baker, Peter E; Ferguson, Kelly; Webber, Siri

    2009-04-08

    Analytical instrumentation continues its amazing evolution, especially in regard to generating ever more sensitive, faster, and reliable measurements. Perhaps the most difficult challenges are making these instruments small enough to use in the field, equipping them with well-designed software that facilitates and simplifies their use by nonexperts while preserving enough of their analytical capabilities to render them useful for a wide variety of applications. Perhaps the most impressive and underappreciated example of instruments that meet these criteria are field-portable X-ray fluorescence (XRF) analyzers. In the past, these analyzers have been routinely used for environmental applications (lead in paint and soil, metal particulates in air samples collected onto filters), geology studies (ore and soil analysis, precious metal identification), and recycling industries (alloy identification). However, their use in the analysis of toxic elements in food, food ingredients, dietary supplements, and medicinal and herbal products, especially within the FDA and regulatory environments, has been surprisingly limited to date. Although XRF will not replace atomic spectrometry techniques such as ICP-MS for sub-parts per million level analyses, it offers a number of significant advantages including minimal sample preparation, high sample throughputs, rapid and definitive identification of many toxic elements, and accurate quantitative results. As should be obvious from many recent news reports on elevated levels of toxic elements in children's lunchboxes, toys, and supplements, field-portable XRF analyzers can fill a very important niche and are becoming increasingly popular for a wide variety of elemental analysis applications. This perspective begins with a brief review of the theory of XRF to highlight the underlying principle, instrumentation, and spectra. It includes a discussion of various analytical figures of merit of XRF to illustrate its strengths and limitations

  20. Community Pharmacists’ Classification of Prescription Drugs into an Expanded Class of Nonprescription Drugs under the FDA's Proposed NSURE Initiative

    Directory of Open Access Journals (Sweden)

    Ruchitbhai M. Shah

    2017-10-01

    Full Text Available Objectives: There has been considerable debate over the last few decades about creating a third class of drugs that would not require a prescription or not be available freely over the counter, but require a pharmacist’s consultation upon purchase. These debates reignited again in 2012, when the Food and Drug Administration (FDA held a hearing about a third class of drugs positioned as an expanded nonprescription drug class under the FDAs Nonprescription Safe-Use Regulatory Expansion (NSURE Initiative. The objective of this study was to determine which prescription drugs community pharmacists believe are acceptable additions to an expanded definition of nonprescription drugs that would be available pending pharmacists’ consultation with a patient. Methods: This cross-sectional study was conducted using a self-report, web-based survey administered to a national panel of community pharmacists. The survey contained a list of 24 current “prescription-only” drugs which may be potential candidates for an expanded nonprescription drug class, based on criteria outlined by the FDA, and questions related to respondent demographic and practice characteristics. The respondents were asked to indicate whether a particular drug should be marketed as a prescription drug, nonprescription drug or as part of an expanded non-prescription drug class. Descriptive analyses were conducted to determine the drugs that community pharmacists believed would be suitable additions to an expanded non-prescription drug class under the NSURE initiative. Results: 462 completed surveys were received. Most respondents indicated that clopidogrel bisulfate (85.3% and zolpidem (86.6% should continue to be dispensed as prescription drugs. Atorvastatin, metformin, and sildenafil (among others were considered appropriate to be marketed as an expanded nonprescription drug, in other words, dispensed without a prescription but upon pharmacist consultation. Desloratadine (64.6% and

  1. 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.

  2. 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.

  3. AGR core safety assessment methodologies

    International Nuclear Information System (INIS)

    McLachlan, N.; Reed, J.; Metcalfe, M.P.

    1996-01-01

    To demonstrate the safety of its gas-cooled graphite-moderated AGR reactors, nuclear safety assessments of the cores are based upon a methodology which demonstrates no component failures, geometrical stability of the structure and material properties bounded by a database. All AGRs continue to meet these three criteria. However, predictions of future core behaviour indicate that the safety case methodology will eventually need to be modified to deal with new phenomena. A new approach to the safety assessment of the cores is currently under development, which can take account of these factors while at the same time providing the same level of protection for the cores. This approach will be based on the functionality of the core: unhindered movement of control rods, continued adequate cooling of the fuel and the core, continued ability to charge and discharge fuel. (author). 5 figs

  4. Overview of core disruptive accidents

    International Nuclear Information System (INIS)

    Marchaterre, J.F.

    1977-01-01

    An overview of the analysis of core-disruptive accidents is given. These analyses are for the purpose of understanding and predicting fast reactor behavior in severe low probability accident conditions, to establish the consequences of such conditions and to provide a basis for evaluating consequence limiting design features. The methods are used to analyze core-disruptive accidents from initiating event to complete core disruption, the effects of the accident on reactor structures and the resulting radiological consequences are described

  5. FDA-approved drugs and other compounds tested as inhibitors of human glutathione transferase P1-1.

    Science.gov (United States)

    Musdal, Yaman; Hegazy, Usama M; Aksoy, Yasemin; Mannervik, Bengt

    2013-09-05

    Glutathione transferase P1-1 (GST P1-1) is often overexpressed in tumor cells and is regarded as a contributor to their drug resistance. Inhibitors of GST P1-1 are expected to counteract drug resistance and may therefore serve as adjuvants in the chemotherapy of cancer by increasing the efficacy of cytostatic drugs. Finding useful inhibitors among compounds used for other indications would be a shortcut to clinical applications and a search for GST P1-1 inhibitors among approved drugs and other compounds was therefore conducted. We tested 1040 FDA-approved compounds as inhibitors of the catalytic activity of purified human GST P1-1 in vitro. We identified chlorophyllide, merbromine, hexachlorophene, and ethacrynic acid as the most effective GST P1-1 inhibitors with IC50 values in the low micromolar range. For comparison, these compounds were even more potent in the inhibition of human GST A3-3, an enzyme implicated in steroid hormone biosynthesis. In distinction from the other inhibitors, which showed conventional inhibition patterns, the competitive inhibitor ethacrynic acid elicited strong kinetic cooperativity in the glutathione saturation of GST P1-1. Apparently, ethacrynic acid serves as an allosteric inhibitor of the enzyme. In their own right, the compounds investigated are less potent than desired for adjuvants in cancer chemotherapy, but the structures of the most potent inhibitors could serve as leads for the synthesis of more efficient adjuvants. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  6. 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.

  7. Derivative emission spectrofluorimetry: Application to the analysis of newly approved FDA combination of ibuprofen and famotidine in tablets.

    Science.gov (United States)

    Ragab, Marwa A A; El-Kimary, Eman I

    2015-09-01

    A new combination of ibuprofen (NSAID) and famotidine (H2 receptor antagonist) was recently approved by the FDA. It was formulated to relief pain while decreasing the risk of ulceration, which is a common problem for patients receiving NSAID. A rapid and simple derivative emission spectrofluorimetric method is proposed for the simultaneous analysis of this combination in their pharmaceutical preparation. The method is based upon measurement of the native fluorescence intensity of the two drugs at λex = 233 nm in acetonitrile. The emission data were differentiated using the first (D1) derivative technique. The plots of derivative fluorescence intensity versus concentration were rectilinear over a range of 2-35 and 0.4-8 µg/mL for both ibuprofen (IBU) and famotidine (FAM), respectively. The method was sensitive as the limits of detection were 0.51 and 0.12 µg/mL and limits of quantitation were 1.70 and 0.39 µg/mL, for IBU and FAM respectively. The proposed derivative emission spectrofluorimetric method was successfully applied for the determination of the two drugs in their synthetic mixtures and tablets with good accuracy and precision. The proposed method was validated as per ICH guidelines. Copyright © 2014 John Wiley & Sons, Ltd.

  8. The INTEGRAL Core Observing Programme

    DEFF Research Database (Denmark)

    Winkler, C.; Gehrels, N.; Lund, Niels

    1999-01-01

    The Core Programme of the INTEGRAL mission is defined as the portion of the scientific programme covering the guaranteed time observations for the INTEGRAL Science Working Team. This paper describes the current status of the Core Programme preparations and summarizes the key elements of the obser......The Core Programme of the INTEGRAL mission is defined as the portion of the scientific programme covering the guaranteed time observations for the INTEGRAL Science Working Team. This paper describes the current status of the Core Programme preparations and summarizes the key elements...

  9. Biochemistry Instrumentation Core Technology Center

    Data.gov (United States)

    Federal Laboratory Consortium — The UCLA-DOE Biochemistry Instrumentation Core Facility provides the UCLA biochemistry community with easy access to sophisticated instrumentation for a wide variety...

  10. TMI-2 core debris analysis

    International Nuclear Information System (INIS)

    Cook, B.A.; Carlson, E.R.

    1985-01-01

    One of the ongoing examination tasks for the damaged TMI-2 reactor is analysis of samples of debris obtained from the debris bed presently at the top of the core. This paper summarizes the results reported in the TMI-2 Core Debris Grab Sample Examination and Analysis Report, which will be available early in 1986. The sampling and analysis procedures are presented, and information is provided on the key results as they relate to the present core condition, peak temperatures during the transient, temperature history, chemical interactions, and core relocation. The results are then summarized

  11. Characterizing the Core via K-Core Covers

    NARCIS (Netherlands)

    Sanchez, S.M.; Borm, P.E.M.; Estevez, A.

    2013-01-01

    This paper extends the notion of individual minimal rights for a transferable utility game (TU-game) to coalitional minimal rights using minimal balanced families of a specific type, thus defining a corresponding minimal rights game. It is shown that the core of a TU-game coincides with the core of

  12. Final Technical Report

    Energy Technology Data Exchange (ETDEWEB)

    Schuur, Edward [Northern Arizona Univ., Flagstaff, AZ (United States); Luo, Yiqi [Univ. of Oklahoma, Norman, OK (United States)

    2016-12-01

    This final grant report is a continuation of the final grant report submitted for DE-SC0006982 as the Principle Investigator (Schuur) relocated from the University of Florida to Northern Arizona University. This report summarizes the original project goals, as well as includes new project activities that were completed in the final period of the project.

  13. Origin of metallic surface core-level shifts

    DEFF Research Database (Denmark)

    Aldén, Magnus; Skriver, Hans Lomholt; Abrikosov, I. A.

    1995-01-01

    The unique property of the open 4f energy shell in the lanthanide metals is used to show that the initial-state energy shift gives an insufficient description of surface core-level shifts. Instead a treatment, which fully includes the final-state screening, account for the experimentally observed...

  14. Computerized multiplexing and processing of in-core signals

    International Nuclear Information System (INIS)

    Meyer, J.

    1982-09-01

    After a presentation of the in-core instrumentation the main objectives of electric connection multiplexing are given. The conclusion of a study led to choose the multiplexing solution for the reactor building/electric building connections and to associate an information order management system based on the utilization of microprocessors. Finally, the control system (processors, organization, communication, language) is presented [fr

  15. Thermal Hydraulic Tests for Reactor Core Safety

    Energy Technology Data Exchange (ETDEWEB)

    Moon, S. K.; Baek, W. P.; Chun, S. Y. (and others)

    2007-06-15

    The main objectives of the present project are to resolve the current issues of reactor core thermal hydraulics, to develop an advanced measurement and analytical techniques, and to perform reactor core safety verification tests. 6x6 reflood experiments, various heat transfer experiments using Freon, and experiments on the spacer grids effects on the post-dryout are carried out using spacer grids developed in Korea in order to resolve the current issues of the reactor core thermal hydraulics. In order to develop a reflood heat transfer model, the detailed reflood phenomena are visualized and measured using round tube and 2x2 rod bundle. A detailed turbulent mixing phenomenon for subchannels is measured using advanced measurement techniques such as LDV and PIV. MARS and MATRA codes developed in Korea are assessed, verified and improved using the obtained experimental data. Finally, a systematic quality assurance program and experimental data generation system has been constructed in order to increase the reliability of the experimental data.

  16. Core skills assessment to improve mathematical competency

    Science.gov (United States)

    Carr, Michael; Bowe, Brian; Fhloinn, Eabhnat Ní

    2013-12-01

    Many engineering undergraduates begin third-level education with significant deficiencies in their core mathematical skills. Every year, in the Dublin Institute of Technology, a diagnostic test is given to incoming first-year students, consistently revealing problems in basic mathematics. It is difficult to motivate students to address these problems; instead, they struggle through their degree, carrying a serious handicap of poor core mathematical skills, as confirmed by exploratory testing of final year students. In order to improve these skills, a pilot project was set up in which a 'module' in core mathematics was developed. The course material was basic, but 90% or higher was required to pass. Students were allowed to repeat this module throughout the year by completing an automated examination on WebCT populated by a question bank. Subsequent to the success of this pilot with third-year mechanical engineering students, the project was extended to five different engineering programmes, across three different year-groups. Full results and analysis of this project are presented, including responses to interviews carried out with a selection of the students involved.

  17. IN-CORE FUEL MANAGEMENT: PWR Core Calculations Using MCRAC

    Science.gov (United States)

    PetroviĆ, B. G.

    1991-01-01

    The following sections are included: * INTRODUCTION * IN-CORE FUEL MANAGEMENT CALCULATIONS * In-Core Fuel Management * Methodological Problems of In-Core Fuel Management * In-Core Fuel Management Analytical Tools * PENN STATE FUEL MANAGEMENT PACKAGE * Penn State Fuel Management Package (PFMP) * Assembly Data Description (ADD) * Linking PSU-LEOPARD and MCRAC: An Example * MULTICYCLE REACTOR ANALYSIS CODE (MCRAC) * Main Features and Options of MCRAC code * Core geometry * Diffusion equations * 1.5-group model * Multicycle neutronic analysis * Multicycle cost analysis * Criticality search * Power-dependent xenon feedback calculations * Control rod and burnable absorber simulation * Search for LP with flat BOC power distribution * Artificial ADD option * Variable dimensioning technique * RBI version of MCRAC code * Programming changes in PC version * Fuel interchange option * MCRAC Input/Output * General input description * Sample input * Sample output * EXPERIENCE WITH MCRAC CODE * CONCLUSIONS * REFERENCES

  18. Emergency core cooling system

    International Nuclear Information System (INIS)

    Arai, Kenji; Oikawa, Hirohide.

    1990-01-01

    The device according to this invention can ensure cooling water required for emerency core cooling upon emergence such as abnormally, for example, loss of coolant accident, without using dynamic equipments such as a centrifugal pump or large-scaled tank. The device comprises a pressure accumulation tank containing a high pressure nitrogen gas and cooling water inside, a condensate storage tank, a pressure suppression pool and a jet stream pump. In this device there are disposed a pipeline for guiding cooling water in the pressure accumulation tank as a jetting water to a jetting stream pump, a pipeline for guiding cooling water stored in the condensate storage tank and the pressure suppression pool as pumped water to the jetting pump and, further, a pipeline for guiding the discharged water from the jet stream pump which is a mixed stream of pumped water and jetting water into the reactor pressure vessel. In this constitution, a sufficient amount of water ranging from relatively high pressure to low pressure can be supplied into the reactor pressure vessel, without increasing the size of the pressure accumulation tank. (I.S.)

  19. Uncertainty evaluation of fast reactor core seismic response

    International Nuclear Information System (INIS)

    Martelli, A.; Forni, M.; Amendola, A.; Lucia, A.C.; Maresca, G.

    1983-01-01

    Response Surface Methodology (RSM) has been applied to the evaluation of the uncertainties on the seismic behaviour of a fast reactor core. For this study preliminary data concerning the Italian PEC reactor test facility have been used. The structural dynamic analysis has been performed by means of the SAP IV code for the whole reactor block and CORALIE for the core. Once a certain acceleration time history at the ground has been assumed, the characteristics of the acceleration time-history at the core support grid, related to the vessel-core dynamic interaction, the reactor vessel stiffness, the frequency response, damping and impact coefficients of the core elements, and the number of core element rows assumed in the non-linear core calculations have been identified as the major contributors to the overall uncertainty. For each element type the responses calculated with CORALIE have been approximated by means of polynomial functions, whose adequacy in the variable space investigated has been tested by means of a further set of dynamic calculations. Finally the input uncertainties have been propagated by a Monte Carlo routine (MUP) under different assumptions to assess the sensitivity of the output distribution with respect to the kind of input probability distributions. The aim of this latter analysis step is the proposal of an adequate approach for verifying that the control rods succeed at a high probability to fall inside their guide-tubes in the case of an earth-quake, so that the reactor can be safely shut-down. The paper describes the details of the study and demonstrates RSM adequacy for the analysis of the input uncertainty effects on the core seismic response. It also shows that the core element frequencies and damping coefficients, as well as the vessel-core dynamic interaction parameters, are the main variables affecting such response, which therefore need a sufficiently precise definition. (orig.)

  20. Final Focus Test Stand final report

    CERN Document Server

    Jeremie, A; Burrows, P

    2013-01-01

    Future Linear colliders will need particle beam sizes in the nanometre range. The beam also needs to be stable all along the beam line and especially at the Final Focus section. A dedicated Final Focus test stand has been used for this study and is comprised of several sub-parts. First there is the Stabilisation/Isolation system with sensors and actuators stabilizing down to sub-nanometre level. Then the Magnet itself needs to comply with very specific design constraints. In addition to the mechanical items, the beam can be stabilized acting on the trajectory directly and Beam-based controls have been developed and tested on different accelerator facilities.