WorldWideScience

Sample records for regulation current evidence

  1. Audit Risk Assessment in the Light of Current European Regulations

    Directory of Open Access Journals (Sweden)

    Ciprian-Costel Munteanu

    2015-06-01

    Full Text Available Recent European reforms on audit regulations have been motivated by efforts to increase audit quality, functioning and performance. We believe the adoption of Directive 2014/56 and Regulation 537/2014 strengthened the role of independent audit and risk committees, which will positively contribute towards audit quality. This paper aims to critically assess the status quo of audit risk assessment in current European standards and regulations, by conducting a theoretical analysis of different aspects of audit risk. Our main objective is to stress the importance of detecting inherent and control risk, which lead to material misstatement at the assertion level. They need to be assessed so as to determine the nature, timing and extent of further audit procedures necessary to obtain sufficient appropriate audit evidence. These pieces of evidence enable the auditor to express an opinion on the financial statements at an acceptably low level of audit risk. Therefore, we point to the fact that researchers as well as practitioners and policymakers have to be careful when using audit tools and assessing risk levels, as their conclusions continuously shape the regulations.

  2. Labelling of electronic cigarettes: regulations and current practice.

    Science.gov (United States)

    Buonocore, Federico; Marques Gomes, Ana C N; Nabhani-Gebara, Shereen; Barton, Stephen J; Calabrese, Gianpiero

    2017-01-01

    Over the past decade e-cigarettes have established themselves in the global market. E-cigarettes triggered much interest in relation to their content and efficacy as smoking cessation tools, but less attention has been paid to users and environmental safety warnings and guidance. Several regulations have been introduced to promote their safe handling and disposal. From May 2016, liquids and cartridges will be regulated by European Community Directives (ECDs) 2001/83/EC and 93/42/EEC, or 2014/40/EU if marketed as tobacco-related products. Currently, manufacturers and distributors must abide by the Chemical (Hazard Information and Packaging for Supply) Regulations 2009 (CHIP) or Classification, Labelling and Packaging Regulations (CLP), the latter replacing CHIP in June 2015. In this work, the compliance of marketed e-liquids and e-cigarettes with current European Union and UK legislations is assessed. E-liquids and e-cigarettes (21 and 9 brands, respectively) were evaluated. Evidence of non-compliance was found in relation to the CHIP/CLP toxic (13%) and environmental (37%) pictograms, tactile warning (23%), nominal amount of solution (30%), supplier contact telephone number and address (40%). None of the evaluated e-cigarettes displayed information on the correct disposal/recycling of batteries in line with the ECD 2006/66/EC. More stringent enforcement of regulations is needed to ensure not only the user's safety and awareness, but also the safeguarding of the environment. 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/.

  3. Herbal Supplements for Prostate Enlargement: Current State of the Evidence.

    Science.gov (United States)

    Nabavizadeh, Reza; Zangi, Mahdi; Kim, Michelle M; Yavari Bejestani, Maryam; Tabatabaei, Shahin

    2018-02-01

    To provide a comprehensive review of the current state of herbal supplement market for lower urinary tract symptoms (LUTS) and correlate the ingredients of each product with available scientific evidence. Twenty-seven products from Amazon.com that were advertised as herbal supplements for LUTS and had listed their active ingredients were selected. Active ingredients were reviewed on Google Scholar. Product price, warranty, and consumer review information were also collected. A total of 58 unique active ingredients were identified. The mean number of ingredients was 8.26 (standard deviation 5.25). Whereas 17 (63%) products had an ingredient with a systematic review to support their use, 20 (74%) had an ingredient with conflicting evidence based on systematic reviews. Out of the supplements that contained ingredients supported by literature, all (100%) products simultaneously had other ingredients with no, conflicting, or refuting evidence. There was no (0%) product that contained only scientifically proven ingredients. There is no scientific study to evaluate these supplements as a whole. Despite the widespread use of herbal supplements for LUTS, there is scant scientific evidence to support their safety and efficacy. Lack of adequate regulation and government support for research and development are some of the factors that disincentivize researchers to study safety and efficacy of these products. We encourage physicians to warn their patients on the lack of adequate evidence to support the safety and efficacy of many of these supplements. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Voltage-regulating constant-current sources in a linear induction accelerator

    International Nuclear Information System (INIS)

    Zhao Juan; Cao Kefeng; Deng Jianjun; Zhu Lijun; Yang Jia; Ye Chao; Huang Bin; Cao Ningxiang; Dong Jinxuan; Zhang Jichang; Yu Zhiguo; Chen Min

    2002-01-01

    Constant-current Sources are one of key units in a linear induction accelerator. The requirements for the sources are to supply stable direct current of high power for the induction coil, be easy to computer-control and highly stable and reliable. Applying the technique of linear current source regulating in series, the primary voltage of the power transformer is regulated through an MJYS-JL-350A type three-phase alterative voltage-regulating module. The output current variation is 300-500 A when the load variation is 0.06-0.1 Ω and the voltage drop of the regulator tube is controlled within 8 V±2V when the variation of mains voltage is in ±10%. Both the current ripple and stability meet the technical requirements. The constant-current sources are controlled through an industrial controller. For each of the constant-current sources has a smallest system comprised of 8051 which is communication-controlled through a RS-485 interface, the sources can be controlled remotely

  5. Could Regulator Materialize Potential Demand for Islamic Securities? Evidence from Indonesia

    Directory of Open Access Journals (Sweden)

    Bayu Kariastanto

    2012-01-01

    Full Text Available Objective – The objective of this paper is to provide a discussion whether Islamic securities enjoy larger demands than conventional securities. This paper also investigate whether regulator could effectively take a role in materializing demands for Islamic securities and whether regulator declaration is more convincing than sharia compliance declaration by another institution.Methods - We employ differences in differences (DID regression to see the immediate, medium, and long term market response to this announcement. We also estimate cumulative abnormal returns by employing the standard market model for the robustness test.Results - We find that market reacts to sharia compliance declaration by regulator in the long-run, hence potential demands are realized and the Islamic securities will enjoy greater market power. We also provide evidence that Islamic investors are not too strict in screening Islamic securities and are willing to accept different opinions regarding sharia compliance.Conclusion - This finding could explain why Islamic finance is still growing rapidly even though there are critiques in the genuineness of sharia compliance of the current Islamic financial products/services.Keywords: Regulator, Islamic securities, sharia compliance, demand, investor confidence

  6. Advancing Evidence Based Policymaking and Regulation to Ensure ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Advancing Evidence Based Policymaking and Regulation to Ensure Greater ... which is Communications Policy Research South (CPRsouth), a yearly conference that ... policy intellectuals through tutorials for young scholars and internships.

  7. Current perspectives on shoot branching regulation

    Directory of Open Access Journals (Sweden)

    Cunquan YUAN,Lin XI,Yaping KOU,Yu ZHAO,Liangjun ZHAO

    2015-03-01

    Full Text Available Shoot branching is regulated by the complex interactions among hormones, development, and environmental factors. Recent studies into the regulatory mecha-nisms of shoot branching have focused on strigolactones, which is a new area of investigation in shoot branching regulation. Elucidation of the function of the D53 gene has allowed exploration of detailed mechanisms of action of strigolactones in regulating shoot branching. In addition, the recent discovery that sucrose is key for axillary bud release has challenged the established auxin theory, in which auxin is the principal agent in the control of apical dominance. These developments increase our understan-ding of branching control and indicate that regulation of shoot branching involves a complex network. Here, we first summarize advances in the systematic regulatory network of plant shoot branching based on current information. Then we describe recent developments in the synthesis and signal transduction of strigolactones. Based on these considerations, we further summarize the plant shoot branching regulatory network, including long distance systemic signals and local gene activity mediated by strigolactones following perception of external envi-ronmental signals, such as shading, in order to provide a comprehensive overview of plant shoot branching.

  8. Enhanced current and voltage regulators for stand-alone applications

    DEFF Research Database (Denmark)

    Federico, de Bosio; Pastorelli, Michele; Antonio DeSouza Ribeiro, Luiz

    2016-01-01

    State feedback decoupling permits to achieve a better dynamic response for Voltage Source in stand-alone applications. The design of current and voltage regulators is performed in the discrete-time domain since it provides better accuracy and allows direct pole placement. As the attainable...... bandwidth of the current loop is mainly limited by computational and PWM delays, a lead compensator structure is proposed to overcome this limitation. The design of the voltage regulator is based on the Nyquist criterion, verifying to guarantee a high sensitivity peak. Discrete-time domain implementation...

  9. Institutional Ethics Committee Regulations and Current Updates in India.

    Science.gov (United States)

    Mahuli, Amit V; Mahuli, Simpy A; Patil, Shankargouda; Bhandi, Shilpa

    2017-08-01

    The aim of the review is to provide current updates on regulations for ethics committees and researchers in India. Ethical dilemmas in research since time immemorial have been a major concern for researchers worldwide. The question "what makes clinical research ethical" is significant and difficult to answer as multiple factors are involved. The research involving human participants in clinical trials should follow the required rules, regulations, and guidelines in one's own country. It is a dynamic process, and updates have to be learned by researcher and committee members. The review highlights the ethical regulation from the Drug Controller General of India, Clinical Trial Registry of India, and Indian Council of Medical Research guidelines. In this article, the updates on Indian scenario of the Ethical Committee and guidelines are compiled. The review comes handy for clinical researchers and ethics committee members in academic institutions to check on the current updates and keep abreast with the knowledge on regulations of ethics in India.

  10. Overview of the current National Primary Drinking Water Regulations and regulation development process

    International Nuclear Information System (INIS)

    Cotruvo, J.A.; Regelski, M.

    1989-01-01

    The promulgation of the National Primary Drinking Water Regulations (NPDWR) follows specific steps. First, the Advance Notice of Proposed Rule Making (ANPRM) is published. Second, the EPA, as mandated by the SDWA Amendments, proposes maximum contaminant levels (MCLs), (enforceable standards) and maximum contaminant level goals (MCLGs) simultaneously. The Office of Drinking Water developed a six-phase schedule that has attempted to parallel the SDWA-specified deadlines: Phase I - Voltile organic chemicals - July 8, 1987; Phase II - Synthetic organic chemicals and inorganic chemicals - June 1989, microbials and surface water treatment - June 1989, and Lead/copper - December 1988; Phase III - Radionuclides - December 1988; Phase IV - Disinfectants and disinfection by-products - June 1989; Phase V - Other inorganic chemicals, synthetic organic chemicals, and pesticides - June 1989; and Phase VI - 25 additional chemicals - January 199. In selecting contaminants for regulation, the most relevant criteria are (1) potential health risk; (2) ability to detect a contaminant in the drinking water; and (3) occurrence or potential occurrence in drinking water. The EPA uses a three category approach for setting maximum contaminant level goals for carcinogens: Category I, strong evidence of carcinogenicity-zero; Category II, equivocal evidence - reference dose (RfD) approach or 0.00001 to 0.000001 cancer risk range; and Category III, inadequate or no evidence from animal studies - RfD approach. 10 refs., 5 tabs

  11. Safety of Transcranial Direct Current Stimulation: Evidence Based Update 2016.

    Science.gov (United States)

    Bikson, Marom; Grossman, Pnina; Thomas, Chris; Zannou, Adantchede Louis; Jiang, Jimmy; Adnan, Tatheer; Mourdoukoutas, Antonios P; Kronberg, Greg; Truong, Dennis; Boggio, Paulo; Brunoni, André R; Charvet, Leigh; Fregni, Felipe; Fritsch, Brita; Gillick, Bernadette; Hamilton, Roy H; Hampstead, Benjamin M; Jankord, Ryan; Kirton, Adam; Knotkova, Helena; Liebetanz, David; Liu, Anli; Loo, Colleen; Nitsche, Michael A; Reis, Janine; Richardson, Jessica D; Rotenberg, Alexander; Turkeltaub, Peter E; Woods, Adam J

    2016-01-01

    This review updates and consolidates evidence on the safety of transcranial Direct Current Stimulation (tDCS). Safety is here operationally defined by, and limited to, the absence of evidence for a Serious Adverse Effect, the criteria for which are rigorously defined. This review adopts an evidence-based approach, based on an aggregation of experience from human trials, taking care not to confuse speculation on potential hazards or lack of data to refute such speculation with evidence for risk. Safety data from animal tests for tissue damage are reviewed with systematic consideration of translation to humans. Arbitrary safety considerations are avoided. Computational models are used to relate dose to brain exposure in humans and animals. We review relevant dose-response curves and dose metrics (e.g. current, duration, current density, charge, charge density) for meaningful safety standards. Special consideration is given to theoretically vulnerable populations including children and the elderly, subjects with mood disorders, epilepsy, stroke, implants, and home users. Evidence from relevant animal models indicates that brain injury by Direct Current Stimulation (DCS) occurs at predicted brain current densities (6.3-13 A/m(2)) that are over an order of magnitude above those produced by conventional tDCS. To date, the use of conventional tDCS protocols in human trials (≤40 min, ≤4 milliamperes, ≤7.2 Coulombs) has not produced any reports of a Serious Adverse Effect or irreversible injury across over 33,200 sessions and 1000 subjects with repeated sessions. This includes a wide variety of subjects, including persons from potentially vulnerable populations. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. The current evidence and implications of lingual orthodontics

    Directory of Open Access Journals (Sweden)

    Pratap Saini

    2016-01-01

    Full Text Available The purpose of this review is to investigate the current evidence and implications of lingual orthodontics. The electronic database search was done on PubMed, Cochrane Library, Embase, EBSCOhost, Web of Knowledge, and Google Scholar reporting on appliance design, bonding, and laboratory setup, biomechanics, survey studies, case reports, and treatment outcomes to find the current evidence of lingual orthodontics. The evidence available on lingual orthodontics traces a very clear and predictable pattern. The 80′s was devoted to the limitation and progression of the concept; the 90′s to the comparison between labial and lingual and the evolution of laboratory technique and bracket system. The last decade focuses on innovations, the predictability of outcomes, the impact of white spot lesion, and the patient acceptability. This review also shows that biomechanical principles of lingual orthodontics are well understood and established today, any case that can be treated with labial orthodontic appliance, can also be treated effectively with lingual orthodontic appliance as the completely customized lingual appliance can provide predetermined treatment outcome.

  13. Sulfonylureas in type 2 diabetes mellitus: current evidence, conflicts ...

    African Journals Online (AJOL)

    Introduction: We sought to explore the current state of evidence on sulfonylurea therapy in type 2 diabetes mellitus (T2DM) and critically examine the recommendations of major practice guidelines,and the overall ramifications of the issues thereof in current clinical practice. Method: We searched PUBMED, MEDLINE and ...

  14. Review of the current state of UAV regulations

    NARCIS (Netherlands)

    Stöcker, Elvira Claudia; Bennett, Rohan; Nex, Francesco; Gerke, Markus; Zevenbergen, Jaap

    2017-01-01

    UAVs-unmanned aerial vehicles-facilitate data acquisition at temporal and spatial scales that still remain unachievable for traditional remote sensing platforms. However, current legal frameworks that regulate UAVs present significant barriers to research and development. To highlight the

  15. Role of plasma membrane-associated AKAPs for the regulation of cardiac IK1 current by protein kinase A.

    Science.gov (United States)

    Seyler, Claudia; Scherer, Daniel; Köpple, Christoph; Kulzer, Martin; Korkmaz, Sevil; Xynogalos, Panagiotis; Thomas, Dierk; Kaya, Ziya; Scholz, Eberhard; Backs, Johannes; Karle, Christoph; Katus, Hugo A; Zitron, Edgar

    2017-05-01

    The cardiac I K1 current stabilizes the resting membrane potential of cardiomyocytes. Protein kinase A (PKA) induces an inhibition of I K1 current which strongly promotes focal arrhythmogenesis. The molecular mechanisms underlying this regulation have only partially been elucidated yet. Furthermore, the role of A-kinase anchoring proteins (AKAPs) in this regulation has not been examined to date. The objective of this project was to elucidate the molecular mechanisms underlying the inhibition of I K1 by PKA and to identify novel molecular targets for antiarrhythmic therapy downstream β-adrenoreceptors. Patch clamp and voltage clamp experiments were used to record currents and co-immunoprecipitation, and co-localization experiments were performed to show spatial and functional coupling. Activation of PKA inhibited I K1 current in rat cardiomyocytes. This regulation was markedly attenuated by disrupting PKA-binding to AKAPs with the peptide inhibitor AKAP-IS. We observed functional and spatial coupling of the plasma membrane-associated AKAP15 and AKAP79 to Kir2.1 and Kir2.2 channel subunits, but not to Kir2.3 channels. In contrast, AKAPyotiao had no functional effect on the PKA regulation of Kir channels. AKAP15 and AKAP79 co-immunoprecipitated with and co-localized to Kir2.1 and Kir2.2 channel subunits in ventricular cardiomyocytes. In this study, we provide evidence for coupling of cardiac Kir2.1 and Kir2.2 subunits with the plasma membrane-bound AKAPs 15 and 79. Cardiac membrane-associated AKAPs are a functionally essential part of the regulatory cascade determining I K1 current function and may be novel molecular targets for antiarrhythmic therapy downstream from β-adrenoreceptors.

  16. Design of Current-Controller with PR-regulator for LCL-Filter Based Grid-Connected Converter

    DEFF Research Database (Denmark)

    Zeng, Guohong; Rasmussen, Tonny Wederberg

    2010-01-01

    In the application of LCL-filter based converters, the structure and parameters of current-controller is very important for the system stability and output current quality. This paper presents a filter-capacitor current feedback control scheme for grid-connected converter. The controller...... is consisted of a proportional-resonance regulator and a proportional regulator. Unlike the existing control strategy with unit capacitor current feedback, the proposed method applies the proportional regulator to the feedback path, which can decouple these two regulators, and simplify the tuning process...... of the control strategy and the proposed current controller design method are verified by the simulation results of a 50kVA grid-connected inverter....

  17. On-line monitoring of base current and forward emitter current gain of the voltage regulator's serial pnp transistor in a radiation environment

    Directory of Open Access Journals (Sweden)

    Vukić Vladimir Đ.

    2012-01-01

    Full Text Available A method of on-line monitoring of the low-dropout voltage regulator's operation in a radiation environment is developed in this paper. The method had to enable detection of the circuit's degradation during exploitation, without terminating its operation in an ionizing radiation field. Moreover, it had to enable automatic measurement and data collection, as well as the detection of any considerable degradation, well before the monitored voltage regulator's malfunction. The principal parameters of the voltage regulator's operation that were monitored were the serial pnp transistor's base current and the forward emitter current gain. These parameters were procured indirectly, from the data on the voltage regulator's load and quiescent currents. Since the internal consumption current in moderately and heavily loaded devices was used, the quiescent current of a negligibly loaded voltage regulator of the same type served as a reference. Results acquired by on-line monitoring demonstrated marked agreement with the results acquired from examinations of the voltage regulator's maximum output current and minimum dropout voltage in a radiation environment. The results were particularly consistent in tests with heavily loaded devices. Results obtained for moderately loaded voltage regulators and the risks accompanying the application of the presented method, were also analyzed.

  18. Review of the Current State of UAV Regulations

    Directory of Open Access Journals (Sweden)

    Claudia Stöcker

    2017-05-01

    Full Text Available UAVs—unmanned aerial vehicles—facilitate data acquisition at temporal and spatial scales that still remain unachievable for traditional remote sensing platforms. However, current legal frameworks that regulate UAVs present significant barriers to research and development. To highlight the importance, impact, and diversity of UAV regulations, this paper provides an exploratory investigation of UAV regulations on the global scale. For this, the methodological approach consists of a research synthesis of UAV regulations, including a thorough literature review and a comparative analysis of national regulatory frameworks. Similarities and contrasting elements in the various national UAV regulations are explored including their statuses from the perspectives of past, present, and future trends. Since the early 2000s, countries have gradually established national legal frameworks. Although all UAV regulations have one common goal—minimizing the risks to other airspace users and to both people and property on the ground—the results reveal distinct variations in all the compared variables. Furthermore, besides the clear presence of legal frameworks, market forces such as industry design standards and reliable information about UAVs as public goods are expected to shape future developments.

  19. Audit Risk Assessment in the Light of Current European Regulations

    OpenAIRE

    Ciprian-Costel Munteanu

    2015-01-01

    Recent European reforms on audit regulations have been motivated by efforts to increase audit quality, functioning and performance. We believe the adoption of Directive 2014/56 and Regulation 537/2014 strengthened the role of independent audit and risk committees, which will positively contribute towards audit quality. This paper aims to critically assess the status quo of audit risk assessment in current European standards and regulations, by conducting a theoretical analysis of different as...

  20. Current clinical evidence on pioglitazone pharmacogenomics

    Directory of Open Access Journals (Sweden)

    Marina eKawaguchi-Suzuki

    2013-11-01

    Full Text Available Pioglitazone is the most widely used thiazolidinedione and acts as an insulin-sensitizer through activation of the Peroxisome Proliferator-Activated Receptor-γ (PPARγ. Pioglitazone is approved for use in the management of type 2 diabetes mellitus, but its use in other therapeutic areas is increasing due to pleiotropic effects. In this hypothesis article, the current clinical evidence on pioglitazone pharmacogenomics is summarized and related to variability in pioglitazone response. How genetic variation in the human genome affects the pharmacokinetics and pharmacodynamics of pioglitazone was examined. For pharmacodynamic effects, hypoglycemic and anti-atherosclerotic effects, risks of fracture or edema, and the increase in body mass index in response to pioglitazone based on genotype were examined. The genes CYP2C8 and PPARG are the most extensively studied to date and selected polymorphisms contribute to respective variability in pioglitazone pharmacokinetics and pharmacodynamics. We hypothesized that genetic variation in pioglitazone pathway genes contributes meaningfully to the clinically observed variability in drug response. To test the hypothesis that genetic variation in PPARG associates with variability in pioglitazone response, we conducted a meta-analysis to synthesize the currently available data on the PPARG p.Pro12Ala polymorphism. The results showed that PPARG 12Ala carriers had a more favorable change in fasting blood glucose from baseline as compared to patients with the wild-type Pro12Pro genotype (p=0.018. Unfortunately, findings for many other genes lack replication in independent cohorts to confirm association; further studies are needed. Also, the biological functionality of these polymorphisms is unknown. Based on current evidence, we propose that pharmacogenomics may provide an important tool to individualize pioglitazone therapy and better optimize therapy in patients with T2DM or other conditions for which pioglitazone

  1. Current regulator for the stabilization of an electrostatic Van de Graaff generator

    International Nuclear Information System (INIS)

    Gabet, A.; Taieb, J.

    1953-01-01

    In a previous report (CEA report number 46) we described a current regulator destined to enslave the current of charge of the strap of a model of Van de Graaff. We will now describe the regulator destined to the 5 MeV Van de Graaff built in the Nuclear center of Saclay. (author) [fr

  2. Environmental regulations and industrial competitiveness: evidence from China

    NARCIS (Netherlands)

    S. Stavropoulos (Spyridon); R.S. Wall (Ronald); Xu, Y. (Yuanze)

    2017-01-01

    textabstractEconomic activities are closely related to real-world environmental issues. Currently, more attention is paid to the association between environmental regulations and industrial competitiveness (IC) because of pressures on economic development and environmental protection. In this study,

  3. Regulated-current dc power supply for gaseous-discharge lamps

    Science.gov (United States)

    Freeman, W.; Huguenin, D.

    1970-01-01

    Controlled current source having a high output resistance feeds continuous-flow hydrogen lamps in vacuum-ultraviolet photometric equipment. The power supply, also used with low-pressure sealed lamps, has a short recovery time and smooth regulation without overshoot.

  4. β-Secretase BACE1 regulates hippocampal and reconstituted M-currents in a β-subunit-like fashion.

    Science.gov (United States)

    Hessler, Sabine; Zheng, Fang; Hartmann, Stephanie; Rittger, Andrea; Lehnert, Sandra; Völkel, Meike; Nissen, Matthias; Edelmann, Elke; Saftig, Paul; Schwake, Michael; Huth, Tobias; Alzheimer, Christian

    2015-02-25

    The β-secretase BACE1 is widely known for its pivotal role in the amyloidogenic pathway leading to Alzheimer's disease, but how its action on transmembrane proteins other than the amyloid precursor protein affects the nervous system is only beginning to be understood. We report here that BACE1 regulates neuronal excitability through an unorthodox, nonenzymatic interaction with members of the KCNQ (Kv7) family that give rise to the M-current, a noninactivating potassium current with slow kinetics. In hippocampal neurons from BACE1(-/-) mice, loss of M-current enhanced neuronal excitability. We relate the diminished M-current to the previously reported epileptic phenotype of BACE1-deficient mice. In HEK293T cells, BACE1 amplified reconstituted M-currents, altered their voltage dependence, accelerated activation, and slowed deactivation. Biochemical evidence strongly suggested that BACE1 physically associates with channel proteins in a β-subunit-like fashion. Our results establish BACE1 as a physiologically essential constituent of regular M-current function and elucidate a striking new feature of how BACE1 impacts on neuronal activity in the intact and diseased brain. Copyright © 2015 the authors 0270-6474/15/353298-14$15.00/0.

  5. Pacemaker neuron and network oscillations depend on a neuromodulator-regulated linear current

    Directory of Open Access Journals (Sweden)

    Shunbing Zhao

    2010-05-01

    Full Text Available Linear leak currents have been implicated in the regulation of neuronal excitability, generation of neuronal and network oscillations, and network state transitions. Yet, few studies have directly tested the dependence of network oscillations on leak currents or explored the role of leak currents on network activity. In the oscillatory pyloric network of decapod crustaceans neuromodulatory inputs are necessary for pacemaker activity. A large subset of neuromodulators is known to activate a single voltage-gated inward current IMI, which has been shown to regulate the rhythmic activity of the network and its pacemaker neurons. Using the dynamic clamp technique, we show that the crucial component of IMI for the generation of oscillatory activity is only a close-to-linear portion of the current-voltage relationship. The nature of this conductance is such that the presence or the absence of neuromodulators effectively regulates the amount of leak current and the input resistance in the pacemaker neurons. When deprived of neuromodulatory inputs, pyloric oscillations are disrupted; yet, a linear reduction of the total conductance in a single neuron within the pacemaker group recovers not only the pacemaker activity in that neuron, but also leads to a recovery of oscillations in the entire pyloric network. The recovered activity produces proper frequency and phasing that is similar to that induced by neuromodulators. These results show that the passive properties of pacemaker neurons can significantly affect their capacity to generate and regulate the oscillatory activity of an entire network, and that this feature is exploited by neuromodulatory inputs.

  6. Associations Between Childhood Abuse, Posttraumatic Stress Disorder, and Implicit Emotion Regulation Deficits: Evidence From a Low-Income, Inner-City Population.

    Science.gov (United States)

    Powers, Abigail; Etkin, Amit; Gyurak, Anett; Bradley, Bekh; Jovanovic, Tanja

    2015-01-01

    Childhood abuse is associated with a wide range of negative outcomes, including increased risk for development of emotion dysregulation and psychopathology, such as posttraumatic stress disorder (PTSD). The goal of the present study was to examine associations between child abuse, PTSD symptoms, and performance on an emotional conflict regulation task that assesses implicit emotion regulation abilities. The sample consisted of 67 (94% African American) females recruited from a public, urban hospital. Childhood abuse was measured using the Childhood Trauma Questionnaire, and PTSD was measured using the modified PTSD Symptom Scale. Task accuracy and implicit emotion regulation were measured through an emotional conflict regulation behavioral task. A multivariate analysis of covariance showed that exposure to moderate to severe childhood abuse was significantly related to worse emotional conflict regulation scores independent of current PTSD symptoms, depressive symptoms, and adult trauma exposure, suggesting a deficit in implicit emotion regulation. We also found an interaction between PTSD symptoms and abuse exposure in predicting accuracy on the behavioral task; high levels of PTSD symptoms were associated with poorer task accuracy among individuals who reported moderate to severe exposure to childhood abuse. However, no relationship between implicit emotion regulation abilities and overall PTSD symptom severity was found. This study provides preliminary evidence of an implicit emotion regulation deficit for individuals exposed to significant childhood abuse and further supports the growing evidence that addressing various aspects of emotion dysregulation, such as awareness of emotions and strategies to manage strong emotions, in the context of treatment would be valuable.

  7. Educating physicians in evidence based medicine: current practices and curricular strategies

    NARCIS (Netherlands)

    Maggio, L.A.

    2015-01-01

    Evidence based medicine (EBM) is “the conscientious, explicit and judicious use of current best evidence in making decisions about the care of individual patients.” The practice of EBM is an expectation of professional healthcare and requisite component in many medical school curricula. Yet, despite

  8. ICU nurses' oral-care practices and the current best evidence.

    Science.gov (United States)

    DeKeyser Ganz, Freda; Fink, Naomi Farkash; Raanan, Ofra; Asher, Miriam; Bruttin, Madeline; Nun, Maureen Ben; Benbinishty, Julie

    2009-01-01

    The purpose of this study was to describe the oral-care practices of ICU nurses, to compare those practices with current evidence-based practice, and to determine if the use of evidence-based practice was associated with personal demographic or professional characteristics. A national survey of oral-care practices of ICU nurses was conducted using a convenience sample of 218 practicing ICU nurses in 2004-05. The survey instrument included questions about demographic and professional characteristics and a checklist of oral-care practices. Nurses rated their perceived level of priority concerning oral care on a scale from 0 to 100. A score was computed representing the sum of 14 items related to equipment, solutions, assessments, and techniques associated with the current best evidence. This score was then statistically analyzed using ANOVA to determine differences of EBP based on demographic and professional characteristics. The most commonly used equipment was gauze pads (84%), followed by tongue depressors (55%), and toothbrushes (34%). Chlorhexidine was the most common solution used (75%). Less than half (44%) reported brushing their patients' teeth. The majority performed an oral assessment before beginning oral care (71%); however, none could describe what assessment tool was used. Only 57% of nurses reported documenting their oral care. Nurses rated oral care of intubated patients with a priority of 67+/-27.1. Wide variations were noted within and between units in terms of which techniques, equipment, and solutions were used. No significant relationships were found between the use of an evidence-based protocol and demographic and professional characteristics or with the priority given to oral care. While nurses ranked oral care a high priority, many did not implement the latest evidence into their current practice. The level of research utilization was not related to personal or professional characteristics. Therefore attempts should be made to encourage all

  9. Evidence for current diagnostic criteria of diabetes mellitus

    Institute of Scientific and Technical Information of China (English)

    Ritesh; Kumar[1; Lakshmana; Perumal; Nandhini[1; Sadishkumar; Kamalanathan[1; Jayaprakash; Sahoo[1; Muthupillai; Vivekanadan[1

    2016-01-01

    Diabetes mellitus is a non-communicable metabolic derangement afflicting several millions of individuals globally. It is associated with several micro and macrovascular complications and is also a leading cause of mortality. The unresolved issue is that of definition of the diagnostic threshold for diabetes. The World Health Organization and the American Diabetes Association (ADA) have laid down several diagnostic criteria for diagnosing diabetes and prediabetes based on the accumulating body of evidence.This review has attempted to analyse the scientific evidence supporting the justification of these differing criteria. The evidence for diagnosing diabetes is strong, and there is a concordance between the two professional bodies.The controversy arises when describing the normal lower limit of fasting plasma glucose (FPG) with little evidence favouring the reduction of the FPG by the ADA. Several studies have also shown the development of complications specific for diabetes in patients with prediabetes as defined by the current criteria though there is a significant overlap of such prevalence in individuals with normoglycemia. Large multinational longitudinal prospective studies involving subjects without diabetes and retinopathy at baseline will ideally help identify the threshold of glycemic measurements for future development of diabetes and its complications.

  10. Focused transcranial direct current stimulation (tDCS) over the dorsolateral prefrontal cortex modulates specific domains of self-regulation.

    Science.gov (United States)

    Pripfl, Jürgen; Lamm, Claus

    2015-02-01

    Recent neuroscience theories suggest that different kinds of self-regulation may share a common psychobiological mechanism. However, empirical evidence for a domain general self-regulation mechanism is scarce. The aim of this study was to investigate whether focused anodal transcranial direct current stimulation (tDCS), facilitating the activity of the dorsolateral prefrontal cortex (dlPFC), acts on a domain general self-regulation mechanism and thus modulates both affective and appetitive self-regulation. Twenty smokers participated in this within-subject sham controlled study. Effects of anodal left, anodal right and sham tDCS over the dlPFC on affective picture appraisal and nicotine craving-cue appraisal were assessed. Anodal right tDCS over the dlPFC reduced negative affect in emotion appraisal, but neither modulated regulation of positive emotion appraisal nor of craving appraisal. Anodal left stimulation did not induce any significant effects. The results of our study show that domain specific self-regulation networks are at work in the prefrontal cortex. Focused tDCS modulation of this specific self-regulation network could probably be used during the first phase of nicotine abstinence, during which negative affect might easily result in relapse. These findings have implications for neuroscience models of self-regulation and are of relevance for the development of brain stimulation based treatment methods for neuropsychiatric disorders associated with self-regulation deficits. Copyright © 2014 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

  11. Current therapeutic interventions in the glycation pathway: evidence from clinical studies.

    Science.gov (United States)

    Engelen, L; Stehouwer, C D A; Schalkwijk, C G

    2013-08-01

    The increased formation of advanced glycation endproducts (AGEs) constitutes a potential mechanism of hyperglycaemia-induced micro- and macrovascular disease in diabetes. In vitro and animal experiments have shown that various interventions can inhibit formation and/or actions of AGEs, in particular the specific AGE inhibitor aminoguanidine and the AGEs crosslink breaker alagebrium, and the B vitamins pyridoxamine and thiamine, and the latter's synthetic derivative, benfotiamine. The potential clinical value of these interventions, however, remains to be established. The present review provides, from the clinical point of view, an overview of current evidence on interventions in the glycation pathway relating to (i) the clinical benefits of specific AGE inhibitors and AGE breakers and (ii) the potential AGE-inhibiting effects of therapies developed for purposes unrelated to the glycation pathway. We found that safety and/or efficacy in clinical studies with the specific AGE inhibitor, aminoguanidine and the AGE breaker, alagebrium, appeared to be a concern. The clinical evidence on the potential AGE-inhibiting effects of B vitamins is still limited. Finally, current evidence for AGE inhibition by therapies developed for purposes unrelated to glycation is limited due to a large heterogeneity in study designs and/or measurement techniques, which have often been sub-optimal. We conclude that, clinical evidence on interventions to inhibit formation and/or action of AGEs is currently weak and unconvincing. © 2012 Blackwell Publishing Ltd.

  12. Ownership and environmental regulation: Evidence from the European electricity industry

    International Nuclear Information System (INIS)

    Clò, Stefano; Ferraris, Matteo; Florio, Massimo

    2017-01-01

    The paper investigates how ownership affects the environmental performance in developed countries where environmental regulation is introduced in the form of market-based instrument. By looking at a cross-country panel dataset of 29 power markets around Europe over the period 1990–2012, we find empirical evidence that an increase of public ownership, as measured by the OECD ETCR index, is associated with a reduction of both greenhouse gas emissions and carbon intensity. We also find that the implementation of the European Emissions Trading Scheme (ETS) had a limited impact on emissions' reduction due to lax allocation of allowances. The positive effect of public ownership on environmental performance has been significant even after the introduction of the ETS, giving additional incentives to mitigate emissions when the ETS cap was not stringent enough. This evidence suggests that government control over power companies in Europe can has created idiosyncratic incentives to improve environmental quality, complementing environmental regulation in the achievement of environmental goals when the latter was absent or sub-optimal. - Highlights: • We analyse the power industry's environmental performance in 29 European countries. • Public ownership is associated with lower emissions than private ownership. • Mixed oligopoly is superior to private oligopoly in environmental terms. • The ETS had a limited impact on emissions' reduction due to over-allocation. • Public ownership mitigates the effects of sub-optimal environmental regulation.

  13. Current state and trend of radiation regulation system in Japan

    International Nuclear Information System (INIS)

    Yonehara, Hidenori

    2004-01-01

    Japanese regulation system for safety against radiation essentially started from 'Atomic Energy Basic Law' enacted in 1955 and 'Law Concerning Prevention of Radiation Hazards due to Radioisotopes, etc' enacted in 1957, has been regarded as a central rule for radiation protection and safety. Related laws and regulations have been enacted together with their revision. Radiation Council, established in the Science and Technology Agency in 1962 and now belonging to the Ministry of Education, Culture, Sports, Science and Technology, has deliberated basically on International Commission of Radiological Protection (ICRP) statements for legal revision and has set up working groups for current problems. Activities of the groups have concerned ICRP Publication 60 (1990) and later related publications for incorporating the principle into laws as to concepts of dose limits, effective dose, and then of exemption and exclusion. International status of the Japanese regulation, problems and tasks in the regulation are also commented. (N.I.)

  14. High-voltage integrated linear regulator with current sinking capabilities for portable ultrasound scanners

    DEFF Research Database (Denmark)

    Pausas, Guifre Vendrell; Llimos Muntal, Pere; Jørgensen, Ivan Harald Holger

    2017-01-01

    This paper presents a high-voltage integrated regulator capable of sinking current for driving pulse-triggered level shifters in drivers for ultrasound applications. The regulator utilizes a new topology with a feedback loop and a current sinking circuit to satisfy the requirements of the portable....... The proposed design has been implemented in high-voltage 0.18 μm process whithin an area of 0.11 mm2 and it is suitable for system-on-chip integration due to its low component count and the fully integrated design....

  15. A 1.8 V LDO voltage regulator with foldback current limit and thermal protection

    International Nuclear Information System (INIS)

    Liu Zhiming; Fu Zhongqian; Huang Lu; Xi Tianzuo

    2009-01-01

    This paper introduces the design of a l.8 V low dropout voltage regulator (LDO) and a foldback current limit circuit which limits the output current to 3 mA when load over-current occurs. The LDO was implemented in a 0.18 μm CMOS technology. The measured result reveals that the LDO's power supply rejection (PSR) is about -58 dB and -54 dB at 20 Hz and 1 kHz respectively, the response time is 4 μs and the quiescent current is 20 μA. The designed LDO regulator can work with a supply voltage down to 2.0 V with a drop-out voltage of 200 mV at a maximum load current of 240 mA. (semiconductor integrated circuits)

  16. The Current Evidence for Hayek’s Cultural Group Selection Theory

    Directory of Open Access Journals (Sweden)

    Brad Lowell Stone

    2010-12-01

    Full Text Available In this article I summarize Friedrich Hayek’s cultural group selection theory and describe the evidence gathered by current cultural group selection theorists within the behavioral and social sciences supporting Hayek’s main assertions. I conclude with a few comments on Hayek and libertarianism.

  17. Current control loop design and analysis based on resonant regulators for microgrid applications

    DEFF Research Database (Denmark)

    Federico, de Bosio; Pastorelli, Michelle; de Sousa Ribeiro, Luiz Antonio

    2015-01-01

    Voltage and current control loops play an important role in the performance of microgrids employing power electronics voltage source inverters. Correct design of feedback loops is essential for the proper operation of these systems. This paper analyzes the influence of state feedback cross......-coupling in the design of resonant regulators for inner current loops in power converters operating in standalone microgrids. It is also demonstrated that the effect of state feedback cross-coupling degrades the performance of the control loops by increasing the steady-state error. Different resonant regulators...

  18. Developing Traditional Chinese Medicine in the Era of Evidence-Based Medicine: Current Evidences and Challenges

    Science.gov (United States)

    Fung, Foon Yin; Linn, Yeh Ching

    2015-01-01

    Evidence-based medicine (EBM), by integrating individual clinical expertise with the best available clinical evidence from systematic research, has in recent years been established as the standard of modern medical practice for greater treatment efficacy and safety. Traditional Chinese Medicine (TCM), on the other hand, evolved as a system of medical practice from ancient China more than 2000 years ago based on empirical knowledge as well as theories and concepts which are yet to be mapped by scientific equivalents. Despite the expanding TCM usage and the recognition of its therapeutic benefits worldwide, the lack of robust evidence from the EBM perspective is hindering acceptance of TCM by the Western medicine community and its integration into mainstream healthcare. For TCM to become an integral component of the healthcare system so that its benefits can be rationally harnessed in the best interests of patients, it is essential for TCM to demonstrate its efficacy and safety by high-level evidence in accordance with EBM, though much debate remains on the validity and feasibility of applying the EBM model on this traditional practice. This review aims to discuss the current status of research in TCM, explore the evidences available on its efficacy and safety, and highlight the issues and challenges faced in applying EBM to TCM. PMID:25949261

  19. A 1.8 V LDO voltage regulator with foldback current limit and thermal protection

    Energy Technology Data Exchange (ETDEWEB)

    Liu Zhiming; Fu Zhongqian; Huang Lu; Xi Tianzuo, E-mail: zml1985@mail.ustc.edu.c [Department of Electronic Science and Technology, University of Science and Technology of China, Hefei 230027 (China)

    2009-08-15

    This paper introduces the design of a l.8 V low dropout voltage regulator (LDO) and a foldback current limit circuit which limits the output current to 3 mA when load over-current occurs. The LDO was implemented in a 0.18 {mu}m CMOS technology. The measured result reveals that the LDO's power supply rejection (PSR) is about -58 dB and -54 dB at 20 Hz and 1 kHz respectively, the response time is 4 {mu}s and the quiescent current is 20 {mu}A. The designed LDO regulator can work with a supply voltage down to 2.0 V with a drop-out voltage of 200 mV at a maximum load current of 240 mA. (semiconductor integrated circuits)

  20. Metabotropic Regulation of Extrasynaptic GABAA Receptors

    Directory of Open Access Journals (Sweden)

    William Martin Connelly

    2013-10-01

    Full Text Available A large body of work now shows the importance of GABAA receptor-mediated tonic inhibition in regulating CNS function. However, outside of pathological conditions, there is relatively little evidence that the magnitude of tonic inhibition is itself under regulation. Here we review the mechanisms by which tonic inhibition is known to be modulated, and outline the potential behavioural consequences of this modulation. Specifically, we address the ability of protein kinase A and C to phosphorylate the extrasynaptic receptors responsible for the tonic GABAA current, and how G-protein coupled receptors can regulate tonic inhibition through these effectors. We then speculate about the possible functional consequences of regulating the magnitude of the tonic GABAA current.

  1. Preventing skin cancer through reduction of indoor tanning: current evidence.

    Science.gov (United States)

    Watson, Meg; Holman, Dawn M; Fox, Kathleen A; Guy, Gery P; Seidenberg, Andrew B; Sampson, Blake P; Sinclair, Craig; Lazovich, DeAnn

    2013-06-01

    Exposure to ultraviolet radiation from indoor tanning devices (tanning beds, booths, and sun lamps) or from the sun contributes to the risk of skin cancer, including melanoma, which is the type of skin cancer responsible for most deaths. Indoor tanning is common among certain groups, especially among older adolescents and young adults, adolescent girls and young women, and non-Hispanic whites. Increased understanding of the health risks associated with indoor tanning has led to many efforts to reduce use. Most environmental and systems efforts in the U.S. (e.g., age limits or requiring parental consent/accompaniment) have occurred at the state level. At the national level, the U.S. Food and Drug Administration and the Federal Trade Commission regulate indoor tanning devices and advertising, respectively. The current paper provides a brief review of (1) the evidence on indoor tanning as a risk factor for skin cancer; (2) factors that may influence use of indoor tanning devices at the population level; and (3) various environmental and systems options available for consideration when developing strategies to reduce indoor tanning. This information provides the context and background for the companion paper in this issue of the American Journal of Preventive Medicine, which summarizes highlights from an informal expert meeting convened by the CDC in August 2012 to identify opportunities to prevent skin cancer by reducing use of indoor tanning devices. Published by Elsevier Inc.

  2. Emerging Evidence for MicroRNAs as Regulators of Cancer Stem Cells

    Energy Technology Data Exchange (ETDEWEB)

    Sethi, Aisha [Department of Pathology, Henry Ford Hospital, Detroit, MI 48202 (United States); Sholl, Lynette M., E-mail: lmsholl@partners.org [Department of Pathology, Brigham and Women' s Hospital and Harvard Medical School, Boston, MA 02115 (United States)

    2011-10-24

    Cancer stem cells are defined as a subpopulation of cells within a tumor that are capable of self-renewal and differentiation into the heterogeneous cell lineages that comprise the tumor. Many studies indicate that cancer stem cells may be responsible for treatment failure and relapse in cancer patients. The factors that regulate cancer stem cells are not well defined. MicroRNAs (miRNAs) are small non-coding RNAs that regulate translational repression and transcript degradation. miRNAs play a critical role in embryonic and inducible pluripotent stem cell regulation and emerging evidence supports their role in cancer stem cell evolution. To date, miRNAs have been shown to act either as tumor suppressor genes or oncogenes in driving critical gene expression pathways in cancer stem cells in a wide range of human malignancies, including hematopoietic and epithelial tumors and sarcomas. miRNAs involved in cancer stem cell regulation provide attractive, novel therapeutic targets for cancer treatment. This review attempts to summarize progress to date in defining the role of miRNAs in cancer stem cells.

  3. Emerging Evidence for MicroRNAs as Regulators of Cancer Stem Cells

    International Nuclear Information System (INIS)

    Sethi, Aisha; Sholl, Lynette M.

    2011-01-01

    Cancer stem cells are defined as a subpopulation of cells within a tumor that are capable of self-renewal and differentiation into the heterogeneous cell lineages that comprise the tumor. Many studies indicate that cancer stem cells may be responsible for treatment failure and relapse in cancer patients. The factors that regulate cancer stem cells are not well defined. MicroRNAs (miRNAs) are small non-coding RNAs that regulate translational repression and transcript degradation. miRNAs play a critical role in embryonic and inducible pluripotent stem cell regulation and emerging evidence supports their role in cancer stem cell evolution. To date, miRNAs have been shown to act either as tumor suppressor genes or oncogenes in driving critical gene expression pathways in cancer stem cells in a wide range of human malignancies, including hematopoietic and epithelial tumors and sarcomas. miRNAs involved in cancer stem cell regulation provide attractive, novel therapeutic targets for cancer treatment. This review attempts to summarize progress to date in defining the role of miRNAs in cancer stem cells

  4. Emotion regulation and mental health: recent findings, current challenges, and future directions.

    Science.gov (United States)

    Berking, Matthias; Wupperman, Peggilee

    2012-03-01

    In recent years, deficits in emotion regulation have been studied as a putative maintaining factor and promising treatment target in a broad range of mental disorders. This article aims to provide an integrative review of the latest theoretical and empirical developments in this rapidly growing field of research. Deficits in emotion regulation appear to be relevant to the development, maintenance, and treatment of various forms of psychopathology. Increasing evidence demonstrates that deficits in the ability to adaptively cope with challenging emotions are related to depression, borderline personality disorder, substance-use disorders, eating disorders, somatoform disorders, and a variety of other psychopathological symptoms. Unfortunately, studies differ with regard to the conceptualization and assessment of emotion regulation, thus limiting the ability to compare findings across studies. Future research should systematically work to use comparable methods in order to clarify the following: which individuals have; what kinds of emotion regulation difficulties with; which types of emotions; and what interventions are most effective in alleviating these difficulties. Despite some yet to be resolved challenges, the concept of emotion regulation has a broad and significant heuristic value for research in mental health.

  5. Regulation in the face of uncertainty: the evidence on electronic nicotine delivery systems (e-cigarettes).

    Science.gov (United States)

    Farsalinos, Konstantinos E; Le Houezec, Jacques

    2015-01-01

    Tobacco smoking is the largest single preventable cause of many chronic diseases and death. Effective treatments exist; however, few smokers use them and most try to quit by themselves. Most of the tobacco cigarette's toxicity is related to the combustion process. Models of harm reduction applied to tobacco suggest that switching from inhalation of combustible products to a noncombustible nicotine delivery product would likely result in a vast reduction in tobacco-related death and illness. Currently available evidence raises no doubt that electronic cigarettes (e-cigs) are by far less harmful than smoking (although probably not absolutely safe) and have the potential to be the most effective tobacco harm reduction products due to their unique property of resembling smoking and providing satisfaction to the user. A lot of controversy is surrounding e-cigs and their regulation, much of which is based on the precautionary principle. Although monitoring and further research is definitely needed, the arguments used to implement severe restrictions or bans are mostly hypothetical, weakly supported by evidence, and, in some cases, derived from mispresentation or misinterpretation of the study findings. Regulators should keep in mind that the target population is smokers who want to reduce or quit their deadly tobacco consumption. To achieve this goal, smokers should be honestly informed on the relative harmfulness of the different products. E-cigs are not tobacco products and are not used as medications. For this reason, a specific regulatory scheme is needed, separate from tobacco or medicinal products regulation. Regulation should implement specific quality criteria for products, rules for the exclusion of chemicals of reasonable concern, and appropriate testing for possible contaminants. Additionally, manufacturing standards derived from the food industry should be implemented and adjusted for specific conditions related to e-cigs. Finding the appropriate balance

  6. The Role of Self-Regulation in Corporate Governance : Evidence from the Netherlands

    NARCIS (Netherlands)

    de Jong, A.; DeJong, D.V.; Mertens, G.M.H.; Wasley, C.

    2000-01-01

    The purpose of this paper is to gather evidence on the success of market forces in promoting investor interests through self-regulation.Corporate governance is a complex mechanism design problem that is both economic and legal/political based.As such there is great interest in whether (and when)

  7. The activity of spontaneous action potentials in developing hair cells is regulated by Ca(2+-dependence of a transient K+ current.

    Directory of Open Access Journals (Sweden)

    Snezana Levic

    Full Text Available Spontaneous action potentials have been described in developing sensory systems. These rhythmic activities may have instructional roles for the functional development of synaptic connections. The importance of spontaneous action potentials in the developing auditory system is underpinned by the stark correlation between the time of auditory system functional maturity, and the cessation of spontaneous action potentials. A prominent K(+ current that regulates patterning of action potentials is I(A. This current undergoes marked changes in expression during chicken hair cell development. Although the properties of I(A are not normally classified as Ca(2+-dependent, we demonstrate that throughout the development of chicken hair cells, I(A is greatly reduced by acute alterations of intracellular Ca(2+. As determinants of spike timing and firing frequency, intracellular Ca(2+ buffers shift the activation and inactivation properties of the current to more positive potentials. Our findings provide evidence to demonstrate that the kinetics and functional expression of I(A are tightly regulated by intracellular Ca(2+. Such feedback mechanism between the functional expression of I(A and intracellular Ca(2+ may shape the activity of spontaneous action potentials, thus potentially sculpting synaptic connections in an activity-dependent manner in the developing cochlea.

  8. Effective treatment options for musculoskeletal pain in primary care: A systematic overview of current evidence

    Science.gov (United States)

    Hill, Jonathan C.; Foster, Nadine E.; Protheroe, Joanne

    2017-01-01

    Background & aims Musculoskeletal pain, the most common cause of disability globally, is most frequently managed in primary care. People with musculoskeletal pain in different body regions share similar characteristics, prognosis, and may respond to similar treatments. This overview aims to summarise current best evidence on currently available treatment options for the five most common musculoskeletal pain presentations (back, neck, shoulder, knee and multi-site pain) in primary care. Methods A systematic search was conducted. Initial searches identified clinical guidelines, clinical pathways and systematic reviews. Additional searches found recently published trials and those addressing gaps in the evidence base. Data on study populations, interventions, and outcomes of intervention on pain and function were extracted. Quality of systematic reviews was assessed using AMSTAR, and strength of evidence rated using a modified GRADE approach. Results Moderate to strong evidence suggests that exercise therapy and psychosocial interventions are effective for relieving pain and improving function for musculoskeletal pain. NSAIDs and opioids reduce pain in the short-term, but the effect size is modest and the potential for adverse effects need careful consideration. Corticosteroid injections were found to be beneficial for short-term pain relief among patients with knee and shoulder pain. However, current evidence remains equivocal on optimal dose, intensity and frequency, or mode of application for most treatment options. Conclusion This review presents a comprehensive summary and critical assessment of current evidence for the treatment of pain presentations in primary care. The evidence synthesis of interventions for common musculoskeletal pain presentations shows moderate-strong evidence for exercise therapy and psychosocial interventions, with short-term benefits only from pharmacological treatments. Future research into optimal dose and application of the most

  9. Current Treatment of Toxoplasma Retinochoroiditis: An Evidence-Based Review

    Directory of Open Access Journals (Sweden)

    Meredith Harrell

    2014-01-01

    Full Text Available Objective. To perform an evidence-based review of treatments for Toxoplasma retinochoroiditis (TRC. Methods. A systematic literature search was performed using the PubMed database and the key phrase “ocular toxoplasmosis treatment” and the filter for “controlled clinical trial” and “randomized clinical trial” as well as OVID medline (1946 to May week 2 2014 using the keyword ‘‘ocular toxoplasmosis’’. The included studies were used to evaluate the various treatment modalities of TRC. Results. The electronic search yielded a total of 974 publications of which 44 reported on the treatment of ocular toxoplasmosis. There were 9 randomized controlled studies and an additional 3 comparative studies on the treatment of acute TRC with systemic or intravitreous antibiotics or on reducing the recurrences of TRC. Endpoints of studies included visual acuity improvement, inflammatory response, lesion size changes, recurrences of lesions, and adverse effects of medications. Conclusions. There was conflicting evidence as to the effectiveness of systemic antibiotics for TRC. There is no evidence to support that one antibiotic regimen is superior to another so choice needs to be informed by the safety profile. Intravitreous clindamycin with dexamethasone seems to be as effective as systemic treatments. There is currently level I evidence that intermittent trimethoprim-sulfamethoxazole prevents recurrence of the disease.

  10. Current knowledge of microRNA-mediated regulation of drug metabolism in humans.

    Science.gov (United States)

    Nakano, Masataka; Nakajima, Miki

    2018-05-01

    Understanding the factors causing inter- and intra-individual differences in drug metabolism potencies is required for the practice of personalized or precision medicine, as well as for the promotion of efficient drug development. The expression of drug-metabolizing enzymes is controlled by transcriptional regulation by nuclear receptors and transcriptional factors, epigenetic regulation, such as DNA methylation and histone acetylation, and post-translational modification. In addition to such regulation mechanisms, recent studies revealed that microRNAs (miRNAs), endogenous ~22-nucleotide non-coding RNAs that regulate gene expression through the translational repression and degradation of mRNAs, significantly contribute to post-transcriptional regulation of drug-metabolizing enzymes. Areas covered: This review summarizes the current knowledge regarding miRNAs-dependent regulation of drug-metabolizing enzymes and transcriptional factors and its physiological and clinical significance. We also describe recent advances in miRNA-dependent regulation research, showing that the presence of pseudogenes, single-nucleotide polymorphisms, and RNA editing affects miRNA targeting. Expert opinion: It is unwavering fact that miRNAs are critical factors causing inter- and intra-individual differences in the expression of drug-metabolizing enzymes. Consideration of miRNA-dependent regulation would be a helpful tool for optimizing personalized and precision medicine.

  11. LED Current Balance Using a Variable Voltage Regulator with Low Dropout vDS Control

    Directory of Open Access Journals (Sweden)

    Hung-I Hsieh

    2017-02-01

    Full Text Available A cost-effective light-emitting diode (LED current balance strategy using a variable voltage regulator (VVR with low dropout vDS control is proposed. This can regulate the multiple metal-oxide-semiconductor field-effect transistors (MOSFETs of the linear current regulators (LCR, maintaining low dropout vDS on the flat vGS-characteristic curves and making all drain currents almost the same. Simple group LCRs respectively loaded with a string LED are employed to implement the theme. The voltage VVdc from a VVR is synthesized by a string LED voltage NvD, source voltage vR, and a specified low dropout vDS = VQ. The VVdc updates instantly, through the control loop of the master LCR, which means that all slave MOSFETs have almost the same biases on their flat vGS-characteristic curves. This leads to all of the string LED currents being equal to each other, producing an almost even luminance. An experimental setup with microchip control is built to verify the estimations. Experimental results show that the luminance of all of the string LEDs are almost equal to one another, with a maximum deviation below 1% during a wide dimming range, while keeping all vDS of the MOSFETs at a low dropout voltage, as expected.

  12. Fried Food Consumption and Cardiovascular Health: A Review of Current Evidence

    Directory of Open Access Journals (Sweden)

    Taraka V. Gadiraju

    2015-10-01

    Full Text Available Fried food consumption and its effects on cardiovascular disease are still subjects of debate. The objective of this review was to summarize current evidence on the association between fried food consumption and cardiovascular disease, diabetes, hypertension and obesity and to recommend directions for future research. We used PubMed, Google Scholar and Medline searches to retrieve pertinent publications. Most available data were based on questionnaires as a tool to capture fried food intakes, and study design was limited to case-control and cohort studies. While few studies have reported a positive association between frequencies of fried food intake and risk of coronary artery disease, heart failure, diabetes or hypertension, other investigators have failed to confirm such an association. There is strong evidence suggesting a higher risk of developing chronic disease when fried foods are consumed more frequently (i.e., four or more times per week. Major gaps in the current literature include a lack of detailed information on the type of oils used for frying foods, stratification of the different types of fried food, frying procedure (deep and pan frying, temperature and duration of frying, how often oils were reused and a lack of consideration of overall dietary patterns. Besides addressing these gaps, future research should also develop tools to better define fried food consumption at home versus away from home and to assess their effects on chronic diseases. In summary, the current review provides enough evidence to suggest adverse health effects with higher frequency of fried food consumption. While awaiting confirmation from future studies, it may be advisable to the public to consume fried foods in moderation while emphasizing an overall healthy diet.

  13. How do countries regulate the health sector? Evidence from Tanzania and Zimbabwe.

    Science.gov (United States)

    Kumaranayake, L; Mujinja, P; Hongoro, C; Mpembeni, R

    2000-12-01

    The health sectors in many low- and middle-income countries have been characterized in recent years by extensive private sector activity. This has been complemented by increasing public-private linkages, such as the contracting-out of selected services or facilities, development of new purchasing arrangements, franchising and the introduction of vouchers. Increasingly, however, experience with the private sector has indicated a number of problems with the quality, price and distribution of private health services, and thus led to a growing focus on the role of government in regulation. This paper presents the existing network of regulations governing private activity in the health sectors of Tanzania and Zimbabwe, and their appropriateness in the context of emerging market realities. It draws on a comparative mapping exercise reviewing the complexity of the variables currently being regulated, the level of the health system at which they apply, and the specific instruments being used. Findings indicate that much of the existing regulation occurs through legislation. There is still very much a focus on the 'social' rather than 'economic' aspects of regulation within the health sector. Recent changes have attempted to address aspects of private health provision, but some very key gaps remain. In particular, current regulations in Tanzania and Zimbabwe: (1) focus on individual inputs rather than health system organizations; (2) aim to control entry and quality rather than explicitly quantity, price or distribution; and (3) fail to address the market-level problems of anti-competitive practices and lack of patient rights. This highlights the need for additional measures to promote consumer protection and address the development of new private markets such as for health insurance or laboratory and other ancillary services.

  14. Regulation in the face of uncertainty: the evidence on electronic nicotine delivery systems (e-cigarettes

    Directory of Open Access Journals (Sweden)

    Farsalinos KE

    2015-09-01

    Full Text Available Konstantinos E Farsalinos,1,2 Jacques Le Houezec3,4 1Department of Cardiology, Onassis Cardiac Surgery Center, Kallithea, 2Department of Pharmacy, University of Patras, Patras, Greece; 3Division of Epidemiology and Public Health, UK Centre for Tobacco and Alcohol Studies, University of Nottingham, Nottingham, England, UK; 4Addiction Research Unit, INSERM 1178 (Mental and Public Health, Paris, France Abstract: Tobacco smoking is the largest single preventable cause of many chronic diseases and death. Effective treatments exist; however, few smokers use them and most try to quit by themselves. Most of the tobacco cigarette's toxicity is related to the combustion process. Models of harm reduction applied to tobacco suggest that switching from inhalation of combustible products to a noncombustible nicotine delivery product would likely result in a vast reduction in tobacco-related death and illness. Currently available evidence raises no doubt that electronic cigarettes (e-cigs are by far less harmful than smoking (although probably not absolutely safe and have the potential to be the most effective tobacco harm reduction products due to their unique property of resembling smoking and providing satisfaction to the user. A lot of controversy is surrounding e-cigs and their regulation, much of which is based on the precautionary principle. Although monitoring and further research is definitely needed, the arguments used to implement severe restrictions or bans are mostly hypothetical, weakly supported by evidence, and, in some cases, derived from mispresentation or misinterpretation of the study findings. Regulators should keep in mind that the target population is smokers who want to reduce or quit their deadly tobacco consumption. To achieve this goal, smokers should be honestly informed on the relative harmfulness of the different products. E-cigs are not tobacco products and are not used as medications. For this reason, a specific regulatory

  15. Addressing unwarranted clinical variation: A rapid review of current evidence.

    Science.gov (United States)

    Harrison, Reema; Manias, Elizabeth; Mears, Stephen; Heslop, David; Hinchcliff, Reece; Hay, Liz

    2018-05-15

    Unwarranted clinical variation (UCV) can be described as variation that can only be explained by differences in health system performance. There is a lack of clarity regarding how to define and identify UCV and, once identified, to determine whether it is sufficiently problematic to warrant action. As such, the implementation of systemic approaches to reducing UCV is challenging. A review of approaches to understand, identify, and address UCV was undertaken to determine how conceptual and theoretical frameworks currently attempt to define UCV, the approaches used to identify UCV, and the evidence of their effectiveness. Rapid evidence assessment (REA) methodology was used. A range of text words, synonyms, and subject headings were developed for the major concepts of unwarranted clinical variation, standards (and deviation from these standards), and health care environment. Two electronic databases (Medline and Pubmed) were searched from January 2006 to April 2017, in addition to hand searching of relevant journals, reference lists, and grey literature. Results were merged using reference-management software (Endnote) and duplicates removed. Inclusion criteria were independently applied to potentially relevant articles by 3 reviewers. Findings were presented in a narrative synthesis to highlight key concepts addressed in the published literature. A total of 48 relevant publications were included in the review; 21 articles were identified as eligible from the database search, 4 from hand searching published work and 23 from the grey literature. The search process highlighted the voluminous literature reporting clinical variation internationally; yet, there is a dearth of evidence regarding systematic approaches to identifying or addressing UCV. Wennberg's classification framework is commonly cited in relation to classifying variation, but no single approach is agreed upon to systematically explore and address UCV. The instances of UCV that warrant investigation and

  16. Altered Mental Status: Current Evidence-based Recommendations for Prehospital Care

    Directory of Open Access Journals (Sweden)

    Ashley Sanello

    2018-03-01

    Full Text Available Introduction: In the United States emergency medical services (EMS protocols vary widely across jurisdictions. We sought to develop evidence-based recommendations for the prehospital evaluation and treatment of a patient with an acute change in mental status and to compare these recommendations against the current protocols used by the 33 EMS agencies in the State of California. Methods: We performed a literature review of the current evidence in the prehospital treatment of a patient with altered mental status (AMS and augmented this review with guidelines from various national and international societies to create our evidence-based recommendations. We then compared the AMS protocols of each of the 33 EMS agencies for consistency with these recommendations. The specific protocol components that we analyzed were patient assessment, point-of-care tests, supplemental oxygen, use of standardized scoring, evaluating for causes of AMS, blood glucose evaluation, toxicological treatment, and pediatric evaluation and management. Results: Protocols across 33 EMS agencies in California varied widely. All protocols call for a blood glucose check, 21 (64% suggest treating adults at <60mg/dL, and half allow for the use of dextrose 10%. All the protocols recommend naloxone for signs of opioid overdose, but only 13 (39% give specific parameters. Half the agencies (52% recommend considering other toxicological causes of AMS, often by using the mnemonic AEIOU TIPS. Eight (24% recommend a 12-lead electrocardiogram; others simply suggest cardiac monitoring. Fourteen (42% advise supplemental oxygen as needed; only seven (21% give specific parameters. In terms of considering various etiologies of AMS, 25 (76% give instructions to consider trauma, 20 (61% to consider stroke, and 18 (55% to consider seizure. Twenty-three (70% of the agencies have separate pediatric AMS protocols; others include pediatric considerations within the adult protocol. Conclusion: Protocols

  17. Cost-effectiveness of particle therapy: Current evidence and future needs

    International Nuclear Information System (INIS)

    Pijls-Johannesma, Madelon; Pommier, Pascal; Lievens, Yolande

    2008-01-01

    Purpose: Questions are being raised regarding the cost of particle therapy (PT), and with them criticism that PT is too expensive to allow the expected gain in effectiveness. This paper aims to get more insight in the cost and cost-effectiveness of particle therapy and to discuss a future strategy that allows for critical assessment of this health technology. Material and methods: A systematic literature review based on an earlier published comprehensive review was performed and updated until June 1st 2008. Besides, current business plans of PT projects were examined. Additionally, results retrieved from a cost-simulation tool developed under auspice of the ENLIGHT were discussed. Results: The current literature on cost-effectiveness of PT is scarce, non-comparable, and largely not performed according to standard health technology assessment criteria. Besides, different perspectives for cost evaluations have been used, making it difficult to compare and to determine the relative impact in terms of costs for this new treatment modality. Conclusions: Evidence on the cost-effectiveness of PT is scarce. Adequate reimbursement is necessary to support such innovative yet costly treatments. For now, model-based economic evaluations performed at least from a health care perspective may help us to gain evidence-based insight into cost-effectiveness

  18. Rehabilitation for post-stroke cognitive impairment: an overview of recommendations arising from systematic reviews of current evidence.

    Science.gov (United States)

    Gillespie, David C; Bowen, Audrey; Chung, Charlie S; Cockburn, Janet; Knapp, Peter; Pollock, Alex

    2015-02-01

    Although cognitive impairments are common following stroke, there is considerable uncertainty about the types of interventions that can reduce activity restrictions and improve quality of life. Indeed, a recent project to identify priorities for research into life after stroke determined that the top priority for patients, carers and health professionals was how to improve cognitive impairments. To provide an overview of the evidence for the effectiveness of cognitive rehabilitation for patients with stroke and to determine the main gaps in the current evidence base. Evidence was synthesised for the six Cochrane reviews relating to rehabilitation for post-stroke cognitive impairment and any subsequently published randomized controlled trials to February 2012. Data arising from 44 trials involving over 1500 patients was identified. Though there was support for the effectiveness of cognitive rehabilitation for some cognitive impairments, significant gaps were found in the current evidence base. All of the Cochrane reviews identified major limitations within the evidence they identified. There is currently insufficient research evidence, or evidence of insufficient quality, to support clear recommendations for clinical practice. Recommendations are made as to the research required to strengthen the evidence base, and so facilitate the delivery of effective interventions to individuals with cognitive impairment after stroke. © The Author(s) 2014.

  19. A current-mode voltage regulator with an embedded sub-threshold reference for a passive UHF RFID transponder

    Energy Technology Data Exchange (ETDEWEB)

    Liu Zhongqi [Department of Electronic Engineering, Tsinghua University, Beijing 100084 (China); Zhang Chun; Li Yongming; Wang Zhihua, E-mail: liu-zq04@mails.tsinghua.edu.c [Institute of Microelectronics, Tsinghua University, Beijing 100084 (China)

    2010-06-15

    This paper presents a current-mode voltage regulator for a passive UHF RFID transponder. The passive tag power is extracted from RF energy through the RF-to-DC rectifier. Due to huge variations of the incoming RF power, the rectifier output voltage should be regulated to achieve a stable power supply. By accurately controlling the current flowing into the load with an embedded sub-threshold reference, the regulated voltage varies in a range of 1-1.3 V from -20 to 80 {sup 0}C, and a bandwidth of about 100 kHz is achieved for a fast power recovery. The circuit is fabricated in UMC 0.18 {mu}m mixed-mode CMOS technology, and the current consumption is only 1 {mu}A. (semiconductor integrated circuits)

  20. A current-mode voltage regulator with an embedded sub-threshold reference for a passive UHF RFID transponder

    International Nuclear Information System (INIS)

    Liu Zhongqi; Zhang Chun; Li Yongming; Wang Zhihua

    2010-01-01

    This paper presents a current-mode voltage regulator for a passive UHF RFID transponder. The passive tag power is extracted from RF energy through the RF-to-DC rectifier. Due to huge variations of the incoming RF power, the rectifier output voltage should be regulated to achieve a stable power supply. By accurately controlling the current flowing into the load with an embedded sub-threshold reference, the regulated voltage varies in a range of 1-1.3 V from -20 to 80 0 C, and a bandwidth of about 100 kHz is achieved for a fast power recovery. The circuit is fabricated in UMC 0.18 μm mixed-mode CMOS technology, and the current consumption is only 1 μA. (semiconductor integrated circuits)

  1. Breast-Feeding Analgesia in Infants: An Update on the Current State of Evidence.

    Science.gov (United States)

    Benoit, Britney; Martin-Misener, Ruth; Latimer, Margot; Campbell-Yeo, Marsha

    To provide an updated synthesis of the current state of the evidence for the effectiveness of breast-feeding and expressed breast milk feeding in reducing procedural pain in preterm and full-term born infants. A systematic search of key electronic databases (PubMed, CINAHL, EMBASE) was completed. Of the 1032 abstracts screened, 21 were found eligible for inclusion. Fifteen studies reported on the use of breast-feeding or expressed breast milk in full-term infants and 6 reported on preterm infants. Direct breast-feeding was more effective than maternal holding, maternal skin-to-skin contact, topical anesthetics, and music therapy, and was as or more effective than sweet tasting solutions in full-term infants. Expressed breast milk was not consistently found to reduce pain response in full-term or preterm infants. Studies generally had moderate to high risk of bias. There is sufficient evidence to recommend direct breast-feeding for procedural pain management in full-term infants. Based on current evidence, expressed breast milk alone should not be considered an adequate intervention.

  2. Current regulator for stabilizing electrostatic generators; Regulateur de courant pour stabilisation de generateur electrostatique

    Energy Technology Data Exchange (ETDEWEB)

    Gabet, A; Taieb, J

    1950-07-01

    An instrument consisting of two electronic tubes, a triode and a pentode, connected in series, serves as a stabilizer of the current that charges a working model of a van de Graaff generator. The current is maintained at a level corresponding to an auxiliary variable voltage. The triode maintains that voltage, while the pentode regulates the current. Another application of the circuit, viz., the stabilizing of the generator voltage, will be described elsewhere. (author)

  3. Future carbon regulations and current investments in alternative coal-fired power plant technologies

    International Nuclear Information System (INIS)

    Sekar, Ram C.; Parsons, John E.; Herzog, Howard J.; Jacoby, Henry D.

    2007-01-01

    We analyze how uncertain future US carbon regulations shape the current choice of the type of power plant to build. Our focus is on two coal-fired technologies, pulverized coal (PC) and integrated coal gasification combined cycle technology (IGCC). The PC technology is cheapest-assuming there is no need to control carbon emissions. The IGCC technology may be cheaper if carbon must be captured. Since power plants last many years and future regulations are uncertain, a US electric utility faces a standard decision under uncertainty. A company will confront the range of possible outcomes, assigning its best estimate of the probability of each scenario, averaging the results and determining the power plant technology with the lowest possible cost inclusive of expected future carbon related costs, whether those costs be in the form of emissions charges paid or capital expenditures for retrofitting to capture carbon. If the company assigns high probability to no regulation or to less stringent regulation of carbon, then it makes sense for it to build the PC plant. But if it assigns sufficient probability to scenarios with more stringent regulation, then the IGCC technology is warranted. We provide some useful benchmarks for possible future regulation and show how these relate back to the relative costs of the two technologies and the optimal technology choice. Few of the policy proposals widely referenced in the public discussion warrant the choice of the IGCC technology. Instead, the PC technology remains the least costly. However, recent carbon prices in the European Emissions Trading System are higher than these benchmarks. If it is any guide to possible future penalties for emissions in the US, then current investment in the IGCC technology is warranted. Of course, other factors need to be factored into the decision as well

  4. Process stabilization by peak current regulation in reactive high-power impulse magnetron sputtering of hafnium nitride

    International Nuclear Information System (INIS)

    Shimizu, T; Villamayor, M; Helmersson, U; Lundin, D

    2016-01-01

    A simple and cost effective approach to stabilize the sputtering process in the transition zone during reactive high-power impulse magnetron sputtering (HiPIMS) is proposed. The method is based on real-time monitoring and control of the discharge current waveforms. To stabilize the process conditions at a given set point, a feedback control system was implemented that automatically regulates the pulse frequency, and thereby the average sputtering power, to maintain a constant maximum discharge current. In the present study, the variation of the pulse current waveforms over a wide range of reactive gas flows and pulse frequencies during a reactive HiPIMS process of Hf-N in an Ar–N 2 atmosphere illustrates that the discharge current waveform is a an excellent indicator of the process conditions. Activating the reactive HiPIMS peak current regulation, stable process conditions were maintained when varying the N 2 flow from 2.1 to 3.5 sccm by an automatic adjustment of the pulse frequency from 600 Hz to 1150 Hz and consequently an increase of the average power from 110 to 270 W. Hf–N films deposited using peak current regulation exhibited a stable stoichiometry, a nearly constant power-normalized deposition rate, and a polycrystalline cubic phase Hf-N with (1 1 1)-preferred orientation over the entire reactive gas flow range investigated. The physical reasons for the change in the current pulse waveform for different process conditions are discussed in some detail. (paper)

  5. Sugars and health: a review of current evidence and future policy.

    Science.gov (United States)

    Evans, Charlotte Elizabeth Louise

    2017-08-01

    The automation of the process of extracting sugars in the 1900s reduced cost and increased availability of sugars leading to a dramatic rise in consumption, which reached a peak in the 1970s. There are different definitions for sugars not naturally available in foods, and free sugars is the term used by WHO. The epidemiological evidence of the associations between sugars and obesity and type 2 diabetes mellitus is fairly strong and consistent, particularly for sugar sweetened drinks in adults. The Department of Health in the UK and many other countries have recently updated their recommendations for free sugars as a result of this scientific evidence. In the UK the recommended amount of free sugars is currently 5 % of energy (reduced from 10 %), which is difficult to meet and very different from current British dietary patterns. Reducing intakes of free sugars is a challenge and will necessitate a range of different actions and policies. Public Health England has put forward eight suggestions but the four most likely to improve dietary behaviour based on available evidence are social marketing, reduction of marketing of high sugar foods and drinks to children, reformulation and reductions in portion size and a sugar excise tax. Any action taken needs to be evaluated to check inequalities are not widened. The new childhood obesity strategy has incorporated some but not all of these strategies and may not go far enough. It is likely that government policies alone will not be sufficient and a change in the food culture is necessary to see real progress.

  6. 77 FR 467 - Notice of Tribal Consultation Meetings Regarding How the Current SACWIS Regulations Affect Tribes...

    Science.gov (United States)

    2012-01-05

    ... about current Federal regulations governing child welfare automation, please contact Mr. Peter Howe... consultation reflects our growing familiarity with the automation needs and preferences of Tribes and our... citing the related section of regulations or program guidance. (1) What are the obstacles for your Tribe...

  7. Providing current radiation safety according to new version of 'Ukrytie' object regulation

    International Nuclear Information System (INIS)

    Borovoj, A.A.; Vysotskij, E.D.; Krinitsyn, A.P.; Bogatov, S.A.

    1999-01-01

    Main provisions are given of the 'Ukryttia' object's Regulation related to provision of radiation safety during the object's operation. The safety is provided due to the realization by the object's personnel of functions of global monitoring of current radiation conditions, as well as of the measures of operative or preventive suppression of radiation abnormalities sources

  8. Reconceptualizing Civil Regulation

    DEFF Research Database (Denmark)

    Galang, Roberto Martin; Castello, Itziar

    2011-01-01

    This article re-conceptualizes the notion of civil regulation, through an analysis of 775 projects by firms located in 21 Asian countries, wherein we map the state of civil regulation initiatives in the region. We challenge two established assumptions in the Corporate Social Responsibility litera....... Finally, we argue that, in Asia, governments act as a structuration mechanism which challenges the current understanding of CSR.......This article re-conceptualizes the notion of civil regulation, through an analysis of 775 projects by firms located in 21 Asian countries, wherein we map the state of civil regulation initiatives in the region. We challenge two established assumptions in the Corporate Social Responsibility...... and environmental standards; but also that local, small and medium companies play a key role in the development of Asian civil regulation. We call this second finding the “CSR importation trap”. Our findings are supported by evidence on the limitations in the interchangeable properties of business and governments...

  9. A thermodynamic and theoretical view for enzyme regulation.

    Science.gov (United States)

    Zhao, Qinyi

    2015-01-01

    Precise regulation is fundamental to the proper functioning of enzymes in a cell. Current opinions about this, such as allosteric regulation and dynamic contribution to enzyme regulation, are experimental models and substantially empirical. Here we proposed a theoretical and thermodynamic model of enzyme regulation. The main idea is that enzyme regulation is processed via the regulation of abundance of active conformation in the reaction buffer. The theoretical foundation, experimental evidence, and experimental criteria to test our model are discussed and reviewed. We conclude that basic principles of enzyme regulation are laws of protein thermodynamics and it can be analyzed using the concept of distribution curve of active conformations of enzymes.

  10. Harvest Regulations and Implementation Uncertainty in Small Game Harvest Management

    Directory of Open Access Journals (Sweden)

    Pål F. Moa

    2017-09-01

    Full Text Available A main challenge in harvest management is to set policies that maximize the probability that management goals are met. While the management cycle includes multiple sources of uncertainty, only some of these has received considerable attention. Currently, there is a large gap in our knowledge about implemention of harvest regulations, and to which extent indirect control methods such as harvest regulations are actually able to regulate harvest in accordance with intended management objectives. In this perspective article, we first summarize and discuss hunting regulations currently used in management of grouse species (Tetraonidae in Europe and North America. Management models suggested for grouse are most often based on proportional harvest or threshold harvest principles. These models are all built on theoretical principles for sustainable harvesting, and provide in the end an estimate on a total allowable catch. However, implementation uncertainty is rarely examined in empirical or theoretical harvest studies, and few general findings have been reported. Nevertheless, circumstantial evidence suggest that many of the most popular regulations are acting depensatory so that harvest bag sizes is more limited in years (or areas where game density is high, contrary to general recommendations. A better understanding of the implementation uncertainty related to harvest regulations is crucial in order to establish sustainable management systems. We suggest that scenario tools like Management System Evaluation (MSE should be more frequently used to examine robustness of currently applied harvest regulations to such implementation uncertainty until more empirical evidence is available.

  11. Current environmental regulations

    International Nuclear Information System (INIS)

    Martz, M.K.

    1985-01-01

    An overview of the Federal environmental statutes and implementation regulations is provided, including the National Environmental Policy Act, the Clean Air Act, the Clean Water Act, the Safe Drinking Water Act, the Resource Conservation and Recovery Act, the Comprehensive Environmental Response, Compensation, and Liability Act, the Toxic Substances Control Act, the Federal Insecticide, Fungicide, and Rodenticide Act, and the Endangered Species Act. Recent developments which may have a direct impact on waste repository siting and management activities include: final promulgation of National Emission Standards for hazardous Air Pollutants for radionuclides, the DOE-EPA memorandum of understanding which brings mixed radioactive and chemical waste under the requirements of RCRA, and the proposed designation of additional sole source aquifers

  12. Evidence for Anomalous Effects on the Current Evolution in Tokamak Operating Scenarios

    Energy Technology Data Exchange (ETDEWEB)

    Casper, T; Jayakumar, R; Allen, S; Holcomb, C; Makowski, M; Pearlstein, L; Berk, H; Greenfield, C; Luce, T; Petty, C; Politzer, P; Wade, M; Murakami, M; Kessel, C

    2006-10-03

    Alternatives to the usual picture of advanced tokamak (AT) discharges are those that form when anomalous effects alter the plasma current and pressure profiles and those that achieve stationary characteristics through mechanisms so that a measure of desired AT features is maintained without external current-profile control. Regimes exhibiting these characteristics are those where the safety factor (q) evolves to a stationary profile with the on-axis and minimum q {approx} 1 and those with a deeply hollow current channel and high values of q. Operating scenarios with high fusion performance at low current and where the inductively driven current density achieves a stationary configuration with either small or non-existing sawteeth may enhance the neutron fluence per pulse on ITER and future burning plasmas. Hollow current profile discharges exhibit high confinement and a strong ''box-like'' internal transport barrier (ITB). We present results providing evidence for current profile formation and evolution exhibiting features consistent with anomalous effects or with self-organizing mechanisms. Determination of the underlying physical processes leading to these anomalous effects is important for scaling of current experiments for application in future burning plasmas.

  13. Periodic Safety Review in Interim Storage Facilities - Current Regulation and Experiences in Germany

    International Nuclear Information System (INIS)

    Neles, Julia Mareike; Schmidt, Gerhard

    2014-01-01

    Periodic safety reviews in nuclear power plants in Germany have been performed since the end of the 1980's as an indirect follow-up of the accident in Chernobyl and, in the meantime, are formally required by law. During this process the guidelines governing this review were developed in stages and reached their final form in 1996. Interim storage facilities and other nuclear facilities at that time were not included, so the guidelines were solely focused on the specific safety issues of nuclear power plants. Following IAEA's recommendations, the Western European Nuclear Regulator Association (WENRA) introduced PSRs in its safety reference levels for storage facilities (current version in WGWD report 2.1 as of Feb 2011: SRLs 59 - 61). Based on these formulations, Germany improved its regulation in 2010 with a recommendation of the Nuclear Waste Management Commission (Entsorgungskommission, ESK), an expert advisory commission for the federal regulatory body BMU. The ESK formulated these detailed requirements in the 'ESK recommendation for guides to the performance of periodic safety reviews for interim storage facilities for irradiated fuel elements and heat-generating radioactive waste'. Before finalization of the guideline a test phase was introduced, aimed to test the new regulation in practice and to later include the lessons learned in the final formulation of the guideline. The two-year test phase started in October 2011 in which the performance of a PSR will be tested at two selected interim storage facilities. Currently these recommendations are discussed with interested/concerned institutions. The results of the test phase shall be considered for improvements of the draft and during the final preparation of guidelines. Currently the PSR for the first ISF is in an advanced stage, the second facility just started the process. Preliminary conclusions from the test phase show that the implementation of the draft guideline requires interpretation. The aim of a

  14. Current management of hypertrophic cardiomyopathy: evidence in pathophysiology, diagnosis and treatment

    International Nuclear Information System (INIS)

    Quesada Mena, Luis Diego

    2013-01-01

    Available literary evidence is reviewed on the current management of hypertrophic cardiomyopathy. The bibliographical search is carried out in physical and online texts, cardiology journals, databases (MEDLINE), original studies, reviews and metaanalysis. Literature in English and Spanish is included from the first descriptions of the disease in the fifties, until the date of the investigation. Clinical management of patients is compared and recommendations published by consensus groups of international associations [es

  15. Voltage and Current Regulators Design of Power Converters in Islanded Microgrids based on State Feedback Decoupling

    DEFF Research Database (Denmark)

    Federico, de Bosio; de Sousa Ribeiro, Luiz Antonio; Freijedo Fernandez, Francisco Daniel

    2016-01-01

    In stand-alone microgrids based on voltage source inverters state feedback coupling between the capacitor voltage and inductor current degrades significantly the dynamics performance of voltage and current regulators. The decoupling of the controlled states is proposed, considering the limitations...

  16. Government regulation as an impetus for innovation: Evidence from energy performance regulation in the Dutch residential building sector

    International Nuclear Information System (INIS)

    Beerepoot, Milou; Beerepoot, Niels

    2007-01-01

    The recent implementation of energy performance policy as a way to tackle energy consumption in the building sector in Europe draws attention to the effect it has on the development and diffusion of energy-saving innovations. According to innovation system literature, government regulation through norms and standards is one of the factors stimulating innovation. This paper concentrates on the role of stricter government regulation as an incentive to innovation in the Dutch residential building sector. Innovation in this sector is predominantly a process of applying incremental modifications to comply with new and stricter government regulations and standards. Energy performance policy in its current shape will therefore not contribute to the diffusion of really new innovation in energy techniques for residential buildings in the Netherlands. If diffusion of really new innovation is an explicit aim of energy performance policy then the European wide introduction of this scheme needs reconsideration

  17. Current Evidence and Insights about Genetics in Thoracic Aorta Disease

    Science.gov (United States)

    Muneretto, Claudio

    2013-01-01

    Thoracic aortic aneurysms have been historically considered to be caused by etiologic factors similar to those implied in abdominal aortic aneurysms. However, during the past decade, there has been increasing evidence that almost 20% of thoracic aortic aneurysms may be associated with a genetic disease, often within a syndromic or familial disorder. Moreover, the presence of congenital anomalies, such as bicuspid aortic valve, may have a unique common genetic underlying cause. Finally, also sporadic forms have been found to be potentially associated with genetic disorders, as highlighted by the analysis of rare variants and expression of specific microRNAs. We therefore sought to perform a comprehensive review of the role of genetic causes in the development of thoracic aortic aneurysms, by analyzing in detail the current evidence of genetic alterations in syndromes such as Marfan, Loeys-Dietz, and Ehler-Danlos, familial or sporadic forms, or forms associated with bicuspid aortic valve. PMID:24453931

  18. SOME CONSIDERATIONS OVER THE INTERNAL CONTROL IN THE CONTEXT OF CURRENT ACCOUNTANCY REGULATIONS

    Directory of Open Access Journals (Sweden)

    Lenghel Dorin Radu

    2012-12-01

    Full Text Available Through the hereby study we set ourselves on an analysis over the internal control and the ways of implementation of it. The final purpose of our research is represented by the characteristics of the internal control system in the context of current accountancy regulations. The accomplishment of such goal has forced us to research the current literature in the area and also the legal regulations over internal control. Of course, the accomplishment of such a research was possible only after a pertinent analysis over the opinions expressed in specialty literature regarding this area. Our research wants to be with a theoretical and applicative character. It is based on analysing the internal control system, the methodology of internal control and the steps of internal control. We express our belief that the implementation of the internal control in a very exact manner comes as an aid to the company management and lead to the accomplishment of managerial objectives and policies. In what it regards the result of our research there can be drawn the following conclusions: from the legal regulations (OMFP nr. 3055/2009, there is no clear conclusion over the procedures and policies of implementation of internal control applicable to an economical entity; also there are not presented in a detailed way the types (forms of internal control, being presented in the legal regulations only a classification of them after the time in which they are exercised (before, during or after the finishing of the operations; also in the legal regulations there is developed a certain way of internal control, represented by the financial and accounting internal control, as if the other forms of internal control do not exist; in what regards the components of internal control, these are presented in another way, but similar to already known models of internal control (Coso and Coco; also in the legal regulations there are presented the general objectives of internal control

  19. Somatosensory tinnitus: Current evidence and future perspectives

    Science.gov (United States)

    Greco, Antonio; Turchetta, Rosaria; Altissimi, Giancarlo; de Vincentiis, Marco; Cianfrone, Giancarlo

    2017-01-01

    In some individuals, tinnitus can be modulated by specific maneuvers of the temporomandibular joint, head and neck, eyes, and limbs. Neuroplasticity seems to play a central role in this capacity for modulation, suggesting that abnormal interactions between the sensory modalities, sensorimotor systems, and neurocognitive and neuroemotional networks may contribute to the development of somatosensory tinnitus. Current evidence supports a link between somatic disorders and higher modulation of tinnitus, especially in patients with a normal hearing threshold. Patients with tinnitus who have somatic disorders seems to have a higher chance of modulating their tinnitus with somatic maneuvers; consistent improvements in tinnitus symptoms have been observed in patients with temporomandibular joint disease following targeted therapy for temporomandibular disorders. Somatosensory tinnitus is often overlooked by otolaryngologists and not fully investigated during the diagnostic process. Somatic disorders, when identified and treated, can be a valid therapeutic target for tinnitus; however, somatic screening of subjects for somatosensory tinnitus is imperative for correct selection of patients who would benefit from a multidisciplinary somatic approach. PMID:28553764

  20. Somatosensory tinnitus: Current evidence and future perspectives.

    Science.gov (United States)

    Ralli, Massimo; Greco, Antonio; Turchetta, Rosaria; Altissimi, Giancarlo; de Vincentiis, Marco; Cianfrone, Giancarlo

    2017-06-01

    In some individuals, tinnitus can be modulated by specific maneuvers of the temporomandibular joint, head and neck, eyes, and limbs. Neuroplasticity seems to play a central role in this capacity for modulation, suggesting that abnormal interactions between the sensory modalities, sensorimotor systems, and neurocognitive and neuroemotional networks may contribute to the development of somatosensory tinnitus. Current evidence supports a link between somatic disorders and higher modulation of tinnitus, especially in patients with a normal hearing threshold. Patients with tinnitus who have somatic disorders seems to have a higher chance of modulating their tinnitus with somatic maneuvers; consistent improvements in tinnitus symptoms have been observed in patients with temporomandibular joint disease following targeted therapy for temporomandibular disorders. Somatosensory tinnitus is often overlooked by otolaryngologists and not fully investigated during the diagnostic process. Somatic disorders, when identified and treated, can be a valid therapeutic target for tinnitus; however, somatic screening of subjects for somatosensory tinnitus is imperative for correct selection of patients who would benefit from a multidisciplinary somatic approach.

  1. Aldosterone down-regulates the slowly activated delayed rectifier potassium current in adult guinea pig cardiomyocytes.

    Science.gov (United States)

    Lv, Yankun; Bai, Song; Zhang, Hua; Zhang, Hongxue; Meng, Jing; Li, Li; Xu, Yanfang

    2015-12-01

    There is emerging evidence that the mineralocorticoid hormone aldosterone is associated with arrhythmias in cardiovascular disease. However, the effect of aldosterone on the slowly activated delayed rectifier potassium current (IK s ) remains poorly understood. The present study was designed to investigate the modulation of IK s by aldosterone. Adult guinea pigs were treated with aldosterone for 28 days via osmotic pumps. Standard glass microelectrode recordings and whole-cell patch-clamp techniques were used to record action potentials in papillary muscles and IK s in ventricular cardiomyocytes. The aldosterone-treated animals exhibited a prolongation of the QT interval and action potential duration with a higher incidence of early afterdepolarizations. Patch-clamp recordings showed a significant down-regulation of IK s density in the ventricular myocytes of these treated animals. These aldosterone-induced electrophysiological changes were fully prevented by a combined treatment with spironolactone, a mineralocorticoid receptor (MR) antagonist. In addition, in in vitro cultured ventricular cardiomyocytes, treatment with aldosterone (sustained exposure for 24 h) decreased the IK s density in a concentration-dependent manner. Furthermore, a significant corresponding reduction in the mRNA/protein expression of IKs channel pore and auxiliary subunits, KCNQ1 and KCNE1 was detected in ventricular tissue from the aldosterone-treated animals. Aldosterone down-regulates IK s by inhibiting the expression of KCNQ1 and KCNE1, thus delaying the ventricular repolarization. These results provide new insights into the mechanism underlying K(+) channel remodelling in heart disease and may explain the highly beneficial effects of MR antagonists in HF. © 2015 The British Pharmacological Society.

  2. Robotic general surgery: current practice, evidence, and perspective.

    Science.gov (United States)

    Jung, M; Morel, P; Buehler, L; Buchs, N C; Hagen, M E

    2015-04-01

    Robotic technology commenced to be adopted for the field of general surgery in the 1990s. Since then, the da Vinci surgical system (Intuitive Surgical Inc, Sunnyvale, CA, USA) has remained by far the most commonly used system in this domain. The da Vinci surgical system is a master-slave machine that offers three-dimensional vision, articulated instruments with seven degrees of freedom, and additional software features such as motion scaling and tremor filtration. The specific design allows hand-eye alignment with intuitive control of the minimally invasive instruments. As such, robotic surgery appears technologically superior when compared with laparoscopy by overcoming some of the technical limitations that are imposed on the surgeon by the conventional approach. This article reviews the current literature and the perspective of robotic general surgery. While robotics has been applied to a wide range of general surgery procedures, its precise role in this field remains a subject of further research. Until now, only limited clinical evidence that could establish the use of robotics as the gold standard for procedures of general surgery has been created. While surgical robotics is still in its infancy with multiple novel systems currently under development and clinical trials in progress, the opportunities for this technology appear endless, and robotics should have a lasting impact to the field of general surgery.

  3. Asthma and obesity in children: current evidence and potential systems biology approaches.

    Science.gov (United States)

    Frey, U; Latzin, P; Usemann, J; Maccora, J; Zumsteg, U; Kriemler, S

    2015-01-01

    Both obesity and asthma are highly prevalent, complex diseases modified by multiple factors. Genetic, developmental, lung mechanical, immunological and behavioural factors have all been suggested as playing a causal role between the two entities; however, their complex mechanistic interactions are still poorly understood and evidence of causality in children remains scant. Equally lacking is evidence of effective treatment strategies, despite the fact that imbalances at vulnerable phases in childhood can impact long-term health. This review is targeted at both clinicians frequently faced with the dilemma of how to investigate and treat the obese asthmatic child and researchers interested in the topic. Highlighting the breadth of the spectrum of factors involved, this review collates evidence regarding the investigation and treatment of asthma in obese children, particularly in comparison with current approaches in 'difficult-to-treat' childhood asthma. Finally, the authors propose hypotheses for future research from a systems-based perspective. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  4. Osmosensory mechanisms in cellular and systemic volume regulation

    DEFF Research Database (Denmark)

    Pedersen, Stine Helene Falsig; Kapus, András; Hoffmann, Else K

    2011-01-01

    Perturbations of cellular and systemic osmolarity severely challenge the function of all organisms and are consequently regulated very tightly. Here we outline current evidence on how cells sense volume perturbations, with particular focus on mechanisms relevant to the kidneys and to extracellular...

  5. How can the regulator show evidence of (no) risk selection in health insurance markets? Conceptual framework and empirical evidence.

    Science.gov (United States)

    van de Ven, Wynand P M M; van Vliet, René C J A; van Kleef, Richard C

    2017-03-01

    If consumers have a choice of health plan, risk selection is often a serious problem (e.g., as in Germany, Israel, the Netherlands, the United States of America, and Switzerland). Risk selection may threaten the quality of care for chronically ill people, and may reduce the affordability and efficiency of healthcare. Therefore, an important question is: how can the regulator show evidence of (no) risk selection? Although this seems easy, showing such evidence is not straightforward. The novelty of this paper is two-fold. First, we provide a conceptual framework for showing evidence of risk selection in competitive health insurance markets. It is not easy to disentangle risk selection and the insurers' efficiency. We suggest two methods to measure risk selection that are not biased by the insurers' efficiency. Because these measures underestimate the true risk selection, we also provide a list of signals of selection that can be measured and that, in particular in combination, can show evidence of risk selection. It is impossible to show the absence of risk selection. Second, we empirically measure risk selection among the switchers, taking into account the insurers' efficiency. Based on 2-year administrative data on healthcare expenses and risk characteristics of nearly all individuals with basic health insurance in the Netherlands (N > 16 million) we find significant risk selection for most health insurers. This is the first publication of hard empirical evidence of risk selection in the Dutch health insurance market.

  6. Exploring Faraday's Law of Electrolysis Using Zinc-Air Batteries with Current Regulative Diodes

    Science.gov (United States)

    Kamata, Masahiro; Paku, Miei

    2007-01-01

    Current regulative diodes (CRDs) are applied to develop new educational experiments on Faraday's law by using a zinc-air battery (PR2330) and a resistor to discharge it. The results concluded that the combination of zinc-air batteries and the CRD array is simpler, less expensive, and quantitative and gives accurate data.

  7. The Built Environment and Child Health: An Overview of Current Evidence.

    Science.gov (United States)

    Gascon, Mireia; Vrijheid, Martine; Nieuwenhuijsen, Mark J

    2016-09-01

    Urbanization and the shaping of the built environment have provided a number of socioeconomic benefits, but they have also brought unwanted side effects on health. We aimed to review the current epidemiological evidence of the associations between the built environment, closely related exposures, and child health. We focused on growth and obesity, neuropsychological development, and respiratory and immune health. We used existing review articles and supplemented these with relevant work published and not included in existing reviews. The present review shows that there is good evidence for an association between air pollution and fetal growth restriction and respiratory health, whereas for other exposure and outcome combinations, further evidence is needed. Future studies should make efforts to integrate the different built environment features and to include the evaluation of environments other than home, as well as accessibility, qualitative and perception assessment of the built environment, and, if possible, with improved and standardized tools to facilitate comparability between studies. Efforts are also needed to conduct longitudinal and intervention studies and to understand potential mechanisms behind the associations observed. Finally, studies in low- and middle-income countries are needed.

  8. Evidence for the negative impact of reward on self-regulated learning.

    Science.gov (United States)

    Wehe, Hillary S; Rhodes, Matthew G; Seger, Carol A

    2015-01-01

    The undermining effect refers to the detrimental impact rewards can have on intrinsic motivation to engage in a behaviour. The current study tested the hypothesis that participants' self-regulated learning behaviours are susceptible to the undermining effect. Participants were assigned to learn a set of Swahili-English word pairs. Half of the participants were offered a reward for performance, and half were not offered a reward. After the initial study phase, participants were permitted to continue studying the words during a free period. The results were consistent with an undermining effect: Participants who were not offered a reward spent more time studying the words during the free period. The results suggest that rewards may negatively impact self-regulated learning behaviours and provide support for the encouragement of intrinsic motivation.

  9. Dancing with Hormones: A Current Perspective of Nitrate Signaling and Regulation in Arabidopsis

    Directory of Open Access Journals (Sweden)

    Peizhu Guan

    2017-09-01

    Full Text Available In nature and agriculture, nitrate availability is a main environmental cue for plant growth, development and stress responses. Nitrate signaling and regulation are hence at the center of communications between plant intrinsic programs and the environment. It is also well known that endogenous phytohormones play numerous critical roles in integrating extrinsic cues and intrinsic responses, regulating and refining almost all aspects of plant growth, development and stress responses. Therefore, interaction between nitrate and phytohormones, such as auxins, cytokinins, abscisic acid, gibberellins, and ethylene, is prevalent. The growing evidence indicates that biosynthesis, de-conjugation, transport, and signaling of hormones are partly controlled by nitrate signaling. Recent advances with nitrate signaling and transcriptional regulation in Arabidopsis give rise to new paradigms. Given the comprehensive nitrate transport, sensing, signaling and regulations at the level of the cell and organism, nitrate itself is a local and long-distance signal molecule, conveying N status at the whole-plant level. A direct molecular link between nitrate signaling and cell cycle progression was revealed with TEOSINTE BRANCHED1/CYCLOIDEA/PROLIFERATING CELL FACTOR1-20 (TCP20 – NIN-LIKE PROTEIN 6/7 (NLP6/7 regulatory nexus. NLPs are key regulators of nitrogen responses in plants. TCPs function as the main regulators of plant morphology and architecture, with the emerging role as integrators of plant developmental responses to the environment. By analogy with auxin being proposed as a plant morphogen, nitrate may be an environmental morphogen. The morphogen-gradient-dependent and cell-autonomous mechanisms of nitrate signaling and regulation are an integral part of cell growth and cell identification. This is especially true in root meristem growth that is regulated by intertwined nitrate, phytohormones, and glucose-TOR signaling pathways. Furthermore, the nitrate

  10. Therapeutic Use of Prebiotics, Probiotics, and Postbiotics to Prevent Necrotizing Enterocolitis: What is the Current Evidence?

    Science.gov (United States)

    Patel, Ravi Mangal; Denning, Patricia Wei

    2013-01-01

    Synopsis Necrotizing enterocolitis (NEC) is a leading cause of neonatal morbidity and mortality and preventative therapies that are both effective and safe are urgently needed. Current evidence from therapeutic trials suggests that probiotics are effective in decreasing NEC in preterm infants and probiotics are currently the most promising therapy on the horizon for this devastating disease. However, concerns regarding safety and optimal dosing have limited the widespread adoption of routine clinical use of probiotics in preterm infants. In addition, prebiotics and postbiotics may be potential alternatives or adjunctive therapies to the administration of live microorganisms, although studies demonstrating their clinical efficacy in preventing NEC are lacking. This review summarizes the current evidence regarding the use of probiotics, prebiotics and postbiotics in the preterm infant, including its therapeutic role in preventing NEC. PMID:23415261

  11. Flexible Power Regulation and Current-limited Control of Grid-connected Inverter under Unbalanced Grid Voltage Faults

    DEFF Research Database (Denmark)

    Guo, Xiaoqiang; Liu, Wenzhao; Lu, Zhigang

    2017-01-01

    The grid-connected inverters may experience excessive current stress in case of unbalanced grid voltage Fault Ride Through (FRT), which significantly affects the reliability of the power supply system. In order to solve the problem, the inherent mechanisms of the excessive current phenomenon...... with the conventional FRT solutions are discussed. The quantitative analysis of three phase current peak values are conducted and a novel current-limited control strategy is proposed to achieve the flexible active and reactive power regulation and successful FRT in a safe current operation area with the aim...

  12. Metastatic non-small cell lung cancer Current treatment based on evidence (ONCOL Group)

    International Nuclear Information System (INIS)

    Castro, Carlos; Cardona, Andres Felipe; Reveiz, Ludovic; Serrano, Silvia Juliana; Carranza, Hernan; Vargas, Carlos Alberto; Reguart, Noemi; Campo, Felipe; Ospina, Edgar Guillermo; Sanchez, Oswaldo; Torres, Diana; Otero, Jorge Miguel

    2010-01-01

    to perform a review of evidence about the treatment of non-small cell lung cancer (NSCLC). Source of data: the information was obtained from searches conducted in Medline, CCTR, Biosis, Embase, Lilacs and CINHAL. We also collected the most representative references presented during the last five years at Asco, ESMO and IASLC. Data extraction: data were extracted by associate members to the ONCOL Group. The collection of information did not follow a uniform strategy. Results of data synthesis: therapy for NSCLC can prolong survival and improve quality of life, but the majority of advanced stage patients dies due to disease progression within 2 years, meaning that there is room for improvement. The standard chemotherapy for NSCLC involves one of a number of platinum-based doublets that have been shown to improve survival when compared with single agents or best supportive care. These doublets are generally comparable in terms of efficacy, differing primarily in their toxicity profiles. However, encouraging new options may be approaching, including therapies targeted to specific patient subpopulations, and the use of combinations of current and new drugs to produce synergistic effects. This review present a detailed analysis of current evidence regarding the treatment of NSCLC based on a representative case series. This review didn't conduct a systematic evaluation of the evidence. Conclusion: medical therapy for NSCLC produces positive changes in main outcomes, including quality of life

  13. Evidence and effects of a wave-driven nonlinear current in the equatorial electrojet

    Directory of Open Access Journals (Sweden)

    M. Oppenheim

    1997-07-01

    Full Text Available Ionospheric two-stream waves and gradient-drift waves nonlinearly drive a large-scale (D.C. current in the E-region ionosphere. This current flows parallel to, and with a comparable magnitude to, the fundamental Pedersen current. Evidence for the existence and magnitude of wave-driven currents derives from a theoretical understanding of E-region waves, supported by a series of nonlinear 2D simulations of two-stream waves and by data collected by rocket instruments in the equatorial electrojet. Wave-driven currents will modify the large-scale dynamics of the equatorial electrojet during highly active periods. A simple model shows how a wave-driven current appreciably reduces the horizontally flowing electron current of the electrojet. This reduction may account for the observation that type-I radar echoes almost always have a Doppler velocity close to the acoustic speed, and also for the rocket observation that electrojet regions containing gradient-drift waves do not appear also to contain horizontally propagating two-stream waves. Additionally, a simple model of a gradient-drift instability shows that wave-driven currents can cause nonsinusoidal electric fields similar to those measured in situ.

  14. Deficits in general emotion regulation skills-Evidence of a transdiagnostic factor.

    Science.gov (United States)

    Lukas, Christian Aljoscha; Ebert, David Daniel; Fuentes, Hugo Trevisi; Caspar, Franz; Berking, Matthias

    2017-12-15

    Deficits in emotion regulation (ER) skills are discussed as a transdiagnostic factor contributing to the development and maintenance of various mental disorders. However, systematic comparisons of a broad range of ER skills across diagnostic groups that are based on comparable definitions and measures of ER are still rare. Therefore, we conducted two studies assessing a broad range of ER skills with the Emotion Regulation Skills Questionnaire in individuals meeting criteria for mental disorders (N 1  = 1448; N 2  = 137) and in a general population sample (N = 214). Consistent across the two studies, participants in the clinical samples reported lower general and lower specific ER skills than participants in the general population sample. Also consistent across the two studies, diagnostic subgroups of the clinical samples differed significantly with regard to general and specific ER skills. The studies provide evidence that deficits in ER are associated with various forms of psychopathology. However, mental disorders seem to differ with regard to how strongly they are linked to ER skills. © 2017 Wiley Periodicals, Inc.

  15. Regulating Rumination by Anger: Evidence for the Mutual Promotion and Counteraction (MPMC Theory of Emotionality

    Directory of Open Access Journals (Sweden)

    Jun Zhan

    2017-12-01

    Full Text Available Unlike the strategy of cognitive regulation that relies heavily on the top-down control function of the prefrontal cortex (PFC, which was recently found may be critically impaired in stressful situations, traditional Chinese philosophy and medicine views different types of emotionality as having mutual promotion and counteraction (MPMC relationships, implying a novel approach that requires less cognition to emotional regulation. Actually, our previous studies have indicated that anger responses could be successfully regulated via the induction of sadness, and this efficiency could not be influenced by stress, thus providing evidences for the hypothesis of “sadness counteracts anger” (SCA proposed by the MPMC theory of emotionality (Zhan et al., 2015, 2017. In this study, we experimentally examined the MPMC hypothesis that “anger counteracts rumination” (ACR which postulates that rumination may be alleviated by the anger emotion. In Study 1, all participants were initially caused state rumination and then induced anger, joy or neutral mood, the results showed that the rumination-related affect was alleviated after anger induction relative to that after joy or neutral mood induction. In Study 2, female participants with high trait rumination were recruited and divided into two groups for exposure to an anger or neutral emotion intervention, the result indicated that the anger intervention group exhibited a greater decline in trait rumination than the neutral emotion intervention group. These findings provided preliminary evidence supporting the hypothesis of ACR, which suggested a new strategy that employs less cognitive resources to regulating state and trait rumination by inducing anger.

  16. Regulating Rumination by Anger: Evidence for the Mutual Promotion and Counteraction (MPMC) Theory of Emotionality

    Science.gov (United States)

    Zhan, Jun; Tang, Fan; He, Mei; Fan, Jin; Xiao, Jing; Liu, Chang; Luo, Jing

    2017-01-01

    Unlike the strategy of cognitive regulation that relies heavily on the top-down control function of the prefrontal cortex (PFC), which was recently found may be critically impaired in stressful situations, traditional Chinese philosophy and medicine views different types of emotionality as having mutual promotion and counteraction (MPMC) relationships, implying a novel approach that requires less cognition to emotional regulation. Actually, our previous studies have indicated that anger responses could be successfully regulated via the induction of sadness, and this efficiency could not be influenced by stress, thus providing evidences for the hypothesis of “sadness counteracts anger” (SCA) proposed by the MPMC theory of emotionality (Zhan et al., 2015, 2017). In this study, we experimentally examined the MPMC hypothesis that “anger counteracts rumination” (ACR) which postulates that rumination may be alleviated by the anger emotion. In Study 1, all participants were initially caused state rumination and then induced anger, joy or neutral mood, the results showed that the rumination-related affect was alleviated after anger induction relative to that after joy or neutral mood induction. In Study 2, female participants with high trait rumination were recruited and divided into two groups for exposure to an anger or neutral emotion intervention, the result indicated that the anger intervention group exhibited a greater decline in trait rumination than the neutral emotion intervention group. These findings provided preliminary evidence supporting the hypothesis of ACR, which suggested a new strategy that employs less cognitive resources to regulating state and trait rumination by inducing anger. PMID:29249998

  17. Factors affecting the regulation of pacing: current perspectives

    Directory of Open Access Journals (Sweden)

    Mauger AR

    2014-09-01

    Full Text Available Alexis R Mauger Endurance Research Group, School of Sport and Exercise Sciences, Faculty of Science, University of Kent, Chatham, UK Abstract: During prolonged dynamic and rhythmic exercise, muscular pain and discomfort arises as a result of an increased concentration of deleterious metabolites. Sensed by peripheral nociceptors and transmitted via afferent feedback to the brain, this provides important information regarding the physiological state of the muscle. These sensations ultimately contribute to what is termed "exercise-induced pain". Despite being well recognized by athletes and coaches, and suggested to be integral to exercise performance, this construct has largely escaped attention in experimental work. This perspective article highlights the current understanding of pacing in endurance performance, and the causes of exercise-induced pain. A new perspective is described, which proposes how exercise-induced pain may be a contributing factor in helping individuals to regulate their work rate during exercise and thus provides an important construct in pacing. Keywords: pain, exercise-induced pain, discomfort, exercise performance, self-paced

  18. Environmental regulation and competitiveness: Empirical evidence on the Porter Hypothesis from European manufacturing sectors

    International Nuclear Information System (INIS)

    Rubashkina, Yana; Galeotti, Marzio; Verdolini, Elena

    2015-01-01

    This paper investigates the “weak” and “strong” versions of Porter Hypothesis (PH) focusing on the manufacturing sectors of 17 European countries between 1997 and 2009. The hypothesis that well-crafted and well-enforced regulation would benefit both the environment and the firm was originally proposed by Porter (1991) and Porter and van der Linde (1995). To date, the literature has analyzed the impact of environmental regulation on innovation and on productivity mostly in separate analyses and focusing on the USA. The few existing contributions on Europe study the effect of environmental regulation either on green innovation or on performance indicators such as exports. We instead look at overall innovation and productivity impacts. First, focusing on overall innovative activity allows us to account for potential opportunity costs of induced innovations. Second, productivity impacts are arguably the most relevant indicators for the “strong” PH. As a proxy of environmental policy stringency we use pollution abatement and control expenditures (PACE), one of the few sectoral level indicators available. We remedy upon its main drawback, namely potential endogeneity, by adopting an instrumental variable estimation approach. We find evidence of a positive impact of environmental regulation on the output of innovation activity, as proxied by patents, thus providing support in favor of the “weak” PH. This result is in line with most of the literature. On the other front, we find no evidence in favor of the “strong” PH, as productivity appears to be unaffected by the degree of pollution control and abatement efforts. -- Highlights: •Weak and strong Porter Hypothesis. •Panel of manufacturing sectors of 17 European countries between 1997 and 2009. •Look at overall innovation and productivity impacts. •Pollution abatement & control expenditures proxy of environmental policy stringency. •Account for potential endogeneity of PACE by adopting

  19. Reduced density and altered regulation of rat atrial L-type Ca2+ current in heart failure.

    Science.gov (United States)

    Bond, Richard C; Bryant, Simon M; Watson, Judy J; Hancox, Jules C; Orchard, Clive H; James, Andrew F

    2017-03-01

    Constitutive regulation by PKA has recently been shown to contribute to L-type Ca 2+ current ( I CaL ) at the ventricular t-tubule in heart failure. Conversely, reduction in constitutive regulation by PKA has been proposed to underlie the downregulation of atrial I CaL in heart failure. The hypothesis that downregulation of atrial I CaL in heart failure involves reduced channel phosphorylation was examined. Anesthetized adult male Wistar rats underwent surgical coronary artery ligation (CAL, N =10) or equivalent sham-operation (Sham, N =12). Left atrial myocytes were isolated ~18 wk postsurgery and whole cell currents recorded (holding potential=-80 mV). I CaL activated by depolarizing pulses to voltages from -40 to +50 mV were normalized to cell capacitance and current density-voltage relations plotted. CAL cell capacitances were ~1.67-fold greater than Sham ( P ≤ 0.0001). Maximal I CaL conductance ( G max ) was downregulated more than 2-fold in CAL vs. Sham myocytes ( P 50% more effectively in CAL than in Sham so that differences in I CaL density were abolished. Differences between CAL and Sham G max were not abolished by calyculin A (100 nmol/l), suggesting that increased protein dephosphorylation did not account for I CaL downregulation. Treatment with either H-89 (10 μmol/l) or AIP (5 μmol/l) had no effect on basal currents in Sham or CAL myocytes, indicating that, in contrast to ventricular myocytes, neither PKA nor CaMKII regulated basal I CaL Expression of the L-type α 1C -subunit, protein phosphatases 1 and 2A, and inhibitor-1 proteins was unchanged. In conclusion, reduction in PKA-dependent regulation did not contribute to downregulation of atrial I CaL in heart failure. NEW & NOTEWORTHY Whole cell recording of L-type Ca 2+ currents in atrial myocytes from rat hearts subjected to coronary artery ligation compared with those from sham-operated controls reveals marked reduction in current density in heart failure without change in channel subunit

  20. Vitamin E in Sarcopenia: Current Evidences on Its Role in Prevention and Treatment

    Directory of Open Access Journals (Sweden)

    Shy Cian Khor

    2014-01-01

    Full Text Available Sarcopenia is a geriatric syndrome that is characterized by gradual loss of muscle mass and strength with increasing age. Although the underlying mechanism is still unknown, the contribution of increased oxidative stress in advanced age has been recognized as one of the risk factors of sarcopenia. Thus, eliminating reactive oxygen species (ROS can be a strategy to combat sarcopenia. In this review, we discuss the potential role of vitamin E in the prevention and treatment of sarcopenia. Vitamin E is a lipid soluble vitamin, with potent antioxidant properties and current evidence suggesting a role in the modulation of signaling pathways. Previous studies have shown its possible beneficial effects on aging and age-related diseases. Although there are evidences suggesting an association between vitamin E and muscle health, they are still inconclusive compared to other more extensively studied chronic diseases such as neurodegenerative diseases and cardiovascular diseases. Therefore, we reviewed the role of vitamin E and its potential protective mechanisms on muscle health based on previous and current in vitro and in vivo studies.

  1. Intermittent fasting and cardiovascular disease: current evidence and unresolved questions.

    Science.gov (United States)

    Tinsley, Grant M; Horne, Benjamin D

    2018-01-01

    Intermittent fasting has produced a variety of beneficial health effects in animal models, although high-quality research in humans has been limited. This special report examines current evidences for intermittent fasting in humans, discusses issues that require further examination, and recommends new research that can improve the knowledge base in this emerging research area. While potentially useful for health improvement, intermittent fasting requires further study prior to widespread implementation for health purposes. Randomized, longer-term studies are needed to determine whether using intermittent fasting as a lifestyle rather than a diet is feasible and beneficial for the health of some members of the human population.

  2. Integrative Therapies and Pediatric Inflammatory Bowel Disease: The Current Evidence.

    Science.gov (United States)

    Misra, Sanghamitra M

    2014-08-25

    Inflammatory bowel disease (IBD) primarily describes two distinct chronic conditions with unknown etiology, ulcerative colitis (UC) and Crohn's disease (CD). UC is limited to the colon, while CD may involve any portion of the gastrointestinal tract from mouth to anus. These diseases exhibit a pattern of relapse and remission, and the disease processes are often painful and debilitating. Due to the chronic nature of IBD and the negative side effects of many of the conventional therapies, many patients and their families turn to complementary and alternative medicine (CAM) for symptom relief. This article focuses on the current available evidence behind CAM/integrative therapies for IBD.

  3. Sixty years of fear appeal research: current state of the evidence.

    Science.gov (United States)

    Ruiter, Robert A C; Kessels, Loes T E; Peters, Gjalt-Jorn Y; Kok, Gerjo

    2014-04-01

    Fear arousal is widely used in persuasive campaigns and behavioral change interventions. Yet, experimental evidence argues against the use of threatening health information. The authors reviewed the current state of empirical evidence on the effectiveness of fear appeals. Following a brief overview of the use of fear arousal in health education practice and the structure of effective fear appeals according to two main theoretical frameworks-protection motivation theory and the extended parallel process model-the findings of six meta-analytic studies in the effectiveness of fear appeals are summarized. It is concluded that coping information aimed at increasing perceptions of response effectiveness and especially self-efficacy is more important in promoting protective action than presenting threatening health information aimed at increasing risk perceptions and fear arousal. Alternative behavior change methods than fear appeals should be considered. © 2014 The Authors. International Journal of Psychology published by John Wiley © Sons Ltd on behalf of International Union of Psychological Science.

  4. How Toddlers Think with Their Hands: Social and Private Gestures as Evidence of Cognitive Self-Regulation in Guided Play with Objects

    Science.gov (United States)

    Basilio, Marisol; Rodríguez, Cintia

    2017-01-01

    The role of language as a tool to support the self-regulation has been widely studied, yet there is little evidence on the role of prelinguistic communication in the early development of self-regulation. To address this gap, we developed behavioural indicators of preverbal cognitive self-regulation, and described how can parents support it through…

  5. Male circumcision for HIV prevention: current evidence and implementation in sub-Saharan Africa

    Science.gov (United States)

    2011-01-01

    Heterosexual exposure accounts for most HIV transmission in sub-Saharan Africa, and this mode, as a proportion of new infections, is escalating globally. The scientific evidence accumulated over more than 20 years shows that among the strategies advocated during this period for HIV prevention, male circumcision is one of, if not, the most efficacious epidemiologically, as well as cost-wise. Despite this, and recommendation of the procedure by global policy makers, national implementation has been slow. Additionally, some are not convinced of the protective effect of male circumcision and there are also reports, unsupported by evidence, that non-sex-related drivers play a major role in HIV transmission in sub-Saharan Africa. Here, we provide a critical evaluation of the state of the current evidence for male circumcision in reducing HIV infection in light of established transmission drivers, provide an update on programmes now in place in this region, and explain why policies based on established scientific evidence should be prioritized. We conclude that the evidence supports the need to accelerate the implementation of medical male circumcision programmes for HIV prevention in generalized heterosexual epidemics, as well as in countering the growing heterosexual transmission in countries where HIV prevalence is presently low. PMID:22014096

  6. Evidence-based medicine is affordable: the cost-effectiveness of current compared with optimal treatment in rheumatoid and osteoarthritis.

    Science.gov (United States)

    Andrews, Gavin; Simonella, Leonardo; Lapsley, Helen; Sanderson, Kristy; March, Lyn

    2006-04-01

    To determine the cost-effectiveness of averting the burden of disease. We used secondary population data and metaanalyses of various government-funded services and interventions to investigate the costs and benefits of various levels of treatment for rheumatoid arthritis (RA) and osteoarthritis (OA) in adults using a burden of disease framework. Population burden was calculated for both diseases in the absence of any treatment as years lived with disability (YLD), ignoring the years of life lost. We then estimated the proportion of burden averted with current interventions, the proportion that could be averted with optimally implemented current evidence-based guidelines, and the direct treatment cost-effectiveness ratio in dollars per YLD averted for both treatment levels. The majority of people with arthritis sought medical treatment. Current treatment for RA averted 26% of the burden, with a cost-effectiveness ratio of dollar 19,000 per YLD averted. Optimal, evidence-based treatment would avert 48% of the burden, with a cost-effectiveness ratio of dollar 12,000 per YLD averted. Current treatment of OA in Australia averted 27% of the burden, with a cost-effectiveness ratio of dollar 25,000 per YLD averted. Optimal, evidence-based treatment would avert 39% of the burden, with an unchanged cost-effectiveness ratio of dollar 25,000 per YLD averted. While the precise dollar costs in each country will differ, the relativities at this level of coverage should remain the same. There is no evidence that closing the gap between evidence and practice would result in a drop in efficiency.

  7. Design and implementation of a bidirectional current-controlled voltage-regulated DC-DC switched-mode converter

    CSIR Research Space (South Africa)

    Coetzer, A

    2016-01-01

    Full Text Available The design and implementation of a bidirectional current-controlled voltage-regulated DC-DC converter is presented. The converter is required to connect a battery of electrochemical cells (the battery) to an asynchronous motor-drive unit via a...

  8. Scapulothoracic bursitis and snapping scapula syndrome: a critical review of current evidence.

    Science.gov (United States)

    Warth, Ryan J; Spiegl, Ulrich J; Millett, Peter J

    2015-01-01

    Symptomatic scapulothoracic disorders, such as painful scapular crepitus and/or bursitis, are uncommon; however, they can produce significant pain and disability in many patients. To review the current knowledge pertaining to snapping scapula syndrome and to identify areas of further research that may be helpful to improve clinical outcomes and patient satisfaction. Systematic review. We performed a preliminary search of the PubMed and Embase databases using the search terms "snapping scapula," "scapulothoracic bursitis," "partial scapulectomy," and "superomedial angle resection" in September 2013. All nonreview articles related to the topic of snapping scapula syndrome were included. The search identified a total of 167 unique articles, 81 of which were relevant to the topic of snapping scapula syndrome. There were 36 case series of fewer than 10 patients, 16 technique papers, 11 imaging studies, 9 anatomic studies, and 9 level IV outcomes studies. The level of evidence obtained from this literature search was inadequate to perform a formal systematic review or meta-analysis. Therefore, a critical review of current evidence is presented. Snapping scapula syndrome, a likely underdiagnosed condition, can produce significant shoulder dysfunction in many patients. Because the precise origin is typically unknown, specific treatments that are effective for some patients may not be effective for others. Nevertheless, bursectomy with or without partial scapulectomy is currently the most effective primary method of treatment in patients who fail nonoperative therapy. However, many patients experience continued shoulder disability even after surgical intervention. Future studies should focus on identifying the modifiable factors associated with poor outcomes after operative and nonoperative management for snapping scapula syndrome in an effort to improve clinical outcomes and patient satisfaction. © 2014 The Author(s).

  9. Design and construction of constant voltage and current regulated source with proper characteristics to be used in electronics laboratory designs

    International Nuclear Information System (INIS)

    Peon A, R.

    1978-01-01

    A regulated direct current feeding source was designed for the Nuclear Energy National Institute Electronics Labortory, with the following characteristics: a) voltage input 105-130V a.c. 50-60 Hz; b) voltage output 0.40 V d.c.; c) output current 0-2 Amp d.c.; d) load regulation 0.001%; e) line regulation 0.001%; f) ripple and noise 200 μ Vpp; g) temperature interval 3-60 0 C; h) stability 0.5%; i) output impedance as voltage source 0.01 ohms; j) transient response 50 μ seg. Besides of operating normally, that is as voltage source or current-source through the front controls, the source can be used and interconnected with one or other compatible sources (autoseries, autoparallel and programmed reference). The source will cost 70,000 pesos approximately. (author)

  10. A Novel Wide-Area Backup Protection Based on Fault Component Current Distribution and Improved Evidence Theory

    Directory of Open Access Journals (Sweden)

    Zhe Zhang

    2014-01-01

    Full Text Available In order to solve the problems of the existing wide-area backup protection (WABP algorithms, the paper proposes a novel WABP algorithm based on the distribution characteristics of fault component current and improved Dempster/Shafer (D-S evidence theory. When a fault occurs, slave substations transmit to master station the amplitudes of fault component currents of transmission lines which are the closest to fault element. Then master substation identifies suspicious faulty lines according to the distribution characteristics of fault component current. After that, the master substation will identify the actual faulty line with improved D-S evidence theory based on the action states of traditional protections and direction components of these suspicious faulty lines. The simulation examples based on IEEE 10-generator-39-bus system show that the proposed WABP algorithm has an excellent performance. The algorithm has low requirement of sampling synchronization, small wide-area communication flow, and high fault tolerance.

  11. A Novel Wide-Area Backup Protection Based on Fault Component Current Distribution and Improved Evidence Theory

    Science.gov (United States)

    Zhang, Zhe; Kong, Xiangping; Yin, Xianggen; Yang, Zengli; Wang, Lijun

    2014-01-01

    In order to solve the problems of the existing wide-area backup protection (WABP) algorithms, the paper proposes a novel WABP algorithm based on the distribution characteristics of fault component current and improved Dempster/Shafer (D-S) evidence theory. When a fault occurs, slave substations transmit to master station the amplitudes of fault component currents of transmission lines which are the closest to fault element. Then master substation identifies suspicious faulty lines according to the distribution characteristics of fault component current. After that, the master substation will identify the actual faulty line with improved D-S evidence theory based on the action states of traditional protections and direction components of these suspicious faulty lines. The simulation examples based on IEEE 10-generator-39-bus system show that the proposed WABP algorithm has an excellent performance. The algorithm has low requirement of sampling synchronization, small wide-area communication flow, and high fault tolerance. PMID:25050399

  12. Regulation of alcohol advertising: Policy options for Australia

    Directory of Open Access Journals (Sweden)

    Sandra C. Jones

    2013-06-01

    Full Text Available A systematic search of academic databases was conducted to identify all refereed papers published between 1990 and 2012 on the regulation of alcohol advertising in Australia and three comparison countries (New Zealand, Canada and the UK. This paper reviews the codes that apply to alcohol advertising in each of the four countries, research into the effectiveness of these codes, and the small body of research into consumer attitudes towards alcohol advertising regulation. This review adduces considerable evidence that alcohol advertising influences drinking behaviours, and that current regulatory systems based on co-regulation and voluntary regulation (as is the case in Australia are ineffective. Recommendations are provided regarding the three pillars of regulation: volume restrictions, content restrictions, and infrastructure to support the regulatory environment.

  13. Is There an Opportunity for Current Chemotherapeutics to Up-regulate MIC-A/B Ligands?

    Directory of Open Access Journals (Sweden)

    Kendel Quirk

    2017-10-01

    Full Text Available Natural killer (NK cells are critical effectors of the immune system. NK cells recognize unhealthy cells by specific ligands [e.g., MHC- class I chain related protein A or B (MIC-A/B] for further elimination by cytotoxicity. Paradoxically, cancer cells down-regulate MIC-A/B and evade NK cell’s anticancer activity. Recent data indicate that cellular-stress induces MIC-A/B, leading to enhanced sensitivity of cancer cells to NK cell-mediated cytotoxicity. In this Perspective article, we hypothesize that current chemotherapeutics at sub-lethal, non-toxic dose may promote cellular-stress and up-regulate the expression of MIC-A/B ligands to augment cancer’s sensitivity to NK cell-mediated cytotoxicity. Preliminary data from two human breast cancer cell lines, MDA-MB-231 and T47D treated with clinically relevant therapeutics such as doxorubicin, paclitaxel and methotrexate support the hypothesis. The goal of this Perspective is to underscore the prospects of current chemotherapeutics in NK cell immunotherapy, and discuss potential challenges and opportunities to improve cancer therapy.

  14. Price regulation and relative price convergence: Evidence from the retail gasoline market in Canada

    International Nuclear Information System (INIS)

    Suvankulov, Farrukh; Lau, Marco Chi Keung; Ogucu, Fatma

    2012-01-01

    This paper explores price regulation and relative price convergence in the Canadian retail gasoline market. We use monthly data (2000–2010) on retail gasoline prices in 60 Canadian cities to investigate (i) whether the retail gasoline market in Canada has experienced a relative price convergence to the mean, which is expected, given the increased economic integration across Canadian provinces; and (ii) whether the introduction of price regulation mechanisms in New Brunswick and Nova Scotia in July 2006 had any impact on the price convergence in these provinces. We use a nonlinear panel unit root test and find solid evidence that Canadian retail gasoline markets are well integrated across locales; however, the share of converging cities reveals a significant decline since July of 2006. The impact of price regulation on price convergence is mixed; our results indicate that since the enactment of the regulation in all New Brunswick cities (9) included in the dataset, gasoline prices converge to the national mean. Volatility of price is also significantly reduced. In contrast, in the wake of price regulation in Nova Scotia, all 6 cities of the province are non-convergent to the mean with increased volatility and overall price level. - Highlights: ► The paper examines price regulation and convergence of gasoline prices in Canada. ► Overall in 2000–2010 the Canadian retail gasoline market was well integrated. ► Price convergence across cities has significantly declined since July 2006. ► The impact of price regulation at province level on a price convergence is mixed. ► The paper relies on the most advanced nonlinear panel unit root test.

  15. Can suitable candidates for levodopa/carbidopa intestinal gel therapy be identified using current evidence?

    Directory of Open Access Journals (Sweden)

    Maria José Catalán

    2017-09-01

    In recent years, strong evidence has supported the use of LCIG in treating motor fluctuations associated with APD, and several clinical studies provide emerging evidence for additional benefits of LCIG treatment in certain patients. This article provides an overview of the published literature on the benefits, limitations, and drawbacks of LCIG in relation to PD symptoms, the psychosocial impact of the disease, and the quality of life of patients, with the aim of determining candidates for whom treatment with LCIG would be beneficial. According to current evidence, patients with APD (defined as inability to achieve optimal control of the disease with conventional oral treatment, a relatively well-preserved cognitive-behavioral status, and good family/caregiver would count as suitable candidates for LCIG treatment. Contraindications in the opinion of the authors are severe dementia and active psychosis.

  16. Hypocretin/Orexin Regulation of Dopamine Signaling and Cocaine Self-Administration Is Mediated Predominantly by Hypocretin Receptor 1

    OpenAIRE

    Prince, Courtney D.; Rau, Andrew R.; Yorgason, Jordan T.; Espa?a, Rodrigo A.

    2014-01-01

    Extensive evidence suggests that the hypocretins/orexins influence cocaine reinforcement and dopamine signaling via actions at hypocretin receptor 1. By comparison, the involvement of hypocretin receptor 2 in reward and reinforcement processes has received relatively little attention. Thus, although there is some evidence that hypocretin receptor 2 regulates intake of some drugs of abuse, it is currently unclear to what extent hypocretin receptor 2 participates in the regulation of dopamine s...

  17. Preparing for climate change regulation : an assessment of the current state of date reliability in the Canadian electrical industry

    International Nuclear Information System (INIS)

    Schuh, C.

    2003-01-01

    This presentation provided an overview of current Canadian greenhouse gas (GHG) reporting requirements, predictions about GHG regulations, and the current state of GHGs data reliability in the Canadian electrical industry. The author argued that while potential management strategies are necessary, they are not sufficient to meet Kyoto or similar types of initiatives because they do not provide incentives for reductions, they do not establish accountability, nor do they encourage reliable data. It was predicted that the first climate change regulation will be a sectoral agreement enacted at the federal/provincial level. It was also predicted that future regulations will include a requirement to report GHG emissions in a reliable manner and that regulators will use the data to track performance. The final prediction was that the onus will be on the companies to prove that the data is reliable as regulators will have limited resources to check the data. It was noted that the current state of data is not suitable for analytical testing because of a lack of clear definitions, a lack of industry comparison, inability to compare between companies, inability to compare between different types of power generation, and the inability to compare between years. It was suggested that data reliability could be improved by having the regulators review and monitor the reported data, or by having a third party review and provide assurance on the reported data. It was concluded that there will have to be agreement at the industry level on common measurement and calculation methodology, as well as an agreement on a common scope of reporting. 4 figs

  18. UK medicines regulation: responding to current challenges.

    Science.gov (United States)

    Richards, Natalie; Hudson, Ian

    2016-12-01

    The medicines regulatory environment is evolving rapidly in response to the changing environment. Advances in science and technology have led to a vast field of increasingly complicated pharmaceutical and medical device products; increasing globalization of the pharmaceutical industry, advances in digital technology and the internet, changing patient populations, and shifts in society also affect the regulatory environment. In the UK, the Medicines and Healthcare products Regulatory Agency (MHRA) regulates medicines, medical devices and blood products to protect and improve public health, and supports innovation through scientific research and development. It works closely with other bodies in a single medicines network across Europe and takes forward UK health priorities. This paper discusses the range of initiatives in the UK and across Europe to support innovation in medicines regulation. The MHRA leads a number of initiatives, such as the Innovation Office, which helps innovators to navigate the regulatory processes to progress their products or technologies; and simplification of the Clinical Trials Regulations and the Early Access to Medicines Scheme, to bring innovative medicines to patients faster. The Accelerated Access Review will identify reforms to accelerate access for National Health Service patients to innovative medicines and medical technologies. PRIME and Adaptive Pathways initiatives are joint endeavours within the European regulatory community. The MHRA runs spontaneous reporting schemes and works with INTERPOL to tackle counterfeiting and substandard products sold via the internet. The role of the regulator is changing rapidly, with new risk-proportionate, flexible approaches being introduced. International collaboration is a key element of the work of regulators, and is set to expand. © 2016 The British Pharmacological Society.

  19. A green paper on the regulation and control of sources of ionizing radiation

    International Nuclear Information System (INIS)

    1990-01-01

    This publication reviews the evidences that sources of ionizing radiation are potentially hazardous to the public and the environment unless appropriate measures are taken to regulate and control their possession, use and the ultimate disposal. The current regulations, subject to some amendments are described and the impacts likely to result from the amendments are discussed. 9 tabs

  20. A fast transient response low dropout regulator with current control methodology

    Energy Technology Data Exchange (ETDEWEB)

    Ma Zhuo; Guo Yang; Duan Zhikui; Xie Lunguo; Chen Jihua; Yu Jinshan, E-mail: guoyang@nudt.edu.cn [School of Computer, National University of Defense Technology, Changsha 410073 (China)

    2011-08-15

    A transient performance optimized CCL-LDO regulator is proposed. In the CCL-LDO, the control method of the charge pump phase-locked loop is adopted. A current control loop has the feedback signal and reference current to be compared, and then a loop filter generates the gate voltage of the power MOSFET by integrating the error current. The CCL-LDO has the optimized damping coefficient and natural resonant frequency, while its output voltage can be sub-1-V and is not restricted by the reference voltage. With a 1 {mu}F decoupling capacitor, the experimental results based on a 0.13 {mu}m CMOS process show that the output voltage is 1.0 V; when the workload changes from 100 {mu}A to 100 mA transiently, the stable dropout is 4.25 mV, the settling time is 8.2 {mu}s and the undershoot is 5.11 mV; when the workload changes from 100 mA to 100 {mu}A transiently, the stable dropout is 4.25 mV, the settling time is 23.3 {mu}s and the overshoot is 6.21 mV. The PSRR value is more than -95 dB. Most of the attributes of the CCL-LDO are improved rapidly with a FOM value of 0.0097.

  1. A fast transient response low dropout regulator with current control methodology

    International Nuclear Information System (INIS)

    Ma Zhuo; Guo Yang; Duan Zhikui; Xie Lunguo; Chen Jihua; Yu Jinshan

    2011-01-01

    A transient performance optimized CCL-LDO regulator is proposed. In the CCL-LDO, the control method of the charge pump phase-locked loop is adopted. A current control loop has the feedback signal and reference current to be compared, and then a loop filter generates the gate voltage of the power MOSFET by integrating the error current. The CCL-LDO has the optimized damping coefficient and natural resonant frequency, while its output voltage can be sub-1-V and is not restricted by the reference voltage. With a 1 μF decoupling capacitor, the experimental results based on a 0.13 μm CMOS process show that the output voltage is 1.0 V; when the workload changes from 100 μA to 100 mA transiently, the stable dropout is 4.25 mV, the settling time is 8.2 μs and the undershoot is 5.11 mV; when the workload changes from 100 mA to 100 μA transiently, the stable dropout is 4.25 mV, the settling time is 23.3 μs and the overshoot is 6.21 mV. The PSRR value is more than -95 dB. Most of the attributes of the CCL-LDO are improved rapidly with a FOM value of 0.0097.

  2. Evidence that BDNF regulates heart rate by a mechanism involving increased brainstem parasympathetic neuron excitability

    OpenAIRE

    Wan, Ruiqian; Weigand, Letitia A.; Bateman, Ryan; Griffioen, Kathleen; Mendelowitz, David; Mattson, Mark P.

    2014-01-01

    Autonomic control of heart rate is mediated by cardioinhibitory parasympathetic cholinergic neurons located in the brainstem and stimulatory sympathetic noradrenergic neurons. During embryonic development the survival and cholinergic phenotype of brainstem autonomic neurons is promoted by brain-derived neurotrophic factor (BDNF). We now provide evidence that BDNF regulates heart rate by a mechanism involving increased brainstem cardioinhibitory parasympathetic activity. Mice with a BDNF haplo...

  3. Current status of evidence-based sports medicine.

    Science.gov (United States)

    Harris, Joshua D; Cvetanovich, Gregory; Erickson, Brandon J; Abrams, Geoffrey D; Chahal, Jaskarndip; Gupta, Anil K; McCormick, Frank M; Bach, Bernard R

    2014-03-01

    The purpose of this investigation is to determine the proportion of sports medicine studies that are labeled as Level I Evidence in 5 journals and compare the quality of surgical and nonsurgical studies using simple quality assessment tools (Consolidated Standards of Reporting Trials [CONSORT] and Jadad). By use of PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines over the prior 2 years in the top 5 (citation and impact factor based) sports medicine journals, only Level I Evidence studies were eligible for inclusion and were analyzed. All study types (therapeutic, prognostic, diagnostic, and economic) were analyzed. Study quality was assessed with the level of evidence, Jadad score, and CONSORT 2010 guidelines. Study demographic data were compared among journals and between surgical and nonsurgical studies by use of χ(2), 1-way analysis of variance, and 2-sample Z tests. We analyzed 190 Level I Evidence studies (10% of eligible studies) (119 randomized controlled trials [RCTs]). Therapeutic, nonsurgical, single-center studies from the United States were the most common studies published. Sixty-two percent of studies reported a financial conflict of interest. The knee was the most common body part studied, and track-and-field/endurance sports were the most common sports analyzed. Significant differences (P journals reviewed. Overall, the Jadad and CONSORT scores were 2.71 and 77%, respectively. No differences (P > .05) were shown among journals based on the proportion of Level I studies or appropriate randomization. Significant strengths and limitations of RCTs were identified. This study showed that Level I Evidence and RCTs comprise 10% and 6% of contemporary sports medicine literature, respectively. Therapeutic, nonsurgical, single-center studies are the most common publications with Level I Evidence. Significant differences across sports medicine journals were found in study quality. Surgical studies appropriately described

  4. Anti-cyclic regulation of the Ukrainian economy under current conditions of the international markets volatility

    Directory of Open Access Journals (Sweden)

    Volodymyr Satsyk

    2009-04-01

    Full Text Available In the article there are considered the theoretical and methodological basis of anti-cyclic regulation of the countries’ economy under conditions of the world economy globalization. It suggests the analysis of practices of implementing of anti-cyclic policy in highly developed states, its defining features and directions under current global financial and economic crisis. There has been researched a practical toolkit of economic cycles diagnostics and cyclic fluctuations of total business activity in Ukraine based on this study. There are suggested recommendations concerning the formation of the effective mechanism of anti-cyclic regulation of the Ukrainian economy.

  5. Nuclear regulations: current status and proposed initiatives

    International Nuclear Information System (INIS)

    Domondon, D.B.; Valdezco, E.M.; Mateo, A.J.; Parami, V.K.

    1996-01-01

    The science Act of 1958 created the Philippine Atomic Energy Commission, presently known as the Philippine Nuclear Research Institute (PNRI), under the Department of Science and Technology (DOST). The PNRI is tasked with the dual role of promotion and control of the peaceful applications of atomic energy. To carry its mandate of regulation and control on the use of raioisotopes in various fields, the PNRI had promulgated and issued specific regulations known as the Code of PNRI regulations. This paper summarizes the activities undertaken by PNRI in the continuing process of review and subsequent revisions of the Code of PNRI regulations and related guidance documents. It highlights proposed modifications in the present regulations in an attempt to adopt the new international basic safety standards, the practical problems and related issues attendant to the implementation of these new standards, among others. In line with the overall objective of PNRI to ensure the safe application of nuclear energy and radiation technology in various fields, the institute conducted a series of regulatory information conferences to provide an opportunity for members of the regulatory staff of the PNRI and licenses to discuss safety initiatives and regulatory issues. This paper will also provide an in-depth assessment of the lessons learned from these conferences which were conducted by sector or by specific applications for a more focused approach, e.g. radiopharmaceuticals, industrial radiography, research, among others. Licensees' feedback on the PNRI regulatory process are presented as part of the overall objective of enhancing the operational experiences of the licensing, review and evaluation group as well as that of inspection, enforcement and compliance. Several proposed initiatives for consideration of the PNRI to further strengthen its regulatory functions are also briefly outlined. (author)

  6. The effect of plant growth regulators and their interaction with electric current on winter wheat development

    Czech Academy of Sciences Publication Activity Database

    Biesaga-Koscielniak, J.; Koscielniak, J.; Filek, M.; Marcinska, I.; Krekule, Jan; Macháčková, Ivana; Kubon, M.

    2010-01-01

    Roč. 32, č. 5 (2010), s. 987-995 ISSN 0137-5881 Institutional research plan: CEZ:AV0Z50380511 Keywords : In vitro culture * Plant growth regulators * Electric current Subject RIV: EF - Botanics Impact factor: 1.344, year: 2010

  7. Postpartum family planning: current evidence on successful interventions.

    Science.gov (United States)

    Blazer, Cassandra; Prata, Ndola

    2016-01-01

    We reviewed existing evidence of the efficacy of postpartum family planning interventions targeting women in the 12 months postpartum period in low- and middle-income countries. We searched for studies from January 1, 2004 to September 19, 2015, using the US Preventive Services Task Force recommendations to assess evidence quality. Our search resulted in 26 studies: 11 based in sub-Saharan Africa, six in the Middle East and North Africa, and nine in Asia. Twenty of the included studies assessed health facility-based interventions. Three were focused on community interventions, two had community and facility components, and one was a workplace program. Overall quality of the evidence was moderate, including evidence for counseling interventions. Male partner involvement, integration with other service delivery platforms, such as prevention of mother-to-child transmission of HIV and immunization, and innovative product delivery programs may increase knowledge and use during the postpartum period. Community-based and workplace strategies need a much stronger base of evidence to prompt recommendations.

  8. Renal denervation in the management of resistant hypertension: current evidence and perspectives.

    Science.gov (United States)

    Jin, Yu; Persu, Alexandre; Staessen, Jan A

    2013-09-01

    Catheter-based renal denervation has emerged as a novel treatment modality for resistant hypertension. This review summarizes the current evidence on this procedure in treatment of resistant hypertension, limitations of available evidence and questions to be answered. The SYMPLICITY studies showed that renal denervation is feasible in treating resistant hypertension, but failed to provide conclusive evidence on the size and durability of the antihypertensive, renal and sympatholytic effects, as well as the long-term safety. The definition of resistant hypertension was loose in the SYMPLICITY studies and the management of resistant hypertension was suboptimal. Future studies should have a randomized design and enroll truly resistant hypertension patients by excluding secondary hypertension, white-coat hypertension and nonadherent patients. Questions to be addressed by the ongoing and future trials include the long-term efficacy and safety of this procedure, identification of responders and uncovering of the underlying mechanisms. Only well-designed, randomized clinical trials addressing the limitations of the SYMPLICITY studies will be able to demonstrate whether renal denervation is an efficacious treatment modality in resistant hypertension and in which patients. For now, renal denervation remains an experimental procedure and should only be offered to truly resistant hypertensive patients in a research context after careful selection.

  9. Animal Research on Nicotine Reduction: Current Evidence and Research Gaps.

    Science.gov (United States)

    Smith, Tracy T; Rupprecht, Laura E; Denlinger-Apte, Rachel L; Weeks, Jillian J; Panas, Rachel S; Donny, Eric C; Sved, Alan F

    2017-09-01

    A mandated reduction in the nicotine content of cigarettes may improve public health by reducing the prevalence of smoking. Animal self-administration research is an important complement to clinical research on nicotine reduction. It can fill research gaps that may be difficult to address with clinical research, guide clinical researchers about variables that are likely to be important in their own research, and provide policy makers with converging evidence between clinical and preclinical studies about the potential impact of a nicotine reduction policy. Convergence between clinical and preclinical research is important, given the ease with which clinical trial participants can access nonstudy tobacco products in the current marketplace. Herein, we review contributions of preclinical animal research, with a focus on rodent self-administration, to the science of nicotine reduction. Throughout this review, we highlight areas where clinical and preclinical research converge and areas where the two differ. Preclinical research has provided data on many important topics such as the threshold for nicotine reinforcement, the likelihood of compensation, moderators of the impact of nicotine reduction, the impact of environmental stimuli on nicotine reduction, the impact of nonnicotine cigarette smoke constituents on nicotine reduction, and the impact of nicotine reduction on vulnerable populations. Special attention is paid to current research gaps including the dramatic rise in alternative tobacco products, including electronic nicotine delivery systems (ie, e-cigarettes). The evidence reviewed here will be critical for policy makers as well as clinical researchers interested in nicotine reduction. This review will provide policy makers and clinical researchers interested in nicotine reduction with an overview of the preclinical animal research conducted on nicotine reduction and the regulatory implications of that research. The review also highlights the utility of

  10. Local regulation of interchange turbulence in a dipole-confined plasma torus using current-collection feedback

    International Nuclear Information System (INIS)

    Roberts, T. M.; Mauel, M. E.; Worstell, M. W.

    2015-01-01

    Turbulence in plasma confined by a magnetic dipole is dominated by interchange fluctuations with complex dynamics and short spatial coherence. We report the first use of local current-collection feedback to modify, amplify, and suppress these fluctuations. The spatial extent of turbulence regulation is limited to a correlation length near the collector. Changing the gain and phase of collection results in power either extracted from or injected into the turbulence. The measured plasma response shows some agreement with calculations of the linear response of global interchange-like MHD and entropy modes to current-collection feedback

  11. The 'constructive regulation' of phosphates and phosphogypsum : a new, evidence-based approach to regulating a NORM industry vital to the global community

    International Nuclear Information System (INIS)

    Hilton, Julian; Birky, Brian; Johnston, A.E.

    2008-01-01

    Full text: IAEA has included phosphate production among twelve NORM industries identified for scrutiny and possible regulation. 'Wet' production results in 1) phosphoric acid, as phosphate essential for world-wide food production; and 2) phosphogypsum (PG), which in some countries is used in both agriculture and construction. Phosphate deposits contain 238 U and 232 Th and their decay products; some have sufficient U content for commercial recovery. This puts the industry within the scope of the IAEA Fundamental Safety Principles, and of the International Basic Safety Standards (BSS). Phosphogypsum is a test case for defining and managing NORM industry residues and wastes as typical activity concentrations are extremely low but worldwide stockpiles amount to billions of tonnes. In some jurisdictions, phosphogypsum is regulated as a hazardous, radioactive waste rather than as a resource - with costly results. The phosphate industry is undergoing its most profound change since World War II, led by surging demand from Brazil, Russia, India and China, Established production centres, such as Morocco, are increasing capacity; major new facilities are being built, such as Ma'aden, Saudi Arabia. In consequence, many local jurisdictions face unfamiliar challenges and seek guidance on how to proceed. New research both on phosphate and phosphogypsum has significantly changed our understanding of the domain. A five year study of phosphogypsum use in Huelva, Spain, presents a model of a coherent, evidence-based approach, grounded in sound policy, good science and best practices. The 'constructive regulation' approach builds directly on evidence and lessons learned from a long, continuous tradition of PG use in Spain, Brazil and the United States. It draws on the results of the Stack Free by '53? project to modify John Nash's cooperative game and bargaining theory as a basis for defining a new sustainable point of equilibrium in which phosphogypsum production and consumption are

  12. Improving self-regulation in adolescents: current evidence for the role of mindfulness-based cognitive therapy

    Directory of Open Access Journals (Sweden)

    Perry-Parrish C

    2016-09-01

    Full Text Available Carisa Perry-Parrish,1 Nikeea Copeland-Linder,2 Lindsey Webb,2 Ashley Shields,1 Erica MS Sibinga2 1Department of Psychiatry and Behavioral Sciences, Division of Child and Adolescent Psychiatry, Pediatric Medical Psychology Program, 2Department of Pediatrics and Adolescent Medicine, Johns Hopkins School of Medicine, Baltimore, MD, USA Abstract: Mindfulness-based cognitive therapy (MBCT was introduced in 1995 to address the problem of recurrent depression. MBCT is based on the notion that meditation helps individuals effectively deploy and regulate attention to effectively manage and treat a range of psychological symptoms, including emotional responses to stress, anxiety, and depression. Several studies demonstrate that mindfulness approaches can effectively reduce negative emotional reactions that result from and/or exacerbate psychiatric difficulties and exposure to stressors among children, adolescents, and their parents. Mindfulness may be particularly relevant for youth with maladaptive cognitive processes such as rumination. Clinical experience regarding the utility of mindfulness-based approaches, including MBCT, is being increasingly supported by empirical studies to optimize the effective treatment of youth with a range of challenging symptoms. This paper provides a description of MBCT, including mindfulness practices, theoretical mechanisms of action, and targeted review of studies in adolescents. Keywords: youth, mindfulness-based cognitive therapy, adolescents

  13. The relationship between the nucleolus and cancer: Current evidence and emerging paradigms.

    Science.gov (United States)

    Orsolic, Ines; Jurada, Deana; Pullen, Nick; Oren, Moshe; Eliopoulos, Aristides G; Volarevic, Sinisa

    2016-06-01

    The nucleolus is the most prominent nuclear substructure assigned to produce ribosomes; molecular machines that are responsible for carrying out protein synthesis. To meet the increased demand for proteins during cell growth and proliferation the cell must increase protein synthetic capacity by upregulating ribosome biogenesis. While larger nucleolar size and number have been recognized as hallmark features of many tumor types, recent evidence has suggested that, in addition to overproduction of ribosomes, decreased ribosome biogenesis as well as qualitative changes in this process could also contribute to tumor initiation and cancer progression. Furthermore, the nucleolus has become the focus of intense attention for its involvement in processes that are clearly unrelated to ribosome biogenesis such as sensing and responding to endogenous and exogenous stressors, maintenance of genome stability, regulation of cell-cycle progression, cellular senescence, telomere function, chromatin structure, establishment of nuclear architecture, global regulation of gene expression and biogenesis of multiple ribonucleoprotein particles. The fact that dysregulation of many of these fundamental cellular processes may contribute to the malignant phenotype suggests that normal functioning of the nucleolus safeguards against the development of cancer and indicates its potential as a therapeutic approach. Here we review the recent advances made toward understanding these newly-recognized nucleolar functions and their roles in normal and cancer cells, and discuss possible future research directions. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. Evidence of current impact of climate change on life : A walk from genes to the biosphere

    NARCIS (Netherlands)

    Penuelas, Josep; Sardans, Jordi; Estiarte, Marc; Ogaya, Roma; Carnicer, Jofre; Coll, Marta; Barbeta, Adria; Rivas-Ubach, Albert; Llusia, Joan; Garbulsky, Martin; Filella, Iolanda; Jump, Alistair S.

    We review the evidence of how organisms and populations are currently responding to climate change through phenotypic plasticity, genotypic evolution, changes in distribution and, in some cases, local extinction. Organisms alter their gene expression and metabolism to increase the concentrations of

  15. A Low Input Current and Wide Conversion Ratio Buck Regulator with 75% Efficiency for High-Voltage Triboelectric Nanogenerators

    Science.gov (United States)

    Luo, Li-Chuan; Bao, De-Chun; Yu, Wu-Qi; Zhang, Zhao-Hua; Ren, Tian-Ling

    2016-01-01

    It is meaningful to research the Triboelectric Nanogenerators (TENG), which can create electricity anywhere and anytime. There are many researches on the structures and materials of TENG to explain the phenomenon that the maximum voltage is stable and the current is increasing. The output voltage of the TENG is high about 180-400 V, and the output current is small about 39 μA, which the electronic devices directly integration of TENG with Li-ion batteries will result in huge energy loss due to the ultrahigh TENG impedance. A novel interface circuit with the high-voltage buck regulator for TENG is introduced firstly in this paper. The interface circuit can transfer the output signal of the TENG into the signal fit to a lithium ion battery. Through the circuit of the buck regulator, the average output voltage is about 4.0 V and the average output current is about 1.12 mA. Further, the reliability and availability for the lithium ion battery and the circuit are discussed. The interface circuit is simulated using the Cadence software and verified through PCB experiment. The buck regulator can achieve 75% efficiency for the High-Voltage TENG. This will lead to a research hot and industrialization applications.

  16. Does the intensity of prudential regulation affect banks? Evidence from the 2007-2009 crises

    Directory of Open Access Journals (Sweden)

    Isabel Argimon

    2012-08-01

    Full Text Available The main objective of this research is to gather empirical evidence on the effects of more or less stringency and more or less risk sensitivity in regulatory capital requirements on the observed behaviour of European banks during the initial years of the financial crisis. To do so, we use the indices built in Argimón and Ruiz (2010, which capture such characteristics of capital regulation. We test their incidence using changes in yearly data for individual banks for 25 countries of the European Union covering the period 2007-2009. Our results show that more stringency and risk sensitivity in capital regulation resulted in higher capital increases, with limited effect on risk taking. However, for well capitalized banks, higher risk sensitivity resulted in higher capital and higher risk, thus requiring striking the right balance, so as to lead to increased stability.

  17. A novel flattop current regulated energy discharge type pulsed power supply and magnet yielding 4.4 kGauss-meter for 6 milliseconds

    International Nuclear Information System (INIS)

    Visser, A.T.

    1989-07-01

    Most energy discharge power supplies obtain their bursts of power from the energy stored in charged capacitors when it is suddenly released into a load. This note describes the design of a similar small 800 Joules energy discharge type power supply and magnet. The magnet gap is 2 in.x2 in.x25-1/2 in. long and produces about 4.4 kGauss-meters at a rate of 12 pulses per minute. Each pulse is current regulated at the top for a duration of 6 msec. and varies less than 0.6% of set value. Current regulation at flattop is obtained by switching a resistor in and out of the discharge circuit with an IGBT at a rate of about 5 kHz. Most energy discharge systems produce half sine wave pulses, and current regulation is obtained by controlling the charge voltage at the energy storage capacitor, resulting only in a controlled peak current value of the half sine wave pulse. The current value at the top changes substantially during 6 msec. depending on the operating frequency

  18. Estimating WACC for Regulated Industries on Developing Financial Markets and in Times of Market Uncertainty

    Directory of Open Access Journals (Sweden)

    Igor Stubelj

    2014-03-01

    Full Text Available The paper deals with the estimation of weighted average cost of capital (WACC for regulated industries in developing financial markets from the perspective of the current financial-economic crisis. In current financial market situation some evident changes have occurred: risk-free rates in solid and developed financial markets (e. g. USA, Germany have fallen, but due to increased market volatility, the risk premiums have increased. The latter is especially evident in transition economies where the amplitude of market volatility is extremely high. In such circumstances, there is a question of how to calculate WACC properly. WACC is an important measure in financial management decisions and in our case, business regulation. We argue in the paper that the most accurate method for calculating WACC is the estimation of the long-term WACC, which takes into consideration a long-term stable yield of capital and not the current market conditions. Following this, we propose some solutions that could be used for calculating WACC for regulated industries on the developing financial markets in times of market uncertainty. As an example, we present an estimation of the capital cost for a selected Slovenian company, which operates in the regulated industry of electric distribution.

  19. Postpartum family planning: current evidence on successful interventions

    Directory of Open Access Journals (Sweden)

    Blazer C

    2016-04-01

    Full Text Available Cassandra Blazer, Ndola Prata Bixby Center for Population, Health, and Sustainability, School of Public Health, University of California, Berkeley, CA, USA Abstract: We reviewed existing evidence of the efficacy of postpartum family planning interventions targeting women in the 12 months postpartum period in low- and middle-income countries. We searched for studies from January 1, 2004 to September 19, 2015, using the US Preventive Services Task Force recommendations to assess evidence quality. Our search resulted in 26 studies: 11 based in sub-Saharan Africa, six in the Middle East and North Africa, and nine in Asia. Twenty of the included studies assessed health facility-based interventions. Three were focused on community interventions, two had community and facility components, and one was a workplace program. Overall quality of the evidence was moderate, including evidence for counseling interventions. Male partner involvement, integration with other service delivery platforms, such as prevention of mother-to-child transmission of HIV and immunization, and innovative product delivery programs may increase knowledge and use during the postpartum period. Community-based and workplace strategies need a much stronger base of evidence to prompt recommendations. Keywords: postpartum period, family planning, birth spacing, interventions, systematic review, contraception, less developed countries

  20. Protein kinase A and C regulate leak potassium currents in freshly isolated vascular myocytes from the aorta.

    Directory of Open Access Journals (Sweden)

    Sébastien Hayoz

    Full Text Available We tested the hypothesis that protein kinase A (PKA inhibits K2P currents activated by protein kinase C (PKC in freshly isolated aortic myocytes. PDBu, the PKC agonist, applied extracellularly, increased the amplitude of the K2P currents in the presence of the "cocktail" of K(+ channel blockers. Gö 6976 significantly reduced the increase of the K2P currents by PDBu suggesting the involvement of either α or β isoenzymes of PKC. We found that forskolin, or membrane permeable cAMP, did not inhibit K2P currents activated by the PKC. However, when PKA agonists were added prior to PDBu, they produced a strong decrease in the K2P current amplitudes activated by PKC. Inhibition of PDBu-elicited K2P currents by cAMP agonists was not prevented by the treatment of vascular smooth muscle cells with PKA antagonists (H-89 and Rp-cAMPs. Zn(2+ and Hg(2+ inhibited K2P currents in one population of cells, produced biphasic responses in another population, and increased the amplitude of the PDBu-elicited K(+ currents in a third population of myocytes, suggesting expression of several K2P channel types. We found that cAMP agonists inhibited biphasic responses and increase of amplitude of the PDBu-elicited K2P currents produced by Zn(2+ and Hg(2. 6-Bnz-cAMp produced a significantly altered pH sensitivity of PDBu-elicited K2P-currents, suggesting the inhibition of alkaline-activated K2P-currents. These results indicate that 6-Bnz-cAMP and other cAMP analogs may inhibit K2P currents through a PKA-independent mechanism. cAMP analogs may interact with unidentified proteins involved in K2P channel regulation. This novel cellular mechanism could provide insights into the interplay between PKC and PKA pathways that regulate vascular tone.

  1. Low-level radioactive waste disposal in the United States: An overview of current commercial regulations and concepts

    International Nuclear Information System (INIS)

    Kennedy, W.E. Jr.

    1993-08-01

    Commercial low-level radioactive waste disposal in the United States is regulated by the US Nuclear Regulatory Commission (NRC) under 10 CFR 61 (1991). This regulation was issued in 1981 after a lengthy and thorough development process that considered the radionuclide concentrations and characteristics associated with commercial low-level radioactive waste streams; alternatives for waste classification; alternative technologies for low-level radioactive waste disposal; and data, modeling, and scenario analyses. The development process also included the publication of both draft and final environmental impact statements. The final regulation describes the general provisions; licenses; performance objectives; technical requirements for land disposal; financial assurances; participation by state governments and Indian tribes; and records, reports, tests, and inspections. This paper provides an overview of, and tutorial on, current commercial low-level radioactive waste disposal regulations in the United States

  2. An integrated mechanism of pediatric pseudotumor cerebri syndrome: evidence of bioenergetic and hormonal regulation of cerebrospinal fluid dynamics.

    Science.gov (United States)

    Sheldon, Claire A; Kwon, Young Joon; Liu, Grant T; McCormack, Shana E

    2015-02-01

    Pseudotumor cerebri syndrome (PTCS) is defined by the presence of elevated intracranial pressure (ICP) in the setting of normal brain parenchyma and cerebrospinal fluid (CSF). Headache, vision changes, and papilledema are common presenting features. Up to 10% of appropriately treated patients may experience permanent visual loss. The mechanism(s) underlying PTCS is unknown. PTCS occurs in association with a variety of conditions, including kidney disease, obesity, and adrenal insufficiency, suggesting endocrine and/or metabolic derangements may occur. Recent studies suggest that fluid and electrolyte balance in renal epithelia is regulated by a complex interaction of metabolic and hormonal factors; these cells share many of the same features as the choroid plexus cells in the central nervous system (CNS) responsible for regulation of CSF dynamics. Thus, we posit that similar factors may influence CSF dynamics in both types of fluid-sensitive tissues. Specifically, we hypothesize that, in patients with PTCS, mitochondrial metabolites (glutamate, succinate) and steroid hormones (cortisol, aldosterone) regulate CSF production and/or absorption. In this integrated mechanism review, we consider the clinical and molecular evidence for each metabolite and hormone in turn. We illustrate how related intracellular signaling cascades may converge in the choroid plexus, drawing on evidence from functionally similar tissues.

  3. Evidence of a bigenomic regulation of mitochondrial gene expression by thyroid hormone during rat brain development

    International Nuclear Information System (INIS)

    Sinha, Rohit Anthony; Pathak, Amrita; Mohan, Vishwa; Babu, Satish; Pal, Amit; Khare, Drirh; Godbole, Madan M.

    2010-01-01

    Hypothyroidism during early mammalian brain development is associated with decreased expression of various mitochondrial encoded genes along with evidence for mitochondrial dysfunction. However, in-spite of the similarities between neurological disorders caused by perinatal hypothyroidism and those caused by various genetic mitochondrial defects we still do not know as to how thyroid hormone (TH) regulates mitochondrial transcription during development and whether this regulation by TH is nuclear mediated or through mitochondrial TH receptors? We here in rat cerebellum show that hypothyroidism causes reduction in expression of nuclear encoded genes controlling mitochondrial biogenesis like PGC-1α, NRF-1α and Tfam. Also, we for the first time demonstrate a mitochondrial localization of thyroid hormone receptor (mTR) isoform in developing brain capable of binding a TH response element (DR2) present in D-loop region of mitochondrial DNA. These results thus indicate an integrated nuclear-mitochondrial cross talk in regulation of mitochondrial transcription by TH during brain development.

  4. Evidence of a bigenomic regulation of mitochondrial gene expression by thyroid hormone during rat brain development

    Energy Technology Data Exchange (ETDEWEB)

    Sinha, Rohit Anthony; Pathak, Amrita; Mohan, Vishwa; Babu, Satish; Pal, Amit; Khare, Drirh [Department of Endocrinology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow 226014 (India); Godbole, Madan M., E-mail: madangodbole@yahoo.co.in [Department of Endocrinology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow 226014 (India)

    2010-07-02

    Hypothyroidism during early mammalian brain development is associated with decreased expression of various mitochondrial encoded genes along with evidence for mitochondrial dysfunction. However, in-spite of the similarities between neurological disorders caused by perinatal hypothyroidism and those caused by various genetic mitochondrial defects we still do not know as to how thyroid hormone (TH) regulates mitochondrial transcription during development and whether this regulation by TH is nuclear mediated or through mitochondrial TH receptors? We here in rat cerebellum show that hypothyroidism causes reduction in expression of nuclear encoded genes controlling mitochondrial biogenesis like PGC-1{alpha}, NRF-1{alpha} and Tfam. Also, we for the first time demonstrate a mitochondrial localization of thyroid hormone receptor (mTR) isoform in developing brain capable of binding a TH response element (DR2) present in D-loop region of mitochondrial DNA. These results thus indicate an integrated nuclear-mitochondrial cross talk in regulation of mitochondrial transcription by TH during brain development.

  5. [Effort-reward imbalance at work and depression: current research evidence].

    Science.gov (United States)

    Siegrist, J

    2013-01-01

    In view of highly prevalent stressful conditions in modern working life, in particular increasing work pressure and job insecurity, it is of interest to know whether specific constellations of an adverse psychosocial work environment increase the risk of depressive disorder among employed people. This contribution gives a short overview of current research evidence based on an internationally established work stress model of effort-reward imbalance. Taken together, results from seven prospective epidemiological investigations demonstrate a two-fold elevated relative risk of incident depressive disorder over a mean observation period of 2.7 years among exposed versus non-exposed employees. Additional findings from experimental and quasi-experimental studies point to robust associations of effort-reward imbalance at work with proinflammatory cytokines and markers of reduced immune competence. These latter markers may indicate potential psychobiological pathways. In conclusion, incorporating this new knowledge into medical treatment and preventive efforts seems well justified.

  6. Carbohydrate Metabolism in Archaea: Current Insights into Unusual Enzymes and Pathways and Their Regulation

    Science.gov (United States)

    Esser, Dominik; Rauch, Bernadette

    2014-01-01

    SUMMARY The metabolism of Archaea, the third domain of life, resembles in its complexity those of Bacteria and lower Eukarya. However, this metabolic complexity in Archaea is accompanied by the absence of many “classical” pathways, particularly in central carbohydrate metabolism. Instead, Archaea are characterized by the presence of unique, modified variants of classical pathways such as the Embden-Meyerhof-Parnas (EMP) pathway and the Entner-Doudoroff (ED) pathway. The pentose phosphate pathway is only partly present (if at all), and pentose degradation also significantly differs from that known for bacterial model organisms. These modifications are accompanied by the invention of “new,” unusual enzymes which cause fundamental consequences for the underlying regulatory principles, and classical allosteric regulation sites well established in Bacteria and Eukarya are lost. The aim of this review is to present the current understanding of central carbohydrate metabolic pathways and their regulation in Archaea. In order to give an overview of their complexity, pathway modifications are discussed with respect to unusual archaeal biocatalysts, their structural and mechanistic characteristics, and their regulatory properties in comparison to their classic counterparts from Bacteria and Eukarya. Furthermore, an overview focusing on hexose metabolic, i.e., glycolytic as well as gluconeogenic, pathways identified in archaeal model organisms is given. Their energy gain is discussed, and new insights into different levels of regulation that have been observed so far, including the transcript and protein levels (e.g., gene regulation, known transcription regulators, and posttranslational modification via reversible protein phosphorylation), are presented. PMID:24600042

  7. A Small Potassium Current in AgRP/NPY Neurons Regulates Feeding Behavior and Energy Metabolism.

    Science.gov (United States)

    He, Yanlin; Shu, Gang; Yang, Yongjie; Xu, Pingwen; Xia, Yan; Wang, Chunmei; Saito, Kenji; Hinton, Antentor; Yan, Xiaofeng; Liu, Chen; Wu, Qi; Tong, Qingchun; Xu, Yong

    2016-11-08

    Neurons that co-express agouti-related peptide (AgRP) and neuropeptide Y (NPY) are indispensable for normal feeding behavior. Firing activities of AgRP/NPY neurons are dynamically regulated by energy status and coordinate appropriate feeding behavior to meet nutritional demands. However, intrinsic mechanisms that regulate AgRP/NPY neural activities during the fed-to-fasted transition are not fully understood. We found that AgRP/NPY neurons in satiated mice express high levels of the small-conductance calcium-activated potassium channel 3 (SK3) and are inhibited by SK3-mediated potassium currents; on the other hand, food deprivation suppresses SK3 expression in AgRP/NPY neurons, and the decreased SK3-mediated currents contribute to fasting-induced activation of these neurons. Genetic mutation of SK3 specifically in AgRP/NPY neurons leads to increased sensitivity to diet-induced obesity, associated with chronic hyperphagia and decreased energy expenditure. Our results identify SK3 as a key intrinsic mediator that coordinates nutritional status with AgRP/NPY neural activities and animals' feeding behavior and energy metabolism. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

  8. Bipolar disorder and complementary medicine: current evidence, safety issues, and clinical considerations.

    Science.gov (United States)

    Sarris, Jerome; Lake, James; Hoenders, Rogier

    2011-10-01

    Bipolar disorder (BD) is a debilitating syndrome that is often undiagnosed and undertreated. Population surveys show that persons with BD often self-medicate with complementary and alternative medicine (CAM) or integrative therapies in spite of limited research evidence supporting their use. To date, no review has focused specifically on nonconventional treatments of BD. The study objectives were to present a review of nonconventional (complementary and integrative) interventions examined in clinical trials on BD, and to offer provisional guidelines for the judicious integrative use of CAM in the management of BD. PubMed, CINAHL,(®) Web of Science, and Cochrane Library databases were searched for human clinical trials in English during mid-2010 using Bipolar Disorder and CAM therapy and CAM medicine search terms. Effect sizes (Cohen's d) were also calculated where data were available. Several positive high-quality studies on nutrients in combination with conventional mood stabilizers and antipsychotic medications in BD depression were identified, while branched-chain amino acids and magnesium were effective (small studies) in attenuating mania in BD. In the treatment of bipolar depression, evidence was mixed regarding omega-3, while isolated studies provide provisional support for a multinutrient formula, n-acetylcysteine, and l-tryptophan. In one study, acupuncture was found to have favorable but nonsignificant effects on mania and depression outcomes. Current evidence supports the integrative treatment of BD using combinations of mood stabilizers and select nutrients. Other CAM or integrative modalities used to treat BD have not been adequately explored to date; however, some early findings are promising. Select CAM and integrative interventions add to established conventional treatment of BD and may be considered when formulating a treatment plan. It is hoped that the safety issues and clinical considerations addressed in this article may encourage the practice

  9. A 3 A sink/source current fast transient response low-dropout Gm driven linear regulator

    International Nuclear Information System (INIS)

    Chu Xiuqin; Li Qingwei; Lai Xinquan; Yuan Bing; Li Yanming; Zhao Yongrui

    2011-01-01

    A 3 A sink/source G m -driven CMOS low-dropout regulator (LDO), specially designed for low input voltage and low cost, is presented by utilizing the structure of a current mirror G m (transconductance) driving technique, which provides high stability as well as a fast load transient response. The proposed LDO was fabricated by a 0.5 μm standard CMOS process, and the die size is as small as 1.0 mm 2 . The proposed LDO dissipates 220 μA of quiescent current in no-load conditions and is able to deliver up to 3 A of load current. The measured results show that the output voltage can be resumed within 2 μs with a less than 1 mV overshoot and undershoot in the output current step from -1.8 to 1.8 A with a 0.1 μs rising and falling time at three 10 μF ceramic capacitors. (semiconductor integrated circuits)

  10. Do you do Damon®? What is the current evidence base underlying the philosophy of this appliance system?

    Science.gov (United States)

    Wright, Natasha; Modarai, Faranak; Cobourne, Martyn T; Dibiase, Andrew T

    2011-09-01

    Self-ligating bracket systems are increasing in popularity amongst orthodontists. This reflects their high quality engineering, improved reliability and relative ease of use. However, it might also be related to claims of superior function made by the manufacturers of these appliances. In particular, the Damon(®) appliance system claims to offer significant advantages to both orthodontist and patient over conventional-ligation and other forms of self-ligated appliances. We have reviewed current literature relating to use of the Damon(®) appliance system. There is some evidence to suggest this appliance may lead to reductions in chairside time for the orthodontist, particularly those experienced with this system, in comparison to conventional-ligation. However, evidence that pain experience is reduced for the patient when using Damon(®) brackets is not conclusive. In the presence of identical archwire sequences, there is no evidence that Damon(®) brackets can align teeth faster or in a qualitatively differently manner, when compared with conventional-ligation. There is no high quality evidence that treatment with the Damon(®) appliance takes place more rapidly or leads to a superior occlusal or aesthetic result. Indeed, the best available evidence would suggest there is no difference in treatment outcome or time, at least in extraction cases. There is no evidence that treatment with the Damon(®) appliance is more stable. Claims relating to improved clinical performance of the Damon(®) appliance system are currently being made to orthodontists and patients that are not substantiated in the scientific literature.

  11. Central regulation of metabolism by protein tyrosine phosphatases

    Directory of Open Access Journals (Sweden)

    Ryan eTsou

    2013-01-01

    Full Text Available Protein tyrosine phosphatases (PTPs are important regulators of intracellular signaling pathways via the dephosphorylation of phosphotyrosyl residues on various receptor and non-receptor substrates. The phosphorylation state of central nervous system (CNS signaling components underlies the molecular mechanisms of a variety of physiological functions including the control of energy balance and glucose homeostasis. In this review, we summarize the current evidence implicating PTPs as central regulators of metabolism, specifically highlighting their interactions with the neuronal leptin and insulin signaling pathways. We discuss the role of a number of PTPs (PTP1B, SHP2, TCPTP, RPTPe, and PTEN, reviewing the findings from genetic mouse models and in vitro studies which highlight these phosphatases as key central regulators of energy homeostasis.

  12. Role of sleep duration in the regulation of glucose metabolism and appetite.

    Science.gov (United States)

    Morselli, Lisa; Leproult, Rachel; Balbo, Marcella; Spiegel, Karine

    2010-10-01

    Sleep curtailment has become a common behavior in modern society. This review summarizes the current laboratory evidence indicating that sleep loss may contribute to the pathophysiology of diabetes mellitus and obesity. Experimentally induced sleep loss in healthy volunteers decreases insulin sensitivity without adequate compensation in beta-cell function, resulting in impaired glucose tolerance and increased diabetes risk. Lack of sleep also down-regulates the satiety hormone leptin, up-regulates the appetite-stimulating hormone ghrelin, and increases hunger and food intake. Taken together with the epidemiologic evidence for an association between short sleep and the prevalence or incidence of diabetes mellitus and/or obesity, these results support a role for reduced sleep duration in the current epidemic of these metabolic disorders. Screening for habitual sleep patterns in patients with "diabesity" is therefore of great importance. Studies are warranted to investigate the putative therapeutic impact of extending sleep in habitual short sleepers with metabolic disorders. Copyright © 2010 Elsevier Ltd. All rights reserved.

  13. Regulation of mitogen-activated protein kinase pathways by the plasma membrane Na+/H+ exchanger, NHE1

    DEFF Research Database (Denmark)

    Pedersen, Stine Helene Falsig; Darborg, Barbara Vasek; Rentsch, Maria Louise

    2006-01-01

    activity is regulated by a three-tiered phosphorelay system, which is in turn regulated by a complex network of signaling events and scaffolding proteins. The ubiquitous plasma membrane Na(+)/H(+) exchanger NHE1 is activated by, and implicated in, the physiological/pathophysiological responses to many...... of the same stimuli that modulate MAPK activity. While under some conditions, NHE1 is regulated by MAPKs, a number of studies have, conversely, implicated NHE1 in the regulation of MAPK activity. Here, we discuss the current evidence indicating the involvement of NHE1 in MAPK regulation, the mechanisms...

  14. Current Thoughts on Fat Grafting: Using the Evidence to Determine Fact or Fiction.

    Science.gov (United States)

    Sinno, Sammy; Wilson, Stelios; Brownstone, Nicholas; Levine, Steven M

    2016-03-01

    Autologous fat grafting is an increasingly popular procedure used for facial rejuvenation and body contouring. The purpose of this article is to perform an evidence-based review to determine fact from fiction for the hot topics in autologous fat grafting. A comprehensive literature search was performed. The following key words were then searched: "fat grafting," "autologous fat grafting," "autologous fat transfer," "lipotransfer," "liposculping," and "lipofilling." The authors then assessed each modality individually for the level of evidence that exists and whether the majority of evidence supports or refutes it. A review of the literature demonstrated that there is no standard test for determining fat viability or volume augmentation after grafting. Furthermore, there is no difference in cell viability seen between syringe aspiration and liposuction pump aspiration harvest techniques (Level II). The decision to wash or centrifuge the fat plays very little role in fat graft survival (Level III). There is no difference between cell viability as a function of harvest location (Level IV). Nearly all studies show no significant effect of local anesthesia on adipocyte cells (Level IV). There are excellent data that support the fact that low-shear devices maintain fat structural integrity (Level IV). There is quality evidence that supports longevity of fat grafted to the breast (Level III). Two studies support large-volume fat grafting longevity but fail to prove their results using objective measures or with sufficiently large sample sizes (Level IV). External preexpansion devices improve total graft survival rate (Level IV). There is quality evidence to support that fat should be injected soon after harvesting, as properties of fat begin to change after processing (Level IV). Microneedling (preconditioning) before fat grafting has been demonstrated to improve fat survival (Level III). Currently, the highest levels of evidence derive from human studies of clinical

  15. Culture, mind, and the brain: current evidence and future directions.

    Science.gov (United States)

    Kitayama, Shinobu; Uskul, Ayse K

    2011-01-01

    Current research on culture focuses on independence and interdependence and documents numerous East-West psychological differences, with an increasing emphasis placed on cognitive mediating mechanisms. Lost in this literature is a time-honored idea of culture as a collective process composed of cross-generationally transmitted values and associated behavioral patterns (i.e., practices). A new model of neuro-culture interaction proposed here addresses this conceptual gap by hypothesizing that the brain serves as a crucial site that accumulates effects of cultural experience, insofar as neural connectivity is likely modified through sustained engagement in cultural practices. Thus, culture is "embrained," and moreover, this process requires no cognitive mediation. The model is supported in a review of empirical evidence regarding (a) collective-level factors involved in both production and adoption of cultural values and practices and (b) neural changes that result from engagement in cultural practices. Future directions of research on culture, mind, and the brain are discussed.

  16. Collectivism and coping: current theories, evidence, and measurements of collective coping.

    Science.gov (United States)

    Kuo, Ben C H

    2013-01-01

    A burgeoning body of cultural coping research has begun to identify the prevalence and the functional importance of collective coping behaviors among culturally diverse populations in North America and internationally. These emerging findings are highly significant as they evidence culture's impacts on the stress-coping process via collectivistic values and orientation. They provide a critical counterpoint to the prevailing Western, individualistic stress and coping paradigm. However, current research and understanding about collective coping appear to be piecemeal and not well integrated. To address this issue, this review attempts to comprehensively survey, summarize, and evaluate existing research related to collective coping and its implications for coping research with culturally diverse populations from multiple domains. Specifically, this paper reviews relevant research and knowledge on collective coping in terms of: (a) operational definitions; (b) theories; (c) empirical evidence based on studies of specific cultural groups and broad cultural values/dimensions; (d) measurements; and (e) implications for future cultural coping research. Overall, collective coping behaviors are conceived as a product of the communal/relational norms and values of a cultural group across studies. They also encompass a wide array of stress responses ranging from value-driven to interpersonally based to culturally conditioned emotional/cognitive to religion- and spirituality-grounded coping strategies. In addition, this review highlights: (a) the relevance and the potential of cultural coping theories to guide future collective coping research; (b) growing evidence for the prominence of collective coping behaviors particularly among Asian nationals, Asian Americans/Canadians and African Americans/Canadians; (c) preference for collective coping behaviors as a function of collectivism and interdependent cultural value and orientation; and (d) six cultural coping scales. This

  17. Regulation of zebrafish sleep and arousal states: current and prospective approaches

    Directory of Open Access Journals (Sweden)

    Cindy N Chiu

    2013-04-01

    Full Text Available Every day, we shift among various states of sleep and arousal to meet the many demands of our bodies and environment. A central puzzle in neurobiology is how the brain controls these behavioral states, which are essential to an animal’s well-being and survival. Mammalian models have predominated sleep and arousal research, although in the past decade, invertebrate models have made significant contributions to our understanding of the genetic underpinnings of behavioral states. More recently, the zebrafish has emerged as a promising model system for sleep and arousal research. Here we review experimental evidence that the zebrafish, a diurnal vertebrate, exhibits fundamental behavioral and neurochemical characteristics of mammalian sleep and arousal. We also propose how specific advantages of the zebrafish can be harnessed to advance the field. These include tractable genetics to identify and manipulate molecular and cellular regulators of behavioral states, optical transparency to facilitate in vivo observation of neural structure and function, and amenability to high-throughput drug screens to discover novel therapies for neurological disorders.

  18. Interlink Converter with Linear Quadratic Regulator Based Current Control for Hybrid AC/DC Microgrid

    Directory of Open Access Journals (Sweden)

    Dwi Riana Aryani

    2017-11-01

    Full Text Available A hybrid alternate current/direct current (AC/DC microgrid consists of an AC subgrid and a DC subgrid, and the subgrids are connected through the interlink bidirectional AC/DC converter. In the stand-alone operation mode, it is desirable that the interlink bidirectional AC/DC converter manages proportional power sharing between the subgrids by transferring power from the under-loaded subgrid to the over-loaded one. In terms of system security, the interlink bidirectional AC/DC converter takes an important role, so proper control strategies need to be established. In addition, it is assumed that a battery energy storage system is installed in one subgrid, and the coordinated control of interlink bidirectional AC/DC converter and battery energy storage system converter is required so that the power sharing scheme between subgrids becomes more efficient. For the purpose of designing a tracking controller for the power sharing by interlink bidirectional AC/DC converter in a hybrid AC/DC microgrid, a droop control method generates a power reference for interlink bidirectional AC/DC converter based on the deviation of the system frequency and voltages first and then interlink bidirectional AC/DC converter needs to transfer the power reference to the over-loaded subgrid. For efficiency of this power transferring, a linear quadratic regulator with exponential weighting for the current regulation of interlink bidirectional AC/DC converter is designed in such a way that the resulting microgrid can operate robustly against various uncertainties and the power sharing is carried out quickly. Simulation results show that the proposed interlink bidirectional AC/DC converter control strategy provides robust and efficient power sharing scheme between the subgrids without deteriorating the secure system operation.

  19. Investigating Relationships among Pre-Service Science Teachers' Conceptual Knowledge of Electric Current, Motivational Beliefs and Self-Regulation

    Science.gov (United States)

    Inaltun, Hüseyin; Ates, Salih

    2015-01-01

    The purpose of this study is to examine relationships among pre-service science teachers' conceptual knowledge of electric current, motivational beliefs, and self-regulation. One hundred and twenty-seven students (female = 107, male = 20) enrolled in the science education program of a public university in Ankara participated the study. A concept…

  20. Role of Environmental Chemicals in Obesity: A Systematic Review on the Current Evidence

    Directory of Open Access Journals (Sweden)

    Roya Kelishadi

    2013-01-01

    Full Text Available The purpose of this paper is to systematically review the experimental and human studies on obesogenic chemicals and their mechanisms of action to provide a comprehensive view on the multifactorial aspects of obesity. The literatures were searched in available databases. The relevant papers were selected in three phases. After quality assessment, two reviewers extracted the data while another checked their extracted data. In this review, we summarized information regarding environmental chemicals that can be associated with obesity. Most evidence comes from experimental and laboratory studies; however a growing number of human studies also support the role of obesogenic chemicals. The current evidence proposes that the systemic responses to exposure to environmental factors could potentially increase the risk of excess weight. The effects of exposure to these chemicals are of crucial importance during developmental phases of life, when preprogramming for an adipogenic outcome may occur. By considering the adverse transgenerational effects of obesogen chemicals on human health, the global obesity epidemic should be considered as a multifactorial complex disorder necessitating the emphasis of public health interventions for environmental protection.

  1. Current Knowledge on the Acute Regulation of Steroidogenesis.

    Science.gov (United States)

    Selvaraj, Vimal; Stocco, Douglas M; Clark, Barbara J

    2018-04-27

    How rapid induction of steroid hormone biosynthesis occurs in response to trophic hormone stimulation of steroidogenic cells has been a subject of intensive investigation for approximately six decades. A key observation made very early was that acute regulation of steroid biosynthesis required swift and timely synthesis of a new protein whose role appeared to be involved in the delivery of the substrate for all steroid hormones, cholesterol, from the outer to the inner mitochondrial membrane where the process of steroidogenesis begins. It was quickly learned that this transfer of cholesterol to the inner mitochondrial membrane was the regulated and rate limiting step in steroidogenesis. Following this observation, the quest for this putative regulator protein(s) began in earnest in the late 1950s. This review provides a history of this quest, the candidate proteins that arose over the years, and facts surrounding their rise or decline. Only two have persisted-Translocator Protein (TSPO) and the Steroidogenic Acute Regulatory Protein (StAR). We present a detailed summary of the work that has been published for each of these two proteins, the specific data that has appeared in support of their role in cholesterol transport and steroidogenesis, and the ensuing observations that have arisen in recent years that have refuted the role of TSPO in this process. We believe that the only viable candidate that has been shown to be indispensable is the StAR protein. Lastly, we provide our view on what may be the most important questions concerning the acute regulation of steroidogenesis that need to be asked in future.

  2. Rapamycin up-regulates triglycerides in hepatocytes by down-regulating Prox1.

    Science.gov (United States)

    Kwon, Sora; Jeon, Ji-Sook; Kim, Su Bin; Hong, Young-Kwon; Ahn, Curie; Sung, Jung-Suk; Choi, Inho

    2016-02-27

    Although the prolonged use of rapamycin may cause unwanted side effects such as hyperlipidemia, the underlying mechanism remains unknown. Prox1 is a transcription factor responsible for the development of several tissues including lymphatics and liver. There is growing evidences that Prox1 participates in metabolism in addition to embryogenesis. However, whether Prox1 is directly related to lipid metabolism is currently unknown. HepG2 human hepatoma cells were treated with rapamycin and total lipids were analyzed by thin layer chromatography. The effect of rapamycin on the expression of Prox1 was determined by western blotting. To investigate the role of Prox1 in triglycerides regulation, siRNA and overexpression system were employed. Rapamycin was injected into mice for 2 weeks and total lipids and proteins in liver were measured by thin layer chromatography and western blot analysis, respectively. Rapamycin up-regulated the amount of triglyceride and down-regulated the expression of Prox1 in HepG2 cells by reducing protein half-life but did not affect its transcript. The loss-of-function of Prox1 was coincident with the increase of triglycerides in HepG2 cells treated with rapamycin. The up-regulation of triglycerides by rapamycin in HepG2 cells reverted to normal levels by the compensation of Prox1 using the overexpression system. Rapamycin also down-regulated Prox1 expression but increased triglycerides in mouse liver. This study suggests that rapamycin can increase the amount of triglycerides by down-regulating Prox1 expression in hepatocytes, which means that the mammalian target of rapamycin (mTOR) signaling is important for the regulation of triglycerides by maintaining Prox1 expression.

  3. Minimally Invasive Transforaminal Lumbar Interbody Fusion: A Perspective on Current Evidence and Clinical Knowledge

    Directory of Open Access Journals (Sweden)

    Ali Habib

    2012-01-01

    Full Text Available This paper reviews the current published data regarding open transforaminal lumbar interbody fusion (TLIF in relation to minimally invasive transforaminal lumbar interbody fusion (MI-TLIF. Introduction. MI-TLIF, a modern method for lumbar interbody arthrodesis, has allowed for a minimally invasive method to treat degenerative spinal pathologies. Currently, there is limited literature that compares TLIF directly to MI-TLIF. Thus, we seek to discuss the current literature on these techniques. Methods. Using a PubMed search, we reviewed recent publications of open and MI-TLIF, dating from 2002 to 2012. We discussed these studies and their findings in this paper, focusing on patient-reported outcomes as well as complications. Results. Data found in 14 articles of the literature was analyzed. Using these reports, we found mean follow-up was 20 months. The mean patient study size was 52. Seven of the articles directly compared outcomes of open TLIF with MI-TLIF, such as mean duration of surgery, length of post-operative stay, blood loss, and complications. Conclusion. Although high-class data comparing these two techniques is lacking, the current evidence supports MI-TLIF with outcomes comparable to that of the traditional, open technique. Further prospective, randomized studies will help to further our understanding of this minimally invasive technique.

  4. Capital Regulation, the Cost of Financial Intermediation and Bank Profitability: Evidence from Bangladesh

    Directory of Open Access Journals (Sweden)

    Changjun Zheng

    2017-04-01

    Full Text Available In response to the recent global financial crisis, the regulatory authorities in many countries have imposed stringent capital requirements in the form of the BASEL III Accord to ensure financial stability. On the other hand, bankers have criticized new regulation on the ground that it would enhance the cost of funds for bank borrowers and deteriorate the bank profitability. In this study, we examine the impact of capital requirements on the cost of financial intermediation and bank profitability using a panel dataset of 32 Bangladeshi banks over the period from 2000 to 2015. By employing a dynamic panel generalized method of moments (GMM estimator, we find robust evidence that higher bank regulatory capital ratios reduce the cost of financial intermediation and increase bank profitability. The results hold when we use equity to total assets ratio as an alternative measure of bank capital. We also observe that switching from BASEL I to BASEL II has no measurable impact on the cost of financial intermediation and bank profitability in Bangladesh. In the empirical analysis, we further observe that higher bank management and cost efficiencies are associated with the lower cost of financial intermediation and higher bank profitability. These results have important implications for bank regulators, academicians, and bankers.

  5. Inward Rectifier K+ Currents Are Regulated by CaMKII in Endothelial Cells of Primarily Cultured Bovine Pulmonary Arteries.

    Science.gov (United States)

    Qu, Lihui; Yu, Lei; Wang, Yanli; Jin, Xin; Zhang, Qianlong; Lu, Ping; Yu, Xiufeng; Zhong, Weiwei; Zheng, Xiaodong; Cui, Ningren; Jiang, Chun; Zhu, Daling

    2015-01-01

    Endothelium lines the interior surface of vascular walls and regulates vascular tones. The endothelial cells sense and respond to chemical and mechanical stimuli in the circulation, and couple the stimulus signals to vascular smooth muscles, in which inward rectifier K+ currents (Kir) play an important role. Here we applied several complementary strategies to determine the Kir subunit in primarily cultured pulmonary arterial endothelial cells (PAECs) that was regulated by the Ca2+/calmodulin (CaM)-dependent protein kinase II (CaMKII). In whole-cell voltage clamp, the Kir currents were sensitive to micromolar concentrations of extracellular Ba2+. In excised inside-out patches, an inward rectifier K+ current was observed with single-channel conductance 32.43 ± 0.45 pS and Popen 0.27 ± 0.04, which were consistent with known unitary conductance of Kir 2.1. RT-PCR and western blot results showed that expression of Kir 2.1 was significantly stronger than that of other subtypes in PAECs. Pharmacological analysis of the Kir currents demonstrated that insensitivity to intracellular ATP, pinacidil, glibenclamide, pH, GDP-β-S and choleratoxin suggested that currents weren't determined by KATP, Kir2.3, Kir2.4 and Kir3.x. The currents were strongly suppressed by exposure to CaMKII inhibitor W-7 and KN-62. The expression of Kir2.1 was inhibited by knocking down CaMKII. Consistently, vasodilation was suppressed by Ba2+, W-7 and KN-62 in isolated and perfused pulmonary arterial rings. These results suggest that the PAECs express an inward rectifier K+ current that is carried dominantly by Kir2.1, and this K+ channel appears to be targeted by CaMKII-dependent intracellular signaling systems.

  6. Differential roles of two delayed rectifier potassium currents in regulation of ventricular action potential duration and arrhythmia susceptibility.

    Science.gov (United States)

    Devenyi, Ryan A; Ortega, Francis A; Groenendaal, Willemijn; Krogh-Madsen, Trine; Christini, David J; Sobie, Eric A

    2017-04-01

    Arrhythmias result from disruptions to cardiac electrical activity, although the factors that control cellular action potentials are incompletely understood. We combined mathematical modelling with experiments in heart cells from guinea pigs to determine how cellular electrical activity is regulated. A mismatch between modelling predictions and the experimental results allowed us to construct an improved, more predictive mathematical model. The balance between two particular potassium currents dictates how heart cells respond to perturbations and their susceptibility to arrhythmias. Imbalances of ionic currents can destabilize the cardiac action potential and potentially trigger lethal cardiac arrhythmias. In the present study, we combined mathematical modelling with information-rich dynamic clamp experiments to determine the regulation of action potential morphology in guinea pig ventricular myocytes. Parameter sensitivity analysis was used to predict how changes in ionic currents alter action potential duration, and these were tested experimentally using dynamic clamp, a technique that allows for multiple perturbations to be tested in each cell. Surprisingly, we found that a leading mathematical model, developed with traditional approaches, systematically underestimated experimental responses to dynamic clamp perturbations. We then re-parameterized the model using a genetic algorithm, which allowed us to estimate ionic current levels in each of the cells studied. This unbiased model adjustment consistently predicted an increase in the rapid delayed rectifier K + current and a drastic decrease in the slow delayed rectifier K + current, and this prediction was validated experimentally. Subsequent simulations with the adjusted model generated the clinically relevant prediction that the slow delayed rectifier is better able to stabilize the action potential and suppress pro-arrhythmic events than the rapid delayed rectifier. In summary, iterative coupling of

  7. Inward Rectifier K+ Currents Are Regulated by CaMKII in Endothelial Cells of Primarily Cultured Bovine Pulmonary Arteries.

    Directory of Open Access Journals (Sweden)

    Lihui Qu

    Full Text Available Endothelium lines the interior surface of vascular walls and regulates vascular tones. The endothelial cells sense and respond to chemical and mechanical stimuli in the circulation, and couple the stimulus signals to vascular smooth muscles, in which inward rectifier K+ currents (Kir play an important role. Here we applied several complementary strategies to determine the Kir subunit in primarily cultured pulmonary arterial endothelial cells (PAECs that was regulated by the Ca2+/calmodulin (CaM-dependent protein kinase II (CaMKII. In whole-cell voltage clamp, the Kir currents were sensitive to micromolar concentrations of extracellular Ba2+. In excised inside-out patches, an inward rectifier K+ current was observed with single-channel conductance 32.43 ± 0.45 pS and Popen 0.27 ± 0.04, which were consistent with known unitary conductance of Kir 2.1. RT-PCR and western blot results showed that expression of Kir 2.1 was significantly stronger than that of other subtypes in PAECs. Pharmacological analysis of the Kir currents demonstrated that insensitivity to intracellular ATP, pinacidil, glibenclamide, pH, GDP-β-S and choleratoxin suggested that currents weren't determined by KATP, Kir2.3, Kir2.4 and Kir3.x. The currents were strongly suppressed by exposure to CaMKII inhibitor W-7 and KN-62. The expression of Kir2.1 was inhibited by knocking down CaMKII. Consistently, vasodilation was suppressed by Ba2+, W-7 and KN-62 in isolated and perfused pulmonary arterial rings. These results suggest that the PAECs express an inward rectifier K+ current that is carried dominantly by Kir2.1, and this K+ channel appears to be targeted by CaMKII-dependent intracellular signaling systems.

  8. An energy-efficient, adiabatic electrode stimulator with inductive energy recycling and feedback current regulation.

    Science.gov (United States)

    Arfin, Scott K; Sarpeshkar, Rahul

    2012-02-01

    In this paper, we present a novel energy-efficient electrode stimulator. Our stimulator uses inductive storage and recycling of energy in a dynamic power supply. This supply drives an electrode in an adiabatic fashion such that energy consumption is minimized. It also utilizes a shunt current-sensor to monitor and regulate the current through the electrode via feedback, thus enabling flexible and safe stimulation. Since there are no explicit current sources or current limiters, wasteful energy dissipation across such elements is naturally avoided. The dynamic power supply allows efficient transfer of energy both to and from the electrode and is based on a DC-DC converter topology that we use in a bidirectional fashion in forward-buck or reverse-boost modes. In an exemplary electrode implementation intended for neural stimulation, we show how the stimulator combines the efficiency of voltage control and the safety and accuracy of current control in a single low-power integrated-circuit built in a standard .35 μm CMOS process. This stimulator achieves a 2x-3x reduction in energy consumption as compared to a conventional current-source-based stimulator operating from a fixed power supply. We perform a theoretical analysis of the energy efficiency that is in accord with experimental measurements. This theoretical analysis reveals that further improvements in energy efficiency may be achievable with better implementations in the future. Our electrode stimulator could be widely useful for neural, cardiac, retinal, cochlear, muscular and other biomedical implants where low power operation is important.

  9. Complementary Medicine, Exercise, Meditation, Diet, and Lifestyle Modification for Anxiety Disorders: A Review of Current Evidence

    Directory of Open Access Journals (Sweden)

    J. Sarris

    2012-01-01

    Full Text Available Use of complementary medicines and therapies (CAM and modification of lifestyle factors such as physical activity, exercise, and diet are being increasingly considered as potential therapeutic options for anxiety disorders. The objective of this metareview was to examine evidence across a broad range of CAM and lifestyle interventions in the treatment of anxiety disorders. In early 2012 we conducted a literature search of PubMed, Scopus, CINAHL, Web of Science, PsycInfo, and the Cochrane Library, for key studies, systematic reviews, and metaanalyses in the area. Our paper found that in respect to treatment of generalized anxiety or specific disorders, CAM evidence revealed current support for the herbal medicine Kava. One isolated study shows benefit for naturopathic medicine, whereas acupuncture, yoga, and Tai chi have tentative supportive evidence, which is hampered by overall poor methodology. The breadth of evidence does not support homeopathy for treating anxiety. Strong support exists for lifestyle modifications including adoption of moderate exercise and mindfulness meditation, whereas dietary improvement, avoidance of caffeine, alcohol, and nicotine offer encouraging preliminary data. In conclusion, certain lifestyle modifications and some CAMs may provide a beneficial role in the treatment of anxiety disorders.

  10. Emotion regulation reduces loss aversion and decreases amygdala responses to losses.

    Science.gov (United States)

    Sokol-Hessner, Peter; Camerer, Colin F; Phelps, Elizabeth A

    2013-03-01

    Emotion regulation strategies can alter behavioral and physiological responses to emotional stimuli and the neural correlates of those responses in regions such as the amygdala or striatum. The current study investigates the brain systems engaged when using an emotion regulation technique during financial decisions. In decision making, regulating emotion with reappraisal-focused strategies that encourage taking a different perspective has been shown to reduce loss aversion as observed both in choices and in the relative arousal responses to actual loss and gain outcomes. In the current study, we find using fMRI that behavioral loss aversion correlates with amygdala activity in response to losses relative to gains. Success in regulating loss aversion also correlates with the reduction in amygdala responses to losses but not to gains. Furthermore, across both decisions and outcomes, we find the reappraisal strategy increases baseline activity in dorsolateral and ventromedial prefrontal cortex and the striatum. The similarity of the neural circuitry observed to that seen in emotion regulation, despite divergent tasks, serves as further evidence for a role of emotion in decision making, and for the power of reappraisal to change assessments of value and thereby choices.

  11. Gene regulation by growth factors

    International Nuclear Information System (INIS)

    Metz, R.; Gorham, J.; Siegfried, Z.; Leonard, D.; Gizang-Ginsberg, E.; Thompson, M.A.; Lawe, D.; Kouzarides, T.; Vosatka, R.; MacGregor, D.; Jamal, S.; Greenberg, M.E.; Ziff, E.B.

    1988-01-01

    To coordinate the proliferation and differentiation of diverse cell types, cells of higher eukaryotes communicate through the release of growth factors. These peptides interact with specific transmembrane receptors of other cells and thereby generate intracellular messengers. The many changes in cellular physiology and activity that can be induced by growth factors imply that growth factor-induced signals can reach the nucleus and control gene activity. Moreover, current evidence also suggests that unregulated signaling along such pathways can induce aberrant proliferation and the formation of tumors. This paper reviews investigations of growth factor regulation of gene expression conducted by the authors' laboratory

  12. Current Evidence Supporting Obstetric Fistula Prevention Strategies ...

    African Journals Online (AJOL)

    Evidences from the articles were linked to prevention strategies retrieved from grey literature. The strategies were classified using an innovative target-focused method. Gaps in the literature show the need for fistula prevention research to aim at systematically measuring incidence and prevalence of the disease, identify the ...

  13. PRESCRIBING OF ANTIHYPERTENSIVE AGENTS IN PUBLIC PRIMARY CARE CLINICS – IS IT IN ACCORDANCE WITH CURRENT EVIDENCE?

    Directory of Open Access Journals (Sweden)

    SAJARI J

    2010-01-01

    Full Text Available Background: Large population surveys in Malaysia have consistently shown minimal improvement of blood pressure control rates over the last 10 years. Poor adherence to antihypertensive medication has been recognized as a major reason for poor control of hypertension. This study aimed to describe the prescribing pattern of antihypertensive agents in 2 public primary care clinics and assess its appropriateness in relation to current evidence and guidelines. Methods: A cross-sectional survey to describe the prescribing pattern of antihypertensive agents was carried out in 2 publicprimary care clinics in Selangor from May to June 2009. Hypertensive patients on pharmacological treatment for ≥1 year who attended the clinics within the study period of 7 weeks were selected. Appropriate use of antihypertensive agents was defined based on current evidence and the recommendations by the Malaysian Clinical Practice Guidelines (CPG on the Management of Hypertension, 2008. Data were obtained from patients’ medical records and were analysed using the SPSS software version 16.0. Results: A total of 400 hypertensive patients on treatment were included. Mean age was 59.5 years (SD ±10.9, range 28 to91 years, of which 52.8% were females and 47.2% were males. With regards to pharmacotherapy, 45.7% were on monotherapy,43.3% were on 2 agents and 11.0% were on ≥3 agents. Target blood pressure of <140/90mmHg was achieved in 51.4% of patients on monotherapy, and 33.2% of patients on combination of ≥2 agents. The commonest monotherapy agents being prescribed were β-blockers (atenolol or propranolol, followed by the short-acting calcium channel blocker (nifedipine. The commonest combination of 2-drug therapy prescribed was β-blockers and short-acting calcium channel blocker. Conclusion: This study shows that the prescribing pattern of antihypertensive agents in the 2 primary care clinics was not in accordance with current evidence and guidelines.

  14. Integrating Radiology and Anatomy Teaching in Medical Education in the UK--The Evidence, Current Trends, and Future Scope.

    Science.gov (United States)

    Heptonstall, N B; Ali, T; Mankad, K

    2016-04-01

    This review article presents the current evidence of the importance of integrating radiology and anatomy in medical education in the UK, a recommendation by a number of key anatomy, education, and radiology organizations. Current evidence highlights that on average only 5% of total teaching time in medical education is dedicated to radiology. Often, radiology teaching does not adequately fulfill students' learning needs and potentially leaves them underprepared for medical practice. Benefits of integrating radiology and anatomy include improved clinical application of anatomy, an increase in student's interest in anatomy, and ultimately improved radiological interpretation. Various modalities exist for the integration of radiology and anatomy, facilitated by the vast portability of radiological images. It appears that combining radiological resources with traditional anatomy teaching methodology in a blended approach is most beneficial. Copyright © 2016 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.

  15. Hypocretin/orexin regulation of dopamine signaling: implications for reward and reinforcement mechanisms

    Directory of Open Access Journals (Sweden)

    Rodrigo eEspaña

    2012-08-01

    Full Text Available The hypocretins/orexins are comprised of two neuroexcitatory peptides that are synthesized exclusively within a circumscribed region of the lateral hypothalamus. These peptides project widely throughout the brain and interact with a variety of regions involved in the regulation of arousal-related processes including those associated with motivated behavior. The current review focuses on emerging evidence indicating that the hypocretins influence reward and reinforcement processing via actions on the mesolimbic dopamine system. We discuss contemporary perspectives of hypocretin regulation of mesolimbic dopamine signaling in both drug free and drug states, as well as hypocretin regulation of behavioral responses to drugs of abuse, particularly as it relates to cocaine.

  16. Hypocretin/orexin regulation of dopamine signaling: implications for reward and reinforcement mechanisms

    Science.gov (United States)

    Calipari, Erin S.; España, Rodrigo A.

    2012-01-01

    The hypocretins/orexins are comprised of two neuroexcitatory peptides that are synthesized exclusively within a circumscribed region of the lateral hypothalamus. These peptides project widely throughout the brain and interact with a variety of regions involved in the regulation of arousal-related processes including those associated with motivated behavior. The current review focuses on emerging evidence indicating that the hypocretins influence reward and reinforcement processing via actions on the mesolimbic dopamine system. We discuss contemporary perspectives of hypocretin regulation of mesolimbic dopamine signaling in both drug free and drug states, as well as hypocretin regulation of behavioral responses to drugs of abuse, particularly as it relates to cocaine. PMID:22933994

  17. [100 years of drinking water regulation. Retrospective review, current situation and prospects].

    Science.gov (United States)

    Rakhmanin, Yu A; Krasovsky, G N; Egorova, N A; Mikhailova, R I

    2014-01-01

    There is considered the history of the development of legislative requirements to the regulation of the quality of drinking water in different countries and international organizations during the period from 1912 to the present time. In terms of comparative analysis there is analyzed the current state of regulatory frameworks of the Russian Federation, WHO, EU, Finland, the UK, Singapore, Australia, Japan, China, Nigeria, the United States and Canada in the field of providing favorable conditions of population drinking water use. There has been noted the significant progress in standardization of the content of the biogenic elements and chemical pollution of drinking water in the absence of uniform requirements to the composition and properties of drinking water globally, that is bound to the need to take into account the national peculiarities of drinking water supply within the separate countries. As promising directions for improving regulation of drinking water quality there are noted: the development of new standards for prioritized water pollution, periodic review ofstandards after appearance of the new scientific data on the biological action of substances, the use of the concept of risk, the harmonization of the normative values and the assessment of the possibility of introduction into the practice the one more criterion of profitableness of population water use--the bioenergetic state of the water.

  18. Expert opinion vs. empirical evidence

    Science.gov (United States)

    Herman, Rod A; Raybould, Alan

    2014-01-01

    Expert opinion is often sought by government regulatory agencies when there is insufficient empirical evidence to judge the safety implications of a course of action. However, it can be reckless to continue following expert opinion when a preponderance of evidence is amassed that conflicts with this opinion. Factual evidence should always trump opinion in prioritizing the information that is used to guide regulatory policy. Evidence-based medicine has seen a dramatic upturn in recent years spurred by examples where evidence indicated that certain treatments recommended by expert opinions increased death rates. We suggest that scientific evidence should also take priority over expert opinion in the regulation of genetically modified crops (GM). Examples of regulatory data requirements that are not justified based on the mass of evidence are described, and it is suggested that expertise in risk assessment should guide evidence-based regulation of GM crops. PMID:24637724

  19. Food and Beverage Marketing in Schools: A Review of the Evidence

    OpenAIRE

    Velazquez, Cayley E.; Black, Jennifer L.; Potvin Kent, Monique

    2017-01-01

    Despite growing interest from government agencies, non-governmental organizations and school boards in restricting or regulating unhealthy food and beverage marketing to children, limited research has examined the emerging knowledge base regarding school-based food and beverage marketing in high-income countries. This review examined current approaches for measuring school food and beverage marketing practices, and evidence regarding the extent of exposure and hypothesized associations with c...

  20. Emotion regulation choice : A conceptual framework and supporting evidence

    NARCIS (Netherlands)

    Sheppes, Gal; Scheibe, Susanne; Suri, Gaurav; Radu, Peter; Blechert, Jens; Gross, James J.

    Choice behavior is considered the fundamental means by which individuals exert control over their environments. One important choice domain that remains virtually unexplored is that of emotion regulation. This is surprising given that healthy adaptation requires flexibly choosing between regulation

  1. Power-MOSFET Voltage Regulator

    Science.gov (United States)

    Miller, W. N.; Gray, O. E.

    1982-01-01

    Ninety-six parallel MOSFET devices with two-stage feedback circuit form a high-current dc voltage regulator that also acts as fully-on solid-state switch when fuel-cell out-put falls below regulated voltage. Ripple voltage is less than 20 mV, transient recovery time is less than 50 ms. Parallel MOSFET's act as high-current dc regulator and switch. Regulator can be used wherever large direct currents must be controlled. Can be applied to inverters, industrial furnaces photovoltaic solar generators, dc motors, and electric autos.

  2. Metastatic castration-resistant prostate cancer: a current view on drug therapy and alternative tumor cell regulation

    Directory of Open Access Journals (Sweden)

    R. A. Gafanov

    2018-01-01

    Full Text Available Prostate cancer (PC is one of the most common causes of death from malignant neoplasms in men in many countries around the world. Transmission of the signal in the androgenic axis of regulation is crucial for the development and progression of PC. Despite the constant dependence on androgen receptor signals in castration resistance, the use of new anti-androgenic drugs invariably leads to the stability  of the ongoing treatment. The interaction of androgen receptor and alternative (phosphoinositide-3-kinases, PI3K pathways in the regulation of cells can be one of the mechanisms of resistance to treatment. In this article, we describe current treatments for metastatic castration-resistant PC and the possible role of the PI3K pathway in the pathogenesis and progression of PC.

  3. E-cigarette regulation and policy: UK vapers' perspectives.

    Science.gov (United States)

    Farrimond, Hannah

    2016-06-01

    The rapid increase in use of electronic cigarettes (e-cigarettes) has created an international policy dilemma concerning how to use these products. This study assesses the types of beliefs that e-cigarette users in the United Kingdom may hold concerning regulation. Qualitative thematic analysis of written answers to open-ended questions. United Kingdom, questionnaire conducted by post, 44% recruited from online forums and 56% non-online. Fifty-five UK vapers, 55% male, mean age 46 years, 84% sole users of e-cigarettes, 95% vaping daily. Open-ended questions on regulatory and policy options. 'Protecting youth' was seen as a fundamental regulatory requirement which should be achieved through childproofing, age limits, no advertising aimed at children and health warnings about addictiveness of nicotine, but not the restriction of flavours. There was little support for regulating e-cigarettes as medicines or limiting the strength of nicotine liquids. In terms of public use, participants argued against a blanket ban on public vaping given perceptions of a lack of scientific evidence of harm. However, they supported the principle of autonomy, that individuals and organizations have the right to restrict vaping. Some participants suggested banning vaping in places such as schools, hospitals or around food, in line with current smoking norms. Vapers' regulatory positions were accompanied by political concerns about the use (and misuse) of scientific evidence. With regard to regulation of e-cigarettes, issues that are salient to UK vapers may include the need for youth protection, regulation as medicines, strength of e-liquids, bans on public vaping and concerns about the misuse of scientific evidence. © 2016 Society for the Study of Addiction.

  4. Are Management-Based Regulations Effective? Evidence from State Pollution Prevention Programs

    Science.gov (United States)

    Bennear, Lori Snyder

    2007-01-01

    This paper evaluates a recent innovation in regulating risk called management-based regulation. Traditionally, risk regulation has either specified a particular means of achieving a risk-reduction goal or specified the goal and left the means of achieving that goal up to the regulated entity. In contrast, management-based regulation neither…

  5. Medicinal mushroom science: Current perspectives, advances, evidences, and challenges

    Directory of Open Access Journals (Sweden)

    Solomon P Wasser

    2014-12-01

    Full Text Available The main target of the present review is to draw attention to the current perspectives, advances, evidences, challenges, and future development of medicinal mushroom science in the 21 st century. Medicinal mushrooms and fungi are thought to possess approximately 130 medicinal functions, including antitumor, immunomodulating, antioxidant, radical scavenging, cardiovascular, anti-hypercholesterolemic, antiviral, antibacterial, anti-parasitic, antifungal, detoxification, hepatoprotective, and antidiabetic effects. Many, if not all, higher Basidiomycetes mushrooms contain biologically active compounds in fruit bodies, cultured mycelium, and cultured broth. Special attention is paid to mushroom polysaccharides. The data on mushroom polysaccharides and different secondary metabolites are summarized for approximately 700 species of higher hetero- and homobasidiomycetes. Numerous bioactive polysaccharides or polysaccharide-protein complexes from the medicinal mushrooms described appear to enhance innate and cell-mediated immune responses, and exhibit antitumor activities in animals and humans. Whilst the mechanism of their antitumor actions is still not completely understood, stimulation and modulation of key host immune responses by these mushroom compounds appear central. Polysaccharides and low-molecular-weight secondary metabolites are particularly important due to their antitumor and immunostimulating properties. Several of the mushroom compounds have been subjected to Phase I, II, and III clinical trials, and are used extensively and successfully in Asia to treat various cancers and other diseases. Special attention is given to many important unsolved problems in the study of medicinal mushrooms.

  6. Health Considerations in Regulation and Taxation of Electronic Cigarettes.

    Science.gov (United States)

    Mainous, Arch G; Tanner, Rebecca J; Mainous, Ryan W; Talbert, Jeffery

    2015-01-01

    The use of electronic cigarettes (e-cigarettes) is experiencing unprecedented growth. This can be contrasted to the use of conventional cigarettes which showed a decrease among adults with the current smoker prevalence dropping from 20.9% in 2005 to 17.8% in 2013. There is some data that e-cigarettes are attracting both former smokers and never smokers, and in particular, young people as users. Currently most states do not tax e-cigarettes. Taxation and regulation may have a similar overall goal of decreasing smoking but regulation tends to focus reduced availability of products. In terms of tobacco control, taxation focuses on the demand side of the equation. Taxation is a distinct strategy from regulation and has been shown to decrease new adopters of conventional cigarettes. A variety of potential taxation strategies can be considered by policymakers based on different assumptions about e-cigarettes and their utility, ranging from untaxed to taxation at moderate levels compared to conventional cigarettes to taxation equal to conventional cigarettes. Until more evidence for the benefits of e-cigarettes is presented, it seems prudent to view them as a potentially harmful and addictive product that ought to be regulated and taxed in an equivalent manner to conventional cigarettes. © Copyright 2015 by the American Board of Family Medicine.

  7. Behavioural and Autonomic Regulation of Response to Sensory Stimuli among Children: A Systematic Review of Relationship and Methodology.

    Science.gov (United States)

    Gomez, Ivan Neil; Lai, Cynthia Y Y; Morato-Espino, Paulin Grace; Chan, Chetwyn C H; Tsang, Hector W H

    2017-01-01

    Previous studies have explored the correlates of behavioural and autonomic regulation of response to sensory stimuli in children; however, a comprehensive review of such relationship is lacking. This systematic review was performed to critically appraise the current evidence on such relationship and describe the methods used in these studies. Online databases were systematically searched for peer-reviewed, full-text articles in the English language between 1999 and 2016, initially screened by title and abstract, and appraised and synthesized by two independent review authors. Fourteen Level III-3 cross-sectional studies were included for systematic review, among which six studies explored the relationship between behaviour and physiological regulation of responses to sensory stimuli. Three studies reported significant positive weak correlations among ASD children; however, no correlations were found in typically developing children. Methodological differences related to individual differences among participants, measures used, and varied laboratory experimental setting were noted. This review suggests inconclusive evidence supporting the relationship between behavioural and physiological regulation of responses to sensory stimuli among children. Methodological differences may likely have confounded the results of the current evidence. We present methodological recommendations to address this matter for future researches. This trial is registered with PROSPERO registration number CRD42016043887.

  8. Behavioural and Autonomic Regulation of Response to Sensory Stimuli among Children: A Systematic Review of Relationship and Methodology

    Directory of Open Access Journals (Sweden)

    Ivan Neil Gomez

    2017-01-01

    Full Text Available Background. Previous studies have explored the correlates of behavioural and autonomic regulation of response to sensory stimuli in children; however, a comprehensive review of such relationship is lacking. This systematic review was performed to critically appraise the current evidence on such relationship and describe the methods used in these studies. Methods. Online databases were systematically searched for peer-reviewed, full-text articles in the English language between 1999 and 2016, initially screened by title and abstract, and appraised and synthesized by two independent review authors. Results. Fourteen Level III-3 cross-sectional studies were included for systematic review, among which six studies explored the relationship between behaviour and physiological regulation of responses to sensory stimuli. Three studies reported significant positive weak correlations among ASD children; however, no correlations were found in typically developing children. Methodological differences related to individual differences among participants, measures used, and varied laboratory experimental setting were noted. Conclusion. This review suggests inconclusive evidence supporting the relationship between behavioural and physiological regulation of responses to sensory stimuli among children. Methodological differences may likely have confounded the results of the current evidence. We present methodological recommendations to address this matter for future researches. This trial is registered with PROSPERO registration number CRD42016043887.

  9. A 3 A sink/source current fast transient response low-dropout G{sub m} driven linear regulator

    Energy Technology Data Exchange (ETDEWEB)

    Chu Xiuqin; Li Qingwei; Lai Xinquan; Yuan Bing [Institute of Electronic CAD, Xidian University, Xi' an 710071 (China); Li Yanming [School of Electronic and Control Engineering, Chang' an University, Xi' an 710064 (China); Zhao Yongrui, E-mail: liqw309@163.com, E-mail: xqchu@mail.xidian.edu.cn [Key Laboratory of High-Speed Circuit Design and EMC, Ministry of Education, Xidian University, Xi' an 710071 (China)

    2011-06-15

    A 3 A sink/source G{sub m}-driven CMOS low-dropout regulator (LDO), specially designed for low input voltage and low cost, is presented by utilizing the structure of a current mirror G{sub m} (transconductance) driving technique, which provides high stability as well as a fast load transient response. The proposed LDO was fabricated by a 0.5 {mu}m standard CMOS process, and the die size is as small as 1.0 mm{sup 2}. The proposed LDO dissipates 220 {mu}A of quiescent current in no-load conditions and is able to deliver up to 3 A of load current. The measured results show that the output voltage can be resumed within 2 {mu}s with a less than 1 mV overshoot and undershoot in the output current step from -1.8 to 1.8 A with a 0.1 {mu}s rising and falling time at three 10 {mu}F ceramic capacitors. (semiconductor integrated circuits)

  10. Serine/threonine/tyrosine phosphorylation regulates DNA binding of bacterial transcriptional regulators

    DEFF Research Database (Denmark)

    Kalantari, Aida; Derouiche, Abderahmane; Shi, Lei

    2015-01-01

    Reversible phosphorylation of bacterial transcriptional regulators (TRs) belonging to the family of two-component systems (TCSs) is a well-established mechanism for regulating gene expression. Recent evidence points to the fact that reversible phosphorylation of bacterial TRs on other types...

  11. Design considerations for high current regulated DC power supplies with reference to 600 kW variable DC power supply

    International Nuclear Information System (INIS)

    Ushakumari; Garud, A.N.; Nadkarni, S.S.

    1980-01-01

    High current regulated dc power supplies find increasing applications in industry and research. The power rating of these supplies vary from few killowatts to megawatts. The general requirements of these supplies for various applications and the techniques used to achieve the desired performance are presented. The design and selection of various circuit blocks namely the rectifier transformer, multiphase rectifier arrangement, SCR paralleling and current sensing techniques, are discussed in detail for a 600 killowatt current controlled supply developed in the Bhabha Atomic Research Centre, Bombay, and used for the thermal studies of reactor components. The power supply incorporates paralleled phase controlled thyristors with a closed loop feedback circuitary to achieve a current stability of 0.1% and smooth output variation from 10 to 100%. (auth.)

  12. Current Account Adjustment: Some New Theory and Evidence

    OpenAIRE

    Jiandong Ju; Shang-Jin Wei

    2007-01-01

    This paper aims to provide a theory of current account adjustment that generalizes the textbook version of the intertemporal approach to current account and places domestic labor market institutions at the center stage. In general, in response to a shock, an economy adjusts through a combination of a change in the composition of goods trade (i.e., intra-temporal trade channel) and a change in the current account (i.e., intertemporal trade channel). The more rigid the labor market, the slower ...

  13. Serotonin Regulates the Firing of Principal Cells of the Subiculum by Inhibiting a T-type Ca(2+) Current

    DEFF Research Database (Denmark)

    Petersen, Anders V; Jensen, Camilla S; Crépel, Valérie

    2017-01-01

    The subiculum is the main output of the hippocampal formation. A high proportion of its principal neurons fire action potentials in bursts triggered by the activation of low threshold calcium currents. This firing pattern promotes synaptic release and regulates spike-timing-dependent plasticity. ...... of epileptiform discharges induced in in vitro models for temporal lobe epilepsy (TLE)....

  14. New GMO regulations for old: Determining a new future for EU crop biotechnology

    Science.gov (United States)

    2017-01-01

    ABSTRACT In this review, current EU GMO regulations are subjected to a point-by point analysis to determine their suitability for agriculture in modern Europe. Our analysis concerns present GMO regulations as well as suggestions for possible new regulations for genome editing and New Breeding Techniques (for which no regulations presently exist). Firstly, the present GMO regulations stem from the early days of recombinant DNA and are not adapted to current scientific understanding on this subject. Scientific understanding of GMOs has changed and these regulations are now, not only unfit for their original purpose, but, the purpose itself is now no longer scientifically valid. Indeed, they defy scientific, economic, and even common, sense. A major EU regulatory preconception is that GM crops are basically different from their parent crops. Thus, the EU regulations are “process based” regulations that discriminate against GMOs simply because they are GMOs. However current scientific evidence shows a blending of classical crops and their GMO counterparts with no clear demarcation line between them. Canada has a “product based” approach and determines the safety of each new crop variety independently of the process used to obtain it. We advise that the EC re-writes it outdated regulations and moves toward such a product based approach.  Secondly, over the last few years new genomic editing techniques (sometimes called New Breeding Techniques) have evolved. These techniques are basically mutagenesis techniques that can generate genomic diversity and have vast potential for crop improvement. They are not GMO based techniques (any more than mutagenesis is a GMO technique), since in many cases no new DNA is introduced. Thus they cannot simply be lumped together with GMOs (as many anti-GMO NGOs would prefer). The EU currently has no regulations to cover these new techniques. In this review, we make suggestions as to how these new gene edited crops may be regulated

  15. New GMO regulations for old: Determining a new future for EU crop biotechnology.

    Science.gov (United States)

    Davison, John; Ammann, Klaus

    2017-01-02

    In this review, current EU GMO regulations are subjected to a point-by point analysis to determine their suitability for agriculture in modern Europe. Our analysis concerns present GMO regulations as well as suggestions for possible new regulations for genome editing and New Breeding Techniques (for which no regulations presently exist). Firstly, the present GMO regulations stem from the early days of recombinant DNA and are not adapted to current scientific understanding on this subject. Scientific understanding of GMOs has changed and these regulations are now, not only unfit for their original purpose, but, the purpose itself is now no longer scientifically valid. Indeed, they defy scientific, economic, and even common, sense. A major EU regulatory preconception is that GM crops are basically different from their parent crops. Thus, the EU regulations are "process based" regulations that discriminate against GMOs simply because they are GMOs. However current scientific evidence shows a blending of classical crops and their GMO counterparts with no clear demarcation line between them. Canada has a "product based" approach and determines the safety of each new crop variety independently of the process used to obtain it. We advise that the EC re-writes it outdated regulations and moves toward such a product based approach.  Secondly, over the last few years new genomic editing techniques (sometimes called New Breeding Techniques) have evolved. These techniques are basically mutagenesis techniques that can generate genomic diversity and have vast potential for crop improvement. They are not GMO based techniques (any more than mutagenesis is a GMO technique), since in many cases no new DNA is introduced. Thus they cannot simply be lumped together with GMOs (as many anti-GMO NGOs would prefer). The EU currently has no regulations to cover these new techniques. In this review, we make suggestions as to how these new gene edited crops may be regulated. The EU is at a

  16. Cell cycle-dependent regulation of kainate-induced inward currents in microglia

    International Nuclear Information System (INIS)

    Yamada, Jun; Sawada, Makoto; Nakanishi, Hiroshi

    2006-01-01

    Microglia are reported to have α-amino-hydroxy-5-methyl-isoxazole-4-propionate/kainate (KA) types. However, only small population of primary cultured rat microglia (approximately 20%) responded to KA. In the present study, we have attempted to elucidate the regulatory mechanism of responsiveness to KA in GMIR1 rat microglial cell line. When the GMIR1 cells were plated at a low density in the presence of granulocyte macrophage colony-stimulating factor, the proliferation rate increased and reached the peak after 2 days in culture and then gradually decreased because of density-dependent inhibition. At cell proliferation stage, approximately 80% of the GMIR1 cells exhibited glutamate (Glu)- and KA-induced inward currents at cell proliferation stage, whereas only 22.5% of the cells showed responsiveness to Glu and KA at cell quiescent stage. Furthermore, the mean amplitudes of inward currents induced by Glu and KA at cell proliferation stage (13.8 ± 3.0 and 8.4 ± 0.6 pA) were significantly larger than those obtained at cell quiescent stage (4.7 ± 0.8 and 6.2 ± 1.2 pA). In the GMIR1 cells, KA-induced inward currents were markedly inhibited by (RS)-3-(2-carboxybenzyl) willardiine (UBP296), a selective antagonist for KA receptors. The KA-responsive cells also responded to (RS)-2-amino-3-(3-hydroxy-5-tert-butylisoxazol-4-yl) propanoic acid (ATPA), a selective agonist for GluR5, in both GMIR1 cells and primary cultured rat microglia. Furthermore, mRNA levels of the KA receptor subunits, GluR5 and GluR6, at the cell proliferation stage were significantly higher than those at the cell quiescent stage. Furthermore, the immunoreactivity for GluR6/7 was found to increase in activated microglia in the post-ischemic hippocampus. These results strongly suggest that microglia have functional KA receptors mainly consisting of GluR5 and GluR6, and the expression levels of these subunits are closely regulated by the cell cycle mechanism

  17. UK: the current state of regulation of complementary and alternative medicine.

    Science.gov (United States)

    Walker, L A; Budd, S

    2002-03-01

    There is no legislation that restricts the practice of CAM in the UK apart from the practice of chiropractic and osteopathy and limits on advertising the treatments of certain conditions such as cancer and tuberculosis. The UK government has increasingly recognised the need for comprehensive regulation of CAM, though it abandoned its original plan for a single overarching regulatory body. Initiatives to examine and hasten the process of regulation have included setting up a central, well-recognised charitable body to facilitate progress for individual professions, and an authoritative survey of the existing professional organisations. One pathway open to individual professions is statutory self-regulation, which requires a single governing body, a systematic corpus of knowledge, recognised training courses and demonstrated efficacy. The other pathway is voluntary self-regulation. Chiropractic and osteopathy have adopted statutory self-regulation, though this has proved expensive for individual members of these professions. A recent House of Lords report on CAM has recommended that the herbal medicine and acupuncture professions should also develop a system of statutory regulation. Other professions, such as aromatherapy, are in the process of establishing single professional bodies as a first step towards self-regulation. Among the issues that remain to be resolved is the relationship between the CAM professions and statutory registered practitioners who also practise CAM.

  18. The evaluation of drug regulation - economic approaches into the valuation and evaluation of the drug regulatory framework

    NARCIS (Netherlands)

    Bouvy, J.C.

    2013-01-01

    The European pharmaceutical market is strictly regulated. Sufficient levels of quality, safety, and efficacy will have to be demonstrated before a pharmaceutical is allowed to enter the market. There is little evidence, however, that the current drug regulatory framework is achieving its goals of

  19. Current Guidelines Have Limited Applicability to Patients with Comorbid Conditions: A Systematic Analysis of Evidence-Based Guidelines

    Science.gov (United States)

    Lugtenberg, Marjolein; Burgers, Jako S.; Clancy, Carolyn; Westert, Gert P.; Schneider, Eric C.

    2011-01-01

    Background Guidelines traditionally focus on the diagnosis and treatment of single diseases. As almost half of the patients with a chronic disease have more than one disease, the applicability of guidelines may be limited. The aim of this study was to assess the extent that guidelines address comorbidity and to assess the supporting evidence of recommendations related to comorbidity. Methodology/Principal Findings We conducted a systematic analysis of evidence-based guidelines focusing on four highly prevalent chronic conditions with a high impact on quality of life: chronic obstructive pulmonary disease, depressive disorder, diabetes mellitus type 2, and osteoarthritis. Data were abstracted from each guideline on the extent that comorbidity was addressed (general comments, specific recommendations), the type of comorbidity discussed (concordant, discordant), and the supporting evidence of the comorbidity-related recommendations (level of evidence, translation of evidence). Of the 20 guidelines, 17 (85%) addressed the issue of comorbidity and 14 (70%) provided specific recommendations on comorbidity. In general, the guidelines included few recommendations on patients with comorbidity (mean 3 recommendations per guideline, range 0 to 26). Of the 59 comorbidity-related recommendations provided, 46 (78%) addressed concordant comorbidities, 8 (14%) discordant comorbidities, and for 5 (8%) the type of comorbidity was not specified. The strength of the supporting evidence was moderate for 25% (15/59) and low for 37% (22/59) of the recommendations. In addition, for 73% (43/59) of the recommendations the evidence was not adequately translated into the guidelines. Conclusions/Significance Our study showed that the applicability of current evidence-based guidelines to patients with comorbid conditions is limited. Most guidelines do not provide explicit guidance on treatment of patients with comorbidity, particularly for discordant combinations. Guidelines should be more

  20. Current insights into hormonal regulation of microspore embryogenesis

    Directory of Open Access Journals (Sweden)

    Iwona eŻur

    2015-06-01

    Full Text Available Plant growth regulator (PGR crosstalk and interaction with the plant’s genotype and environmental factors play a crucial role in microspore embryogenesis (ME, controlling microspore-derived embryo differentiation and development as well as haploid/doubled haploid plant regeneration. The complexity of the PGR network which could exist at the level of biosynthesis, distribution, gene expression or signaling pathways, renders the creation of an integrated model of ME-control crosstalk impossible at present. However, the analysis of the published data together with the results received recently with the use of modern analytical techniques brings new insights into hormonal regulation of this process. This review presents a short historical overview of the most important milestones in the recognition of hormonal requirements for effective ME in the most important crop plant species and complements it with new concepts that evolved over the last decade of ME studies.

  1. Federal Aviation Regulations - National Aviation Regulations of Russia

    Science.gov (United States)

    Chernykh, O.; Bakiiev, M.

    2018-03-01

    Chinese Aerospace Engineering is currently developing cooperation with Russia on a wide-body airplane project that has directed the work towards better understanding of Russian airworthiness management system. The paper introduces national Aviation regulations of Russia, presents a comparison of them with worldwide recognized regulations, and highlights typical differences. They have been found to be: two general types of regulations used in Russia (Aviation Regulations and Federal Aviation Regulations), non-unified structure of regulations on Aircraft Operation management, various separate agencies responsible for regulation issuance instead of one national aviation authority, typical confusions in references. The paper also gives a list of effective Russian Regulations of both types.

  2. Infant Nutrition and Later Health: A Review of Current Evidence

    Directory of Open Access Journals (Sweden)

    Caroline Fall

    2012-07-01

    Full Text Available There is a growing recognition of the need for a lifecourse approach to understanding the aetiology of adult disease, and there is now significant evidence that links patterns of infant feeding to differences in health outcomes, both in the short and longer term. Breastfeeding is associated with lower rates of infection in infancy; in high-income populations, it is associated with reductions in blood pressure and total blood cholesterol, and lower risks of obesity and diabetes in adult life. Breastfeeding rates are suboptimal in many countries, and strategies to promote breastfeeding could therefore confer important benefits for health at a population level. However, there are particular challenges in defining nutritional exposures in infancy, including marked social gradients in initiation and duration of breastfeeding. In recent studies of low and middle-income populations of children and young adults, where the influences on infant feeding practice differ, beneficial effects of breastfeeding on blood pressure, BMI and risk of diabetes have not been confirmed, and further information is needed. Little is currently known about the long-term consequences of differences in the timing and nature of the weaning diet. Future progress will depend on new studies that provide detailed prospective data on duration and exclusivity of breastfeeding together with appropriate characterisation of the weaning diet.

  3. Evidence for a role of Collapsin response mediator protein-2 in signaling pathways that regulate the proliferation of non-neuronal cells

    International Nuclear Information System (INIS)

    Tahimic, Candice Ginn T.; Tomimatsu, Nozomi; Nishigaki, Ryuichi; Fukuhara, Akiko; Toda, Tosifusa; Kaibuchi, Kozo; Shiota, Goshi; Oshimura, Mitsuo; Kurimasa, Akihiro

    2006-01-01

    Collapsin response mediator protein-2 or Crmp-2 plays a critical role in the establishment of neuronal polarity. In this study, we present evidence that apart from its functions in neurodevelopment, Crmp-2 is also involved in pathways that regulate the proliferation of non-neuronal cells through its phosphorylation by regulatory proteins. We show that Crmp-2 undergoes dynamic phosphorylation changes in response to contact inhibition-induced quiescence and that hyperphosphorylation of Crmp-2 occurs in a tumor. We further suggest that de-regulation of Crmp-2 phosphorylation levels at certain amino acid residues may lead to aberrant cell proliferation and consequently, tumorigenesis

  4. Dynamic, nonlinear feedback regulation of slow pacemaking by A-type potassium current in ventral tegmental area neurons.

    Science.gov (United States)

    Khaliq, Zayd M; Bean, Bruce P

    2008-10-22

    We analyzed ionic currents that regulate pacemaking in dopaminergic neurons of the mouse ventral tegmental area by comparing voltage trajectories during spontaneous firing with ramp-evoked currents in voltage clamp. Most recordings were made in brain slice, with key experiments repeated using acutely dissociated neurons, which gave identical results. During spontaneous firing, net ionic current flowing between spikes was calculated from the time derivative of voltage multiplied by cell capacitance, signal-averaged over many firing cycles to enhance resolution. Net inward interspike current had a distinctive nonmonotonic shape, reaching a minimum (generally current that peaked near -55 mV. This current was undetectable with 5 mV/s ramps and increased steeply with depolarization rate over the range (10-50 mV/s) typical of natural pacemaking. Ramp-evoked subthreshold current was resistant to alpha-dendrotoxin, paxilline, apamin, and tetraethylammonium but sensitive to 4-aminopyridine and 0.5 mM Ba2+, consistent with A-type potassium current (I(A)). Same-cell comparison of currents elicited by various ramp speeds with natural spontaneous depolarization showed how the steep dependence of I(A) on depolarization rate results in small net inward currents during pacemaking. These results reveal a mechanism in which subthreshold I(A) is near zero at steady state, but is engaged at depolarization rates >10 mV/s to act as a powerful, supralinear feedback element. This feedback mechanism explains how net ionic current can be constrained to <1-2 pA but reliably inward, thus enabling slow, regular firing.

  5. The behavioral regulation in sport questionnaire (BRSQ): instrument development and initial validity evidence.

    Science.gov (United States)

    Lonsdale, Chris; Hodge, Ken; Rose, Elaine A

    2008-06-01

    The purpose of the four studies described in this article was to develop and test a new measure of competitive sport participants' intrinsic motivation, extrinsic motivation, and amotivation (self-determination theory; Deci & Ryan, 1985). The items for the new measure, named the Behavioral Regulation in Sport Questionnaire (BRSQ), were constructed using interviews, expert review, and pilot testing. Analyses supported the internal consistency, test-retest reliability, and factorial validity of the BRSQ scores. Nomological validity evidence was also supportive, as BRSQ subscale scores were correlated in the expected pattern with scores derived from measures of motivational consequences. When directly compared with scores derived from the Sport Motivation Scale (SMS; Pelletier, Fortier, Vallerand, Tuson, & Blais, 1995) and a revised version of that questionnaire (SMS-6; Mallett, Kawabata, Newcombe, Otero-Forero, & Jackson, 2007), BRSQ scores demonstrated equal or superior reliability and factorial validity as well as better nomological validity.

  6. Current evidence does not support the use of Kinesio Taping in clinical practice: a systematic review

    Directory of Open Access Journals (Sweden)

    Patrícia do Carmo Silva Parreira

    2014-03-01

    Full Text Available Questions: Is Kinesio Taping more effective than a sham taping/placebo, no treatment or other interventions in people with musculoskeletal conditions? Is the addition of Kinesio Taping to other interventions more effective than other interventions alone in people with musculoskeletal conditions? Design: Systematic review of randomised trials. Participants: People with musculoskeletal conditions. Intervention: Kinesio Taping was compared with sham taping/placebo, no treatment, exercises, manual therapy and conventional physiotherapy. Outcome measures: Pain intensity, disability, quality of life, return to work, and global impression of recovery. Results: Twelve randomised trials involving 495 participants were included in the review. The effectiveness of the Kinesio Taping was tested in participants with: shoulder pain in two trials; knee pain in three trials; chronic low back pain in two trials; neck pain in three trials; plantar fasciitis in one trial; and multiple musculoskeletal conditions in one trial. The methodological quality of eligible trials was moderate, with a mean of 6.1 points on the 10-point PEDro Scale score. Overall, Kinesio Taping was no better than sham taping/placebo and active comparison groups. In all comparisons where Kinesio Taping was better than an active or a sham control group, the effect sizes were small and probably not clinically significant or the trials were of low quality. Conclusion: This review provides the most updated evidence on the effectiveness of the Kinesio Taping for musculoskeletal conditions. The current evidence does not support the use of this intervention in these clinical populations. PROSPERO registration: CRD42012003436. [Parreira PdCS, Costa LdCM, Hespanhol Junior LC, Lopes AD, Costa LOP (2014 Current evidence does not support the use of Kinesio Taping in clinical practice: a systematic review. Journal of Physiotherapy 60: 31–39

  7. Complex regulation of AprA metalloprotease in Pseudomonas fluorescens M114: evidence for the involvement of iron, the ECF sigma factor, PbrA and pseudobactin M114 siderophore.

    Science.gov (United States)

    Maunsell, Bláithín; Adams, Claire; O'Gara, Fergal

    2006-01-01

    In the soil bacterium Pseudomonas fluorescens M114, extracellular proteolytic activity and fluorescent siderophore (pseudobactin M114) production were previously shown to be co-ordinately negatively regulated in response to environmental iron levels. An iron-starvation extracytoplasmic function sigma factor, PbrA, required for the transcription of siderophore biosynthetic genes, was also implicated in M114 protease regulation. The current study centred on the characterization and genetic regulation of the gene(s) responsible for protease production in M114. A serralysin-type metalloprotease gene, aprA, was identified and found to encode the major, if not only, extracellular protease produced by this strain. The expression of aprA and its protein product were found to be subject to complex regulation. Transcription analysis confirmed that PbrA was required for full aprA transcription under low iron conditions, while the ferric uptake regulator, Fur, was implicated in aprA repression under high iron conditions. Interestingly, the iron regulation of AprA was dependent on culture conditions, with PbrA-independent AprA-mediated proteolytic activity observed on skim milk agar supplemented with yeast extract, when supplied with iron or purified pseudobactin M114. These effects were not observed on skim milk agar without yeast extract. PbrA-independent aprA expression was also observed from a truncated transcriptional fusion when grown in sucrose asparagine tryptone broth supplied with iron or purified pseudobactin M114. Thus, experimental evidence suggested that iron mediated its effects via transcriptional activation by PbrA under low iron conditions, while an as-yet-unidentified sigma factor(s) may be required for the PbrA-independent aprA expression and AprA proteolytic activity induced by siderophore and iron.

  8. Evidence for parity nonconservation in the weak neutral current

    International Nuclear Information System (INIS)

    Benvenuti, A.; Cline, D.; Messing, F.; Ford, W.; Imlay, R.; Ling, T.Y.; Mann, A.K.; Reeder, D.D.; Rubbia, C.; Stefanski, R.; Sulak, L.; Wanderer, P.

    1976-01-01

    Measurements of R/sup nu/ and R/sup nu-bar/, the ratios of neutral current to charged current ν and nu-bar cross sections, yield neutral current rates for ν and nu-bar that are consistent with a pure V-A interaction but 3 standard deviations from pure V or pure A, indicating the presence of parity nonconservation in the weak neutral current

  9. The role of massage in sports performance and rehabilitation: current evidence and future direction.

    Science.gov (United States)

    Brummitt, Jason

    2008-02-01

    Massage is a popular treatment choice of athletes, coaches, and sports physical therapists. Despite its purported benefits and frequent use, evidence demonstrating its efficacy is scarce. To identify current literature relating to sports massage and its role in effecting an athlete's psychological readiness, in enhancing sports performance, in recovery from exercise and competition, and in the treatment of sports related musculoskeletal injuries. Electronic databases were used to identify papers relevant to this review. The following keywords were searched: massage, sports injuries, athletic injuries, physical therapy, rehabilitation, delayed onset muscle soreness, sports psychology, sports performance, sports massage, sports recovery, soft tissue mobilization, deep transverse friction massage, pre-event, and post exercise. RESEARCH STUDIES PERTAINING TO THE FOLLOWING GENERAL CATEGORIES WERE IDENTIFIED AND REVIEWED: pre-event (physiological and psychological variables), sports performance, recovery, and rehabilitation. Despite the fact clinical research has been performed, a poor appreciation exists for the appropriate clinical use of sports massage. Additional studies examining the physiological and psychological effects of sports massage are necessary in order to assist the sports physical therapist in developing and implementing clinically significant evidence based programs or treatments.

  10. Former Soviet Regulations for seismic design of NPPs and comparison with current international practice

    International Nuclear Information System (INIS)

    Kostarev, V.; Schukin, A.; Berkovski, A.

    1997-01-01

    This paper presents a summary of current earthquake design criteria used in former Soviet Regulations for equipment and piping systems of nuclear power plants in light of those used in United States and Japan. The detailed comparative seismic analysis of PWR (WWER) Primary Coolant Loop System (PCLS) according to Former Soviet (Russian) PNAE Code and ASME BPV Code with some comments regarding to Japan Code JEAG - 4601 was undertaken for better understanding of the differences and coincidences of seismic design criteria and requirements. The selection of these three guides for the study has very simple explanation: according to ASME BVPC, JEAG and PNAE the huge majority of existing NPPs has been designed. (J.P.N.)

  11. Former Soviet Regulations for seismic design of NPPs and comparison with current international practice

    Energy Technology Data Exchange (ETDEWEB)

    Kostarev, V; Schukin, A; Berkovski, A [CKTI-Vibroseism Co. Ltd. (Cape Verde)

    1997-03-01

    This paper presents a summary of current earthquake design criteria used in former Soviet Regulations for equipment and piping systems of nuclear power plants in light of those used in United States and Japan. The detailed comparative seismic analysis of PWR (WWER) Primary Coolant Loop System (PCLS) according to Former Soviet (Russian) PNAE Code and ASME BPV Code with some comments regarding to Japan Code JEAG - 4601 was undertaken for better understanding of the differences and coincidences of seismic design criteria and requirements. The selection of these three guides for the study has very simple explanation: according to ASME BVPC, JEAG and PNAE the huge majority of existing NPPs has been designed. (J.P.N.)

  12. Profound regulation of Na/K pump activity by transient elevations of cytoplasmic calcium in murine cardiac myocytes.

    Science.gov (United States)

    Lu, Fang-Min; Deisl, Christine; Hilgemann, Donald W

    2016-09-14

    Small changes of Na/K pump activity regulate internal Ca release in cardiac myocytes via Na/Ca exchange. We now show conversely that transient elevations of cytoplasmic Ca strongly regulate cardiac Na/K pumps. When cytoplasmic Na is submaximal, Na/K pump currents decay rapidly during extracellular K application and multiple results suggest that an inactivation mechanism is involved. Brief activation of Ca influx by reverse Na/Ca exchange enhances pump currents and attenuates current decay, while repeated Ca elevations suppress pump currents. Pump current enhancement reverses over 3 min, and results are similar in myocytes lacking the regulatory protein, phospholemman. Classical signaling mechanisms, including Ca-activated protein kinases and reactive oxygen, are evidently not involved. Electrogenic signals mediated by intramembrane movement of hydrophobic ions, such as hexyltriphenylphosphonium (C6TPP), increase and decrease in parallel with pump currents. Thus, transient Ca elevation and Na/K pump inactivation cause opposing sarcolemma changes that may affect diverse membrane processes.

  13. Public utility regulation and national energy policy

    Energy Technology Data Exchange (ETDEWEB)

    Navarro, P.

    1980-09-01

    The linkage between Public Utility Commission (PUC) regulation, the deteriorating financial health of the electric utility industry, and implementation of national energy policy, particularly the reduction of foreign petroleum consumption in the utility sector is examined. The role of the Nation's utilities in the pursuit of national energy policy goals and postulates a linkage between PUC regulation, the poor financial health of the utility industry, and the current and prospective failure to displace foreign petroleum in the utility sector is discussed. A brief history of PUC regulation is provided. The concept of regulatory climate and how the financial community has developed a system of ranking regulatory climate in the various State jurisdictions are explained. The existing evidence on the hypothesis that the cost of capital to a utility increases and its availability is reduced as regulatory climate grows more unfavorable from an investor's point of view is analyzed. The implications of this cost of capital effect on the electric utilities and collaterally on national energy policy and electric ratepayers are explained. Finally various State, regional and Federal regulatory responses to problems associated with PUC regulation are examined.

  14. Current evidence on dietary pattern and cognitive function.

    Science.gov (United States)

    Cheung, Bernice H K; Ho, Ivan C H; Chan, Ruth S M; Sea, Mandy M M; Woo, Jean

    2014-01-01

    With global aging population, age-related cognitive decline becomes epidemic. Lifestyle-related factor is one of the key preventative measures. Dietary pattern analysis which considers dietary complexity has recently used to examine the linkage between nutrition and cognitive function. A priori approach defines dietary pattern based on existing knowledge. Results of several dietary pattern scores were summarized. The heterogeneity of assessment methods and outcome measurements lead to inconsistent results. Posteriori approach derives a dietary pattern independently of the existing nutrition-disease knowledge. It showed a dietary pattern abundant with plant-based food, oily fish, lower consumption of processed food, saturated fat, and simple sugar which appears to be beneficial to cognitive health. Despite inconclusive evidence from both approaches, diet and exercise, beneficial for other diseases, remains to be the two key modifiable factors for cognitive function. Large-scale prospective studies in multiethics population are required to provide stronger evidence in the future. © 2014 Elsevier Inc. All rights reserved.

  15. Attentional deployment is not necessary for successful emotion regulation via cognitive reappraisal or expressive suppression.

    Science.gov (United States)

    Bebko, Genna M; Franconeri, Steven L; Ochsner, Kevin N; Chiao, Joan Y

    2014-06-01

    According to appraisal theories of emotion, cognitive reappraisal is a successful emotion regulation strategy because it involves cognitively changing our thoughts, which, in turn, change our emotions. However, recent evidence has challenged the importance of cognitive change and, instead, has suggested that attentional deployment may at least partly explain the emotion regulation success of cognitive reappraisal. The purpose of the current study was to examine the causal relationship between attentional deployment and emotion regulation success. We examined 2 commonly used emotion regulation strategies--cognitive reappraisal and expressive suppression-because both depend on attention but have divergent behavioral, experiential, and physiological outcomes. Participants were either instructed to regulate emotions during free-viewing (unrestricted image viewing) or gaze-controlled (restricted image viewing) conditions and to self-report negative emotional experience. For both emotion regulation strategies, emotion regulation success was not altered by changes in participant control over the (a) direction of attention (free-viewing vs. gaze-controlled) during image viewing and (b) valence (negative vs. neutral) of visual stimuli viewed when gaze was controlled. Taken together, these findings provide convergent evidence that attentional deployment does not alter subjective negative emotional experience during either cognitive reappraisal or expressive suppression, suggesting that strategy-specific processes, such as cognitive appraisal and response modulation, respectively, may have a greater impact on emotional regulation success than processes common to both strategies, such as attention.

  16. Psychodynamic Emotional Regulation in View of Wolpe's Desensitization Model.

    Science.gov (United States)

    Rabinovich, Merav

    2016-01-01

    The current research belongs to the stream of theoretical integration and establishes a theoretical platform for integrative psychotherapy in anxiety disorders. Qualitative metasynthesis procedures were applied to 40 peer-reviewed psychoanalytic articles involving emotional regulation. The concept of psychodynamic emotional regulation was found to be connected with the categories of desensitization, gradual exposure, containment, and transference. This article presents a model according to which psychoanalytic psychotherapy allows anxiety to be tolerated while following the core principles of systematic desensitization. It is shown that despite the antiresearch image of psychoanalytic psychotherapy, its foundations obey evidence-based principles. The findings imply that anxiety tolerance might be a key goal in which the cumulative wisdom of the different therapies can be used to optimize psychotherapy outcomes.

  17. Epigenetic regulation of miRNA-cancer stem cells nexus by nutraceuticals.

    Science.gov (United States)

    Ahmad, Aamir; Li, Yiwei; Bao, Bin; Kong, Dejuan; Sarkar, Fazlul H

    2014-01-01

    Nutraceuticals, the bioactive food components represented by many naturally occurring dietary compounds, have been investigated for a few decades for their numerous beneficial effects, including their anticancer properties. The initial interest in the cancer-preventing/therapeutic ability of these agents was based on their ability to affect multiple signaling pathways that are deregulated in cancer cells. With a shift in the focus of cancer research to the emerging areas such as epigenetic regulation, microRNAs (miRNAs) and the cancer stem cells (CSCs), nutraceuticals initially appeared out of place. However, research investigations over the last several years have slowly but firmly presented evidence that supports a relevance of these agents in modern day research. While nutraceuticals are increasingly being realized to alter miRNA/CSCs expression and function, the molecular mechanism(s) are not very clearly understood. Epigenetic regulation is one mechanism by which these agents exert their anticancer effects. In this focused mini review, we summarize our current understanding of epigenetic regulation of miRNAs and CSCs by nutraceuticals. We discuss both direct and indirect evidences that support such an activity of these compounds. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. Corporate Governance Convergence : Evidence from Takeover Regulation Reforms in Europe

    NARCIS (Netherlands)

    Goergen, M.; Martynova, M.; Renneboog, L.D.R.

    2005-01-01

    This paper contributes to the research on corporate governance by predicting the effects of European takeover regulation.In particular, we investigate whether the recent reforms of takeover regulation in Europe are leading to a harmonization of the national legislations.With the help of 150

  19. Ras signaling in aging and metabolic regulation.

    Science.gov (United States)

    Slack, Cathy

    2017-12-07

    Aberrant signal transduction downstream of the Ras GTPase has a well-established role in tumorigenesis. Mutations that result in hyperactivation of Ras are responsible for a third of all human cancers. Hence, small molecule inhibitors of the Ras signal transduction cascade have been under intense focus as potential cancer treatments. In both invertebrate and mammalian models, emerging evidence has also implicated components of the Ras signaling pathway in aging and metabolic regulation. Here, I review the current evidence for Ras signaling in these newly discovered roles highlighting the interactions between the Ras pathway and other longevity assurance mechanisms. Defining the role of Ras signaling in maintaining age-related health may have important implications for the development of interventions that could not only increase lifespan but also delay the onset and/or progression of age-related functional decline.

  20. Adjuvant chemotherapy for gastric cancer: Current evidence and future challenges

    Science.gov (United States)

    Miceli, Rosalba; Tomasello, Gianluca; Bregni, Giacomo; Di Bartolomeo, Maria; Pietrantonio, Filippo

    2014-01-01

    Gastric cancer still represents one of the major causes of cancer mortality worldwide. Patients survival is mainly related to stage, with a high proportion of patients with metastatic disease at presentation. Thus, the cure rate largely depend upon surgical resection. Despite the additional, albeit small, benefit of adjuvant chemotherapy has been clearly demonstrated, no general consensus has been reached on the best treatment option. Moreover, the narrow therapeutic index of adjuvant chemotherapy (i.e., limited survival benefit with considerable toxicity) requires a careful assessment of expected risks and benefits for individual patients. Treatment choices vary widely based on the different geographic areas, with chemotherapy alone more often preferred in Europe or Asia and chemoradiotherapy in the United States. In the present review we discuss the current evidence and future challenges regarding adjuvant chemotherapy in curatively resected gastric cancer with particular emphasis on the recently completed landmark studies and meta-analyses. The most recent patient-level meta-analysis demonstrated the benefit of adjuvant chemotherapy over curative surgery; the same Authors also showed that disease-free survival may be used as a surrogate end-point for overall survival. We finally discuss future research issues such as the need of economic evaluations, development of prognostic or predictive biomarkers, and the unmet clinical need of trials comparing perioperative chemotherapy with adjuvant treatment. PMID:24782604

  1. Incretin-based therapies in prediabetes: Current evidence and future perspectives

    Science.gov (United States)

    Papaetis, Georgios S

    2014-01-01

    The prevalence of type 2 diabetes (T2D) is evolving globally at an alarming rate. Prediabetes is an intermediate state of glucose metabolism that exists between normal glucose tolerance (NGT) and the clinical entity of T2D. Relentless β-cell decline and failure is responsible for the progression from NGT to prediabetes and eventually T2D. The huge burden resulting from the complications of T2D created the need of therapeutic strategies in an effort to prevent or delay its development. The beneficial effects of incretin-based therapies, dipeptidyl peptidase-4 inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists, on β-cell function in patients with T2D, together with their strictly glucose-depended mechanism of action, suggested their possible use in individuals with prediabetes when greater β-cell mass and function are preserved and the possibility of β-cell salvage is higher. The present paper summarizes the main molecular intracellular mechanisms through which GLP-1 exerts its activity on β-cells. It also explores the current evidence of incretin based therapies when administered in a prediabetic state, both in animal models and in humans. Finally it discusses the safety of incretin-based therapies as well as their possible role in order to delay or prevent T2D. PMID:25512784

  2. The regulation of OXPHOS by extramitochondrial calcium.

    Science.gov (United States)

    Gellerich, Frank N; Gizatullina, Zemfira; Trumbeckaite, Sonata; Nguyen, Huu P; Pallas, Thilo; Arandarcikaite, Odeta; Vielhaber, Stephan; Seppet, Enn; Striggow, Frank

    2010-01-01

    Despite extensive research, the regulation of mitochondrial function is still not understood completely. Ample evidence shows that cytosolic Ca2+ has a strategic task in co-ordinating the cellular work load and the regeneration of ATP by mitochondria. Currently, the paradigmatic view is that Cacyt2+ taken up by the Ca2+ uniporter activates the matrix enzymes pyruvate dehydrogenase, alpha-ketoglutarate dehydrogenase and isocitrate dehydrogenase. However, we have recently found that Ca2+ regulates the glutamate-dependent state 3 respiration by the supply of glutamate to mitochondria via aralar, a mitochondrial glutamate/aspartate carrier. Since this activation is not affected by ruthenium red, glutamate transport into mitochondria is controlled exclusively by extramitochondrial Ca2+. Therefore, this discovery shows that besides intramitochondrial also extramitochondrial Ca2+ regulates oxidative phosphorylation. This new mechanism acts as a mitochondrial "gas pedal", supplying the OXPHOS with substrate on demand. These results are in line with recent findings of Satrustegui and Palmieri showing that aralar as part of the malate-aspartate shuttle is involved in the Ca2+-dependent transport of reducing hydrogen equivalents (from NADH) into mitochondria. This review summarises results and evidence as well as hypothetical interpretations of data supporting the view that at the surface of mitochondria different regulatory Ca2+-binding sites exist and can contribute to cellular energy homeostasis. Moreover, on the basis of our own data, we propose that these surface Ca2+-binding sites may act as targets for neurotoxic proteins such as mutated huntingtin and others. The binding of these proteins to Ca2+-binding sites can impair the regulation by Ca2+, causing energetic depression and neurodegeneration. Copyright © 2010 Elsevier B.V. All rights reserved.

  3. Role of sleep duration in the regulation of glucose metabolism and appetite

    OpenAIRE

    Morselli, Lisa; Leproult, Rachel; Balbo, Marcella; Spiegel, Karine

    2010-01-01

    Sleep curtailment has become a common behavior in modern society. This review summarizes the current laboratory evidence indicating that sleep loss may contribute to the pathophysiology of diabetes mellitus and obesity. Experimentally-induced sleep loss in healthy volunteers decreases insulin sensitivity without adequate compensation in beta-cell function, resulting in impaired glucose tolerance and increased diabetes risk. Lack of sleep also down-regulates the satiety hormone leptin, up-regu...

  4. AMP-activated protein kinase in contraction regulation of skeletal muscle metabolism: necessary and/or sufficient?

    DEFF Research Database (Denmark)

    Jensen, Thomas Elbenhardt; Wojtaszewski, Jørgen; Richter, Erik

    2009-01-01

    In skeletal muscle, the contraction-activated heterotrimeric 5'-AMP-activated protein kinase (AMPK) protein is proposed to regulate the balance between anabolic and catabolic processes by increasing substrate uptake and turnover in addition to regulating the transcription of proteins involved...... in mitochondrial biogenesis and other aspects of promoting an oxidative muscle phenotype. Here, the current knowledge on the expression of AMPK subunits in human quadriceps muscle and evidence from rodent studies suggesting distinct AMPK subunit expression pattern in different muscle types is reviewed. Then......, the intensity and time dependence of AMPK activation in human quadriceps and rodent muscle are evaluated. Subsequently, a major part of this review critically examines the evidence supporting a necessary and/or sufficient role of AMPK in a broad spectrum of skeletal muscle contraction-relevant processes...

  5. Evidence for P-Glycoprotein Involvement in Cell Volume Regulation Using Coulter Sizing in Flow Cytometry

    Directory of Open Access Journals (Sweden)

    Jennifer Pasquier

    2015-06-01

    Full Text Available The regulation of cell volume is an essential function that is coupled to a variety of physiological processes such as receptor recycling, excitability and contraction, cell proliferation, migration, and programmed cell death. Under stress, cells undergo emergency swelling and respond to such a phenomenon with a regulatory volume decrease (RVD where they release cellular ions, and other osmolytes as well as a concomitant loss of water. The link between P-glycoprotein, a transmembrane transporter, and cell volume regulation is controversial, and changes in cells volume are measured using microscopy or electrophysiology. For instance, by using the patch-clamp method, our team demonstrated that chloride currents activated in the RVD were more intense and rapid in a breast cancer cell line overexpressing the P-glycoprotein (P-gp. The Cell Lab Quanta SC is a flow cytometry system that simultaneously measures electronic volume, side scatter and three fluorescent colors; altogether this provides unsurpassed population resolution and accurate cell counting. Therefore, here we propose a novel method to follow cellular volume. By using the Coulter-type channel of the cytometer Cell Lab Quanta SC MPL (multi-platform loading, we demonstrated a role for the P-gp during different osmotic treatments, but also a differential activity of the P-gp through the cell cycle. Altogether, our data strongly suggests a role of P-gp in cell volume regulation.

  6. Phospholipase C δ4 regulates cold sensitivity in mice.

    Science.gov (United States)

    Yudin, Yevgen; Lutz, Brianna; Tao, Yuan-Xiang; Rohacs, Tibor

    2016-07-01

    The cold- and menthol-activated transient receptor potential melastatin 8 (TRPM8) channels are thought to be regulated by phospholipase C (PLC), but neither the specific PLC isoform nor the in vivo relevance of this regulation has been established. Here we identify PLCδ4 as the key PLC isoform involved in regulation of TRPM8 channels in vivo. We show that in small PLCδ4(-/-) TRPM8-positive dorsal root ganglion neurons cold, menthol and WS-12, a selective TRPM8 agonist, evoked significantly larger currents than in wild-type neurons, and action potential frequencies induced by menthol or by current injections were also higher in PLCδ4(-/-) neurons. PLCδ4(-/-) mice showed increased behavioural responses to evaporative cooling, and this effect was inhibited by a TRPM8 antagonist; behavioural responses to heat and mechanical stimuli were not altered. We provide evidence for the involvement of a specific PLC isoform in the regulation of cold sensitivity in mice by regulating TRPM8 activity. The transient receptor potential melastatin 8 (TRPM8) ion channel is a major sensor of environmental low temperatures. Ca(2+) -induced activation of phospholipase C (PLC) has been implied in the regulation of TRPM8 channels during menthol- and cold-induced desensitization in vitro. Here we identify PLCδ4 as the key PLC isoform involved in regulation of TRPM8 in sensory dorsal root ganglion (DRG) neurons. We identified two TRPM8-positive neuronal subpopulations, based on their cell body size. Most TRPM8-positive small neurons also responded to capsaicin, and had significantly larger menthol-induced inward current densities than medium-large cells, most of which did not respond to capsaicin. Small, but not medium-large, PLCδ4(-/-) neurons showed significantly larger currents induced by cold, menthol or WS-12, a specific TRPM8 agonist, compared to wild-type (WT) neurons, but TRPM8 protein levels were not different between the two groups. In current-clamp experiments small neurons

  7. Evidence of extra-telomeric effects of hTERT and its regulation involving a feedback loop

    International Nuclear Information System (INIS)

    Lai, Serene R.; Cunningham, Amanda P.; Huynh, Vu Q.; Andrews, Lucy G.; Tollefsbol, Trygve O.

    2007-01-01

    The human telomerase reverse transcriptase (hTERT) is the catalytic subunit of the enzyme telomerase which is responsible for telomeric maintenance and extension. Using RNA interference to knock down hTERT mRNA expression, we provide evidence that hTERT exerts extra-telomeric effects on the cell cycle and on its own regulatory proteins, specifically: p53 and p21. We tested our hypothesis that hTERT regulates its own expression through effects on upstream regulatory genes using transformed human embryonic kidney (HEK 293) cells, p53 and p16 INK4a null human ovarian cancer SKOV-3 cells, and p53-null MDA-MB-157 human mammary cancer cells. In HEK 293 cells, hTERT knockdown resulted in elevated p53 and p21 transcription and a decrease in cellular proliferation. Similar results were observed in the MDA-MB-157 cell line where p21 was upregulated, correlating with cell growth inhibition. In contrast, we observed a decrease in expression of p21 in SKOV-3 cells with hTERT knockdown and cell growth appeared to be unaffected. These findings suggest that hTERT may be involved in a feedback loop system, thereby playing a role in its own regulation

  8. Rebalancing; Evidence from Current Account Adjustment in Europe

    OpenAIRE

    Ruben V Atoyan; Jonathan F Manning; Jesmin Rahman

    2013-01-01

    After the 2003-2007 economic boom, European countries with large pre-crisis current account imbalances are undergoing adjustments. Countries are adjusting at different paces and ways reflecting the source and magnitude of imbalances, availability of financing, competitiveness of the tradable sector and external environment. While emerging European countries with large pre-crisis imbalances and a fixed exchange rate regime have seen sharp current account adjustments and a rebound in growth, ad...

  9. Current regulator for the stabilization of an electrostatic Van de Graaff generator; Regulateur de courant pour stabilisation d'un generateur electrostatique Van de Graaff

    Energy Technology Data Exchange (ETDEWEB)

    Gabet, A; Taieb, J [Commissariat a l' Energie Atomique, Saclay(France). Centre d' Etudes Nucleaires

    1953-07-01

    In a previous report (CEA report number 46) we described a current regulator destined to enslave the current of charge of the strap of a model of Van de Graaff. We will now describe the regulator destined to the 5 MeV Van de Graaff built in the Nuclear center of Saclay. (author) [French] Dans un precedent rapport (rapport C.E.A. numero 46) nous avons decrit un regulateur de courant destine a asservir le courant de charge de la courroie d'une maquette de Van de Graaff. Nous decrirons maintenant le regulateur destine au Van de Graaff de 5 MeV construit au Centre d'Etudes Nucleaires de Saclay. (auteur)

  10. Measuring Individual Differences in Emotion Regulation: The Emotion Regulation Profile-Revised (ERP-R

    Directory of Open Access Journals (Sweden)

    Delphine Nelis

    2011-02-01

    Full Text Available The main purpose of this study was to validate a new instrument aimed to assess emotion regulation: the Emotion Regulation Profile-Revised (ERP-R. Exploratory factor analyses yielded two theoretically meaningful factors: down-regulation of negative emotions and up-regulation of positive emotions. Internal reliability scores of the two factors were good. Findings showed evidence of convergent/discriminant validity, with ERP-R scores being independent of non verbal reasoning and verbal skills while positively related to emotional intelligence and to relevant personality dimensions. There was also preliminary evidence of criterion validity. ERP-R scores also demonstrated incremental validity to predict a number of criteria over and above emotional intelligence and emotional stability. Overall, the results show a clear 2 factors solution for the ERP-R and high correlations with convergent and divergent scales as well as good criterion and incremental validities.

  11. Advancing Implementation of Evidence-Based Public Health in China: An Assessment of the Current Situation and Suggestions for Developing Regions.

    Science.gov (United States)

    Shi, Jianwei; Jiang, Chenghua; Tan, Duxun; Yu, Dehua; Lu, Yuan; Sun, Pengfei; Pan, Ying; Zhang, Hanzhi; Wang, Zhaoxin; Yang, Beilei

    2016-01-01

    Objective. Existing research shows a serious scarcity of EBPH practice in China and other developing regions; as an exploratory study, this study aimed to assess the current EBPH implementation status in Shanghai of China qualitatively. Methods. Using semistructured key informant interviews, we examined the status of and impediments to the lagging EBPH in China. Data were analyzed based on the Consolidated Framework for Implementation Research (CFIR). Results. Chinese public health practitioners knew more about evidence-based medicine but less about EBPH. The situation was worse in community healthcare centers. Participants perceived that evidence sources were limited and the quality of evidence was low. Concerning the inner setting factors, the structural characteristics, networks and communications, implementation climate, and leadership engagement were confronted with many problems. Among the outer setting factors, external government policies and incentives and low patient compliance were the key problems. Additionally, public health practitioners in Shanghai lacked sufficient awareness of EBPH. Furthermore, the current project-based EBPH lacks a systematic implementation system. Conclusions. Existing practical perspectives on EBPH indicate a lag in the advocacy of this new ideology in China. It would be advisable for healthcare institutions to take the initiative to explore feasible and multiple methods of EBPH promotion.

  12. Advancing Implementation of Evidence-Based Public Health in China: An Assessment of the Current Situation and Suggestions for Developing Regions

    Directory of Open Access Journals (Sweden)

    Jianwei Shi

    2016-01-01

    Full Text Available Objective. Existing research shows a serious scarcity of EBPH practice in China and other developing regions; as an exploratory study, this study aimed to assess the current EBPH implementation status in Shanghai of China qualitatively. Methods. Using semistructured key informant interviews, we examined the status of and impediments to the lagging EBPH in China. Data were analyzed based on the Consolidated Framework for Implementation Research (CFIR. Results. Chinese public health practitioners knew more about evidence-based medicine but less about EBPH. The situation was worse in community healthcare centers. Participants perceived that evidence sources were limited and the quality of evidence was low. Concerning the inner setting factors, the structural characteristics, networks and communications, implementation climate, and leadership engagement were confronted with many problems. Among the outer setting factors, external government policies and incentives and low patient compliance were the key problems. Additionally, public health practitioners in Shanghai lacked sufficient awareness of EBPH. Furthermore, the current project-based EBPH lacks a systematic implementation system. Conclusions. Existing practical perspectives on EBPH indicate a lag in the advocacy of this new ideology in China. It would be advisable for healthcare institutions to take the initiative to explore feasible and multiple methods of EBPH promotion.

  13. Decreased inward rectifier potassium current IK1 in dystrophin-deficient ventricular cardiomyocytes.

    Science.gov (United States)

    Rubi, Lena; Koenig, Xaver; Kubista, Helmut; Todt, Hannes; Hilber, Karlheinz

    2017-03-04

    Kir2.x channels in ventricular cardiomyocytes (most prominently Kir2.1) account for the inward rectifier potassium current I K1 , which controls the resting membrane potential and the final phase of action potential repolarization. Recently it was hypothesized that the dystrophin-associated protein complex (DAPC) is important in the regulation of Kir2.x channels. To test this hypothesis, we investigated potential I K1 abnormalities in dystrophin-deficient ventricular cardiomyocytes derived from the hearts of Duchenne muscular dystrophy mouse models. We found that I K1 was substantially diminished in dystrophin-deficient cardiomyocytes when compared to wild type myocytes. This finding represents the first functional evidence for a significant role of the DAPC in the regulation of Kir2.x channels.

  14. Towards trust in regulation. Moving to a public value regulation

    Energy Technology Data Exchange (ETDEWEB)

    Mitchell, Catherine; Woodman, Bridget [Energy Policy Group, University of Exeter Cornwall Campus, Treliever Road, Penryn, TR10 9EZ (United Kingdom)

    2010-06-15

    The UK Government has committed itself to reducing its carbon dioxide emissions. The challenge of successfully achieving a transition to a sustainable energy system, in the context of the UK's largely privately owned energy industry, rests on the ability of policy makers to encourage and enable the necessary changes or innovation at all levels of the energy system. This paper argues that the UK's current, dominant political paradigm or framework (the regulatory state paradigm (RSP)) and within it, the role of the economic regulator, Ofgem acts as a fundamental block to this challenge. The current economic regulatory system is based on trust in the market, or on predicted (albeit theoretical) known outcomes. To expand our regulatory system to one which can deliver a sustainable energy system requires innovation in a certain direction (as opposed to any innovation). That is the antithesis of the current process of regulation. Trust is required that Ofgem, the economic regulator, will develop rules and incentives which deliver an agreed sustainable energy goal, which is 'trusted' to be the 'right' goal. This requires Ofgem moving away from ex-ante regulation to a type of regulation where all costs, benefits and outcomes cannot be known beforehand and where they cannot necessarily be quantifiable. This has, very provisionally, been called Public Value Regulation (PVR). (author)

  15. Towards trust in regulation-moving to a public value regulation

    Energy Technology Data Exchange (ETDEWEB)

    Mitchell, Catherine, E-mail: catherine.mitchell@exeter.ac.u [Energy Policy Group, University of Exeter Cornwall Campus, Treliever Road, Penryn, TR10 9EZ (United Kingdom); Woodman, Bridget [Energy Policy Group, University of Exeter Cornwall Campus, Treliever Road, Penryn, TR10 9EZ (United Kingdom)

    2010-06-15

    The UK Government has committed itself to reducing its carbon dioxide emissions. The challenge of successfully achieving a transition to a sustainable energy system, in the context of the UK's largely privately owned energy industry, rests on the ability of policy makers to encourage and enable the necessary changes or innovation at all levels of the energy system. This paper argues that the UK's current, dominant political paradigm or framework (the regulatory state paradigm (RSP)) and within it, the role of the economic regulator, Ofgem acts as a fundamental block to this challenge. The current economic regulatory system is based on trust in the market, or on predicted (albeit theoretical) known outcomes. To expand our regulatory system to one which can deliver a sustainable energy system requires innovation in a certain direction (as opposed to any innovation). That is the antithesis of the current process of regulation. Trust is required that Ofgem, the economic regulator, will develop rules and incentives which deliver an agreed sustainable energy goal, which is 'trusted' to be the 'right' goal. This requires Ofgem moving away from ex-ante regulation to a type of regulation where all costs, benefits and outcomes cannot be known beforehand and where they cannot necessarily be quantifiable. This has, very provisionally, been called Public Value Regulation (PVR).

  16. Towards trust in regulation-moving to a public value regulation

    International Nuclear Information System (INIS)

    Mitchell, Catherine; Woodman, Bridget

    2010-01-01

    The UK Government has committed itself to reducing its carbon dioxide emissions. The challenge of successfully achieving a transition to a sustainable energy system, in the context of the UK's largely privately owned energy industry, rests on the ability of policy makers to encourage and enable the necessary changes or innovation at all levels of the energy system. This paper argues that the UK's current, dominant political paradigm or framework (the regulatory state paradigm (RSP)) and within it, the role of the economic regulator, Ofgem acts as a fundamental block to this challenge. The current economic regulatory system is based on trust in the market, or on predicted (albeit theoretical) known outcomes. To expand our regulatory system to one which can deliver a sustainable energy system requires innovation in a certain direction (as opposed to any innovation). That is the antithesis of the current process of regulation. Trust is required that Ofgem, the economic regulator, will develop rules and incentives which deliver an agreed sustainable energy goal, which is 'trusted' to be the 'right' goal. This requires Ofgem moving away from ex-ante regulation to a type of regulation where all costs, benefits and outcomes cannot be known beforehand and where they cannot necessarily be quantifiable. This has, very provisionally, been called Public Value Regulation (PVR).

  17. Regulating nanomedicine - can the FDA handle it?

    Science.gov (United States)

    Bawa, Raj

    2011-05-01

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

  18. Cell Cycle Regulation of Stem Cells by MicroRNAs.

    Science.gov (United States)

    Mens, Michelle M J; Ghanbari, Mohsen

    2018-06-01

    MicroRNAs (miRNAs) are a class of small non-coding RNA molecules involved in the regulation of gene expression. They are involved in the fine-tuning of fundamental biological processes such as proliferation, differentiation, survival and apoptosis in many cell types. Emerging evidence suggests that miRNAs regulate critical pathways involved in stem cell function. Several miRNAs have been suggested to target transcripts that directly or indirectly coordinate the cell cycle progression of stem cells. Moreover, previous studies have shown that altered expression levels of miRNAs can contribute to pathological conditions, such as cancer, due to the loss of cell cycle regulation. However, the precise mechanism underlying miRNA-mediated regulation of cell cycle in stem cells is still incompletely understood. In this review, we discuss current knowledge of miRNAs regulatory role in cell cycle progression of stem cells. We describe how specific miRNAs may control cell cycle associated molecules and checkpoints in embryonic, somatic and cancer stem cells. We further outline how these miRNAs could be regulated to influence cell cycle progression in stem cells as a potential clinical application.

  19. Capnography during cardiopulmonary resuscitation: Current evidence and future directions

    Directory of Open Access Journals (Sweden)

    Bhavani Shankar Kodali

    2014-01-01

    Full Text Available Capnography continues to be an important tool in measuring expired carbon dioxide (CO 2 . Most recent Advanced Cardiac Life Support (ACLS guidelines now recommend using capnography to ascertain the effectiveness of chest compressions and duration of cardiopulmonary resuscitation (CPR. Based on an extensive review of available published literature, we selected all available peer-reviewed research investigations and case reports. Available evidence suggests that there is significant correlation between partial pressure of end-tidal CO 2 (PETCO 2 and cardiac output that can indicate the return of spontaneous circulation (ROSC. Additional evidence favoring the use of capnography during CPR includes definitive proof of correct placement of the endotracheal tube and possible prediction of patient survival following cardiac arrest, although the latter will require further investigations. There is emerging evidence that PETCO 2 values can guide the initiation of extracorporeal life support (ECLS in refractory cardiac arrest (RCA. There is also increasing recognition of the value of capnography in intensive care settings in intubated patients. Future directions include determining the outcomes based on capnography waveforms PETCO 2 values and determining a reasonable duration of CPR. In the future, given increasing use of capnography during CPR large databases can be analyzed to predict outcomes.

  20. Newborn screening for proximal urea cycle disorders: Current evidence supporting recommendations for newborn screening.

    Science.gov (United States)

    Merritt, J Lawrence; Brody, Linnea L; Pino, Gisele; Rinaldo, Piero

    2018-04-20

    Current newborn screening (NBS) for urea cycle disorders (UCD) is incomplete as only distal UCDs are included in most NBS programs by measuring elevated amino acid concentrations. NBS for the proximal UCDs involves the detection in NBS spots of low citrulline values, a finding which is often overlooked because it is considered to be inadequate. We retrospectively analyzed NBS blood spots from known UCD patients comparing the utility of the Region 4 Stork (R4S) interpretive tools to conventional cutoff based interpretation. This study shows the utility of R4S tools in detecting all UCDs, and provides evidence to support the nomination to add proximal UCDs to the recommended uniform screening panel. Copyright © 2018 Elsevier Inc. All rights reserved.

  1. Robotic-Assisted Procedures in Pediatric Surgery: A Critical Appraisal of the Current Best Evidence in Comparison to Conventional Minimally Invasive Surgery.

    Science.gov (United States)

    Friedmacher, Florian; Till, Holger

    2015-11-01

    In recent years, the use of robotic-assisted surgery (RAS) has expanded within pediatric surgery. Although increasing numbers of pediatric RAS case-series have been published, the level of evidence remains unclear, with authors mainly focusing on the comparison with open surgery rather than the corresponding laparoscopic approach. The aim of this study was to critically appraise the published literature comparing pediatric RAS with conventional minimally invasive surgery (MIS) in order to evaluate the current best level of evidence. A systematic literature-based search for studies comparing pediatric RAS with corresponding MIS procedures was performed using multiple electronic databases and sources. The level of evidence was determined using the Oxford Centre for Evidence-based Medicine (OCEBM) criteria. A total of 20 studies met defined inclusion criteria, reporting on five different procedures: fundoplication (n=8), pyeloplasty (n=8), nephrectomy (n=2), gastric banding (n=1), and sleeve gastrectomy (n=1). Included publications comprised 5 systematic reviews and 15 cohort/case-control studies (OCEBM Level 3 and 4, respectively). No studies of OCEBM Level 1 or 2 were identified. Limited evidence indicated reduced operative time (pyeloplasty) and shorter hospital stay (fundoplication) for pediatric RAS, whereas disadvantages were longer operative time (fundoplication, nephrectomy, gastric banding, and sleeve gastrectomy) and higher total costs (fundoplication and sleeve gastrectomy). There were no differences reported for complications, success rates, or short-term outcomes between pediatric RAS and conventional MIS in these procedures. Inconsistency was found in study design and follow-up with large clinical heterogeneity. The best available evidence for pediatric RAS is currently OCEBM Level 3, relating only to fundoplication and pyeloplasty. Therefore, higher-quality studies and comparative data for other RAS procedures in pediatric surgery are required.

  2. Regulation of Wnt/β-catenin signaling by posttranslational modifications

    Science.gov (United States)

    2014-01-01

    The canonical Wnt signaling pathway (or Wnt/β-catenin pathway) plays a pivotal role in embryonic development and adult homeostasis; deregulation of the Wnt pathway contributes to the initiation and progression of human diseases including cancer. Despite its importance in human biology and disease, how regulation of the Wnt/β-catenin pathway is achieved remains largely undefined. Increasing evidence suggests that post-translational modifications (PTMs) of Wnt pathway components are essential for the activation of the Wnt/β-catenin pathway. PTMs create a highly dynamic relay system that responds to Wnt stimulation without requiring de novo protein synthesis and offer a platform for non-Wnt pathway components to be involved in the regulation of Wnt signaling, hence providing alternative opportunities for targeting the Wnt pathway. This review highlights the current status of PTM-mediated regulation of the Wnt/β-catenin pathway with a focus on factors involved in Wnt-mediated stabilization of β-catenin. PMID:24594309

  3. Thoughts on How to Regulate Behaviours: An Overview of the Current Debate

    Science.gov (United States)

    Etienne, Julien

    2013-01-01

    The article intends to present the debate on behaviour modification in the regulation studies literature, at a time of renewed interest among regulators for new ideas and strategies. As the financial crisis has led to the most public critique yet of the rational choice view of individuals that has informed regulation in the last few decades, other…

  4. The E2F transcription factors: key regulators of cell proliferation

    DEFF Research Database (Denmark)

    Müller, H; Helin, K

    2000-01-01

    Ever since its discovery, the RB-1 gene and the corresponding protein, pRB, have been a focal point of cancer research. The isolation of E2F transcription factors provided the key to our current understanding of RB-1 function in the regulation of the cell cycle and in tumor suppression....... It is becoming more and more evident that the regulatory circuits governing the cell cycle are very complex and highly interlinked. Certain aspects of RB-1 function, for instance its role in differentiation, cannot be easily explained by the current models of pRB-E2F interaction. One reason is that pRB has...

  5. Implicit emotion regulation in the context of viewing artworks: ERP evidence in response to pleasant and unpleasant pictures.

    Science.gov (United States)

    Van Dongen, Noah N N; Van Strien, Jan W; Dijkstra, Katinka

    2016-08-01

    Presenting affective pictures as a work of art could change perceivers' judgment and strength in emotional reactions. Aesthetic theory states that perceivers of art emotionally distance themselves, allowing them to appreciate works of art depicting gruesome events. To examine whether implicit emotion regulation is induced by an art context, we assessed whether presenting pleasant and unpleasant IAPS pictures as either "works of art comprising paintings, digital renderings, and photographs of staged scenes" or "photographs depicting real events" modulated perceivers' Late Positive Potentials (LPP) and likability ratings. In line with previous research and aesthetic theory, participants evaluated the IAPS pictures as more likable when they were presented as works of art than when they were presented as photographs. Moreover, participants' late LPP amplitudes (600-900ms post picture onset) in response to the pictures were attenuated in the art context condition. These results provide evidence for an implicit emotion regulation induced by the art context. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Frontiers of environmental regulation: environmental management systems: a regulator`s perspective

    Energy Technology Data Exchange (ETDEWEB)

    Stone, M.J. [South Australian Dept. of Mines and Energy, Adelaide, SA (Australia)

    1996-12-31

    Leading edge companies throughout the world have embraced management systems to achieve optimal sustainable performance in the ever changing business environment of the 1990s. Given that the natural environment and environmental performance have become major issues affecting organizations, the need for integrating environmental management with all the other components of an organization`s overall management approach is now widely recognized. This paper is organized in five parts. The first explores recently released environmental standards, the interim environmental management systems (EMS) general guidelines standard AS/NZS ISO 14004 (Int) and identifies how this has dealt with the regulator/community/company interface. The second identifies company requirements for addressing environmental issues. The third, considers regulatory theory to identify current requirements for an effective regulatory system and how this can interface with a company`s EMS. These form the basis in the fourth section for identifying some opportunities which occur at the company/ regulator interface. The fifth and final section draws a number of conclusions about the current frontiers of environmental regulation. The coincidence of the requirements of a regulatory framework with the areas of interface between what is referred to in the draft International Standard for EMS as `Interested Parties`, the regulators and community, are identified. (author). 1 tab., 2 figs., 20 refs.

  7. Does rumination mediate the relationship between emotion regulation ability and posttraumatic stress disorder?

    OpenAIRE

    Ehring, Thomas; Ehlers, Anke

    2014-01-01

    Background and objectives: Trauma-related rumination has been suggested to be involved in the maintenance of posttraumatic stress disorder (PTSD). This view has empirically been supported by extensive evidence using cross-sectional, prospective, and experimental designs. However, it is unclear why trauma survivors engage in rumination despite its negative consequences. The current study aimed to explore the hypothesis that low emotion regulation ability underlies trauma-related rumination.Met...

  8. Epigenetic microRNA Regulation

    DEFF Research Database (Denmark)

    Wiklund, Erik Digman

    2011-01-01

    MicroRNAs (miRNAs) are small non-coding RNAs (ncRNAs) that negatively regulate gene expression post-transcriptionally by binding to complementary sequences in the 3’UTR of target mRNAs in the cytoplasm. However, recent evidence suggests that certain miRNAs are enriched in the nucleus, and their t......MicroRNAs (miRNAs) are small non-coding RNAs (ncRNAs) that negatively regulate gene expression post-transcriptionally by binding to complementary sequences in the 3’UTR of target mRNAs in the cytoplasm. However, recent evidence suggests that certain miRNAs are enriched in the nucleus...

  9. Current perspectives in Set7 mediated stem cell differentiation

    Directory of Open Access Journals (Sweden)

    Nazanin Karimnia

    2016-12-01

    Full Text Available Set7 is a key regulatory enzyme involved in the methylation of lysine residues of histone and non-histone proteins. This lysine methyltransferase is induced during stem cell differentiation and regulates lineage specific gene transcription and cell fate. In this article we discuss recent experimental evidence identifying regulatory targets under the control of Set7 as well as emerging evidence of regulation in stem cell differentiation. Furthermore, we discuss the function of non-coding RNAs regulated by Set7 implicated in cell plasticity.

  10. Does rumination mediate the relationship between emotion regulation ability and posttraumatic stress disorder?

    Directory of Open Access Journals (Sweden)

    Thomas Ehring

    2014-08-01

    Full Text Available Background and objectives: Trauma-related rumination has been suggested to be involved in the maintenance of posttraumatic stress disorder (PTSD. This view has empirically been supported by extensive evidence using cross-sectional, prospective, and experimental designs. However, it is unclear why trauma survivors engage in rumination despite its negative consequences. The current study aimed to explore the hypothesis that low emotion regulation ability underlies trauma-related rumination. Methods: Emotion regulation ability and trauma-related rumination were assessed in 93 road traffic accident survivors 2 weeks post-trauma. In addition, symptom levels of PTSD were assessed at 2 weeks as well as 1, 3, and 6 months follow-up. Results: Emotion regulation ability was significantly related to trauma-related rumination as well as levels of PTSD symptoms. In addition, the association between low emotion regulation ability and PTSD was mediated by rumination. Conclusions: The findings support the view that rumination is used as a dysfunctional emotion regulation strategy by trauma survivors.

  11. Current standardisation for nanotechnology

    International Nuclear Information System (INIS)

    Bard, Delphine; Mark, David; Moehlmann, Carsten

    2009-01-01

    Standardisation and standards provide an important mechanism to support both innovation and the application of regulations. There is currently no specific regulation for any nanomaterials. Health, safety and environmental protection aspects associated with nanomaterials are however in principle covered to different levels by current EU regulatory framework. There are a number of national, European and international organisations developing standards associated with the development, description and use of nanomaterials as well as the protection of human health and the environment from the production and use of chemicals and consumer products, including nanomaterials. These organisations have also established specific committees on nanotechnology. This paper outlines the different relevant regulations and standards. This paper will mainly be focused on a European health and safety perspective.

  12. Evidence for systems-level molecular mechanisms of tumorigenesis

    Directory of Open Access Journals (Sweden)

    Capellá Gabriel

    2007-06-01

    Full Text Available Abstract Background Cancer arises from the consecutive acquisition of genetic alterations. Increasing evidence suggests that as a consequence of these alterations, molecular interactions are reprogrammed in the context of highly connected and regulated cellular networks. Coordinated reprogramming would allow the cell to acquire the capabilities for malignant growth. Results Here, we determine the coordinated function of cancer gene products (i.e., proteins encoded by differentially expressed genes in tumors relative to healthy tissue counterparts, hereafter referred to as "CGPs" defined as their topological properties and organization in the interactome network. We show that CGPs are central to information exchange and propagation and that they are specifically organized to promote tumorigenesis. Centrality is identified by both local (degree and global (betweenness and closeness measures, and systematically appears in down-regulated CGPs. Up-regulated CGPs do not consistently exhibit centrality, but both types of cancer products determine the overall integrity of the network structure. In addition to centrality, down-regulated CGPs show topological association that correlates with common biological processes and pathways involved in tumorigenesis. Conclusion Given the current limited coverage of the human interactome, this study proposes that tumorigenesis takes place in a specific and organized way at the molecular systems-level and suggests a model that comprises the precise down-regulation of groups of topologically-associated proteins involved in particular functions, orchestrated with the up-regulation of specific proteins.

  13. Efficacy and safety of haloperidol for in-hospital delirium prevention and treatment: A systematic review of current evidence.

    Science.gov (United States)

    Schrijver, E J M; de Graaf, K; de Vries, O J; Maier, A B; Nanayakkara, P W B

    2016-01-01

    Haloperidol is generally considered the drug of choice for in-hospital delirium management. We conducted a systematic review to evaluate the evidence for the efficacy and safety of haloperidol for the prevention and treatment of delirium in hospitalized patients. PubMed, Embase, Cumulative Index to Nursing and Allied Health (CINAHL), PsycINFO, and the Cochrane Library were systematically searched up to April 21, 2015. We included English full-text randomized controlled trials using haloperidol for the prevention or treatment of delirium in adult hospitalized patients reporting on delirium incidence, duration, or severity as primary outcome. Quality of evidence was graded. Meta-analysis was not conducted because of between-study heterogeneity. Twelve studies met our inclusion criteria, four prevention and eight treatment trials. Methodological limitations decreased the graded quality of included studies. Results from placebo-controlled prevention studies suggest a haloperidol-induced protective effect for delirium in older patients scheduled for surgery: two studies reported a significant reduction in ICU delirium incidence and one study found a significant reduction in delirium severity and duration. Although placebo-controlled trials are missing, pharmacological treatment of established delirium reduced symptom severity. Haloperidol administration was not associated with treatment-limiting side-effects, but few studies used a systematic approach to identify adverse events. Although results on haloperidol for delirium management seem promising, current prevention trials lack external validity and treatment trials did not include a placebo arm on top of standard nonpharmacological care. We therefore conclude that the current use of haloperidol for in-hospital delirium is not based on robust and generalizable evidence. Copyright © 2015 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

  14. Validation of the FEEL-KJ: An Instrument to Measure Emotion Regulation Strategies in Children and Adolescents.

    Directory of Open Access Journals (Sweden)

    Emiel Cracco

    Full Text Available Although the field of emotion regulation in children and adolescents is growing, there is need for age-adjusted measures that assess a large variety of strategies. An interesting instrument in this respect is the FEEL-KJ because it measures 7 adaptive and 5 maladaptive emotion regulation strategies in response to three different emotions. However, the FEEL-KJ has not yet been validated extensively. Therefore, the current study aims to test the internal structure and validity of the FEEL-KJ in a large sample of Dutch-speaking Belgian children and adolescents (N = 1102, 8-18 years old. The investigation of the internal structure confirms earlier reports of a two-factor structure with Adaptive and Maladaptive Emotion Regulation as overarching categories. However, it also suggests that the two-factor model is more complex than what was previously assumed. The evaluation of the FEEL-KJ validity furthermore provides evidence for its construct and external validity. In sum, the current study confirms that the FEEL-KJ is a valuable and reliable measure of emotion regulation strategies in children and adolescents.

  15. Reflections on Competition, Competition Regulation and the Current Crises

    DEFF Research Database (Denmark)

    Buch-Hansen, Hubert; Wigger, Angela

    2013-01-01

    competition came to enjoy such an exalted status in Europe and then challenges conventional wisdom by bringing into focus the downsides of competition. It argues that excessive competition and neoliberal competition regulation have contributed to intensify the economic, political, social and environmental...

  16. Impaired Na⁺-dependent regulation of acetylcholine-activated inward-rectifier K⁺ current modulates action potential rate dependence in patients with chronic atrial fibrillation.

    Science.gov (United States)

    Voigt, Niels; Heijman, Jordi; Trausch, Anne; Mintert-Jancke, Elisa; Pott, Lutz; Ravens, Ursula; Dobrev, Dobromir

    2013-08-01

    Shortened action-potential duration (APD) and blunted APD rate adaptation are hallmarks of chronic atrial fibrillation (cAF). Basal and muscarinic (M)-receptor-activated inward-rectifier K(+) currents (IK1 and IK,ACh, respectively) contribute to regulation of human atrial APD and are subject to cAF-dependent remodeling. Intracellular Na(+) ([Na(+)]i) enhances IK,ACh in experimental models but the effect of [Na(+)]i-dependent regulation of inward-rectifier K(+) currents on APD in human atrial myocytes is currently unknown. Here, we report a [Na(+)]i-dependent inhibition of outward IK1 in atrial myocytes from sinus rhythm (SR) or cAF patients. In contrast, IK,ACh activated by carbachol, a non-selective M-receptor agonist, increased with elevation of [Na(+)]i in SR. This [Na(+)]i-dependent IK,ACh regulation was absent in cAF. Including [Na(+)]i dependence of IK1 and IK,ACh in a recent computational model of the human atrial myocyte revealed that [Na(+)]i accumulation at fast rates inhibits IK1 and blunts physiological APD rate dependence in both groups. [Na(+)]i-dependent IK,ACh augmentation at fast rates increased APD rate dependence in SR, but not in cAF. These results identify impaired Na(+)-sensitivity of IK,ACh as one potential mechanism contributing to the blunted APD rate dependence in patients with cAF. This article is part of a Special Issue entitled "Na(+) Regulation in Cardiac Myocytes". Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

  17. Electrical installations and regulations

    CERN Document Server

    Whitfield, J F

    1966-01-01

    Electrical Installations and Regulations focuses on the regulations that apply to electrical installations and the reasons for them. Topics covered range from electrical science to alternating and direct current supplies, as well as equipment for providing protection against excess current. Cables, wiring systems, and final subcircuits are also considered, along with earthing, discharge lighting, and testing and inspection.Comprised of 12 chapters, this book begins with an overview of electrical installation work, traits of a good electrician, and the regulations governing installations. The r

  18. Brain PET imaging in obesity and food addiction: current evidence and hypothesis.

    Science.gov (United States)

    Iozzo, Patricia; Guiducci, Letizia; Guzzardi, Maria Angela; Pagotto, Uberto

    2012-01-01

    The ongoing epidemics of obesity is one main health concern of the present time. Overeating in some obese individuals shares similarities with the loss of control and compulsive behavior observed in drug-addicted subjects, suggesting that obesity may involve food addiction. Here, we review the contributions provided by the use of positron emission tomography to the current understanding of the cerebral control of obesity and food intake in humans. The available studies have shown that multiple areas in the brain are involved with the reward properties of food, such as prefrontal, orbitofrontal, somatosensory cortices, insula, thalamus, hypothalamus, amygdala, and others. This review summarizes the current evidence, supporting the concepts that i) regions involved in the somatosensory response to food sight, taste, and smell are activated by palatable foods and may be hyperresponsive in obese individuals, ii) areas controlling executive drive seem to overreact to the anticipation of pleasure during cue exposure, and iii) those involved in cognitive control and inhibitory behavior may be resistant to the perception of reward after food exposure in obese subjects. All of these features may stimulate, for different reasons, ingestion of highly palatable and energy-rich foods. Though these same regions are similarly involved in drug abusers and game-addicted individuals, any direct resemblance may be an oversimplification, especially as the heterogeneities between studies and the prevalent exclusion of sensitive groups still limit a coherent interpretation of the findings. Further work is required to comprehensively tackle the multifaceted phenotype of obesity and identify the role of food dependency in its pathophysiology. Copyright © 2012 S. Karger GmbH, Freiburg.

  19. Bumetanide increases Cl--dependent short-circuit current in late distal colon: Evidence for the presence of active electrogenic Cl- absorption.

    Science.gov (United States)

    Tang, Lieqi; Fang, Xiefan; Winesett, Steven P; Cheng, Catherine Y; Binder, Henry J; Rivkees, Scott A; Cheng, Sam X

    2017-01-01

    Mammalian colonic epithelia consist of cells that are capable of both absorbing and secreting Cl-. The present studies employing Ussing chamber technique identified two opposing short-circuit current (Isc) responses to basolateral bumetanide in rat distal colon. Apart from the transepithelial Cl--secretory Isc in early distal colon that was inhibited by bumetanide, bumetanide also stimulated Isc in late distal colon that had not previously been identified. Since bumetanide inhibits basolateral Na+-K+-2Cl- cotransporter (NKCC) in crypt cells and basolateral K+-Cl- cotransporter (KCC) in surface epithelium, we proposed this stimulatory Isc could represent a KCC-mediated Cl- absorptive current. In support of this hypothesis, ion substitution experiments established Cl- dependency of this absorptive Isc and transport inhibitor studies demonstrated the involvement of an apical Cl- conductance. Current distribution and RNA sequencing analyses revealed that this Cl- absorptive Isc is closely associated with epithelial Na+ channel (ENaC) but is not dependent on ENaC activity. Thus, inhibition of ENaC by 10 μM amiloride or benzamil neither altered the direction nor its activity. Physiological studies suggested that this Cl- absorptive Isc senses dietary Cl- content; thus when dietary Cl- was low, Cl- absorptive Isc was up-regulated. In contrast, when dietary Cl- was increased, Cl- absorptive Isc was down-regulated. We conclude that an active Cl- extrusion mechanism exists in ENaC-expressing late distal colon and likely operates in parallel with ENaC to facilitate NaCl absorption.

  20. Review of Virtual Reality Treatment in Psychiatry: Evidence Versus Current Diffusion and Use.

    Science.gov (United States)

    Mishkind, Matthew C; Norr, Aaron M; Katz, Andrea C; Reger, Greg M

    2017-09-18

    This review provides an overview of the current evidence base for and clinical applications of the use of virtual reality (VR) in psychiatric practice, in context of recent technological developments. The use of VR in psychiatric practice shows promise with much of the research demonstrating clinical effectiveness for conditions including post-traumatic stress disorder, anxiety and phobias, chronic pain, rehabilitation, and addictions. However, more research is needed before the use of VR is considered a clinical standard of practice in some areas. The recent release of first generation consumer VR products signals a change in the viability of further developing VR systems and applications. As applications increase so will the need for good quality research to best understand what makes VR effective, and when VR is not appropriate for clinical services. As the field progresses, it is hopeful that the flexibility afforded by this technology will yield superior outcomes and a better understanding of the underlying mechanisms impacting those outcomes.

  1. The territorial approach to EU cohesion policy: Current issues and evidence from Greece

    Directory of Open Access Journals (Sweden)

    Thoidou Elisavet

    2011-01-01

    Full Text Available The importance attributed to the territorial dimension of the European Union cohesion policy steadily influences its successive reforms and adaptations, while in recent years there has been an evolution in the way this particular dimension of cohesion policy is perceived. Important evidence for this is the way in which the Community Strategic Guidelines on cohesion 2007-13 take account of the territorial dimension of cohesion policy. This paper discusses the territorial approach to cohesion policy in relation to both policy and practice. Specifically, it examines the territorial dimension of regional development planning in Greece as it has emerged in the relevant official documents, namely the successive three Community Support Frameworks since 1989 and the National Strategic Reference Framework for the current 2007-13 period. The territorial dimension of the organization of the planning system is also considered in an effort to understand limitations and prospects, in light of the importance of the territorial approach to cohesion policy post-2013.

  2. Constructing regulation and regulating for energy efficient construction

    Energy Technology Data Exchange (ETDEWEB)

    Shove, Elizabeth [Lancaster University (United Kingdom). Centre for the Study of Environmental Change

    1998-07-01

    This project considers the process of formulating energy-related building regulation in the light of the revisions to Part L (Conservation of Fuel and Power) of the Building Regulations for England and Wales. Details are given of the main objectives of the research, namely, the examination of the roles of the UK government, local government and pressure groups in shaping energy efficiency standards, the impacts of environmental regulations, the limits of energy-related regulation, environmental regulation of the building sector, and the features of energy related building control. This control is compared with current practice in other European countries. The methodology of the project involving the review of governmental documents and interviews is described. (UK)

  3. Mindfulness meditation-related pain relief: Evidence for unique brain mechanisms in the regulation of pain

    Science.gov (United States)

    Zeidan, F.; Grant, J.A.; Brown, C.A.; McHaffie, J.G.; Coghill, R.C.

    2013-01-01

    The cognitive modulation of pain is influenced by a number of factors ranging from attention, beliefs, conditioning, expectations, mood, and the regulation of emotional responses to noxious sensory events. Recently, mindfulness meditation has been found attenuate pain through some of these mechanisms including enhanced cognitive and emotional control, as well as altering the contextual evaluation of sensory events. This review discusses the brain mechanisms involved in mindfulness meditation-related pain relief across different meditative techniques, expertise and training levels, experimental procedures, and neuroimaging methodologies. Converging lines of neuroimaging evidence reveal that mindfulness meditation-related pain relief is associated with unique appraisal cognitive processes depending on expertise level and meditation tradition. Moreover, it is postulated that mindfulness meditation-related pain relief may share a common final pathway with other cognitive techniques in the modulation of pain. PMID:22487846

  4. A survey of Canadian regulated complementary and alternative medicine schools about research, evidence-based health care and interprofessional training, as well as continuing education.

    Science.gov (United States)

    Toupin April, Karine; Gaboury, Isabelle

    2013-12-28

    While some effort has been made to integrate complementary and alternative medicine (CAM) information in conventional biomedical training, it is unclear whether regulated Canadian CAM schools' students are exposed to research activities and continuing education, or whether topics such as evidence-based health care and interprofessional collaboration (IPC) are covered during their training. Since these areas are valued by the biomedical training field, this may help to bridge the attitudinal and communication gaps between these different practices. The aim of this study was to describe the training offered in these areas and gather the perceptions of curriculum/program directors in regulated Canadian CAM schools. A two-phase study consisting of an electronic survey and subsequent semi-structured telephone interviews was conducted with curriculum/program (C/P) directors in regulated Canadian CAM schools. Questions assessed the extent of the research, evidence-based health care, IPC training and continuing education, as well as the C/P directors' perceptions about the training. Descriptive statistics were used to describe the schools', curriculum's and the C/P directors' characteristics. Content analysis was conducted on the interview material. Twenty-eight C/P directors replied to the electronic survey and 11 participated in the interviews, representing chiropractic, naturopathy, acupuncture and massage therapy schools. Canadian regulated CAM schools offered research and evidence-based health care training as well as opportunities for collaboration with biomedical peers and continuing education to a various extent (58% to 91%). Although directors were generally satisfied with the training offered at their school, they expressed a desire for improvements. They felt future CAM providers should understand research findings and be able to rely on high quality research and to communicate with conventional care providers as well as to engage in continuing education

  5. Evidence-based approach for continuous improvement of occupational health.

    Science.gov (United States)

    Manzoli, Lamberto; Sotgiu, Giovanni; Magnavita, Nicola; Durando, Paolo

    2015-01-01

    It was recognized early on that an Evidence-Based Medicine (EBM) approach could be applied to Public Health (PH), including the area of Occupational Health (OH). The aim of Evidence-Based Occupational Health (EBOH) is to ensure safety, health, and well-being in the workplace. Currently, high-quality research is necessary in order to provide arguments and scientific evidence upon which effective, efficient, and sustainable preventive measures and policies are to be developed in the workplace in Western countries. Occupational physicians need to integrate available scientific evidence and existing recommendations with a framework of national employment laws and regulations. This paper addresses the state of the art of scientific evidence available in the field (i.e., efficacy of interventions, usefulness of education and training of workers, and need of a multidisciplinary strategy integrated within the national PH programs) and the main critical issues for their implementation. Promoting good health is a fundamental part of the smart, inclusive growth objectives of Europe 2020 - Europe's growth strategy: keeping people healthy and active for longer has a positive impact on productivity and competitiveness. It appears clear that health quality and safety in the workplace play a key role for smart, sustainable, and inclusive growth in Western countries.

  6. Xenobiotic Receptor-Mediated Regulation of Intestinal Barrier Function and Innate Immunity

    Directory of Open Access Journals (Sweden)

    Harmit S. Ranhotra

    2016-07-01

    Full Text Available The molecular basis for the regulation of the intestinal barrier is a very fertile research area. A growing body of knowledge supports the targeting of various components of intestinal barrier function as means to treat a variety of diseases, including the inflammatory bowel diseases. Herein, we will summarize the current state of knowledge of key xenobiotic receptor regulators of barrier function, highlighting recent advances, such that the field and its future are succinctly reviewed. We posit that these receptors confer an additional dimension of host-microbe interaction in the gut, by sensing and responding to metabolites released from the symbiotic microbiota, in innate immunity and also in host drug metabolism. The scientific evidence for involvement of the receptors and its molecular basis for the control of barrier function and innate immunity regulation would serve as a rationale towards development of non-toxic probes and ligands as drugs.

  7. Incentive regulation of nuclear power plants by state regulators

    International Nuclear Information System (INIS)

    Martin, R.L.; Baker, K.; Olson, J.

    1991-02-01

    The Nuclear Regulatory Commission (NRC) monitors incentive programs established by state regulators in order to obtain current information and to consider the potential safety effects of the incentive programs as applied to nuclear units. The current report is an update of NUREG/CR-5509, Incentive Regulation of Nuclear Power Plants by State Public Utility Commissions, published in December 1989. The information in this report was obtained from interviews conducted with each state regulator and each utility with a minimum entitlement of 10%. The agreements, orders, and settlements from which each incentive program was implemented were reviewed as required. The interviews and supporting documentation form the basis for the individual state reports describing the structure and financial impact of each incentive program. The programs currently in effect represent the adoption of an existing nuclear performance incentive program proposal and one new program. In addition, since 1989 a number of nuclear units have been included in one existing program; while one program was discontinued and another one concluded. 6 refs., 27 tabs

  8. An updated systematic review of the evolution of ALPPS and evaluation of its advantages and disadvantages in accordance with current evidence.

    Science.gov (United States)

    Cai, Yu-Long; Song, Pei-Pei; Tang, Wei; Cheng, Nan-Sheng

    2016-06-01

    The main obstacle to achieving an R0 resection after a major hepatectomy is inability to preserve an adequate future liver remnant (FLR) to avoid postoperative liver failure (PLF). Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) is a novel technique for resecting tumors that were previously considered unresectable, and this technique results in a vast increase in the volume of the FLR in a short period of time. However, this technique continues to provoke heated debate because of its high mortality and morbidity.The evolution of ALPPS and its advantages and disadvantages have been systematically reviewed and evaluated in accordance with current evidence. Electronic databases (PubMed and Medline) were searched for potentially relevant articles from January 2007 to January 2016.ALPPS has evolved into various modified forms. Some of these modified techniques have reduced the difficulty of the procedure and enhanced its safety. Current evidence indicates that the advantages of ALPPS are rapid hypertrophy of the FLR, the feasibility of the procedure, and a higher rate of R0 resection in comparison to other techniques. However, ALPPS is associated with worse major complications, more deaths, and early tumor recurrence.Hepatobiliary surgeons should carefully consider whether to perform ALPPS. Some modified forms of ALPPS have reduced the mortality and morbidity of the procedure, but they cannot be recommended over the original procedure currently. Portal vein embolization (PVE) is still the procedure of choice for patients with a tumor-free FLR, and ALPPS could be used as a salvage procedure when PVE fails. More persuasive evidence needs to be assembled to determine whether ALPPS or two-stage hepatectomy (TSH) is better for patients with a tumor involving the FLR. Evidence with regard to long-term oncological outcomes is still limited. More meticulous comparative studies and studies of the 5-year survival rate of ALPPS could ultimately

  9. Hydrological regulation drives regime shifts: evidence from paleolimnology and ecosystem modeling of a large shallow Chinese lake.

    Science.gov (United States)

    Kong, Xiangzhen; He, Qishuang; Yang, Bin; He, Wei; Xu, Fuliu; Janssen, Annette B G; Kuiper, Jan J; van Gerven, Luuk P A; Qin, Ning; Jiang, Yujiao; Liu, Wenxiu; Yang, Chen; Bai, Zelin; Zhang, Min; Kong, Fanxiang; Janse, Jan H; Mooij, Wolf M

    2017-02-01

    Quantitative evidence of sudden shifts in ecological structure and function in large shallow lakes is rare, even though they provide essential benefits to society. Such 'regime shifts' can be driven by human activities which degrade ecological stability including water level control (WLC) and nutrient loading. Interactions between WLC and nutrient loading on the long-term dynamics of shallow lake ecosystems are, however, often overlooked and largely underestimated, which has hampered the effectiveness of lake management. Here, we focus on a large shallow lake (Lake Chaohu) located in one of the most densely populated areas in China, the lower Yangtze River floodplain, which has undergone both WLC and increasing nutrient loading over the last several decades. We applied a novel methodology that combines consistent evidence from both paleolimnological records and ecosystem modeling to overcome the hurdle of data insufficiency and to unravel the drivers and underlying mechanisms in ecosystem dynamics. We identified the occurrence of two regime shifts: one in 1963, characterized by the abrupt disappearance of submerged vegetation, and another around 1980, with strong algal blooms being observed thereafter. Using model scenarios, we further disentangled the roles of WLC and nutrient loading, showing that the 1963 shift was predominantly triggered by WLC, whereas the shift ca. 1980 was attributed to aggravated nutrient loading. Our analysis also shows interactions between these two stressors. Compared to the dynamics driven by nutrient loading alone, WLC reduced the critical P loading and resulted in earlier disappearance of submerged vegetation and emergence of algal blooms by approximately 26 and 10 years, respectively. Overall, our study reveals the significant role of hydrological regulation in driving shallow lake ecosystem dynamics, and it highlights the urgency of using multi-objective management criteria that includes ecological sustainability perspectives when

  10. Role of pelvic and para-aortic lymphadenectomy in endometrial cancer: Current evidence

    Science.gov (United States)

    Bogani, Giorgio; Dowdy, Sean C.; Cliby, William A.; Ghezzi, Fabio; Rossetti, Diego; Mariani, Andrea

    2015-01-01

    The aim of the present review is to summarize the current evidence on the role of pelvic and para-aortic lymphadenectomy in endometrial cancer. In 1988, the International Federation of Obstetrics and Gynecology recommended surgical staging for endometrial cancer patients. However, 25 years later, the role of lymph node dissection remains controversial. Although the findings of two large independent randomized trials suggested that pelvic lymphadenectomy provides only adjunctive morbidity with no clear influence on survival outcomes, the studies have many pitfalls that limit interpretation of the results. Theoretically, lymphadenectomy may help identify patients with metastatic dissemination, who may benefit from adjuvant therapy, thus reducing radiation-related morbidity. Also, lymphadenectomy may eradicate metastatic disease. Because lymphatic spread is relatively uncommon, our main effort should be directed at identifying patients who may potentially benefit from lymph node dissection, thus reducing the rate of unnecessary treatment and associated morbidity. This review will discuss the role of lymphadenectomy in endometrial cancer, focusing on patient selection, extension of the surgical procedure, postoperative outcomes, quality of life and costs. The need for new surgical studies and efficacious systemic drugs is recommended. PMID:24472047

  11. Voltage Dependence of a Neuromodulator-Activated Ionic Current123

    Science.gov (United States)

    2016-01-01

    Abstract The neuromodulatory inward current (IMI) generated by crab Cancer borealis stomatogastric ganglion neurons is an inward current whose voltage dependence has been shown to be crucial in the activation of oscillatory activity of the pyloric network of this system. It has been previously shown that IMI loses its voltage dependence in conditions of low extracellular calcium, but that this effect appears to be regulated by intracellular calmodulin. Voltage dependence is only rarely regulated by intracellular signaling mechanisms. Here we address the hypothesis that the voltage dependence of IMI is mediated by intracellular signaling pathways activated by extracellular calcium. We demonstrate that calmodulin inhibitors and a ryanodine antagonist can reduce IMI voltage dependence in normal Ca2+, but that, in conditions of low Ca2+, calmodulin activators do not restore IMI voltage dependence. Further, we show evidence that CaMKII alters IMI voltage dependence. These results suggest that calmodulin is necessary but not sufficient for IMI voltage dependence. We therefore hypothesize that the Ca2+/calmodulin requirement for IMI voltage dependence is due to an active sensing of extracellular calcium by a GPCR family calcium-sensing receptor (CaSR) and that the reduction in IMI voltage dependence by a calmodulin inhibitor is due to CaSR endocytosis. Supporting this, preincubation with an endocytosis inhibitor prevented W7 (N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide hydrochloride)-induced loss of IMI voltage dependence, and a CaSR antagonist reduced IMI voltage dependence. Additionally, myosin light chain kinase, which is known to act downstream of the CaSR, seems to play a role in regulating IMI voltage dependence. Finally, a Gβγ-subunit inhibitor also affects IMI voltage dependence, in support of the hypothesis that this process is regulated by a G-protein-coupled CaSR. PMID:27257619

  12. Direct Interaction of CaVβ with Actin Up-regulates L-type Calcium Currents in HL-1 Cardiomyocytes*

    Science.gov (United States)

    Stölting, Gabriel; de Oliveira, Regina Campos; Guzman, Raul E.; Miranda-Laferte, Erick; Conrad, Rachel; Jordan, Nadine; Schmidt, Silke; Hendriks, Johnny; Gensch, Thomas; Hidalgo, Patricia

    2015-01-01

    Expression of the β-subunit (CaVβ) is required for normal function of cardiac L-type calcium channels, and its up-regulation is associated with heart failure. CaVβ binds to the α1 pore-forming subunit of L-type channels and augments calcium current density by facilitating channel opening and increasing the number of channels in the plasma membrane, by a poorly understood mechanism. Actin, a key component of the intracellular trafficking machinery, interacts with Src homology 3 domains in different proteins. Although CaVβ encompasses a highly conserved Src homology 3 domain, association with actin has not yet been explored. Here, using co-sedimentation assays and FRET experiments, we uncover a direct interaction between CaVβ and actin filaments. Consistently, single-molecule localization analysis reveals streaklike structures composed by CaVβ2 that distribute over several micrometers along actin filaments in HL-1 cardiomyocytes. Overexpression of CaVβ2-N3 in HL-1 cells induces an increase in L-type current without altering voltage-dependent activation, thus reflecting an increased number of channels in the plasma membrane. CaVβ mediated L-type up-regulation, and CaVβ-actin association is prevented by disruption of the actin cytoskeleton with cytochalasin D. Our study reveals for the first time an interacting partner of CaVβ that is directly involved in vesicular trafficking. We propose a model in which CaVβ promotes anterograde trafficking of the L-type channels by anchoring them to actin filaments in their itinerary to the plasma membrane. PMID:25533460

  13. Current products and future plan of regulatory research for risk-informed regulation in Korea

    International Nuclear Information System (INIS)

    Sung, Key Yong; Lee, Chang Ju; Kim, Woong Sik; Kim, Hho Jung

    2003-01-01

    The first phase of a regulatory research project for risk-informed regulation (RIR) and applications (RIA) was finished in March of 2002. Various results that could be useful for preparing Korean RIR system have been developed. One of the remarkable outputs is development of reactor safety goals and acceptance criteria for RIR and RIA in Korea. The Safety Goal has a 4-tier hierarchical structure and each tier has specified goals classified for their usage. Regulatory review guides for probabilistic safety assessment (PSA) including level-1, level-2 and low power and shutdown PSA have been updated by reflecting new information obtained from not only the overseas documents but also experience and insights from regulatory review in Korea. In addition, draft regulatory guides for risk-informed in-service inspection, in-service testing, importance ranking of motor-operated valves, and AOT/STI change of Technical Specifications have been developed for preparing ongoing and future licensing work. Risk-based inspection guides with inspection items selected from a viewpoint of risk importance have been suggested for Korean standard NPPs as well. In the second phase of a research project (April of 2002 to March of 2005), two regulatory research projects on RIR were initiated. One is a study on institutionalization of risk-informed and performance-based regulation. Main topics of this project are evaluation of benefit and characteristics of RIR, development of optimized Korean RIR model, impact analysis for the change of current regulation framework, and suggestion of RIR-related laws and rules. The other is focusing on the development in the areas of a regulatory audit PSA model and regulatory guides for risk monitoring, and application techniques of risk information to the significance determination of plant performance indicators and inspection findings. It is expected that a concrete scheme and detailed regulatory techniques for embodiment of RIR system in Korea will be

  14. The Acute Relationships Between Affect, Physical Feeling States, and Physical Activity in Daily Life: A Review of Current Evidence

    OpenAIRE

    Liao, Yue; Shonkoff, Eleanor T.; Dunton, Genevieve F.

    2015-01-01

    Until recently, most studies investigating the acute relationships between affective and physical feeling states and physical activity were conducted in controlled laboratory settings, whose results might not translate well to everyday life. This review was among the first attempts to synthesize current evidence on the acute (e.g., within a few hours) relationships between affective and physical feeling states and physical activity from studies conducted in free-living, naturalistic settings ...

  15. The BASES expert statement on emotion regulation in sport.

    Science.gov (United States)

    Lane, Andrew M; Beedie, Chris J; Jones, Marc V; Uphill, Mark; Devonport, Tracey J

    2012-01-01

    Emotions experienced before and during sports competition have been found to influence sports performance. Emotion regulation is defined as the automatic or deliberate use of strategies to initiate, maintain, modify or display emotions (Gross & Thompson, 2007) and is proposed to occur when a discrepancy exists between current and desired emotions. Two distinct motivations to regulate emotion - hedonic and instrumental (in short, for pleasure or for purpose) - have been proposed (Tamir, 2009). The instrumental approach might provide a more fruitful area of investigation for sports researchers as some athletes hold beliefs that supposedly pleasant emotions such as happiness and calmness associate with poor performance and supposedly unpleasant emotions such as anxiety and anger associate with good performance (Hanin, 2010). Athletes are more likely to try to regulate an emotion if they believe that doing so will facilitate performance. Strategies that encourage re-appraisal of factors that trigger emotions are proposed to be preferable. In this British Association of Sport and Exercise Sciences (BASES) expert statement, a summary of the key theoretical issues are offered leading to evidence-based recommendations for practitioners and researchers.

  16. GABA-independent GABAA Receptor Openings Maintain Tonic Currents

    Science.gov (United States)

    Wlodarczyk, Agnieszka I.; Sylantyev, Sergiy; Herd, Murray B.; Kersanté, Flavie; Lambert, Jeremy J.; Rusakov, Dmitri A.; Linthorst, Astrid C.E.; Semyanov, Alexey; Belelli, Delia; Pavlov, Ivan; Walker, Matthew C.

    2013-01-01

    Activation of GABAA receptors (GABAARs) produces two forms of inhibition: ‘phasic’ inhibition generated by the rapid, transient activation of synaptic GABAARs by presynaptic GABA release, and tonic inhibition generated by the persistent activation of peri- or extrasynaptic GABAARs which can detect extracellular GABA. Such tonic GABAAR-mediated currents are particularly evident in dentate granule cells in which they play a major role in regulating cell excitability. Here we show that in rat dentate granule cells in ex-vivo hippocampal slices, tonic currents are predominantly generated by GABA-independent GABAA receptor openings. This tonic GABAAR conductance is resistant to the competitive GABAAR antagonist SR95531, which at high concentrations acts as a partial agonist, but can be blocked by an open channel blocker picrotoxin. When slices are perfused with 200 nM GABA, a concentration that is comparable to cerebrospinal fluid concentrations but is twice that measured by us in the hippocampus in vivo using zero-net-flux microdialysis, negligible GABA is detected by dentate granule cells. Spontaneously opening GABAARs, therefore, maintain dentate granule cell tonic currents in the face of low extracellular GABA concentrations. PMID:23447601

  17. Practical considerations on the introduction of sacubitril/valsartan in clinical practice: Current evidence and early experience.

    Science.gov (United States)

    Farmakis, Dimitrios; Bistola, Vassiliki; Karavidas, Apostolos; Parissis, John

    2016-11-15

    The combination of neprilysin inhibitor sacubitril with the angiotensin II receptor 1 blocker valsartan is the first agent from the angiotensin receptor neprilysin inhibitors (ARNI) class authorized for clinical use in heart failure (HF) patients with reduced ejection fraction (HFrEF). Sacubitril/valsartan resulted in 20% reduction in the incidence rate of death or HF hospitalization compared to enalapril in symptomatic HFrEF patients in the seminal PARADIGM-HF trial. As a result, the recently updated European and American HF guidelines granted this agent a class IB indication for the treatment of ambulatory/chronic symptomatic HFrEF patients. However, translating the positive results of trials into true clinical benefit is often challenging. This is particularly true in the case of sacubitril/valsartan, as HF is a heterogeneous syndrome including many severely ill patients who are prone to decompensation, while this new agent comes to replace a cornerstone of current evidence-based HF therapy. In the present paper, we address a number of practical issues regarding the introduction of sacubitril/valsartan and propose an algorithm based on available evidence and early clinical experience. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  18. Reducing Ripple In A Switching Voltage Regulator

    Science.gov (United States)

    Paulkovich, John; Rodriguez, G. Ernest

    1994-01-01

    Ripple voltage in output of switching voltage regulator reduced substantially by simple additional circuitry adding little to overall weight and size of regulator. Heretofore, additional filtering circuitry needed to obtain comparable reductions in ripple typically as large and heavy as original regulator. Current opposing ripple current injected into filter capacitor.

  19. Do Market Regulation and Financial Imperfections Affect Firm Size? New Empirical Evidence

    OpenAIRE

    Raquel Fonseca; Natalia Utrero González

    2004-01-01

    This paper investigates the importance that market regulation and financial imperfections have in firm size. We analyse institutions affecting labour market as Employment Protection Laws (EPL) and Product Market Regulation (PMR). Moreover, we study the effects of these institutions on firm growth. We use data from 29 industrial sectors across 15 developed countries. We find that market regulations related to financial imperfections help to explain differences in firm structure across countries.

  20. The Nav1.2 channel is regulated by GSK3

    Science.gov (United States)

    James, Thomas F.; Nenov, Miroslav N.; Wildburger, Norelle C.; Lichti, Cheryl; Luisi, Jonathan; Vergara, Fernanda; Panova-Electronova, Neli I.; Nilsson, Carol L.; Rudra, Jai; Green, Thomas A.; Labate, Demetrio; Laezza, Fernanda

    2015-01-01

    Background Phosphorylation plays an essential role in regulating the voltage-gated sodium (Nav) channels and excitability. Yet, a surprisingly limited number of kinases have been identified as regulators of Nav channels. Herein, we posited that glycogen synthase kinase 3 (GSK3), a critical kinase found associated with numerous brain disorders, might directly regulate neuronal Nav channels. Methods We used patch-clamp electrophysiology to record sodium currents from Nav1.2 channels stably expressed in HEK-293 cells. mRNA and protein levels were quantified with RT-PCR, Western blot, or confocal microscopy, and in vitro phosphorylation and mass spectrometry to identify phosphorylated residues. Results We found that exposure of cells to GSK3 inhibitor XIII significantly potentiates the peak current density of Nav1.2, a phenotype reproduced by silencing GSK3 with siRNA. Contrarily, overexpression of GSK3β suppressed Nav1.2-encoded currents. Neither mRNA nor total protein expression were changed upon GSK3 inhibition. Cell surface labeling of CD4-chimeric constructs expressing intracellular domains of the Nav1.2 channel indicates that cell surface expression of CD4-Nav1.2-Ctail was up-regulated upon pharmacological inhibition of GSK3, resulting in an increase of surface puncta at the plasma membrane. Finally, using in vitro phosphorylation in combination with high resolution mass spectrometry, we further demonstrate that GSK3β phosphorylates T1966 at the C-terminal tail of Nav1.2. Conclusion These findings provide evidence for a new mechanism by which GSK3 modulate Nav channel function via its C-terminal tail. General Significance These findings provide fundamental knowledge in understanding signaling dysfunction common in several neuropsychiatric disorders. PMID:25615535

  1. TLX: A master regulator for neural stem cell maintenance and neurogenesis.

    Science.gov (United States)

    Islam, Mohammed M; Zhang, Chun-Li

    2015-02-01

    The orphan nuclear receptor TLX, also known as NR2E1, is an essential regulator of neural stem cell (NSC) self-renewal, maintenance, and neurogenesis. In vertebrates, TLX is specifically localized to the neurogenic regions of the forebrain and retina throughout development and adulthood. TLX regulates the expression of genes involved in multiple pathways, such as the cell cycle, DNA replication, and cell adhesion. These roles are primarily performed through the transcriptional repression or activation of downstream target genes. Emerging evidence suggests that the misregulation of TLX might play a role in the onset and progression of human neurological disorders making this factor an ideal therapeutic target. Here, we review the current understanding of TLX function, expression, regulation, and activity significant to NSC maintenance, adult neurogenesis, and brain plasticity. This article is part of a Special Issue entitled: Nuclear receptors in animal development. Copyright © 2014 Elsevier B.V. All rights reserved.

  2. [Emotional regulation and motivation in children with ADHD].

    Science.gov (United States)

    Høvik, Marie Farstad; Plessen, Kerstin J

    2010-12-02

    Impaired cognitive control functions have long been regarded as the main problem in the development of Attention-Deficit/Hyperactivity Disorder (ADHD). A more recent model emphasizes the importance of emotional and motivational problems. We have reviewed the evidence for this model, which may have important implications for clinical practice. The article is based on literature identified through a non-systematic search in PubMed. Although limited research was carried out in this topic earlier, studies are currently emerging. Persons with ADHD react differently than controls on tasks that include rewards and on tasks that stress their capacity to regulate emotions. Abnormal signals during examination with electroencephalography (EEG) and anatomical and functional magnetic resonance imaging (fMRI) reflect problems with emotional regulation in patients with ADHD. Neurobiological research supports a model that includes emotional and motivational problems in the development of ADHD. Increased knowledge about emotional and motivational problems may improve treatment of these patients through development of more individually adapted therapy.

  3. The neuroendocrine regulation of food intake in fish: a review of current knowledge

    Directory of Open Access Journals (Sweden)

    Helene Volkoff

    2016-11-01

    Full Text Available Fish are the most diversified group of vertebrates and, although progress has been made in the past years, only relatively few fish species have been examined to date, with regards to the endocrine regulation of feeding in fish. In fish, as in mammals, feeding behavior is ultimately regulated by central effectors within feeding centers of the brain, which receive and process information from endocrine signals from both brain and peripheral tissues. Although basic endocrine mechanisms regulating feeding appear to be conserved among vertebrates, major physiological differences between fish and mammals and the diversity of fish, in particular in regard to feeding habits, digestive tract anatomy and physiology, suggest the existence of fish- and species-specific regulating mechanisms. This review provides an overview of hormones known to regulate food intake in fish, emphasizing on major hormones and the main fish groups studied to date.

  4. The RB/E2F pathway and regulation of RNA processing

    Energy Technology Data Exchange (ETDEWEB)

    Ahlander, Joseph [Department of Molecular and Cellular Biology, 1007 East Lowell Street, University of Arizona, Tucson, AZ 85721 (United States); Bosco, Giovanni, E-mail: gbosco@email.arizona.edu [Department of Molecular and Cellular Biology, 1007 East Lowell Street, University of Arizona, Tucson, AZ 85721 (United States)

    2009-07-03

    The retinoblastoma tumor suppressor protein (RB) is inactivated in a majority of cancers. RB restricts cell proliferation by inhibiting the E2F family of transcription factors. The current model for RB/E2F function describes its role in regulating transcription at gene promoters. Whether the RB or E2F proteins might play a role in gene expression beyond transcription initiation is not well known. This review describes evidence that points to a novel role for the RB/E2F network in the regulation of RNA processing, and we propose a model as a framework for future research. The elucidation of a novel role of RB in RNA processing will have a profound impact on our understanding of the role of this tumor suppressor family in cell and developmental biology.

  5. The international radioactive transportation regulations: A model for national regulations

    International Nuclear Information System (INIS)

    Pope, R.B.; Rawl, R.R.

    1990-06-01

    The International Atomic Energy Agency's (IAEA) Regulations for the Safe Transport of Radioactive Material, Safety Series No. 6 (herein after denoted as the ''International Regulations'') serve as the model for the regulations for individual countries and international modal organizations controlling the packaging and transportation of radioactive materials. The purpose of this paper is to outline the background and history of the International Regulations, the general principles behind the requirements of the International Regulations, the structure and general contents of the latest edition of the International Regulations, and the roles of various international bodies in the development and implementation of the International Regulations and the current status of regulatory and supportive document development at both the international and domestic level. This review will provide a basis for users and potential users to better understand the source and application of the International Regulations. 1 tab

  6. Evidence for the role of a Na(+)/HCO(3)(-) cotransporter in trout hepatocyte pHi regulation.

    Science.gov (United States)

    Furimsky, M; Moon, T W; Perry, S F

    2000-07-01

    The mechanisms of intracellular pH (pHi) regulation were examined in hepatocytes of the rainbow trout Oncorhynchus mykiss. pHi was monitored using the pH-sensitive fluorescent dye BCECF, and the effects of various media and pharmacological agents were examined for their influence on baseline pHi and recovery rates from acid and base loading. Rates of Na(+) uptake were measured using (22)Na, and changes in membrane potential were examined using the potentiometric fluorescent dye Oxonol VI. The rate of proton extrusion following acid loading was diminished by the blockade of either Na(+)/H(+) exchange (using amiloride) or anion transport (using DIDS). The removal of external HCO(3)(-) and the abolition of outward K(+) diffusion by the channel blocker Ba(2+) also decreased the rate of proton extrusion following acid load. Depolarization of the cell membrane with 50 mmol l(-)(1) K(+), however, did not affect pHi. The rate of recovery from base loading was significantly diminished by the blockade of anion transport, removal of external HCO(3)(-) and, to a lesser extent, by blocking Na(+)/H(+) exchange. The blockade of K(+) conductance had no effect. The decrease in Na(+) uptake rate observed in the presence of the anion transport blocker DIDS and the DIDS-sensitive hyperpolarization of membrane potential during recovery from acid loading suggest that a Na(+)-dependent electrogenic transport system is involved in the restoration of pHi after intracellular acidification. The effects on baseline pHi indicate that the different membrane exchangers are tonically active in the maintenance of steady-state pHi. This study confirms the roles of a Na(+)/H(+) exchanger and a Cl(-)/HCO(3)(-) exchanger in the regulation of trout hepatocyte pHi and provides new evidence that a Na(+)/HCO(3)(-) cotransporter contributes to pHi regulation.

  7. Regulation of behaviour by the nuclear receptor TLX.

    Science.gov (United States)

    O'Leary, J D; O'Leary, O F; Cryan, J F; Nolan, Y M

    2018-03-01

    The orphan nuclear receptor Tlx (Nr2e1) is a key regulator of both embryonic and adult hippocampal neurogenesis. Several different mouse models have been developed which target Tlx in vivo including spontaneous deletion models (from birth) and targeted and conditional knockouts. Although some conflicting findings have been reported, for the most part studies have demonstrated that Tlx is important in regulating processes that underlie neurogenesis, spatial learning, anxiety-like behaviour and interestingly, aggression. More recent data have demonstrated that disrupting Tlx during early life induces hyperactivity and that Tlx plays a role in emotional regulation. Moreover, there are sex- and age-related differences in some behaviours in Tlx knockout mice during adolescence and adulthood. Here, we discuss the role of Tlx in motor-, cognitive-, aggressive- and anxiety-related behaviours during adolescence and adulthood. We examine current evidence which provides insight into Tlx during neurodevelopment, and offer our thoughts on the function of Tlx in brain and behaviour. We further hypothesize that Tlx is a key target in understanding the emergence of neurobiological disorders during adolescence and early adulthood. © 2016 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

  8. Evidence for current recommendations concerning the management of foot health for people with chronic long-term conditions: a systematic review

    Directory of Open Access Journals (Sweden)

    Katherine Edwards

    2017-11-01

    Full Text Available Abstract Background Research focusing on management of foot health has become more evident over the past decade, especially related to chronic conditions such as diabetes. The level of methodological rigour across this body of work however is varied and outputs do not appear to have been developed or translated into clinical practice. The aim of this systematic review was to assess the latest guidelines, standards of care and current recommendations relative to people with chronic conditions to ascertain the level of supporting evidence concerning the management of foot health. Methods A systematic search of electronic databases (Medline, Embase, Cinahl, Web of Science, SCOPUS and The Cochrane Library for literature on recommendations for foot health management for people with chronic conditions was performed between 2000 and 2016 using predefined criteria. Data from the included publications was synthesised via template analysis, employing a thematic organisation and structure. The methodological quality of all included publications was appraised using the Appraisal for Research and Evaluation (AGREE II instrument. A more in-depth analysis was carried out that specifically considered the levels of evidence that underpinned the strength of their recommendations concerning management of foot health. Results The data collected revealed 166 publications in which the majority (102 were guidelines, standards of care or recommendations related to the treatment and management of diabetes. We noted a trend towards a systematic year on year increase in guidelines standards of care or recommendations related to the treatment and management of long term conditions other than diabetes over the past decade. The most common recommendation is for preventive care or assessments (e.g. vascular tests, followed by clinical interventions such as foot orthoses, foot ulcer care and foot health education. Methodological quality was spread across the range of AGREE II

  9. Direct interaction of CaVβ with actin up-regulates L-type calcium currents in HL-1 cardiomyocytes.

    Science.gov (United States)

    Stölting, Gabriel; de Oliveira, Regina Campos; Guzman, Raul E; Miranda-Laferte, Erick; Conrad, Rachel; Jordan, Nadine; Schmidt, Silke; Hendriks, Johnny; Gensch, Thomas; Hidalgo, Patricia

    2015-02-20

    Expression of the β-subunit (CaVβ) is required for normal function of cardiac L-type calcium channels, and its up-regulation is associated with heart failure. CaVβ binds to the α1 pore-forming subunit of L-type channels and augments calcium current density by facilitating channel opening and increasing the number of channels in the plasma membrane, by a poorly understood mechanism. Actin, a key component of the intracellular trafficking machinery, interacts with Src homology 3 domains in different proteins. Although CaVβ encompasses a highly conserved Src homology 3 domain, association with actin has not yet been explored. Here, using co-sedimentation assays and FRET experiments, we uncover a direct interaction between CaVβ and actin filaments. Consistently, single-molecule localization analysis reveals streaklike structures composed by CaVβ2 that distribute over several micrometers along actin filaments in HL-1 cardiomyocytes. Overexpression of CaVβ2-N3 in HL-1 cells induces an increase in L-type current without altering voltage-dependent activation, thus reflecting an increased number of channels in the plasma membrane. CaVβ mediated L-type up-regulation, and CaVβ-actin association is prevented by disruption of the actin cytoskeleton with cytochalasin D. Our study reveals for the first time an interacting partner of CaVβ that is directly involved in vesicular trafficking. We propose a model in which CaVβ promotes anterograde trafficking of the L-type channels by anchoring them to actin filaments in their itinerary to the plasma membrane. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  10. Extraperitoneal Robotic-Assisted Para-Aortic Lymphadenectomy in Gynecologic Cancer Staging: Current Evidence.

    Science.gov (United States)

    Bogani, Giorgio; Ditto, Antonino; Martinelli, Fabio; Signorelli, Mauro; Chiappa, Valentina; Sabatucci, Ilaria; Scaffa, Cono; Lorusso, Domenica; Raspagliesi, Francesco

    2016-01-01

    We reviewed the current evidence on the safety, effectiveness, and applicability of extraperitoneal robotic-assisted para-aortic lymphadenectomy (ExtRA-PAL) as the staging procedure of gynecologic malignancies. PubMed (MEDLINE), Scopus, Web of Science databases, and ClinicalTrials.gov were searched for original studies reporting outcomes of ExtRA-PAL. Quality of the included studies and their level of recommendation were assessed using the Grading of Recommendations, Assessment, Development, and Evaluation and the American College of Obstetricians and Gynecologists guidelines, respectively. Overall, 62 studies were identified; after a process of evidence acquisition 5 original investigations were available for this review that included 98 patients undergoing ExtRA-PAL. The main surgical indication was staging for cervical cancer (n = 71, 72%). The mean (SD) number of para-aortic node yielded was 15.4 (±4.7) nodes. Blood transfusion and intraoperative complication rates were 2% and 6%, respectively. ExtRA-PAL was completed in 88 patients (90%). Six (6%) and 4 (4%) patients had conversion to other minimally invasive procedures and open surgery, respectively. Success rate was 99% among patients undergoing ExtRA-PAL without concomitant procedures. Overall, mean (SD) length of hospital stay was 2.8 (±0.5) days. Twenty-four patients (24%) developed postoperative events. According to the Clavien-Dindo grading system, grades IIIa and IIIb morbidity rates were 12% and 2%, respectively. No grades IV and V morbidity occurred. ExtRA-PAL is associated with a high success rate and a relative low morbidity rate. However, because of the limited data on this issue, further studies are warranted to assess the long-term effectiveness of this procedure. Copyright © 2016 AAGL. Published by Elsevier Inc. All rights reserved.

  11. The link between motor and cognitive development in children born preterm and/or with low birth weight : A review of current evidence

    NARCIS (Netherlands)

    Oudgenoeg-Paz, Ora; Mulder, Hanna; Jongmans, Marian J.; van der Ham, Ineke J.M.; Van der Stigchel, Stefan

    2017-01-01

    The current review focuses on evidence for a link between early motor development and later cognitive skills in children born preterm or with Low Birth Weight (LBW). Studies with term born children consistently show such a link. Motor and cognitive impairments or delays are often seen in children

  12. Professional Development for Sessional Staff in Higher Education: A Review of Current Evidence

    Science.gov (United States)

    Hitch, Danielle; Mahoney, Paige; Macfarlane, Susie

    2018-01-01

    The aim of this study was to provide an integrated review of evidence published in the past decade around professional development for sessional staff in higher education. Using the Integrating Theory, Evidence and Action method, the review analysed recent evidence using the three principles of the Benchmarking Leadership and Advancement of…

  13. 46 CFR 5.69 - Evidence of criminal liability.

    Science.gov (United States)

    2010-10-01

    ... INVESTIGATION REGULATIONS-PERSONNEL ACTION Statement of Policy and Interpretation § 5.69 Evidence of criminal liability. Evidence of criminal liability discovered during an investigation or hearing conducted pursuant... 46 Shipping 1 2010-10-01 2010-10-01 false Evidence of criminal liability. 5.69 Section 5.69...

  14. The 'antisocial' person: an insight in to biology, classification and current evidence on treatment

    Directory of Open Access Journals (Sweden)

    Rajapakse Senaka

    2010-07-01

    Full Text Available Abstract Background This review analyses and summarises the recent advances in understanding the neurobiology of violence and empathy, taxonomical issues on defining personality disorders characterised by disregard for social norms, evidence for efficacy of different treatment modalities and ethical implications in defining 'at-risk' individuals for preventive interventions. Methods PubMed was searched with the keywords 'antisocial personality disorder', 'dissocial personality disorder' and 'psychopathy'. The search was limited to articles published in English over the last 10 years (1999 to 2009 Results Both diagnostic manuals used in modern psychiatry, the Diagnostic and Statistical Manual published by the American Psychiatric Association and the International Classification of Diseases published by the World Health Organization, identify a personality disorder sharing similar traits. It is termed antisocial personality disorder in the diagnostic and statistical manual and dissocial personality disorder in the International Classification of Diseases. However, some authors query the ability of the existing manuals to identify a special category termed 'psychopathy', which in their opinion deserves special attention. On treatment-related issues, many psychological and behavioural therapies have shown success rates ranging from 25% to 62% in different cohorts. Multisystemic therapy and cognitive behaviour therapy have been proven efficacious in many trials. There is no substantial evidence for the efficacy of pharmacological therapy. Currently, the emphasis is on early identification and prevention of antisocial behaviour despite the ethical implications of defining at-risk children. Conclusions Further research is needed in the areas of neuroendocrinological associations of violent behaviour, taxonomic existence of psychopathy and efficacy of treatment modalities.

  15. Respiratory medicines for children: current evidence, unlicensed use and research priorities

    DEFF Research Database (Denmark)

    Smyth, A R; Barbato, A; Beydon, N

    2010-01-01

    deficiency. We hope that this summary of the evidence for respiratory medicines in children, highlighting gaps and research priorities, will be useful for the pharmaceutical industry, the paediatric committee of the European Medicines Agency, academic investigators and the lay public.......This European Respiratory Society task force has reviewed the evidence for paediatric medicines in respiratory disease occurring in adults and children. We describe off-licence use, research priorities and ongoing studies. Off-licence and off-label prescribing in children is widespread...

  16. Revisiting reflexology: Concept, evidence, current practice, and practitioner training.

    Science.gov (United States)

    Embong, Nurul Haswani; Soh, Yee Chang; Ming, Long Chiau; Wong, Tin Wui

    2015-10-01

    Reflexology is basically a study of how one part of the human body relates to another part of the body. Reflexology practitioners rely on the reflexes map of the feet and hands to all the internal organs and other human body parts. They believe that by applying the appropriate pressure and massage certain spots on the feet and hands, all other body parts could be energized and rejuvenated. This review aimed to revisit the concept of reflexology and examine its effectiveness, practices, and the training for reflexology practitioners. PubMed, SCOPUS, Google Scholar, and SpringerLink databases were utilized to search the following medical subject headings or keywords: foot massage, reflexology, foot reflexotherapy, reflexological treatment, and zone therapy. The articles published for the last 10 years were included. Previous systematic reviews failed to show concrete evidence for any specific effect of reflexology in any conditions. Due to its non-invasive, non-pharmacological complementary nature, reflexology is widely accepted and anecdotal evidence of positive effect reflexology in a variety of health conditions are available. Adequate training for practitioners is necessary to ensure the consistency of service provided.

  17. Revisiting reflexology: Concept, evidence, current practice, and practitioner training

    Directory of Open Access Journals (Sweden)

    Nurul Haswani Embong

    2015-10-01

    Full Text Available Reflexology is basically a study of how one part of the human body relates to another part of the body. Reflexology practitioners rely on the reflexes map of the feet and hands to all the internal organs and other human body parts. They believe that by applying the appropriate pressure and massage certain spots on the feet and hands, all other body parts could be energized and rejuvenated. This review aimed to revisit the concept of reflexology and examine its effectiveness, practices, and the training for reflexology practitioners. PubMed, SCOPUS, Google Scholar, and SpringerLink databases were utilized to search the following medical subject headings or keywords: foot massage, reflexology, foot reflexotherapy, reflexological treatment, and zone therapy. The articles published for the last 10 years were included. Previous systematic reviews failed to show concrete evidence for any specific effect of reflexology in any conditions. Due to its non-invasive, non-pharmacological complementary nature, reflexology is widely accepted and anecdotal evidence of positive effect reflexology in a variety of health conditions are available. Adequate training for practitioners is necessary to ensure the consistency of service provided.

  18. The relation between external governance environment and over-investment: Evidence from industry regulation

    Directory of Open Access Journals (Sweden)

    Kejing Chen

    2014-11-01

    Full Text Available Based on the Law and Finance theory, and the regulatory capture theory, external governance environment and industrial regulations can exert a certain influence on corporate over-investment. On the basis of qualitative analysis of the relationship between external governance environment and corporate over-investment under different industrial regulation conditions, this paper, using data of non-financial companies listed in Shanghai and Shenzhen Stock Exchanges in the period 2001-2010, describes the regional distribution characteristics of over-investment of Chinese listed companies, and establishes an OLS regression model of the relationship between external governance environment and over-investment. The study respectively groups data from regulated and non-regulated industries as a sample and empirically tests the OLS regression model. Results show that: from the perspective of economic geography, there exists a local spatial cluster phenomenon in the distribution of over-investment of listed companies in regulated industries, while non-regulated industries conform to no regularity. In regulated industries, external governance environment factors (level of government intervention, rule of law and financial development may exert a significant negative influence on the degree of over-investment of listed companies, but on non-regulated industries, their effect is reversed. Also, government intervention, legal enforcement and financial development are positively correlated to over-investment. Further research indicates that, compared with government intervention and financial development, legal enforcement influences over-investment the most.

  19. Web 2.0 for health promotion: reviewing the current evidence.

    Science.gov (United States)

    Chou, Wen-ying Sylvia; Prestin, Abby; Lyons, Claire; Wen, Kuang-yi

    2013-01-01

    As Web 2.0 and social media make the communication landscape increasingly participatory, empirical evidence is needed regarding their impact on and utility for health promotion. Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we searched 4 medical and social science databases for literature (2004-present) on the intersection of Web 2.0 and health. A total of 514 unique publications matched our criteria. We classified references as commentaries and reviews (n = 267), descriptive studies (n = 213), and pilot intervention studies (n = 34). The scarcity of empirical evidence points to the need for more interventions with participatory and user-generated features. Innovative study designs and measurement methods are needed to understand the communication landscape and to critically assess intervention effectiveness. To address health disparities, interventions must consider accessibility for vulnerable populations.

  20. Chrono-nutrition: a review of current evidence from observational studies on global trends in time-of-day of energy intake and its association with obesity.

    Science.gov (United States)

    Almoosawi, S; Vingeliene, S; Karagounis, L G; Pot, G K

    2016-11-01

    The importance of the circadian rhythm in regulating human food intake behaviour and metabolism has long been recognised. However, little is known as to how energy intake is distributed over the day in existing populations, and its potential association with obesity. The present review describes global trends in time-of-day of energy intake in the general population based on data from cross-sectional surveys and longitudinal cohorts. Evidence of the association between time-of-day of energy intake and obesity is also summarised. Overall, there were a limited number of cross-sectional surveys and longitudinal cohorts that provided data on time-of-day of energy intake. In the identified studies, a wide variation in time-of-day of energy intake was observed, with patterns of energy distribution varying greatly by country and geographical area. In relation to obesity, eight cross-sectional surveys and two longitudinal cohorts were identified. The association between time-of-day of energy intake and obesity varied widely, with several studies reporting a positive link between evening energy intake and obesity. In conclusion, the current review summarises global trends in time-of-day of energy intake. The large variations across countries and global regions could have important implications to health, emphasising the need to understand the socio-environmental factors guiding such differences in eating patterns. Evidence of the association between time-of-day of energy intake and BMI also varied. Further larger scale collaborations between various countries and regions are needed to sum data from existing surveys and cohorts, and guide our understanding of the role of chrono-nutrition in health.

  1. An assessment of the fire protection requirements throughout a NPP life related to current IAEA regulations and American, Canadian and UE regulations

    International Nuclear Information System (INIS)

    Branzeu, N.; Necula, D.; Badea, M.; Teodorescu, D.; Peteu, M.

    2006-01-01

    Statistics on fires has surprisingly shown that the frequency of fires in a nuclear power plant are as high as in the conventional industrial units. The analyses on fires occurred in a NPP need to consider both their well-known severe damages and the nuclear consequences. In 1975 a severe fire occurred in BROWNS FERRY NPP due to the ignition of the polyurethane foam used in the electric cable penetration sealings. The fire propagated to the cable channels and damaged over 1600 cables. The fire event revealed important shortcomings in the fire protection design and procedures. The fire represented a crucial event that changed fundamentally the fire protection regulation in the United States nuclear industry. The fire protection programs, standards and guides currently applied, have been developed on basis of this fire analysis and gained conclusions/experience. The purpose of the article is to be a short presentation of the fire protection requirements for all NPP life stages (i.e. design, construction, commissioning, operation and decommissioning), including the most recent issues of the standards, codes, guides and regulations in US, Canada, IAEA and some European countries. Such documentation represented the main technical support in establishing the national fire protection standard design regarding all the stages of a CANDU-6 NPP life, all the types of operational NPPs, particularly for Cernavoda NPP Unit 1 and Unit 2 (now in an advanced stage of construction). In order to satisfy the requirements provided by this documentation, as practically as possible, a list of analyses and fire protection improvement measures for Cernavoda NPP is presented. (authors)

  2. Basally activated nonselective cation currents regulate the resting membrane potential in human and monkey colonic smooth muscle

    Science.gov (United States)

    Dwyer, Laura; Rhee, Poong-Lyul; Lowe, Vanessa; Zheng, Haifeng; Peri, Lauren; Ro, Seungil; Sanders, Kenton M.

    2011-01-01

    Resting membrane potential (RMP) plays an important role in determining the basal excitability of gastrointestinal smooth muscle. The RMP in colonic muscles is significantly less negative than the equilibrium potential of K+, suggesting that it is regulated not only by K+ conductances but by inward conductances such as Na+ and/or Ca2+. We investigated the contribution of nonselective cation channels (NSCC) to the RMP in human and monkey colonic smooth muscle cells (SMC) using voltage- and current-clamp techniques. Qualitative reverse transcriptase-polymerase chain reaction was performed to examine potential molecular candidates for these channels among the transient receptor potential (TRP) channel superfamily. Spontaneous transient inward currents and holding currents were recorded in human and monkey SMC. Replacement of extracellular Na+ with equimolar tetraethylammonium or Ca2+ with Mn2+ inhibited basally activated nonselective cation currents. Trivalent cations inhibited these channels. Under current clamp, replacement of extracellular Na+ with N-methyl-d-glucamine or addition of trivalent cations caused hyperpolarization. Three unitary conductances of NSCC were observed in human and monkey colonic SMC. Molecular candidates for basally active NSCC were TRPC1, C3, C4, C7, M2, M4, M6, M7, V1, and V2 in human and monkey SMC. Comparison of the biophysical properties of these TRP channels with basally active NSCC (bINSCC) suggests that TRPM4 and specific TRPC heteromultimer combinations may underlie the three single-channel conductances of bINSCC. In conclusion, these findings suggest that basally activated NSCC contribute to the RMP in human and monkey colonic SMC and therefore may play an important role in determining basal excitability of colonic smooth muscle. PMID:21566016

  3. Electric Currents along Astrophysical Jets

    Directory of Open Access Journals (Sweden)

    Ioannis Contopoulos

    2017-10-01

    Full Text Available Astrophysical black holes and their surrounding accretion disks are believed to be threaded by grand design helical magnetic fields. There is strong theoretical evidence that the main driver of their winds and jets is the Lorentz force generated by these fields and their associated electric currents. Several researchers have reported direct evidence for large scale electric currents along astrophysical jets. Quite unexpectedly, their directions are not random as would have been the case if the magnetic field were generated by a magnetohydrodynamic dynamo. Instead, in all kpc-scale detections, the inferred electric currents are found to flow away from the galactic nucleus. This unexpected break of symmetry suggests that a battery mechanism is operating around the central black hole. In the present article, we summarize observational evidence for the existence of large scale electric currents and their associated grand design helical magnetic fields in kpc-scale astrophysical jets. We also present recent results of general relativistic radiation magnetohydrodynamic simulations which show the action of the Cosmic Battery in the vicinity of astrophysical black holes.

  4. Nanomaterials: Regulation and Risk Assessment

    DEFF Research Database (Denmark)

    Hansen, Steffen Foss; Grieger, Khara Deanne; Baun, Anders

    2013-01-01

    , the Water Framework Directive, pharmaceuticals regulation, and the Novel Foods Regulation. Current regulation of nanomaterials entail three overall challenges: 1) limitations in regard to terminology and definitions of key terms such as a “substance,” “novel food,” etc.; 2) safety assessment requirements...

  5. 15 CFR 325.13 - Nonadmissibility in evidence.

    Science.gov (United States)

    2010-01-01

    ... 15 Commerce and Foreign Trade 2 2010-01-01 2010-01-01 false Nonadmissibility in evidence. 325.13 Section 325.13 Commerce and Foreign Trade Regulations Relating to Commerce and Foreign Trade (Continued) INTERNATIONAL TRADE ADMINISTRATION, DEPARTMENT OF COMMERCE MISCELLANEOUS REGULATIONS EXPORT TRADE CERTIFICATES...

  6. Evidence for neutral neutrino current coupling to right-handed quarks

    International Nuclear Information System (INIS)

    Allaby, J.V.; Amaldi, U.; Barbiellini, G.; Baubillier, M.; Bergsma, F.; Capone, A.; Flegel, W.; Lanceri, L.; Metcalf, M.; Nieuwenhuis, C.; Pain, R.; Panman, J.; Winter, K.; Abt, I.; Blobel, V.; Buengener, A.; Buesser, F.W.; Gall, P.D.; Hebbeker, T.; Niebergall, F.; Staehelin, P.; Borgia, B.; Diemoz, M.; Dionisi, C.; Dore, U.; Ferroni, F.; Longo, E.; Loverre, P.F.; Luminari, L.; Monacelli, P.; Morganti, S.; De Notaristefani, F.; Santacesaria, R.; Santoni, C.; Rome-1 Univ.

    1989-01-01

    Differential cross sections dσ/dy have been measured in semileptonic neutral- and charged-current reactions induced by neutrinos and antineutrinos. The comparison of the neutral- and the charged-current differential cross sections allows the direct determination of the chiral coupling of the neutral (νanti ν) current to left- and right-handed quarks. The result, with a value of g R 2 =0.042±0.010, is the first direct determination, with a significance of more than four standard deviations, of a non-zero value of g R . (orig.)

  7. Metabolic regulation of manganese superoxide dismutase expression via essential amino acid deprivation.

    Science.gov (United States)

    Aiken, Kimberly J; Bickford, Justin S; Kilberg, Michael S; Nick, Harry S

    2008-04-18

    Organisms respond to available nutrient levels by rapidly adjusting metabolic flux, in part through changes in gene expression. A consequence of adaptations in metabolic rate is the production of mitochondria-derived reactive oxygen species. Therefore, we hypothesized that nutrient sensing could regulate the synthesis of the primary defense of the cell against superoxide radicals, manganese superoxide dismutase. Our data establish a novel nutrient-sensing pathway for manganese superoxide dismutase expression mediated through essential amino acid depletion concurrent with an increase in cellular viability. Most relevantly, our results are divergent from current mechanisms governing amino acid-dependent gene regulation. This pathway requires the presence of glutamine, signaling via the tricarboxylic acid cycle/electron transport chain, an intact mitochondrial membrane potential, and the activity of both the MEK/ERK and mammalian target of rapamycin kinases. Our results provide evidence for convergence of metabolic cues with nutrient control of antioxidant gene regulation, revealing a potential signaling strategy that impacts free radical-mediated mutations with implications in cancer and aging.

  8. Psychopharmacological and Other Treatments in Preschool Children with Attention-Deficit/Hyperactivity Disorder: Current Evidence and Practice

    Science.gov (United States)

    Arnold, L. Eugene; Anthony, Bruno J.

    2008-01-01

    Abstract Objective This article reviews rational approaches to treating attention-deficit/hyperactivity disorder (ADHD) in preschool children, including pharmacological and nonpharmacological treatments. Implications for clinical practice are discussed. Data Sources We searched MEDLINE, PsychINFO, Cumulative Index to Nursing & Allied Health, Educational Resources Information Center, Cochrane Database of Systematic Reviews and Database of Abstracts of Reviews of Effects for relevant literature published in English from 1967 to 2007 on preschool ADHD. We also reviewed the references cited in identified reports. Study Selection Studies were reviewed if the sample included at least some children younger than 6 years of age or attending kindergarten, the study participants had a diagnosis of ADHD or equivalent symptoms, received intervention aimed at ADHD symptoms, and included a relevant outcome measure. Data Extraction Studies were reviewed for type of intervention and outcome relevant to ADHD and were rated for the level of evidence for adequacy of the data to inform clinical practice. Conclusions The current level of evidence for adequacy of empirical data to inform clinical practice for short-term treatment of ADHD in preschool children is Level A for methylphenidate and Level B for parent behavior training, child training, and additive-free elimination diet. PMID:18844482

  9. Brd4 and HEXIM1: Multiple Roles in P-TEFb Regulation and Cancer

    Directory of Open Access Journals (Sweden)

    Ruichuan Chen

    2014-01-01

    Full Text Available Bromodomain-containing protein 4 (Brd4 and hexamethylene bisacetamide (HMBA inducible protein 1 (HEXIM1 are two opposing regulators of the positive transcription elongation factor b (P-TEFb, which is the master modulator of RNA polymerase II during transcriptional elongation. While Brd4 recruits P-TEFb to promoter-proximal chromatins to activate transcription, HEXIM1 sequesters P-TEFb into an inactive complex containing the 7SK small nuclear RNA. Besides regulating P-TEFb’s transcriptional activity, recent evidence demonstrates that both Brd4 and HEXIM1 also play novel roles in cell cycle progression and tumorigenesis. Here we will discuss the current knowledge on Brd4 and HEXIM1 and their implication as novel therapeutic options against cancer.

  10. CodY-Dependent Regulation of Sporulation in Clostridium difficile.

    Science.gov (United States)

    Nawrocki, Kathryn L; Edwards, Adrianne N; Daou, Nadine; Bouillaut, Laurent; McBride, Shonna M

    2016-08-01

    Clostridium difficile must form a spore to survive outside the gastrointestinal tract. The factors that trigger sporulation in C. difficile remain poorly understood. Previous studies have suggested that a link exists between nutritional status and sporulation initiation in C. difficile In this study, we investigated the impact of the global nutritional regulator CodY on sporulation in C. difficile strains from the historical 012 ribotype and the current epidemic 027 ribotype. Sporulation frequencies were increased in both backgrounds, demonstrating that CodY represses sporulation in C. difficile The 027 codY mutant exhibited a greater increase in spore formation than the 012 codY mutant. To determine the role of CodY in the observed sporulation phenotypes, we examined several factors that are known to influence sporulation in C. difficile Using transcriptional reporter fusions and quantitative reverse transcription-PCR (qRT-PCR) analysis, we found that two loci associated with the initiation of sporulation, opp and sinR, are regulated by CodY. The data demonstrate that CodY is a repressor of sporulation in C. difficile and that the impact of CodY on sporulation and expression of specific genes is significantly influenced by the strain background. These results suggest that the variability of CodY-dependent regulation is an important contributor to virulence and sporulation in current epidemic isolates. This report provides further evidence that nutritional state, virulence, and sporulation are linked in C. difficile This study sought to examine the relationship between nutrition and sporulation in C. difficile by examining the global nutritional regulator CodY. CodY is a known virulence and nutritional regulator of C. difficile, but its role in sporulation was unknown. Here, we demonstrate that CodY is a negative regulator of sporulation in two different ribotypes of C. difficile We also demonstrate that CodY regulates known effectors of sporulation, Opp and Sin

  11. Evidence of a local negative role for cocaine and amphetamine regulated transcript (CART, inhibins and low molecular weight insulin like growth factor binding proteins in regulation of granulosa cell estradiol production during follicular waves in cattle

    Directory of Open Access Journals (Sweden)

    Ireland James J

    2006-04-01

    Full Text Available Abstract The ability of ovarian follicles to produce large amounts of estradiol is a hallmark of follicle health status. Estradiol producing capacity is lost in ovarian follicles before morphological signs of atresia. A prominent wave like pattern of growth of antral follicles is characteristic of monotocous species such as cattle, horses and humans. While our knowledge of the role of pituitary gonadotropins in support of antral follicle growth and development is well established, the intrinsic factors that suppress estradiol production and may help promote atresia during follicular waves are not well understood. Numerous growth factors and cytokines have been reported to suppress granulosa cell estradiol production in vitro, but the association of expression of many such factors in vivo with follicle health status and their physiological significance are not clear. The purpose of this review is to discuss the in vivo and in vitro evidence supporting a local physiological role for cocaine and amphetamine regulated transcript, inhibins and low molecular weight insulin like growth factor binding proteins in negative regulation of granulosa cell estradiol production, with emphasis on evidence from the bovine model system.

  12. Regulating danger on the highways: hours of service regulations.

    Science.gov (United States)

    Mansfield, Daniel; Kryger, Meir

    2015-12-01

    Current hours of service regulations governing commercial truck drivers in place in the United States, Canada, Australia, and the European Union are summarized and compared to facilitate the assessment of the effectiveness of such provisions in preventing fatigue and drowsiness among truck drivers. Current hours of service provisions governing commercial truck drivers were derived from governmental sources. The commercial truck driver hours of service provisions in the United States, Canada, and the European Union permit drivers to work 14 hours and those of Australia permit drivers to work 12 hours a day on a regular basis. The regulations do not state what a driver may do with time off. They are consistent with a driver being able to drive after 24 hours without sleep. They do not take into account circadian rhythm by linking driving or rest to time of day. Current hours of service regulations governing commercial truck drivers leave gaps--permitting drivers to work long hours on a regular basis, permitting driving after no sleep for 24 hours, and failing to take into account the importance of circadian rhythm, endangering the public safety and the truck drivers themselves. Copyright © 2015 National Sleep Foundation. Published by Elsevier Inc. All rights reserved.

  13. Transcranial direct current stimulation in obsessive-compulsive disorder: emerging clinical evidence and considerations for optimal montage of electrodes.

    Science.gov (United States)

    Senço, Natasha M; Huang, Yu; D'Urso, Giordano; Parra, Lucas C; Bikson, Marom; Mantovani, Antonio; Shavitt, Roseli G; Hoexter, Marcelo Q; Miguel, Eurípedes C; Brunoni, André R

    2015-07-01

    Neuromodulation techniques for obsessive-compulsive disorder (OCD) treatment have expanded with greater understanding of the brain circuits involved. Transcranial direct current stimulation (tDCS) might be a potential new treatment for OCD, although the optimal montage is unclear. To perform a systematic review on meta-analyses of repetitive transcranianal magnetic stimulation (rTMS) and deep brain stimulation (DBS) trials for OCD, aiming to identify brain stimulation targets for future tDCS trials and to support the empirical evidence with computer head modeling analysis. Systematic reviews of rTMS and DBS trials on OCD in Pubmed/MEDLINE were searched. For the tDCS computational analysis, we employed head models with the goal of optimally targeting current delivery to structures of interest. Only three references matched our eligibility criteria. We simulated four different electrodes montages and analyzed current direction and intensity. Although DBS, rTMS and tDCS are not directly comparable and our theoretical model, based on DBS and rTMS targets, needs empirical validation, we found that the tDCS montage with the cathode over the pre-supplementary motor area and extra-cephalic anode seems to activate most of the areas related to OCD.

  14. Treatment of intracerebral haemorrhage with tranexamic acid – A review of current evidence and ongoing trials

    DEFF Research Database (Denmark)

    Law, Zhe Kang; Meretoja, Atte; Engelter, Stefan T

    2017-01-01

    Purpose Haematoma expansion is a devastating complication of intracerebral haemorrhage (ICH) with no established treatment. Tranexamic acid had been an effective haemostatic agent in reducing post-operative and traumatic bleeding. We review current evidence examining the efficacy of tranexamic acid...... in improving clinical outcome after ICH. Method We searched MEDLINE, EMBASE, CENTRAL and clinical trial registers for studies using search strategies incorporating the terms ‘intracerebral haemorrhage’, ‘tranexamic acid’ and ‘antifibrinolytic’. Authors of ongoing clinical trials were contacted for further...... details. Findings We screened 268 publications and retrieved 17 articles after screening. Unpublished information from three ongoing clinical trials was obtained. We found five completed studies. Of these, two randomised controlled trials (RCTs) comparing intravenous tranexamic acid to placebo (n = 54...

  15. Whither tobacco product regulation?

    Science.gov (United States)

    McNeill, Ann; Hammond, David; Gartner, Coral

    2012-03-01

    Despite decades of industry innovation and regulatory efforts, the harmfulness of conventional cigarettes has not changed. There are several pitfalls in this area, including the long time lag before health impacts of product regulatory changes become apparent, the danger of consumers deriving false reassurance of lesser harm in the interim period, the lack of relevant expertise and the lack of an internationally agreed and evidence-based strategic approach. Articles 9 and 10 of the Framework Convention on Tobacco Control provide the potential for such a global strategy, and knowledge and research has increased significantly over recent years. However, there are huge opportunity costs in implementing product disclosure and regulatory strategies: most national regulators have very limited human and financial resources, which should be focused on other evidence-based tobacco control interventions. We believe therefore that it is now time to abandon the notion of safe or safer cigarettes while moving consumers towards cleaner nicotine products as soon as possible. In parallel to this, we recommend a number of other strategies be implemented including: reducing the appeal of all tobacco products, forbidding new tobacco products or brand variants being marketed without evidence of reduced harm, appeal or addictiveness, and developing a tobacco industry resourced, but industry independent, Framework Convention on Tobacco Control global repository to assist national regulators in understanding and regulating the products on their markets.

  16. Evidence-based guidelines on the therapeutic use of transcranial direct current stimulation (tDCS).

    Science.gov (United States)

    Lefaucheur, Jean-Pascal; Antal, Andrea; Ayache, Samar S; Benninger, David H; Brunelin, Jérôme; Cogiamanian, Filippo; Cotelli, Maria; De Ridder, Dirk; Ferrucci, Roberta; Langguth, Berthold; Marangolo, Paola; Mylius, Veit; Nitsche, Michael A; Padberg, Frank; Palm, Ulrich; Poulet, Emmanuel; Priori, Alberto; Rossi, Simone; Schecklmann, Martin; Vanneste, Sven; Ziemann, Ulf; Garcia-Larrea, Luis; Paulus, Walter

    2017-01-01

    A group of European experts was commissioned by the European Chapter of the International Federation of Clinical Neurophysiology to gather knowledge about the state of the art of the therapeutic use of transcranial direct current stimulation (tDCS) from studies published up until September 2016, regarding pain, Parkinson's disease, other movement disorders, motor stroke, poststroke aphasia, multiple sclerosis, epilepsy, consciousness disorders, Alzheimer's disease, tinnitus, depression, schizophrenia, and craving/addiction. The evidence-based analysis included only studies based on repeated tDCS sessions with sham tDCS control procedure; 25 patients or more having received active treatment was required for Class I, while a lower number of 10-24 patients was accepted for Class II studies. Current evidence does not allow making any recommendation of Level A (definite efficacy) for any indication. Level B recommendation (probable efficacy) is proposed for: (i) anodal tDCS of the left primary motor cortex (M1) (with right orbitofrontal cathode) in fibromyalgia; (ii) anodal tDCS of the left dorsolateral prefrontal cortex (DLPFC) (with right orbitofrontal cathode) in major depressive episode without drug resistance; (iii) anodal tDCS of the right DLPFC (with left DLPFC cathode) in addiction/craving. Level C recommendation (possible efficacy) is proposed for anodal tDCS of the left M1 (or contralateral to pain side, with right orbitofrontal cathode) in chronic lower limb neuropathic pain secondary to spinal cord lesion. Conversely, Level B recommendation (probable inefficacy) is conferred on the absence of clinical effects of: (i) anodal tDCS of the left temporal cortex (with right orbitofrontal cathode) in tinnitus; (ii) anodal tDCS of the left DLPFC (with right orbitofrontal cathode) in drug-resistant major depressive episode. It remains to be clarified whether the probable or possible therapeutic effects of tDCS are clinically meaningful and how to optimally perform t

  17. Bayesian evidences for dark energy models in light of current observational data

    Science.gov (United States)

    Lonappan, Anto. I.; Kumar, Sumit; Ruchika; Dinda, Bikash R.; Sen, Anjan A.

    2018-02-01

    We do a comprehensive study of the Bayesian evidences for a large number of dark energy models using a combination of latest cosmological data from SNIa, CMB, BAO, strong lensing time delay, growth measurements, measurements of Hubble parameter at different redshifts and measurements of angular diameter distance by Megamaser Cosmology Project. We consider a variety of scalar field models with different potentials as well as different parametrizations for the dark energy equation of state. Among 21 models that we consider in our study, we do not find strong evidences in favor of any evolving dark energy model compared to Λ CDM . For the evolving dark energy models, we show that purely nonphantom models have much better evidences compared to those models that allow both phantom and nonphantom behaviors. Canonical scalar field with exponential and tachyon field with square potential have highest evidences among all the models considered in this work. We also show that a combination of low redshift measurements decisively favors an accelerating Λ CDM model compared to a nonaccelerating power law model.

  18. Current Evidence for Developmental, Structural, and Functional Brain Defects following Prenatal Radiation Exposure

    Directory of Open Access Journals (Sweden)

    Tine Verreet

    2016-01-01

    Full Text Available Ionizing radiation is omnipresent. We are continuously exposed to natural (e.g., radon and cosmic and man-made radiation sources, including those from industry but especially from the medical sector. The increasing use of medical radiation modalities, in particular those employing low-dose radiation such as CT scans, raises concerns regarding the effects of cumulative exposure doses and the inappropriate utilization of these imaging techniques. One of the major goals in the radioprotection field is to better understand the potential health risk posed to the unborn child after radiation exposure to the pregnant mother, of which the first convincing evidence came from epidemiological studies on in utero exposed atomic bomb survivors. In the following years, animal models have proven to be an essential tool to further characterize brain developmental defects and consequent functional deficits. However, the identification of a possible dose threshold is far from complete and a sound link between early defects and persistent anomalies has not yet been established. This review provides an overview of the current knowledge on brain developmental and persistent defects resulting from in utero radiation exposure and addresses the many questions that still remain to be answered.

  19. The adventitia: essential regulator of vascular wall structure and function.

    Science.gov (United States)

    Stenmark, Kurt R; Yeager, Michael E; El Kasmi, Karim C; Nozik-Grayck, Eva; Gerasimovskaya, Evgenia V; Li, Min; Riddle, Suzette R; Frid, Maria G

    2013-01-01

    The vascular adventitia acts as a biological processing center for the retrieval, integration, storage, and release of key regulators of vessel wall function. It is the most complex compartment of the vessel wall and is composed of a variety of cells, including fibroblasts, immunomodulatory cells (dendritic cells and macrophages), progenitor cells, vasa vasorum endothelial cells and pericytes, and adrenergic nerves. In response to vascular stress or injury, resident adventitial cells are often the first to be activated and reprogrammed to influence the tone and structure of the vessel wall; to initiate and perpetuate chronic vascular inflammation; and to stimulate expansion of the vasa vasorum, which can act as a conduit for continued inflammatory and progenitor cell delivery to the vessel wall. This review presents the current evidence demonstrating that the adventitia acts as a key regulator of vascular wall function and structure from the outside in.

  20. [Occlusion and posture: is there evidence of correlation?].

    Science.gov (United States)

    Michelotti, A; Manzo, P; Farella, M; Martina, R

    1999-11-01

    The observation that the masticatory system and the postural body regulating system are anatomically and functionally related, has led to postulate several hypotheses of correlation between occlusal and postural disturbances. In the last decade, these arguments have gained a great social impact, also because they have been broadly spread by the mass-media. As a consequence, there has been a growing number of patients seeking concomitant occlusal and postural treatments. The aim of this study was to review critically the current evidence of correlation between the two systems; this in order to address clinical issues for the management of patients. Methodology of the studies reviewed has been evaluated according to the criteria suggested by Storey and Rugh 20 rif. Although there are some evidences of correlation between occlusion and posture, this appears limited to the cranio-cervical tract of the column and tends to disappear when descending in cranio-caudal direction. On the basis of this review of the literature, it's not advisable to treat postural imbalance by means of occlusal treatment or vice versa, particularly if the therapeutic modalities are irreversible.

  1. Teaching with Evidence

    Science.gov (United States)

    Crocco, Margaret; Halvorsen, Anne-Lise; Jacobsen, Rebecca; Segall, Avner

    2017-01-01

    In this age of real and fake news, students need to be able to assess the trustworthiness of evidence. The authors' current research examines students' use of evidence in secondary social studies classrooms as students deliberate contemporary public policy issues. The authors found that students shifted their evaluations of the trustworthiness of…

  2. [International reference prices and cost minimization analysis for the regulation of medicine prices in Colombia].

    Science.gov (United States)

    Vacca, Caludia; Acosta, Angela; Rodriguez, Ivan

    2011-01-01

    To suggest a scheme of decision making on pricing for medicines that are part of Free Regulated Regime, a regulation way of the pharmaceutical pricing policy in Colombia. It includes two regulation tools: international reference prices and a cost minimization analysis methodology. Following the current pricing policy, international reference prices were built with data from five countries for selected medicines, which are under Free Regulated Regime. The cost minimization analysis methodology includes selection of those medicines under Free Regulated Regime with possible comparable medicines, selection of comparable medicines, and treatment costs evaluation. As a result of the estimate of International Reference Prices, four medicines showed in the domestic pharmaceutical market a bigger price than the Reference Price. A scheme of decision-making was design containing two possible regulation tools for medicines that are part of Free Regulated Regime: estimate of international reference prices and cost minimization analysis methodology. This diagram would be useful to assist the pricing regulation of Free Regulated Regime in Colombia. As present results shows, international reference prices make clear when domestic prices are higher than those of reference countries. In the current regulation of pharmaceutical prices in Colombia, the international reference price has been applied for four medicines. Would be suitable to extend this methodology to other medicines of high impact on the pharmaceutical expenditure, in particular those covered by public funding. The availability of primary sources about treatment costs in Colombia needs to be improved as a requirement to develop pharmaco-economic evidence. SISMED is an official database that represents an important primary source of medicines prices in Colombia. Nevertheless, having into account that SISMED represents an important advantage of transparency in medicines prices, it needs to be improved in quality and data

  3. Fusion safety regulations in the United States: Progress and trends

    International Nuclear Information System (INIS)

    DeLooper, J.

    1994-01-01

    This paper explores the issue of regulations as they apply to current and future fusion experimental machines. It addresses fusion regulatory issues, current regulations used for fusion, the Tokamak Fusion Test Reactor experience with regulations, and future regulations to achieve fusion's safety and environmental potential

  4. Assessing tobacco marketing regulation implementation level in Georgia: evidence from Non Communicable Disease Risk Factors STEPS Survey Georgia 2016

    Directory of Open Access Journals (Sweden)

    Lela Sturua

    2018-03-01

    Full Text Available Background Tobacco use continues to be the leading cause of preventable deaths worldwide; the biggest burden of it falls on low- and middle-income countries and this trend is expected to widen further in case of inaction. The overall objective of the study is to describe and analyze the findings of the Noncommunicable Disease Risk Factors STEPS Survey Georgia 2016 related to tobacco marketing regulation. Methods The current study in Georgia was a population-based STEPS survey of randomly selected adults aged 18-69 within each sex and 10-year age-group. A multi-stage cluster sample design was used to produce representative data for that age range in Georgia. A total of 5554 adults participated in the current survey. We assessed level o tobacco marketing regulation implementation in Georgia. Results Study results reported high prevalence of tobacco use in Georgian population (31.1% (95 % CI: 29.0-33.1. Study findings showed that about half of the current smokers are exposed to anti-tobacco information on TV or radio 52.3% (95% CI: 48.9 - 55.7, whereas 35.5% (95% CI: 32.2 - 38.8 reported being exposed to cigarette marketing at points of sales of tobacco products and 4.7% (95% CI: 3.2-6.1 to any cigarette promotions. Health warnings on cigarette packs was reported to be noticed by 88.7% (95% CI: 85.8-91.6 of current smokers; only 33% (95% CI: 25.4 - 40.7 of them reported having thought about quitting because of these warnings. Conclusions The prevalence of smoking in Georgia is high compared to other countries of the European Region and it is very likely that smoking related NCDs burden will increase. Stricter tobacco control policies coupled with anti-tobacco media campaigns can address this problem. Improved health warnings on tobacco packages and total ban of tobacco advertisement, promotion and sponsorship should be implemented in order to overcome prevailed tobacco industry marketing strategies.

  5. Current evidence supporting "letrozole" for ovulation induction

    Directory of Open Access Journals (Sweden)

    Sujata Kar

    2013-01-01

    Full Text Available Aromatase inhibitor "letrozole" was first introduced as a potential ovulation induction (OI drug almost a decade back. Large number of studies has been published using letrozole for OI: In polycystic ovary syndrome (PCOS women, clomiphene citrate (CC resistant women, for intrauterine insemination and also in various protocols of mild stimulation for in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI. Letrozole appears to be a good option, with its oral route of administration, cost, shorter half-life and negligible side effects. However, the verdict on efficacy and safety of letrozole is still uncertain. This review explores the current scientific data supporting letrozole for OI.

  6. Current Evaluation of the Millennium Phytomedicine- Ginseng (I): Etymology, Pharmacognosy, Phytochemistry, Market and Regulations

    Science.gov (United States)

    Jia, Lee; Zhao, Yuqing

    2009-01-01

    The dawning of this millennium broke new ground in life science and technology, presented us genomic and proteomic revolution, nanotechnology innovation, and high performance liquid chromatography coupled with tandem mass spectrometry (LC/MS/MS) used for separating and identifying new chemical entities at pico-, or even femto-concentrations. Applications of these high technologies to the traditional Chinese medicine (TCM) opened a new chapter in the ancient medicine, and prompted us to re-evaluate the thousand-year-old phytomedicine–ginseng from current perspectives. We, therefore, collected the latest information (mostly within 10 years) on ginseng, and condensed the information into two parts of this review serial. The present part covers etymology of ginseng, its pharmacognosy (natural origin, physical appearance, chemical properties, and specie identification), its cultivation and processing-related metabolic changes in active ingredients, standardized analytical methods used for quality control of various ginseng products, modern analytical methods used to identify and classify more than 100 chemical entities (many were recently unfolded) derived from ginseng species and their metabolites. The global markets and production of ginseng and relevant government regulations are herein updated to exchange information and understandings about current people’s uses and cultivation of ginseng. The second part of the review serial will classify all these 100 chemical entities separated from various ginseng species into different groups based on their structural similarities, and summarize bioactivities of these entities. The second part of the review serial will also focus on recent findings of ginseng pharmacology and its clinical trials for various diseases, and brief side effects of ginseng. PMID:19601793

  7. Current evaluation of the millennium phytomedicine--ginseng (I): etymology, pharmacognosy, phytochemistry, market and regulations.

    Science.gov (United States)

    Jia, Lee; Zhao, Yuqing

    2009-01-01

    The dawning of this millennium broke new ground in life science and technology, presented us genomic and proteomic revolution, nanotechnology innovation, and high performance liquid chromatography coupled with tandem mass spectrometry (LC/MS/MS) used for separating and identifying new chemical entities at pico-, or even femto-concentrations. Applications of these high technologies to the traditional Chinese medicine (TCM) opened a new chapter in the ancient medicine, and prompted us to re-evaluate the thousand-year-old phytomedicine- ginseng from current perspectives. We, therefore, collected the latest information (mostly within 10 years) on ginseng, and condensed the information into two parts of this review serial. The present part covers etymology of ginseng, its pharmacognosy (natural origin, physical appearance, chemical properties, and specie identification), its cultivation and processing-related metabolic changes in active ingredients, standardized analytical methods used for quality control of various ginseng products, modern analytical methods used to identify and classify more than 100 chemical entities (many were recently unfolded) derived from ginseng species and their metabolites. The global markets and production of ginseng and relevant government regulations are herein updated to exchange information and understandings about current people's uses and cultivation of ginseng. The second part of the review serial will classify all these 100 chemical entities separated from various ginseng species into different groups based on their structural similarities, and summarize bioactivities of these entities. The second part of the review serial will also focus on recent findings of ginseng pharmacology and its clinical trials for various diseases, and brief side effects of ginseng.

  8. Regulations applicable to plant food supplements and related products in the European Union.

    Science.gov (United States)

    Silano, Vittorio; Coppens, Patrick; Larrañaga-Guetaria, Ainhoa; Minghetti, Paola; Roth-Ehrang, René

    2011-12-01

    This paper deals with the current regulatory and legal settings of traditional plant food supplements and herbal medicinal products in the European Union (EU). Marketing of botanicals in foods and food supplements in the EU is subject to several provisions of food law, which cover aspects of safety, production, labelling and product composition, including the use of additives and maximum levels of contaminants and residues. However, due to limited harmonization at the EU level, specific national regulations adopted at a Member State level also apply and mutual recognition is the mechanism through which such products can be marketed in EU countries other than those of origin. Unlike food supplements, marketing of traditional herbal medicinal products is regulated by an ad hoc Directive (i.e. Directive 2004/24/EC) covering in detail all the relevant aspects of these products, including a facilitated registration procedure at national level. However, by distinguishing traditional herbal medicinal products from plant food supplements and establishing selective marketing modalities for these two product categories, the EU has been confronted with implementation difficulties for traditional herbal medicinal products and a lack of homogeneity in the regulatory approaches adopted in different EU Member States. In fact, currently the nature of the commercial botanical products made available to consumers as traditional medicinal products or food supplements, depends largely on the EU Member State under consideration as a consequence of how competent National Authorities and manufacturing companies interpret and apply current regulations rather than on the intrinsic properties of the botanical products and their constituents. When the EU approach is compared with approaches adopted in some non-European countries to regulate these product categories, major differences become evident.

  9. Hypocretin-1 receptors regulate the reinforcing and reward-enhancing effects of cocaine: Pharmacological and behavioral genetics evidence

    Directory of Open Access Journals (Sweden)

    Jonathan eHollander

    2012-07-01

    Full Text Available Considerable evidence suggests that transmission at hypocretin-1 (orexin-1 receptors (Hcrt-R1 plays an important role in the reinstatement of extinguished cocaine-seeking behaviors in rodents. However, far less is known about the role for hypocretin transmission in regulating ongoing cocaine-taking behavior. Here, we investigated the effects of the selective Hcrt-R1 antagonist SB-334867 on cocaine intake, as measured by intravenous (IV cocaine self-administration in rats. The stimulatory effects of cocaine on brain reward systems contribute to the establishment and maintenance of cocaine-taking behaviors. Therefore, we also assessed the effects of SB-334867 on the reward-enhancing properties of cocaine, as measured by cocaine-induced lowering of intracranial self-stimulation (ICSS thresholds. Finally, to definitively establish a role for Hcrt-R1 in regulating cocaine intake, we assessed IV cocaine self-administration in Hcrt-R1 knockout mice. We found that SB-334867 (1-4 mg/kg dose-dependently decreased cocaine (0.5 mg/kg/infusion self-administration in rats but did not alter responding for food rewards under the same schedule of reinforcement. This suggests that SB-334867 decreased cocaine reinforcement without negatively impacting operant performance. SB-334867 (1-4 mg/kg also dose-dependently attenuated the stimulatory effects of cocaine (10 mg/kg on brain reward systems, as measured by reversal of cocaine-induced lowering of ICSS thresholds in rats. Finally, we found that Hcrt-R1 knockout mice self-administered far less cocaine than wildtype mice across the entire dose-response function. These data demonstrate that Hcrt-R1 play an important role in regulating the reinforcing and reward-enhancing properties of cocaine, and suggest that hypocretin transmission is likely essential for establishing and maintaining the cocaine habit in human addicts.

  10. Cell cycle regulation in human embryonic stem cells: links to adaptation to cell culture.

    Science.gov (United States)

    Barta, Tomas; Dolezalova, Dasa; Holubcova, Zuzana; Hampl, Ales

    2013-03-01

    Cell cycle represents not only a tightly orchestrated mechanism of cell replication and cell division but it also plays an important role in regulation of cell fate decision. Particularly in the context of pluripotent stem cells or multipotent progenitor cells, regulation of cell fate decision is of paramount importance. It has been shown that human embryonic stem cells (hESCs) show unique cell cycle characteristics, such as short doubling time due to abbreviated G1 phase; these properties change with the onset of differentiation. This review summarizes the current understanding of cell cycle regulation in hESCs. We discuss cell cycle properties as well as regulatory machinery governing cell cycle progression of undifferentiated hESCs. Additionally, we provide evidence that long-term culture of hESCs is accompanied by changes in cell cycle properties as well as configuration of several cell cycle regulatory molecules.

  11. Ebola Virus Shedding and Transmission: Review of Current Evidence.

    Science.gov (United States)

    Vetter, Pauline; Fischer, William A; Schibler, Manuel; Jacobs, Michael; Bausch, Daniel G; Kaiser, Laurent

    2016-10-15

     The magnitude of the 2013-2016 Ebola virus disease outbreak in West Africa was unprecedented, with >28 500 reported cases and >11 000 deaths. Understanding the key elements of Ebola virus transmission is necessary to implement adequate infection prevention and control measures to protect healthcare workers and halt transmission in the community.  We performed an extensive PubMed literature review encompassing the period from discovery of Ebola virus, in 1976, until 1 June 2016 to evaluate the evidence on modes of Ebola virus shedding and transmission.  Ebola virus has been isolated by cell culture from blood, saliva, urine, aqueous humor, semen, and breast milk from infected or convalescent patients. Ebola virus RNA has been noted in the following body fluids days or months after onset of illness: saliva (22 days), conjunctiva/tears (28 days), stool (29 days), vaginal fluid (33 days), sweat (44 days), urine (64 days), amniotic fluid (38 days), aqueous humor (101 days), cerebrospinal fluid (9 months), breast milk (16 months [preliminary data]), and semen (18 months). Nevertheless, the only documented cases of secondary transmission from recovered patients have been through sexual transmission. We did not find strong evidence supporting respiratory or fomite-associated transmission. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

  12. Chemonucleolysis and intradiscal electrothermal therapy: What is the current evidence?

    International Nuclear Information System (INIS)

    Relder-Puig, Rosemarie; Gyimesi, M.; Mittermayr, T.; Geiger-Gritsch, S.

    2009-01-01

    We evaluated the efficacy and safety of chemonucleolysis and intradiscal electrothermal therapy (IDET) on the basis of the data presented in recently published papers with respect to pain relief, function, and complication rates. Detailed searches for English and German articles published between 2003 and 2008 were performed in a number of electronic databases. Further publications were identified by manual search. For summarizing the evidence, we considered only systematic reviews and controlled studies. The internal validity of reviews and studies was judged by two authors independently. Data extraction was performed by one author, and the extracted data was checked for completeness and correctness by a second author. The evidence of the efficacy of chemonucleolysis using chymopapain or collagenase is summarized in two recent, high-quality systematic reviews. We found 5 controlled studies evaluating nucleolysis using an oxygen-ozone mixture (O 2 O 3 -nucleolysis). Some of those studies were of limited methodological quality, but all showed the efficacy of O 2 O 3 -nucleolysis in comparison to microdiscectomy or the use of alternative substances. There is hardly any data regarding O 2 O 3 -nucleolysis complications. Regarding IDET, the authors of the 6 identified systematic reviews come to different conclusions about the efficacy of the procedure. The results of the 3 included controlled IDET studies, of which 2 are of high methodological quality, are also conflicting. The complication rates range from 0 to 15%. In summary, the evidence of efficacy is presently more compelling for chemonucleolysis than for IDET. This may also be because indications for chemonucleolysis are more firmly established. However, safety aspects should be better evaluated and presented in the literature. (orig.)

  13. Evidence and evidence gaps in tinnitus therapy

    Science.gov (United States)

    Hesse, Gerhard

    2016-01-01

    A nearly endless number of procedures has been tried and in particular sold for the treatment of tinnitus, unfortunately they have not been evaluated appropriately in an evidence-based way. A causal therapy, omitting the tinnitus still does not exist, actually it cannot exist because of the various mechanisms of its origin. However or perhaps because of that, medical interventions appear and reappear like fashion trends that can never be proven by stable and reliable treatment success. This contribution will discuss and acknowledge all current therapeutic procedures and the existing or non-existing evidence will be assessed. Beside external evidence, the term of evidence also encompasses the internal evidence, i.e. the experience of the treating physician and the patient’s needs shall be included. While there is no evidence for nearly all direct procedures that intend modulating or stimulating either the cochlea or specific cervical regions such as the auditory cortex, there are therapeutic procedures that are acknowledged in clinical practice and have achieved at least a certain degree of evidence and generate measurable effect sizes. Those are in particular habituation therapy and psychotherapeutic measures, especially if they are combined with concrete measures for improved audio perception (hearing aids, CI, hearing therapies). PMID:28025604

  14. Evidence for intrinsic critical current density in high Tc superconductors

    International Nuclear Information System (INIS)

    Freltoft, T.; Minnhagen, P.; Jeldtoft Jensen, H.

    1991-01-01

    We present measurements of the voltage-current characteristics of high quality epitaxial YBaCuO films in zero magnetic field. According to the predictions of a current induced vortex pair breaking picture the voltage should follow the functional form V∝I(I-I c ) a-1 . An analysis designed to test this functional behavior is carried out. Consistency is found. (orig.)

  15. Current evidence demonstrates similar effects of kilohertz-frequency and low-frequency current on quadriceps evoked torque and discomfort in healthy individuals: a systematic review with meta-analysis.

    Science.gov (United States)

    da Silva, Vinicius Zacarias Maldaner; Durigan, João Luiz Quaglioti; Arena, Ross; de Noronha, Marcos; Gurney, Burke; Cipriano, Gerson

    2015-01-01

    Neuromuscular electrical stimulation (NMES) is widely utilized to enhance muscle performance. However, the optimal NMES waveform with respect to treatment effect has not been established. To investigate the effects of kilohertz-frequency alternating current (KFAC) and low-frequency pulsed current (PC) on quadriceps evoked torque and self-reported discomfort. PubMed, The Cochrane Library, EMBASE, MEDLINE, Physiotherapy Evidence Database (PEDro), SinoMed, ISI Web of Knowledge, and CINAHL were searched for randomized controlled trials (RCTs) and quasi-randomized controlled trials (QRCTs). Two reviewers independently selected potential studies according to the inclusion criteria, extracted data, and assessed methodological quality. Studies were eligible if they compared KFAC versus PC interventions. Studies that included outcome measures for percentage of maximal isometric voluntary contraction (%MIVC) torque and self-reported discomfort level were eligible for evaluation. Seven studies involving 127 individuals were included. The methodological quality of eligible trials was moderate, with a mean of 5 on the 10-point PEDro scale. Overall, PC was no better than KFAC in terms of evoked torque and there was no difference in self-reported discomfort level. KFAC and PC have similar effects on quadriceps evoked torque and self-reported discomfort level in healthy individuals. The small number and overall methodological quality of currently available studies included in this meta-analysis indicate that new RCTs are needed to better determine optimal NMES treatment parameters.

  16. Smart-grid Investments, Regulation and Organization

    DEFF Research Database (Denmark)

    Agrell, Per J.; Bogetoft, Peter; Mikkers, Misja

    2013-01-01

    Grid infrastructure managers worldwide are facing demands for reinvestments in new assets with higher on-grid and off-grid functionality in order to meet new environmental targets. The roles of the current actors will change as the vertical interfaces between regulated and unregulated tasks become...... blurred. In this paper, we characterize some of the effects of new asset investments policy on the network tasks, assets and costs and contrast this with the assumptions of the current economic network regulation. To provide structure, we present a model of investment provision under regulation between...

  17. Cell cycle-dependent activity of the volume- and Ca2+-activated anion currents in Ehrlich lettre ascites cells

    DEFF Research Database (Denmark)

    Klausen, Thomas Kjaer; Bergdahl, Andreas; Christophersen, Palle

    2007-01-01

    Recent evidence implicates the volume-regulated anion current (VRAC) and other anion currents in control or modulation of cell cycle progression; however, the precise involvement of anion channels in this process is unclear. Here, Cl- currents in Ehrlich Lettre Ascites (ELA) cells were monitored...... during cell cycle progression, under three conditions: (i) after osmotic swelling (i.e., VRAC), (ii) after an increase in the free intracellular Ca2+ concentration (i.e., the Ca2+-activated Cl- current, CaCC), and (iii) under steady-state isotonic conditions. The maximal swelling-activated VRAC current......+ in the pipette), was unaltered from G0 to G1, but decreased in early S phase. A novel high-affinity anion channel inhibitor, the acidic di-aryl-urea NS3728, which inhibited both VRAC and CaCC, attenuated ELA cell growth, suggesting a possible mechanistic link between cell cycle progression and cell cycle...

  18. Current practice patterns of drain usage amongst UK and Irish surgeons performing bilateral breast reductions: Evidence down the drain.

    Science.gov (United States)

    Sugrue, Conor M; McInerney, Niall; Joyce, Cormac W; Jones, Deidre; Hussey, Alan J; Kelly, Jack L; Kerin, Michael J; Regan, Padraic J

    2015-01-01

    Bilateral breast reduction (BBR) is one of the most frequently performed female breast operations. Despite no evidence supporting efficacy of drain usage in BBRs, postoperative insertion is common. Recent high quality evidence demonstrating potential harm from drain use has subsequently challenged this traditional practice. The aim of this study is to assess the current practice patterns of drains usage by Plastic & Reconstructive and Breast Surgeons in UK and Ireland performing BBRs. An 18 question survey was created evaluating various aspects of BBR practice. UK and Irish Plastic & Reconstructive and Breast Surgeons were invited to participate by an email containing a link to a web-based survey. Statistical analysis was performed with student t-test and chi-square test. Two hundred and eleven responding surgeons were analysed, including 80.1% (171/211) Plastic Surgeons and 18.9% (40/211) Breast Surgeons. Of the responding surgeons, 71.6% (151/211) routinely inserted postoperative drains, for a mean of 1.32 days. Drains were used significantly less by surgeons performing ≥20 BBRs (p = 0.02). With the majority of BBRs performed as an inpatient procedure, there was a trend towards less drain usage in surgeons performing this procedure as an outpatient; however, this was not statistically significant (p = 0.07). Even with the high level of evidence demonstrating the safety of BBR without drains, they are still routinely utilised. In an era of evidence- based medicine, surgeons performing breast reductions must adopt the results from scientific research into their clinical practice.

  19. Distributed Nonlinear Control with Event-Triggered Communication to Achieve Current-Sharing and Voltage Regulation in DC Microgrids

    DEFF Research Database (Denmark)

    Han, Renke; Meng, Lexuan; Guerrero, Josep M.

    2018-01-01

    combining the state-dependent tolerance with a nonnegative offset. In order to design the event-triggered principle and guarantee the global stability, a generalized dc microgrid model is proposed and proven to be positive definite, based on which Lyapunov-based approach is applied. Furthermore, considering......A distributed nonlinear controller is presented to achieve both accurate current-sharing and voltage regulation simultaneously in dc microgrids considering different line impedances’ effects among converters. Then, an improved event-triggered principle for the controller is introduced through...... for precise real-time information transmission, without sacrificing system performance. Experimental results obtained from a dc microgrid setup show the robustness of the new proposal under normal, communication failure, communication delay and plug-and-play operation conditions. Finally, communication...

  20. Effects of different lower-limb sensory stimulation strategies on postural regulation?A systematic review and meta-analysis

    OpenAIRE

    Woo, Mei Teng; Davids, Keith; Liukkonen, Jarmo; Orth, Dominic; Chow, Jia Yi; Jaakkola, Timo

    2017-01-01

    Systematic reviews of balance control have tended to only focus on the effects of single lower-limb stimulation strategies, and a current limitation is the lack of comparison between different relevant stimulation strategies. The aim of this systematic review and meta-analysis was to examine evidence of effects of different lower-limb sensory stimulation strategies on postural regulation and stability. Moderate- to high- pooled effect sizes (Unbiased (Hedges’ g) standardized mean differences ...

  1. Climate change and regulation of hepatotoxin production in Cyanobacteria.

    Science.gov (United States)

    Gehringer, Michelle M; Wannicke, Nicola

    2014-04-01

    Harmful, bloom-forming cyanobacteria (CyanoHABs) are occurring with increasing regularity in freshwater and marine ecosystems. The most commonly occurring cyanobacterial toxins are the hepatotoxic microcystin and nodularin. These cyclic hepta- and pentapeptides are synthesised nonribosomally by the gene products of the toxin gene clusters mcy and nda, respectively. Understanding of the regulation of hepatotoxin production is incomplete, although there is strong evidence supporting the roles of iron, light, higher nitrate availability and inorganic carbon in modulating microcystin levels. The majority of these studies have focused on the unicellular freshwater, microcystin-producing strain of Microcystis aeruginosa, with little attention being paid to terrestrial or marine toxin producers. This review intends to investigate the regulation of microcystin and nodularin production in unicellular and filamentous diazotrophic cyanobacteria against the background of changing climate conditions. Special focus is given to diazotrophic filamentous cyanobacteria, for example Nodularia spumigena, capable of regulating their nitrogen levels by actively fixing dinitrogen. By combining data from significant studies, an overall scheme of the regulation of toxin production is presented, focussing specifically on nodularin production in diazotrophs against the background of increasing carbon dioxide concentrations and temperatures envisaged under current climate change models. Furthermore, the risk of sustaining and spreading CyanoHABs in the future ocean is evaluated. © 2014 Federation of European Microbiological Societies. Published by John Wiley & Sons Ltd. All rights reserved.

  2. Cultural regulation of emotion: individual, relational, and structural sources.

    Science.gov (United States)

    De Leersnyder, Jozefien; Boiger, Michael; Mesquita, Batja

    2013-01-01

    The most prevalent and intense emotional experiences differ across cultures. These differences in emotional experience can be understood as the outcomes of emotion regulation, because emotions that fit the valued relationships within a culture tend to be most common and intense. We review evidence suggesting that emotion regulation underlying cultural differences in emotional experience often takes place at the point of emotion elicitation through the promotion of situations and appraisals that are consistent with culturally valued relationships. These regulatory processes depend on individual tendencies, but are also co-regulated within relationships-close others shape people's environment and help them appraise events in culturally valued ways-and are afforded by structural conditions-people's daily lives "limit" the opportunities for emotion, and afford certain appraisals. The combined evidence suggests that cultural differences in emotion regulation go well beyond the effortful regulation based on display rules.

  3. Programming of the appetite-regulating neural network: a link between maternal overnutrition and the programming of obesity?

    Science.gov (United States)

    Mühlhäusler, B S

    2007-01-01

    The concept of a functional foetal "appetite regulatory neural network" is a new and potentially critical one. There is a growing body of evidence showing that the nutritional environment to which the foetus is exposed during prenatal and perinatal development has long-term consequences for the function of the appetite-regulating neural network and therefore the way in which an individual regulates energy balance throughout later life. This is of particular importance in the context of evidence obtained from a wide range of epidemiological studies, which have shown that individuals exposed to an elevated nutrient supply before birth have an increased risk of becoming obese as children and adults. This review summarises the key pieces of experimental evidence, by our group and others, that have contributed to our current understanding of the programming of appetite, and highlights the important questions that are yet to be answered. It is clear that this area of research has the potential to generate, within the next few years, interventions that could begin to alleviate the adverse long-term consequences of being exposed to an elevated nutrient supply before birth.

  4. Future orientation in the self-system: possible selves, self-regulation, and behavior.

    Science.gov (United States)

    Hoyle, Rick H; Sherrill, Michelle R

    2006-12-01

    Possible selves are representations of the self in the future. Early theoretical accounts of the construct suggested that possible selves directly influence motivation and behavior. We propose an alternative view of possible selves as a component in self-regulatory processes through which motivation and behavior are influenced. We demonstrate the advantages of this conceptualization in two studies that test predictions generated from theoretical models of self-regulation in which the possible selves construct could be embedded. In one study, we show how viewing possible selves as a source of behavioral standards in a control-process model of self-regulation yields support for a set of predictions about the influence of possible selves on current behavior. In the other study, we examine possible selves in the context of an interpersonal model of self-regulation, showing strong evidence of concern for relational value in freely generated hoped-for and feared selves. These findings suggest that the role of possible selves in motivation and behavior can be profitably studied in models that fully specify the process of self-regulation and that those models can be enriched by a consideration of future-oriented self-representations. We offer additional recommendations for strengthening research on possible selves and self-regulation.

  5. DUB3 Deubiquitylating Enzymes Regulate Hippo Pathway Activity by Regulating the Stability of ITCH, LATS and AMOT Proteins

    DEFF Research Database (Denmark)

    Nguyen, Thanh Hung; Kugler, Jan-Michael; Cohen, Stephen Michael

    2017-01-01

    /TAZ, is regulated by ubiquitin mediated protein turnover and several ubiquitin ligase complexes have been implicated in human cancer. However, little is known about the deubiquitylating enzymes that counteract these ubiquitin ligases in regulation of the Hippo pathway. Here we identify the DUB3 family...... deubiquitylating enzymes as regulators of Hippo pathway activity. We provide evidence that DUB3 proteins regulate YAP/TAZ activity by controlling the stability of the E3 ligase ITCH, the LATS kinases and the AMOT family proteins. As a novel Hippo pathway regulator, DUB3 has the potential to act a tumor suppressor...

  6. 29 CFR 458.78 - Rules of evidence.

    Science.gov (United States)

    2010-07-01

    ... 29 Labor 2 2010-07-01 2010-07-01 false Rules of evidence. 458.78 Section 458.78 Labor Regulations Relating to Labor OFFICE OF LABOR-MANAGEMENT STANDARDS, DEPARTMENT OF LABOR STANDARDS OF CONDUCT STANDARDS.... Every party shall have a right to present his case by oral and documentary evidence and to submit...

  7. Benefits of donor human milk for preterm infants: current evidence.

    Science.gov (United States)

    Bertino, Enrico; Giuliani, Francesca; Occhi, Luciana; Coscia, Alessandra; Tonetto, Paola; Marchino, Federica; Fabris, Claudio

    2009-10-01

    It's undoubted that optimum nutrition for term infants is breastfeeding, exclusive for the first six months, then followed by a complementary diet and carried on, if possible, for the first year of life or even more. During the last decades several data confirmed the great advantages of fresh mother's milk use also for feeding very low and extremely low birthweight preterm infants. When mother's milk is unavailable or in short supply, pasteurized donor breast milk is widely used in neonatal intensive care units. Pasteurization partially affects nutritional and immunological properties of breast milk, however it is known that pasteurized milk maintains some biological properties and clinical benefits. The substantial benefits of mother's own milk feeding of preterm infants are supported by strong evidence. However, there is increasing evidence also on specific benefits of donor breast milk. Future research is needed to compare formula vs. nutrient fortified donor breast milk, to compare formula and DM as supplements to maternal milk rather than as sole diet and to compare effects of different methods of heat treatments on donor human milk quality.

  8. Current evidence of percutaneous nucleoplasty for the cervical herniated disk: a systematic review.

    Science.gov (United States)

    Wullems, Jorgen A; Halim, Willy; van der Weegen, Walter

    2014-07-01

    Although percutaneous cervical nucleoplasty (PCN) has been shown to be both safe and effective, its application is still debated. PCN applied in disk herniation has not been systematically reviewed before, resulting in a limited insight into its effectiveness and safety, and the quality of available evidence. Therefore, we systematically reviewed the evidence on the efficacy and safety of PCN in patients with a (contained) herniated disk. MEDLINE, EMBASE, and the Cochrane Library (Central Register of Controlled Trials) were searched for randomized controlled trials (RCTs) and nonrandomized studies using the following keywords: "Nucleoplasty," "Cervical," "Hernia," "Herniation," "Prolapse," "Protrusion," "Intervertebral disk," and "Percutaneous disk decompression." First, all articles were appraised for methodological quality, and then, RCTs were graded for the level of evidence according a best-evidence synthesis, because a meta-analysis was not possible. Finally, the RCTs' applicability and clinical relevance also was assessed. Of 75 identified abstracts, 10 full-text articles were included (3 RCTs and 7 nonrandomized studies). These studies represented a total of 1021 patients: 823 patients (≥ 892 disks) were treated by PCN. All studies showed low methodological quality, except for two. The level of evidence of the RCTs was graded as moderate, with low to moderate applicability and clinical relevance. All included studies showed PCN to be an effective and safe procedure in the treatment of (contained) herniated disks at short-, mid-, and long-term follow-up. However, the level of evidence is moderate and shows only low to moderate applicability and clinical relevance. © 2013 World Institute of Pain.

  9. Datatrust: Or, the political quest for numerical evidence and the epistemologies of Big Data

    DEFF Research Database (Denmark)

    Rieder, Gernot; Simon, Judith

    2016-01-01

    Recently, there has been renewed interest in so-called evidence-based policy making. Enticed by the grand promises of Big Data, public officials seem increasingly inclined to experiment with more data-driven forms of governance. But while the rise of Big Data and related consequences has been...... how the epistemological claims of Big Data science intersect with specific forms of trust, truth, and objectivity. We conclude by arguing that regulators' faith in numbers can be attributed to a distinct political culture, a representative democracy undermined by pervasive public distrust...... a major issue of concern across different disciplines, attempts to develop a better understanding of the phenomenon's historical foundations have been rare. This short commentary addresses this gap by situating the current push for numerical evidence within a broader socio-political context, demonstrating...

  10. Representation and misrepresentation of scientific evidence in contemporary tobacco regulation: a review of tobacco industry submissions to the UK Government consultation on standardised packaging.

    Directory of Open Access Journals (Sweden)

    Selda Ulucanlar

    2014-03-01

    Full Text Available Standardised packaging (SP of tobacco products is an innovative tobacco control measure opposed by transnational tobacco companies (TTCs whose responses to the UK government's public consultation on SP argued that evidence was inadequate to support implementing the measure. The government's initial decision, announced 11 months after the consultation closed, was to wait for 'more evidence', but four months later a second 'independent review' was launched. In view of the centrality of evidence to debates over SP and TTCs' history of denying harms and manufacturing uncertainty about scientific evidence, we analysed their submissions to examine how they used evidence to oppose SP.We purposively selected and analysed two TTC submissions using a verification-oriented cross-documentary method to ascertain how published studies were used and interpretive analysis with a constructivist grounded theory approach to examine the conceptual significance of TTC critiques. The companies' overall argument was that the SP evidence base was seriously flawed and did not warrant the introduction of SP. However, this argument was underpinned by three complementary techniques that misrepresented the evidence base. First, published studies were repeatedly misquoted, distorting the main messages. Second, 'mimicked scientific critique' was used to undermine evidence; this form of critique insisted on methodological perfection, rejected methodological pluralism, adopted a litigation (not scientific model, and was not rigorous. Third, TTCs engaged in 'evidential landscaping', promoting a parallel evidence base to deflect attention from SP and excluding company-held evidence relevant to SP. The study's sample was limited to sub-sections of two out of four submissions, but leaked industry documents suggest at least one other company used a similar approach.The TTCs' claim that SP will not lead to public health benefits is largely without foundation. The tools of Better

  11. Representation and misrepresentation of scientific evidence in contemporary tobacco regulation: a review of tobacco industry submissions to the UK Government consultation on standardised packaging.

    Science.gov (United States)

    Ulucanlar, Selda; Fooks, Gary J; Hatchard, Jenny L; Gilmore, Anna B

    2014-03-01

    Standardised packaging (SP) of tobacco products is an innovative tobacco control measure opposed by transnational tobacco companies (TTCs) whose responses to the UK government's public consultation on SP argued that evidence was inadequate to support implementing the measure. The government's initial decision, announced 11 months after the consultation closed, was to wait for 'more evidence', but four months later a second 'independent review' was launched. In view of the centrality of evidence to debates over SP and TTCs' history of denying harms and manufacturing uncertainty about scientific evidence, we analysed their submissions to examine how they used evidence to oppose SP. We purposively selected and analysed two TTC submissions using a verification-oriented cross-documentary method to ascertain how published studies were used and interpretive analysis with a constructivist grounded theory approach to examine the conceptual significance of TTC critiques. The companies' overall argument was that the SP evidence base was seriously flawed and did not warrant the introduction of SP. However, this argument was underpinned by three complementary techniques that misrepresented the evidence base. First, published studies were repeatedly misquoted, distorting the main messages. Second, 'mimicked scientific critique' was used to undermine evidence; this form of critique insisted on methodological perfection, rejected methodological pluralism, adopted a litigation (not scientific) model, and was not rigorous. Third, TTCs engaged in 'evidential landscaping', promoting a parallel evidence base to deflect attention from SP and excluding company-held evidence relevant to SP. The study's sample was limited to sub-sections of two out of four submissions, but leaked industry documents suggest at least one other company used a similar approach. The TTCs' claim that SP will not lead to public health benefits is largely without foundation. The tools of Better Regulation

  12. Neutral currents

    International Nuclear Information System (INIS)

    Aubert, B.

    1994-11-01

    The evidence for the existence of weak neutral current has been a very controverted topics in the early 1970's, as well as the muon did in the 1930's. The history is very rich considering the evolution of the experimental techniques in high energy particle physics. The history of the discovery and the study of weak neutral current is reviewed. Later the quest of the intermediate vector boson continues with the decision of the community to build a large proton antiproton collider. (K.A.). 14 refs., 1 fig

  13. Respiratory medicines for children: current evidence, unlicensed use and research priorities

    DEFF Research Database (Denmark)

    Smyth, A R; Barbato, A; Beydon, N

    2010-01-01

    deficiency. We hope that this summary of the evidence for respiratory medicines in children, highlighting gaps and research priorities, will be useful for the pharmaceutical industry, the paediatric committee of the European Medicines Agency, academic investigators and the lay public.......This European Respiratory Society task force has reviewed the evidence for paediatric medicines in respiratory disease occurring in adults and children. We describe off-licence use, research priorities and ongoing studies. Off-licence and off-label prescribing in children is widespread...... and potentially harmful. Research areas in asthma include novel formulations and regimens, and individualised prescribing. In cystic fibrosis, future studies will focus on screened infants and robust outcome measures are needed. Other areas include new enzyme and antibiotic formulations and the basic defect...

  14. Environmental Regulation, Foreign Direct Investment and Green Technological Progress—Evidence from Chinese Manufacturing Industries

    Science.gov (United States)

    Hu, Jiangfeng; Wang, Zhao; Lian, Yuehan; Huang, Qinghua

    2018-01-01

    This study examines the spillover effects of foreign direct investment (FDI) on green technology progress rate (as measured by the green total factor productivity). The analysis utilizes two measures of FDI, labor-based FDI and capital-based FDI, and separately investigates four sets of industry classifications—high/low discharge regulation and high/low emission standard regulation. The results indicate that in the low discharge regulation and low emission standard regulation industry, labor-based FDI has a significant negative spillover effect, and capital-based FDI has a significant positive spillover effect. However, in the high-intensity environmental regulation industry, the negative influence of labor-based FDI is completely restrained, and capital-based FDI continues to play a significant positive green technological spillover effects. These findings have clear policy implications: the government should be gradually reducing the labor-based FDI inflow or increasing stringency of environmental regulation in order to reduce or eliminate the negative spillover effect of the labor-based FDI. PMID:29382112

  15. Environmental Regulation, Foreign Direct Investment and Green Technological Progress—Evidence from Chinese Manufacturing Industries

    Directory of Open Access Journals (Sweden)

    Jiangfeng Hu

    2018-01-01

    Full Text Available This study examines the spillover effects of foreign direct investment (FDI on green technology progress rate (as measured by the green total factor productivity. The analysis utilizes two measures of FDI, labor-based FDI and capital-based FDI, and separately investigates four sets of industry classifications—high/low discharge regulation and high/low emission standard regulation. The results indicate that in the low discharge regulation and low emission standard regulation industry, labor-based FDI has a significant negative spillover effect, and capital-based FDI has a significant positive spillover effect. However, in the high-intensity environmental regulation industry, the negative influence of labor-based FDI is completely restrained, and capital-based FDI continues to play a significant positive green technological spillover effects. These findings have clear policy implications: the government should be gradually reducing the labor-based FDI inflow or increasing stringency of environmental regulation in order to reduce or eliminate the negative spillover effect of the labor-based FDI.

  16. Environmental Regulation, Foreign Direct Investment and Green Technological Progress-Evidence from Chinese Manufacturing Industries.

    Science.gov (United States)

    Hu, Jiangfeng; Wang, Zhao; Lian, Yuehan; Huang, Qinghua

    2018-01-29

    This study examines the spillover effects of foreign direct investment (FDI) on green technology progress rate (as measured by the green total factor productivity). The analysis utilizes two measures of FDI, labor-based FDI and capital-based FDI, and separately investigates four sets of industry classifications-high/low discharge regulation and high/low emission standard regulation. The results indicate that in the low discharge regulation and low emission standard regulation industry, labor-based FDI has a significant negative spillover effect, and capital-based FDI has a significant positive spillover effect. However, in the high-intensity environmental regulation industry, the negative influence of labor-based FDI is completely restrained, and capital-based FDI continues to play a significant positive green technological spillover effects. These findings have clear policy implications: the government should be gradually reducing the labor-based FDI inflow or increasing stringency of environmental regulation in order to reduce or eliminate the negative spillover effect of the labor-based FDI.

  17. Increasing the quantity and quality of searching for current best evidence to answer clinical questions: protocol and intervention design of the MacPLUS FS Factorial Randomized Controlled Trials.

    Science.gov (United States)

    Agoritsas, Thomas; Iserman, Emma; Hobson, Nicholas; Cohen, Natasha; Cohen, Adam; Roshanov, Pavel S; Perez, Miguel; Cotoi, Chris; Parrish, Rick; Pullenayegum, Eleanor; Wilczynski, Nancy L; Iorio, Alfonso; Haynes, R Brian

    2014-09-20

    Finding current best evidence for clinical decisions remains challenging. With 3,000 new studies published every day, no single evidence-based resource provides all answers or is sufficiently updated. McMaster Premium LiteratUre Service--Federated Search (MacPLUS FS) addresses this issue by looking in multiple high quality resources simultaneously and displaying results in a one-page pyramid with the most clinically useful at the top. Yet, additional logistical and educational barriers need to be addressed to enhance point-of-care evidence retrieval. This trial seeks to test three innovative interventions, among clinicians registered to MacPLUS FS, to increase the quantity and quality of searching for current best evidence to answer clinical questions. In a user-centered approach, we designed three interventions embedded in MacPLUS FS: (A) a web-based Clinical Question Recorder; (B) an Evidence Retrieval Coach composed of eight short educational videos; (C) an Audit, Feedback and Gamification approach to evidence retrieval, based on the allocation of 'badges' and 'reputation scores.' We will conduct a randomized factorial controlled trial among all the 904 eligible medical doctors currently registered to MacPLUS FS at the hospitals affiliated with McMaster University, Canada. Postgraduate trainees (n=429) and clinical faculty/staff (n=475) will be randomized to each of the three following interventions in a factorial design (AxBxC). Utilization will be continuously recorded through clinicians’ accounts that track logins and usage, down to the level of individual keystrokes. The primary outcome is the rate of searches per month per user during the six months of follow-up. Secondary outcomes, measured through the validated Impact Assessment Method questionnaire, include: utility of answers found (meeting clinicians’ information needs), use (application in practice), and perceived usefulness on patient outcomes. Built on effective models for the point

  18. Advanced electrical current measurements of microdischarges: evidence of sub-critical pulses and ion currents in barrier discharge in air

    Science.gov (United States)

    Synek, Petr; Zemánek, Miroslav; Kudrle, Vít; Hoder, Tomáš

    2018-04-01

    Electrical current measurements in corona or barrier microdischarges are a challenge as they require both high temporal resolution and a large dynamic range of the current probe used. In this article, we apply a simple self-assembled current probe and compare it to commercial ones. An analysis in the time and frequency domain is carried out. Moreover, an improved methodology is presented, enabling both temporal resolution in sub-nanosecond times and current sensitivity in the order of tens of micro-amperes. Combining this methodology with a high-tech oscilloscope and self-developed software, a unique statistical analysis of currents in volume barrier discharge driven in atmospheric-pressure air is made for over 80 consecutive periods of a 15 kHz applied voltage. We reveal the presence of repetitive sub-critical current pulses and conclude that these can be identified with the discharging of surface charge microdomains. Moreover, extremely low, long-lasting microsecond currents were detected which are caused by ion flow, and are analysed in detail. The statistical behaviour presented gives deeper insight into the discharge physics of these usually undetectable current signals.

  19. Evidence-based practice in Occupational Health Psychology. Current status and further developments

    Directory of Open Access Journals (Sweden)

    Maricutoiu, Laurentiu P.

    2012-04-01

    Full Text Available The present paper discusses the status of evidence-based practice in Occupational Health Psychology (OHP. After several searches on large online databases, we have found that OHP papers that discuss interventions are less than 10% of the overall literature. Furthermore, quantitative reviews research that reports interventions on major OHP topics are generally absent. In the last part of the paper, we formulate some reccomendations for increasing the number of papers relevant for evidence-based practice in OHP.

  20. Quantitative analysis of the Ca2+ -dependent regulation of delayed rectifier K+ current IKs in rabbit ventricular myocytes.

    Science.gov (United States)

    Bartos, Daniel C; Morotti, Stefano; Ginsburg, Kenneth S; Grandi, Eleonora; Bers, Donald M

    2017-04-01

    [Ca 2+ ] i enhanced rabbit ventricular slowly activating delayed rectifier K + current (I Ks ) by negatively shifting the voltage dependence of activation and slowing deactivation, similar to perfusion of isoproterenol. Rabbit ventricular rapidly activating delayed rectifier K + current (I Kr ) amplitude and voltage dependence were unaffected by high [Ca 2+ ] i . When measuring or simulating I Ks during an action potential, I Ks was not different during a physiological Ca 2+ transient or when [Ca 2+ ] i was buffered to 500 nm. The slowly activating delayed rectifier K + current (I Ks ) contributes to repolarization of the cardiac action potential (AP). Intracellular Ca 2+ ([Ca 2+ ] i ) and β-adrenergic receptor (β-AR) stimulation modulate I Ks amplitude and kinetics, but details of these important I Ks regulators and their interaction are limited. We assessed the [Ca 2+ ] i dependence of I Ks in steady-state conditions and with dynamically changing membrane potential and [Ca 2+ ] i during an AP. I Ks was recorded from freshly isolated rabbit ventricular myocytes using whole-cell patch clamp. With intracellular pipette solutions that controlled free [Ca 2+ ] i , we found that raising [Ca 2+ ] i from 100 to 600 nm produced similar increases in I Ks as did β-AR activation, and the effects appeared additive. Both β-AR activation and high [Ca 2+ ] i increased maximally activated tail I Ks , negatively shifted the voltage dependence of activation, and slowed deactivation kinetics. These data informed changes in our well-established mathematical model of the rabbit myocyte. In both AP-clamp experiments and simulations, I Ks recorded during a normal physiological Ca 2+ transient was similar to I Ks measured with [Ca 2+ ] i clamped at 500-600 nm. Thus, our study provides novel quantitative data as to how physiological [Ca 2+ ] i regulates I Ks amplitude and kinetics during the normal rabbit AP. Our results suggest that micromolar [Ca 2+ ] i , in the submembrane or

  1. Mechanisms regulating brain docosahexaenoic acid uptake: what is the recent evidence?

    Science.gov (United States)

    Chouinard-Watkins, Raphaël; Lacombe, R J Scott; Bazinet, Richard P

    2018-03-01

    To summarize recent advances pertaining to the mechanisms regulating brain docosahexaenoic acid (DHA) uptake. DHA is an omega-3 polyunsaturated fatty acid highly enriched in neuronal membranes and it is implicated in several important neurological processes. However, DHA synthesis is extremely limited within the brain. There are two main plasma pools that supply the brain with DHA: the nonesterified pool and the lysophosphatidylcholine (lysoPtdCho) pool. Quantitatively, plasma nonesterified-DHA (NE-DHA) is the main contributor to brain DHA. Fatty acid transport protein 1 (FATP1) in addition to fatty acid-binding protein 5 (FABP5) are key players that regulate brain uptake of NE-DHA. However, the plasma half-life of lysoPtdCho-DHA and its brain partition coefficient are higher than those of NE-DHA after intravenous administration. The mechanisms regulating brain DHA uptake are more complicated than once believed, but recent advances provide some clarity notably by suggesting that FATP1 and FABP5 are key contributors to cellular uptake of DHA at the blood-brain barrier. Elucidating how DHA enters the brain is important as we might be able to identify methods to better deliver DHA to the brain as a potential therapeutic.

  2. 29 CFR 102.39 - Rules of evidence controlling so far as practicable.

    Science.gov (United States)

    2010-07-01

    ... 29 Labor 2 2010-07-01 2010-07-01 false Rules of evidence controlling so far as practicable. 102.39 Section 102.39 Labor Regulations Relating to Labor NATIONAL LABOR RELATIONS BOARD RULES AND REGULATIONS... Hearings § 102.39 Rules of evidence controlling so far as practicable. Any such proceeding shall, so far as...

  3. Large dunes on the outer shelf off the Zambezi Delta, Mozambique: evidence for the existence of a Mozambique Current

    Science.gov (United States)

    Flemming, Burghard W.; Kudrass, Hermann-Rudolf

    2018-02-01

    studies comparing the application of slippage and non-slippage approaches—they suggest that, when applying partial slippage, a western boundary current can exist simultaneously with the southward migrating eddies. Considering the evidence presented in this paper, it is concluded that a quasi-persistent, though seasonally variable Mozambique Current does exist.

  4. Regulator preferences and utility prices: evidence from natural gas distribution utilities

    International Nuclear Information System (INIS)

    Klein, C.C.; Sweeney, G.H.

    1999-01-01

    We investigate the determinants of regulators' relative weighting of the social welfare of customer groups and utilities using panel data on natural gas distribution utilities in the US state of Tennessee. In contrast to previous empirical work on cross-sections of electric utilities, our results are statistically robust and consistent with the interest group theory of regulation. Intervention in rate cases, settlement vs. litigation of cases, and prices of alternative energy sources, as well as the size characteristics of customer groups and the firm, are significant determinants of the elasticity-weighted price-cost margin (Ramsey number) for each group. (Copyright (c) 1999 Elsevier Science B.V., Amsterdam. All rights reserved.)

  5. Banking Regulation and Determinants of Banks’ Profits: Empirical Evidence from Turkey

    Directory of Open Access Journals (Sweden)

    Mahmut ERDOGAN

    2016-05-01

    Full Text Available The crises that are frequently observed in the banking industries of emerging markets which affect banks’ profits necessitate regulations and supervision of these markets. This paper investigates the determinants of Turkish banks’ profits and the effects of the regulations implemented in this industry on profits. In this research, 468 firm year observations for 36 Turkish banks for the period 1995-2007 were used and analyzed with Prais-Winsten regression method. The empirical findings of the study show positive and statistically significant relations between capital, size, offbalance sheet transactions, liquidity and loans and performance and negative and statistically significant relations between quality of loans, concentration and performance.

  6. The regulation of commercial surrogacy: The wrong answers to the wrong questions.

    Science.gov (United States)

    Stuhmcke, Anita

    2015-12-01

    The criminal ban on commercial surrogacy across Australian jurisdictions is the result of the conflation and confusion of two flawed assumptions. The first being that the criminalisation of commercial surrogacy will discourage a surrogacy "industry" and the second that commercial surrogacy and altruistic surrogacy are two distinguishable "types" of surrogacy arrangements. This article argues that the criminalisation of commercial surrogacy has resulted in unforeseen and undesirable consequences, removing opportunity for evidence-based law reform. Moreover, analysis of both the approach of Australian courts and the operation of surrogacy legislation suggests that the binary regulatory approach which distinguishes "commercial" from "altruistic" surrogacy is a legal fiction. In summary, this article argues that the current Australian regulation of surrogacy is both blunt and ineffectual, surrogacy is a nuanced and complex practice which requires a regulatory response which is principled, holistic and evidence based.

  7. Volume Regulated Channels

    DEFF Research Database (Denmark)

    Klausen, Thomas Kjær

    of volume perturbations evolution have developed system of channels and transporters to tightly control volume homeostasis. In the past decades evidence has been mounting, that the importance of these volume regulated channels and transporters are not restricted to the defense of cellular volume...... but are also essential for a number of physiological processes such as proliferation, controlled cell death, migration and endocrinology. The thesis have been focusing on two Channels, namely the swelling activated Cl- channel (ICl, swell) and the transient receptor potential Vanilloid (TRPV4) channel. I: Cl......- serves a multitude of functions in the mammalian cell, regulating the membrane potential (Em), cell volume, protein activity and the driving force for facilitated transporters giving Cl- and Cl- channels a major potential of regulating cellular function. These functions include control of the cell cycle...

  8. Self-Tuning Speed Regulator for CVC Induction Motor Drive

    DEFF Research Database (Denmark)

    Bidstrup, N.; Rasmussen, Henrik; Knudsen, Torben

    1994-01-01

    A self-tuning speed regulator for a current vector controlled induction motor drive has been designed.......A self-tuning speed regulator for a current vector controlled induction motor drive has been designed....

  9. Does oxygen limit thermal tolerance in arthropods? A critical review of current evidence.

    Science.gov (United States)

    Verberk, Wilco C E P; Overgaard, Johannes; Ern, Rasmus; Bayley, Mark; Wang, Tobias; Boardman, Leigh; Terblanche, John S

    2016-02-01

    Over the last decade, numerous studies have investigated the role of oxygen in setting thermal tolerance in aquatic animals, and there has been particular focus on arthropods. Arthropods comprise one of the most species-rich taxonomic groups on Earth, and display great diversity in the modes of ventilation, circulation, blood oxygen transport, with representatives living both in water (mainly crustaceans) and on land (mainly insects). The oxygen and capacity limitation of thermal tolerance (OCLTT) hypothesis proposes that the temperature dependent performance curve of animals is shaped by the capacity for oxygen delivery in relation to oxygen demand. If correct, oxygen limitation could provide a mechanistic framework to understand and predict both current and future impacts of rapidly changing climate. In arthropods, most studies testing the OCLTT hypothesis have considered tolerance to thermal extremes. These studies likely operate from the philosophical viewpoint that if the model can predict these critical thermal limits, then it is more likely to also explain loss of performance at less extreme, non-lethal temperatures, for which much less data is available. Nevertheless, the extent to which lethal temperatures are influenced by limitations in oxygen supply remains unresolved. Here we critically evaluate the support and universal applicability for oxygen limitation being involved in lethal temperatures in crustaceans and insects. The relatively few studies investigating the OCLTT hypothesis at low temperature do not support a universal role for oxygen in setting the lower thermal limits in arthropods. With respect to upper thermal limits, the evidence supporting OCLTT is stronger for species relying on underwater gas exchange, while the support for OCLTT in air-breathers is weak. Overall, strongest support was found for increased anaerobic metabolism close to thermal maxima. In contrast, there was only mixed support for the prediction that aerobic scope

  10. Metabolic Regulation of Manganese Superoxide Dismutase Expression via Essential Amino Acid Deprivation*

    Science.gov (United States)

    Aiken, Kimberly J.; Bickford, Justin S.; Kilberg, Michael S.; Nick, Harry S.

    2008-01-01

    Organisms respond to available nutrient levels by rapidly adjusting metabolic flux, in part through changes in gene expression. A consequence of adaptations in metabolic rate is the production of mitochondria-derived reactive oxygen species. Therefore, we hypothesized that nutrient sensing could regulate the synthesis of the primary defense of the cell against superoxide radicals, manganese superoxide dismutase. Our data establish a novel nutrient-sensing pathway for manganese superoxide dismutase expression mediated through essential amino acid depletion concurrent with an increase in cellular viability. Most relevantly, our results are divergent from current mechanisms governing amino acid-dependent gene regulation. This pathway requires the presence of glutamine, signaling via the tricarboxylic acid cycle/electron transport chain, an intact mitochondrial membrane potential, and the activity of both the MEK/ERK and mammalian target of rapamycin kinases. Our results provide evidence for convergence of metabolic cues with nutrient control of antioxidant gene regulation, revealing a potential signaling strategy that impacts free radical-mediated mutations with implications in cancer and aging. PMID:18187411

  11. Emotion regulation and emotion coherence: evidence for strategy-specific effects.

    Science.gov (United States)

    Dan-Glauser, Elise S; Gross, James J

    2013-10-01

    One of the central tenets of emotion theory is that emotions involve coordinated changes across experiential, behavioral, and physiological response domains. Surprisingly little is known, however, about how the strength of this emotion coherence is altered when people try to regulate their emotions. To address this issue, we recorded experiential, behavioral, and physiological responses while participants watched negative and positive pictures. Cross-correlations were used to quantify emotion coherence. Study 1 tested how two types of suppression (expressive and physiological) influence coherence. Results showed that both strategies decreased the response coherence measured in negative and positive contexts. Study 2 tested how multichannel suppression (simultaneously targeting expressive and physiological responses) and acceptance influence emotion coherence. Results again showed that suppression decreased coherence. By contrast, acceptance was not significantly different from the unregulated condition. These findings help to clarify the nature of emotion response coherence by showing how different forms of emotion regulation may differentially affect it.

  12. Emotion Regulation and Emotion Coherence: Evidence for Strategy-Specific Effects

    Science.gov (United States)

    Dan-Glauser, Elise S.; Gross, James J.

    2014-01-01

    One of the central tenets of emotion theory is that emotions involve coordinated changes across experiential, behavioral, and physiological response domains. Surprisingly little is known, however, on how the strength of this emotion coherence is altered when people try to regulate their emotions. To address this issue, we recorded experiential, behavioral, and physiological responses while participants watched negative and positive pictures. Cross-correlations were used to quantify emotion coherence. Study 1 tested how two types of suppression (expressive and physiological) influence coherence. Results showed that both strategies decreased the response coherence measured in negative and positive contexts. Study 2 tested how multi-channel suppression (simultaneously targeting expressive and physiological responses) and acceptance influence emotion coherence. Results again showed that suppression decreased coherence. By contrast, acceptance was not significantly different from the unregulated condition. These findings help to clarify the nature of emotion response coherence by showing how different forms of emotion regulation may differentially affect it. PMID:23731438

  13. Cultural regulation of emotion: Individual, relational, and structural sources

    Directory of Open Access Journals (Sweden)

    Jozefien eDe Leersnyder

    2013-02-01

    Full Text Available The most prevalent and intense emotional experiences differ across cultures. These differences in emotional experience can be understood as the outcomes of emotion regulation, because emotions that fit the valued relationships within a culture tend to be most common and intense. We review evidence suggesting that emotion regulation underlying cultural differences in emotional experience often takes place at the point of emotion elicitation through the promotion of situations and appraisals that are consistent with culturally valued relationships. These regulatory processes depend on individual tendencies, but are also co-regulated within relationships—close others shape people’s environment and help them appraise events in culturally valued ways—and are afforded by structural conditions—people’s daily lives limit the opportunities for emotion, and afford certain appraisals. The combined evidence suggests that cultural differences in emotion regulation go well beyond the effortful regulation based on display rules.

  14. Epigenetic regulation of female puberty.

    Science.gov (United States)

    Lomniczi, Alejandro; Wright, Hollis; Ojeda, Sergio R

    2015-01-01

    Substantial progress has been made in recent years toward deciphering the molecular and genetic underpinnings of the pubertal process. The availability of powerful new methods to interrogate the human genome has led to the identification of genes that are essential for puberty to occur. Evidence has also emerged suggesting that the initiation of puberty requires the coordinated activity of gene sets organized into functional networks. At a cellular level, it is currently thought that loss of transsynaptic inhibition, accompanied by an increase in excitatory inputs, results in the pubertal activation of GnRH release. This concept notwithstanding, a mechanism of epigenetic repression targeting genes required for the pubertal activation of GnRH neurons was recently identified as a core component of the molecular machinery underlying the central restraint of puberty. In this chapter we will discuss the potential contribution of various mechanisms of epigenetic regulation to the hypothalamic control of female puberty. Copyright © 2014 Elsevier Inc. All rights reserved.

  15. Energy Density, Energy Intake, and Body Weight Regulation in Adults12345

    Science.gov (United States)

    Karl, J. Philip; Roberts, Susan B.

    2014-01-01

    The role of dietary energy density (ED) in the regulation of energy intake (EI) is controversial. Methodologically, there is also debate about whether beverages should be included in dietary ED calculations. To address these issues, studies examining the effects of ED on EI or body weight in nonelderly adults were reviewed. Different approaches to calculating dietary ED do not appear to alter the direction of reported relations between ED and body weight. Evidence that lowering dietary ED reduces EI in short-term studies is convincing, but there are currently insufficient data to determine long-term effectiveness for weight loss. The review also identified key barriers to progress in understanding the role of ED in energy regulation, in particular the absence of a standard definition of ED, and the lack of data from multiple long-term clinical trials examining the effectiveness of low-ED diet recommendations for preventing both primary weight gain and weight regain in nonobese individuals. Long-term clinical trials designed to examine the impact of dietary ED on energy regulation, and including multiple ED calculation methods within the same study, are still needed to determine the importance of ED in the regulation of EI and body weight. PMID:25398750

  16. Lvr, a Signaling System That Controls Global Gene Regulation and Virulence in Pathogenic Leptospira

    Science.gov (United States)

    Adhikarla, Haritha; Wunder, Elsio A.; Mechaly, Ariel E.; Mehta, Sameet; Wang, Zheng; Santos, Luciane; Bisht, Vimla; Diggle, Peter; Murray, Gerald; Adler, Ben; Lopez, Francesc; Townsend, Jeffrey P.; Groisman, Eduardo; Picardeau, Mathieu; Buschiazzo, Alejandro; Ko, Albert I.

    2018-01-01

    Leptospirosis is an emerging zoonotic disease with more than 1 million cases annually. Currently there is lack of evidence for signaling pathways involved during the infection process of Leptospira. In our comprehensive genomic analysis of 20 Leptospira spp. we identified seven pathogen-specific Two-Component System (TCS) proteins. Disruption of two these TCS genes in pathogenic Leptospira strain resulted in loss-of-virulence in a hamster model of leptospirosis. Corresponding genes lvrA and lvrB (leptospira virulence regulator) are juxtaposed in an operon and are predicted to encode a hybrid histidine kinase and a hybrid response regulator, respectively. Transcriptome analysis of lvr mutant strains with disruption of one (lvrB) or both genes (lvrA/B) revealed global transcriptional regulation of 850 differentially expressed genes. Phosphotransfer assays demonstrated that LvrA phosphorylates LvrB and predicted further signaling downstream to one or more DNA-binding response regulators, suggesting that it is a branched pathway. Phylogenetic analyses indicated that lvrA and lvrB evolved independently within different ecological lineages in Leptospira via gene duplication. This study uncovers a novel-signaling pathway that regulates virulence in pathogenic Leptospira (Lvr), providing a framework to understand the molecular bases of regulation in this life-threatening bacterium. PMID:29600195

  17. Current advances and strategies towards fully automated sample preparation for regulated LC-MS/MS bioanalysis.

    Science.gov (United States)

    Zheng, Naiyu; Jiang, Hao; Zeng, Jianing

    2014-09-01

    Robotic liquid handlers (RLHs) have been widely used in automated sample preparation for liquid chromatography-tandem mass spectrometry (LC-MS/MS) bioanalysis. Automated sample preparation for regulated bioanalysis offers significantly higher assay efficiency, better data quality and potential bioanalytical cost-savings. For RLHs that are used for regulated bioanalysis, there are additional requirements, including 21 CFR Part 11 compliance, software validation, system qualification, calibration verification and proper maintenance. This article reviews recent advances in automated sample preparation for regulated bioanalysis in the last 5 years. Specifically, it covers the following aspects: regulated bioanalysis requirements, recent advances in automation hardware and software development, sample extraction workflow simplification, strategies towards fully automated sample extraction, and best practices in automated sample preparation for regulated bioanalysis.

  18. Towards Evidence-Based Initial Teacher Education in Singapore: A Review of Current Literature

    Science.gov (United States)

    Low, Ee-Ling; Hui, Chenri; Taylor, Peter G.; Ng, Pak Tee

    2012-01-01

    Initial teacher education (ITE) in Singapore is shifting towards evidence-based practice. Despite a clear policy orientation, ITE in Singapore has not yet produced the evidence base that it is anticipating. This paper presents an analytical review of previous research into ITE in Singapore and makes comparisons to the larger international context.…

  19. Models accounting for intention-behavior discordance in the physical activity domain: a user's guide, content overview, and review of current evidence.

    Science.gov (United States)

    Rhodes, Ryan E; Yao, Christopher A

    2015-02-07

    There is a growing concern among researchers with the limited effectiveness and yet subsequent stagnation of theories applied to physical activity (PA). One of the most highlighted areas of concern is the established gap between intention and PA, yet the considerable use of models that assume intention is the proximal antecedent of PA. The objective of this review was to: 1) provide a guide and thematic analysis of the available models that include constructs that address intention-behavior discordance and 2) highlight the evidence for these structures in the PA domain. A literature search was conducted among 13 major databases to locate relevant models and PA studies published before August 2014. Sixteen models were identified and nine overall themes for post-intentional constructs were created. Of the 16 models, eight were applied to 36 PA studies. Early evidence supported maintenance self-efficacy, behavioral regulation strategies, affective judgments, perceived control/opportunity, habit, and extraversion as reliable predictors of post-intention PA. Several intention-behavior discordance models exist within the literature, but are not used frequently. Further efforts are needed to test these models, preferably with experimental designs.

  20. The Heart of the Matter of Opinion and Evidence: The Value of Evidence-Based Medicine

    OpenAIRE

    Masvidal, Daniel; Lavie, Carl J.

    2012-01-01

    Evidence-based medicine is an important aspect of continuing medical education. This article reviews previous and current examples of conflicting topics that evidence-based medicine has clarified to allow us to provide the best possible patient care.

  1. Nondissipative optimum charge regulator

    Science.gov (United States)

    Rosen, R.; Vitebsky, J. N.

    1970-01-01

    Optimum charge regulator provides constant level charge/discharge control of storage batteries. Basic power transfer and control is performed by solar panel coupled to battery through power switching circuit. Optimum controller senses battery current and modifies duty cycle of switching circuit to maximize current available to battery.

  2. Regulation of gonadotropin-releasing hormone neurons by glucose

    Science.gov (United States)

    Roland, Alison V.; Moenter, Suzanne M.

    2011-01-01

    Reproduction is influenced by energy balance, but the physiological pathways mediating their relationship have not been fully elucidated. As the central regulators of fertility, gonadotropin-releasing hormone (GnRH) neurons integrate numerous physiological signals, including metabolic cues. Circulating glucose levels regulate GnRH release and may in part mediate the effects of negative energy balance on fertility. Existing evidence suggests that neural pathways originating in the hindbrain, as well as in the hypothalamic feeding nuclei, transmit information concerning glucose availability to GnRH neurons. Here we review recent evidence suggesting that GnRH neurons may directly sense changes in glucose availability by a mechanism involving adenosine monophosphate-activated protein kinase (AMPK). These findings expand our understanding of how metabolic signaling in the brain regulates reproduction. PMID:21855365

  3. Corporate Social Responsibility or Government Regulation? Evidence on Oil Spill Prevention

    Directory of Open Access Journals (Sweden)

    Jedrzej G. Frynas

    2012-12-01

    Full Text Available Major oil spills normally occur from oil pipelines and oil tankers that are under operational control of companies, namely, oil companies and tanker owners. There are two generic responses for changing the behavior of companies with regard to oil spill prevention: mandatory government regulation or voluntary initiatives often pursued under the banner of Corporate Social Responsibility (CSR. Here we investigate to what extent voluntary CSR initiatives can be effective in oil spill prevention. A global perspective on voluntary mechanisms is taken by looking at the progress of 20 oil and gas firms from around the world toward oil spill prevention, using the companies' 2010 sustainability reports for self-reported oil spill information. The analysis includes ten oil companies from OECD countries (including Exxon and Shell, among others and 10 oil companies from non-OECD countries (including Brazil's Petrobras and Indian Oil, among others. The study finds that oil spill prevention has generally improved over recent decades. Government regulation played a significant part in these improvements whereas it is less clear to what extent CSR played a significant part in these improvements. Some of CSR's key limitations are highlighted. It is not suggested that CSR should be abandoned; however, new hybrid forms of regulation that combine voluntary and mandatory elements are advocated.

  4. Expert opinion vs. empirical evidence: the precautionary principle applied to GM crops.

    Science.gov (United States)

    Herman, Rod A; Raybould, Alan

    2014-01-01

    Expert opinion is often sought by government regulatory agencies when there is insufficient empirical evidence to judge the safety implications of a course of action. However, it can be reckless to continue following expert opinion when a preponderance of evidence is amassed that conflicts with this opinion. Factual evidence should always trump opinion in prioritizing the information that is used to guide regulatory policy. Evidence-based medicine has seen a dramatic upturn in recent years spurred by examples where evidence indicated that certain treatments recommended by expert opinions increased death rates. We suggest that scientific evidence should also take priority over expert opinion in the regulation of genetically modified crops (GM). Examples of regulatory data requirements that are not justified based on the mass of evidence are described, and it is suggested that expertise in risk assessment should guide evidence-based regulation of GM crops.

  5. Enforcement actions and their effectiveness in securities regulation: Empirical evidence from management earnings forecasts

    Directory of Open Access Journals (Sweden)

    Yunling Song

    2012-03-01

    Full Text Available Due to resource constraints, securities regulators cannot find or punish all firms that have conducted irregular or even illegal activities (hereafter referred to as fraud. Those who study securities regulations can only find the instances of fraud that have been punished, not those that have not been punished, and it is these unknown cases that would make the best control sample for studies of enforcement action criteria. China’s mandatory management earnings forecasts solve this sampling problem. In the A-share market, firms that have not forecasted as mandated are likely in a position to be punished by securities regulators or are attempting to escape punishment, and their identification allows researchers to build suitable study and control samples when examining securities regulations. Our results indicate that enforcement actions taken by securities regulators are selective. The probability that a firm will be punished for irregular management forecasting is significantly related to proxies for survival rates. Specifically, fraudulent firms with lower return on assets (ROAs or higher cash flow risk are more likely to be punished. Further analysis shows that selective enforcement of regulations has had little positive effect on the quality of listed firms’ management forecasts.

  6. Current Evidence for Clinical Efficacy of Platelet Rich Plasma in Aesthetic Surgery: A Systematic Review.

    Science.gov (United States)

    Frautschi, Russell S; Hashem, Ahmed M; Halasa, Brianna; Cakmakoglu, Cagri; Zins, James E

    2017-03-01

    Platelet rich plasma (PRP) has attracted attention in a number of surgical fields due to a wide variety of potential clinical benefits. Yet PRP has not gained wide popularity in aesthetic surgery as a result of uncertainty surrounding objective clinical evidence. We aim to describe the current applications, define preparation and activation, explore effectiveness, and propose a classification system to facilitate comparisons across studies. A comprehensive review of the literature regarding the use of platelet rich plasma in aesthetic surgery was performed. Data gathered included: PRP application, study type, subject number, centrifugation, anticoagulation, activation, PRP composition, and outcomes. Thirty-eight reports were identified. Applications included injection into aging skin (29%), scalp alopecia (26%), lipofilling (21%), fractional laser (13%), and facial surgery (11%). The majority of studies (53%) were case series without controls. Leucocytes were sparsely defined (32%). The concentration of injected and/or baseline platelets was rarely clarified (18%). The mechanism of activation was described in 27 studies (71%), while anticoagulation was uncommonly elucidated (47%). While most studies (95%) claim effectiveness, objective measures were only utilized in 17 studies (47%). Current studies produce context-dependent results with a lack of consistent reporting of PRP preparation, composition, and activation in aesthetic applications, making meaningful meta-analysis unrealistic. Thus the method of PRP preparation warrants increased attention. We recommend a set of descriptors, FIT PAAW (described below), to produce scientifically grounded conclusions, facilitating a clearer understanding of the situations in which PRP is effective. 4 © 2016 The American Society for Aesthetic Plastic Surgery, Inc. Reprints and permission: journals.permissions@oup.com

  7. Prehospital Care for the Adult and Pediatric Seizure Patient: Current Evidence Based Recommendations

    Directory of Open Access Journals (Sweden)

    Eric C. Silverman

    2017-04-01

    Full Text Available Introduction: We sought to develop evidence-based recommendations for the prehospital evaluation and treatment of adult and pediatric patients with a seizure and to compare these recommendations against the current protocol used by the 33 emergency medical services (EMS agencies in California. Methods: We performed a review of the evidence in the prehospital treatment of patients with a seizure, and then compared the seizure protocols of each of the 33 EMS agencies for consistency with these recommendations. We analyzed the type and route of medication administered, number of additional rescue doses permitted, and requirements for glucose testing prior to medication. The treatment for eclampsia and seizures in pediatric patients were analyzed separately. Results: Protocols across EMS Agencies in California varied widely. We identified multiple drugs, dosages, routes of administration, re-dosing instructions, and requirement for blood glucose testing prior to medication delivery. Blood glucose testing prior to benzodiazepine administration is required by 61% (20/33 of agencies for adult patients and 76% (25/33 for pediatric patients. All agencies have protocols for giving intramuscular benzodiazepines and 76% (25/33 have protocols for intranasal benzodiazepines. Intramuscular midazolam dosages ranged from 2 to 10 mg per single adult dose, 2 to 8 mg per single pediatric dose, and 0.1 to 0.2 mg/kg as a weight-based dose. Intranasal midazolam dosages ranged from 2 to 10 mg per single adult or pediatric dose, and 0.1 to 0.2 mg/kg as a weight-based dose. Intravenous/intrasosseous midazolam dosages ranged from 1 to 6 mg per single adult dose, 1 to 5 mg per single pediatric dose, and 0.05 to 0.1 mg/kg as a weight-based dose. Eclampsia is specifically addressed by 85% (28/33 of agencies. Forty-two percent (14/33 have a protocol for administering magnesium sulfate, with intravenous dosages ranging from 2 to 6 mg, and 58% (19/33 allow benzodiazepines to be

  8. The Heart of the Matter of Opinion and Evidence: The Value of Evidence-Based Medicine

    Science.gov (United States)

    Masvidal, Daniel; Lavie, Carl J.

    2012-01-01

    Evidence-based medicine is an important aspect of continuing medical education. This article reviews previous and current examples of conflicting topics that evidence-based medicine has clarified to allow us to provide the best possible patient care. PMID:22438783

  9. Current Understanding and Future Prospects of Host Selection, Acceptance, Discrimination, and Regulation of Phorid Fly Parasitoids That Attack Ants

    Directory of Open Access Journals (Sweden)

    Kaitlyn A. Mathis

    2012-01-01

    Full Text Available Phorid fly parasitoids (Diptera: Phoridae have evolved a diverse array of cues used to successfully parasitize their ant hosts. Successful parasitism often involves (a host habitat location, (b host location, (c host acceptance, (d host discrimination, and (e host regulation. In this paper we discuss our current understanding of how phorid flies use each of these steps to successfully parasitize ant hosts. We examine the wide variety of strategies and cues used by a multiple species of phorid flies within three separate genera that most commonly parasitize ants (Apocephalus, Pseudacteon, and Neodohrniphora and discuss future directions within this field of study.

  10. Primary Pediatric Hypertension: Current Understanding and Emerging Concepts.

    Science.gov (United States)

    Tiu, Andrew C; Bishop, Michael D; Asico, Laureano D; Jose, Pedro A; Villar, Van Anthony M

    2017-09-01

    The rising prevalence of primary pediatric hypertension and its tracking into adult hypertension point to the importance of determining its pathogenesis to gain insights into its current and emerging management. Considering that the intricate control of BP is governed by a myriad of anatomical, molecular biological, biochemical, and physiological systems, multiple genes are likely to influence an individual's BP and susceptibility to develop hypertension. The long-term regulation of BP rests on renal and non-renal mechanisms. One renal mechanism relates to sodium transport. The impaired renal sodium handling in primary hypertension and salt sensitivity may be caused by aberrant counter-regulatory natriuretic and anti-natriuretic pathways. The sympathetic nervous and renin-angiotensin-aldosterone systems are examples of antinatriuretic pathways. An important counter-regulatory natriuretic pathway is afforded by the renal autocrine/paracrine dopamine system, aberrations of which are involved in the pathogenesis of hypertension, including that associated with obesity. We present updates on the complex interactions of these two systems with dietary salt intake in relation to obesity, insulin resistance, inflammation, and oxidative stress. We review how insults during pregnancy such as maternal and paternal malnutrition, glucocorticoid exposure, infection, placental insufficiency, and treatments during the neonatal period have long-lasting effects in the regulation of renal function and BP. Moreover, these effects have sex differences. There is a need for early diagnosis, frequent monitoring, and timely management due to increasing evidence of premature target organ damage. Large controlled studies are needed to evaluate the long-term consequences of the treatment of elevated BP during childhood, especially to establish the validity of the current definition and treatment of pediatric hypertension.

  11. Executive functions and self-regulation.

    Science.gov (United States)

    Hofmann, Wilhelm; Schmeichel, Brandon J; Baddeley, Alan D

    2012-03-01

    Self-regulation is a core aspect of adaptive human behavior that has been studied, largely in parallel, through the lenses of social and personality psychology as well as cognitive psychology. Here, we argue for more communication between these disciplines and highlight recent research that speaks to their connection. We outline how basic facets of executive functioning (working memory operations, behavioral inhibition, and task-switching) may subserve successful self-regulation. We also argue that temporary reductions in executive functions underlie many of the situational risk factors identified in the social psychological research on self-regulation and review recent evidence that the training of executive functions holds significant potential for improving poor self-regulation in problem populations. Copyright © 2012 Elsevier Ltd. All rights reserved.

  12. β1-adrenergic regulation of rapid component of delayed rectifier K+ currents in guinea-pig cardiac myocytes.

    Science.gov (United States)

    Wang, Sen; Xu, Di; Wu, Ting-Ting; Guo, Yan; Chen, Yan-Hong; Zou, Jian-Gang

    2014-05-01

    Human ether-à-go-go-related gene (hERG) potassium channels conduct the rapid component of the delayed rectifier potassium current (IKr), which is crucial for repolarization of cardiac action potential. Patients with hERG‑associated long QT syndrome usually develop tachyarrhythmias during physical and/or emotional stress, both known to stimulate adrenergic receptors. The present study aimed to investigate a putative functional link between β1-adrenergic stimulation and IKr in guinea-pig left ventricular myocytes and to analyze how IKr is regulated following activation of the β1-adrenergic signaling pathway. The IKr current was measured using a whole-cell patch-clamp technique. A selective β1-adrenergic receptor agonist, xamoterol, at concentrations of 0.01-100 µM decreased IKr in a concentration-dependent manner. The 10 µM xamoterol-induced inhibition of IKr was attenuated by the protein kinase A (PKA) inhibitor KT5720, the protein kinase C (PKC) inhibitor chelerythrine, and the phospholipase (PLC) inhibitor U73122, indicating involvement of PKA, PKC and PLC in β1-adrenergic inhibition of IKr. The results of the present study indicate an association between IKr and the β1-adrenergic receptor in arrhythmogenesis, involving the activation of PKA, PKC and PLC.

  13. The organic seed regulations framework in Europe - current status and recommendations for future development

    NARCIS (Netherlands)

    Döring, T.F.; Bocci, R.; Hitchings, R.; Howlett, S.; Lammerts Van Bueren, E.; Pautasso, M.; Raaijmakers, M.; Rey, F.; Stubsgaard, A.; Weinhappel, M.; Wilbois, K.P.; Winkler, L.R.; Wolfe, M.S.

    2012-01-01

    Organic agriculture regulations, in particular European regulation EC 889/2008, prescribe the use of organically produced seed. For many cultivated plants, however, organic seed is often not available. This is mainly because investment in organic plant breeding and seed production has been low in

  14. 5 CFR 831.1109 - Evidence.

    Science.gov (United States)

    2010-01-01

    ... 5 Administrative Personnel 2 2010-01-01 2010-01-01 false Evidence. 831.1109 Section 831.1109 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT (CONTINUED) CIVIL SERVICE REGULATIONS (CONTINUED... exhibit of a documentary character shall be submitted to the presiding officer, duly marked, and made a...

  15. Hijama therapy (wet cupping) - its potential use to complement British healthcare in practice, understanding, evidence and regulation.

    Science.gov (United States)

    Sajid, Mohammed Imran

    2016-05-01

    Wet cupping was used in the nineteenth century for treatment of patients in the United Kingdom (UK) by a few experienced practitioners. Revival Hijama use by practitioners in the UK in recent years has been observed as well as interest from the public, with developments of specific certified training programmes, established businesses providing tailored Hijama therapy Clinical Waste disposal services, provisions of insurance cover, involvement of medical professionals and membership with the General Regulatory Council for Complementary Therapies (GRCCT). However, there has also been noted that there is not much in the way of guidance or regulation. Therefore, we would like to initiate some communication and understanding of Hijama (wet cupping) to benefit medical professionals, discussing recent research undertaken as a basis for potentially more in the future (evidence-based practice), in the likely event that a patient might request to be referred for this therapy during a consultation. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. Volume regulated anion channel currents of rat hippocampal neurons and their contribution to oxygen-and-glucose deprivation induced neuronal death.

    Directory of Open Access Journals (Sweden)

    Huaqiu Zhang

    2011-02-01

    Full Text Available Volume-regulated anion channels (VRAC are widely expressed chloride channels that are critical for the cell volume regulation. In the mammalian central nervous system, the physiological expression of neuronal VRAC and its role in cerebral ischemia are issues largely unknown. We show that hypoosmotic medium induce an outwardly rectifying chloride conductance in CA1 pyramidal neurons in rat hippocampal slices. The induced chloride conductance was sensitive to some of the VRAC inhibitors, namely, IAA-94 (300 µM and NPPB (100 µM, but not to tamoxifen (10 µM. Using oxygen-and-glucose deprivation (OGD to simulate ischemic conditions in slices, VRAC activation appeared after OGD induced anoxic depolarization (AD that showed a progressive increase in current amplitude over the period of post-OGD reperfusion. The OGD induced VRAC currents were significantly inhibited by inhibitors for glutamate AMPA (30 µM NBQX and NMDA (40 µM AP-5 receptors in the OGD solution, supporting the view that induction of AD requires an excessive Na(+-loading via these receptors that in turn to activate neuronal VRAC. In the presence of NPPB and DCPIB in the post-OGD reperfusion solution, the OGD induced CA1 pyramidal neuron death, as measured by TO-PRO-3-I staining, was significantly reduced, although DCPIB did not appear to be an effective neuronal VRAC blocker. Altogether, we show that rat hippocampal pyramidal neurons express functional VRAC, and ischemic conditions can initial neuronal VRAC activation that may contribute to ischemic neuronal damage.

  17. Food Safety Regulation and Firm Productivity: Evidence from the French Food Industry

    OpenAIRE

    Requillart, Vincent; Nauges, Celine; Simioni, Michel; Bontemps, Christophe

    2012-01-01

    The purpose of this article is to assess whether food safety regulations imposed by the European Union in the 2000s may have induced a slow-down in the productivity of firms in the food processing sector. The impact of regulations on costs and productivity has seldom been studied. This article contributes to the literature by measuring productivity change using a panel of French food processing firms for the years 1996 to 2006. To do so, we develop an original iterative testing procedure b...

  18. Analysis of Alcohol Industry Submissions against Marketing Regulation

    Science.gov (United States)

    Martino, Florentine Petronella; Miller, Peter Graeme; Coomber, Kerri; Hancock, Linda; Kypri, Kypros

    2017-01-01

    A growing body of literature points to the role of vested interests as a barrier to the implementation of effective public health policies. Corporate political activity by the alcohol industry is commonly used to influence policy and regulation. It is important for policy makers to be able to critique alcohol industry claims opposed to improved alcohol marketing regulation. The Australian National Preventive Health Agency reviewed alcohol marketing regulations in 2012 and stakeholders were invited to comment on them. In this study we used thematic analysis to examine submissions from the Australian alcohol industry, based on a system previously developed in relation to tobacco industry corporate political activity. The results show that submissions were a direct lobbying tactic, making claims to government that were contrary to the evidence-base. Five main frames were identified, in which the alcohol industry claimed that increased regulation: (1) is unnecessary; (2) is not backed up by sufficient evidence; (3) will lead to unintended negative consequences; and (4) faces legal barriers to implementation; underpinned by the view (5) that the industry consists of socially responsible companies working toward reducing harmful drinking. In contrast with tobacco industry submissions on public policy, which often focused on legal and economic barriers, the Australian alcohol industry placed a heavier emphasis on notions of regulatory redundancy and insufficient evidence. This may reflect differences in where these industries sit on the ‘regulatory pyramid’, alcohol being less regulated than tobacco. PMID:28118411

  19. Analysis of Alcohol Industry Submissions against Marketing Regulation.

    Directory of Open Access Journals (Sweden)

    Florentine Petronella Martino

    Full Text Available A growing body of literature points to the role of vested interests as a barrier to the implementation of effective public health policies. Corporate political activity by the alcohol industry is commonly used to influence policy and regulation. It is important for policy makers to be able to critique alcohol industry claims opposed to improved alcohol marketing regulation. The Australian National Preventive Health Agency reviewed alcohol marketing regulations in 2012 and stakeholders were invited to comment on them. In this study we used thematic analysis to examine submissions from the Australian alcohol industry, based on a system previously developed in relation to tobacco industry corporate political activity. The results show that submissions were a direct lobbying tactic, making claims to government that were contrary to the evidence-base. Five main frames were identified, in which the alcohol industry claimed that increased regulation: (1 is unnecessary; (2 is not backed up by sufficient evidence; (3 will lead to unintended negative consequences; and (4 faces legal barriers to implementation; underpinned by the view (5 that the industry consists of socially responsible companies working toward reducing harmful drinking. In contrast with tobacco industry submissions on public policy, which often focused on legal and economic barriers, the Australian alcohol industry placed a heavier emphasis on notions of regulatory redundancy and insufficient evidence. This may reflect differences in where these industries sit on the 'regulatory pyramid', alcohol being less regulated than tobacco.

  20. Analysis of Alcohol Industry Submissions against Marketing Regulation.

    Science.gov (United States)

    Martino, Florentine Petronella; Miller, Peter Graeme; Coomber, Kerri; Hancock, Linda; Kypri, Kypros

    2017-01-01

    A growing body of literature points to the role of vested interests as a barrier to the implementation of effective public health policies. Corporate political activity by the alcohol industry is commonly used to influence policy and regulation. It is important for policy makers to be able to critique alcohol industry claims opposed to improved alcohol marketing regulation. The Australian National Preventive Health Agency reviewed alcohol marketing regulations in 2012 and stakeholders were invited to comment on them. In this study we used thematic analysis to examine submissions from the Australian alcohol industry, based on a system previously developed in relation to tobacco industry corporate political activity. The results show that submissions were a direct lobbying tactic, making claims to government that were contrary to the evidence-base. Five main frames were identified, in which the alcohol industry claimed that increased regulation: (1) is unnecessary; (2) is not backed up by sufficient evidence; (3) will lead to unintended negative consequences; and (4) faces legal barriers to implementation; underpinned by the view (5) that the industry consists of socially responsible companies working toward reducing harmful drinking. In contrast with tobacco industry submissions on public policy, which often focused on legal and economic barriers, the Australian alcohol industry placed a heavier emphasis on notions of regulatory redundancy and insufficient evidence. This may reflect differences in where these industries sit on the 'regulatory pyramid', alcohol being less regulated than tobacco.

  1. Laparoscopic Pediatric Inguinal Hernia Repair: Overview of "True Herniotomy" Technique and Review of Current Evidence.

    Science.gov (United States)

    Feehan, Brendan P; Fromm, David S

    2017-05-01

    Inguinal hernia repair is one of the most commonly performed operations in the pediatric population. While the majority of pediatric surgeons routinely use laparoscopy in their practices, a relatively small number prefer a laparoscopic inguinal hernia repair over the traditional open repair. This article provides an overview of the three port laparoscopic technique for inguinal hernia repair, as well as a review of the current evidence with respect to visualization and identification of hernias, recurrence rates, operative times, complication rates, postoperative pain, and cosmesis. The laparoscopic repair presents a viable alternative to open repair and offers a number of benefits over the traditional approach. These include superior visualization of the relevant anatomy, ability to assess and repair a contralateral hernia, lower rates of metachronous hernia, shorter operative times in bilateral hernia, and the potential for lower complication rates and improved cosmesis. This is accomplished without increasing recurrence rates or postoperative pain. Further research comparing the different approaches, including standardization of techniques and large randomized controlled trials, will be needed to definitively determine which is superior. Copyright© South Dakota State Medical Association.

  2. Antibiotics versus appendectomy in the management of acute appendicitis: a review of the current evidence.

    Science.gov (United States)

    Fitzmaurice, Gerard J; McWilliams, Billy; Hurreiz, Hisham; Epanomeritakis, Emanuel

    2011-10-01

    Acute appendicitis remains the most common cause of the acute abdomen in young adults, and the mainstay of treatment in most centres is an appendectomy. However, treatment for other intra-abdominal inflammatory processes, such as diverticulitis, consists initially of conservative management with antibiotics. The aim of this study was to determine the role of antibiotics in the management of acute appendicitis and to assess if appendectomy remains the gold standard of care. A literature search using MEDLINE and the Cochrane Library identified studies published between 1999 and 2009, and we reviewed all relevant articles. The articles were critiqued using the Public Health Resource Unit (2006) appraisal tools. Our search yielded 41 papers, and we identified a total of 13 papers within the criteria specified. All of these papers, while posing pertinent questions and demonstrating the role of antibiotics as a bridge to surgery, failed to adequately justify their findings that antibiotics could be used as a definitive treatment of acute appendicitis. Appendectomy remains the gold standard of treatment for acute appendicitis based on the current evidence.

  3. Antibiotics versus appendectomy in the management of acute appendicitis: a review of the current evidence

    Science.gov (United States)

    Fitzmaurice, Gerard J.; McWilliams, Billy; Hurreiz, Hisham; Epanomeritakis, Emanuel

    2011-01-01

    Background Acute appendicitis remains the most common cause of the acute abdomen in young adults, and the mainstay of treatment in most centres is an appendectomy. However, treatment for other intra-abdominal inflammatory processes, such as diverticulitis, consists initially of conservative management with antibiotics. The aim of this study was to determine the role of antibiotics in the management of acute appendicitis and to assess if appendectomy remains the gold standard of care. Methods A literature search using MEDLINE and the Cochrane Library identified studies published between 1999 and 2009, and we reviewed all relevant articles. The articles were critiqued using the Public Health Resource Unit (2006) appraisal tools. Results Our search yielded 41 papers, and we identified a total of 13 papers within the criteria specified. All of these papers, while posing pertinent questions and demonstrating the role of antibiotics as a bridge to surgery, failed to adequately justify their findings that antibiotics could be used as a definitive treatment of acute appendicitis. Conclusion Appendectomy remains the gold standard of treatment for acute appendicitis based on the current evidence. PMID:21651835

  4. Using Integrative Medicine in Pain Management: An Evaluation of Current Evidence.

    Science.gov (United States)

    Lin, Yuan-Chi; Wan, Limeng; Jamison, Robert N

    2017-12-01

    Complementary medicine therapies are frequently used to treat pain conditions such as headaches and neck, back, and joint pain. Chronic pain, described as pain lasting longer than 3-6 months, can be a debilitating condition that has a significant socioeconomic impact. Pharmacologic approaches are often used for alleviating chronic pain, but recently there has been a reluctance to prescribe opioids for chronic noncancer pain because of concerns about tolerance, dependence, and addiction. As a result, there has been increased interest in integrative medicine strategies to help manage pain and to reduce reliance on prescription opioids to manage pain. This article offers a brief critical review of integrative medical therapies used to treat chronic pain, including nutritional supplements, yoga, relaxation, tai chi, massage, spinal manipulation, and acupuncture. The goal of this article is to identify those treatments that show evidence of efficacy and to identify gaps in the literature where additional studies and controlled trials are needed. An electronic search of the databases of PubMed, The Cochrane Library, EMBASE, PsycINFO, and Science Citation Index Expanded was conducted. Overall, weak positive evidence was found for yoga, relaxation, tai chi, massage, and manipulation. Strong evidence for acupuncture as a complementary treatment for chronic pain that has been shown to decrease the usage of opioids was found. Few studies were found in which integrative medicine approaches were used to address opioid misuse and abuse among chronic pain patients. Additional controlled trials to address the use of integrative medicine approaches in pain management are needed.

  5. Nuclear regulation in transition

    International Nuclear Information System (INIS)

    Tomain, J.P.

    1986-01-01

    The current state of nuclear regulations in the USA is examined. Since Three Mile Island the regulation of the nuclear power industry has been undergoing a noticeable transition. It will be argued here that the transition is characterized by two indicia. First, the primary focus of state and federal regulators has been on the financial aspects of the industry: this is best seen in the context of decisions allocating the costs of nuclear plant cancellations. Second, decisionmaking power has been decentralized: although the regulatory history of nuclear power demonstrates the tradition of centralized decisionmaking power (i.e., formerly the primary decisionmaking body was the Atomic Energy Commission), now States share decisionmaking power with the Nuclear Regulatory Commission. In Section 1 a brief legislative history of nuclear regulation is presented to establish the assertion that nuclear regulation, both de jure and de facto, was centralized. Next, Section 2 canvasses recent United States Supreme Court opinions regarding nuclear regulation. The Court frequently acts as policymaker through the consequences of its opinions, if not by its intent. In the area of nuclear policymaking, the Court has paid allegiance recently both to the tradition of centralization and to the movement toward decentralization. This dualism is reflected in other federal court decisions as well which will be briefly mentioned. Continuing the analysis of Federal regulation, Section 3 examines the current reform efforts of the NRC. Section 4 presents an examination of State responses to nuclear plant cancellations. In this section, State administrative agency and court decisions will be examined and recent State legislation will be discussed. (author)

  6. Nuclear regulation in transition

    Energy Technology Data Exchange (ETDEWEB)

    Tomain, J.P. (Cincinnati Univ., OH, US. Coll. of Law)

    1986-01-01

    The current state of nuclear regulations in the USA is examined. Since Three Mile Island the regulation of the nuclear power industry has been undergoing a noticeable transition. It will be argued here that the transition is characterized by two indicia. First, the primary focus of state and federal regulators has been on the financial aspects of the industry: this is best seen in the context of decisions allocating the costs of nuclear plant cancellations. Second, decisionmaking power has been decentralized: although the regulatory history of nuclear power demonstrates the tradition of centralized decisionmaking power (i.e., formerly the primary decisionmaking body was the Atomic Energy Commission), now States share decisionmaking power with the Nuclear Regulatory Commission. In Section 1 a brief legislative history of nuclear regulation is presented to establish the assertion that nuclear regulation, both de jure and de facto, was centralized. Next, Section 2 canvasses recent United States Supreme Court opinions regarding nuclear regulation. The Court frequently acts as policymaker through the consequences of its opinions, if not by its intent. In the area of nuclear policymaking, the Court has paid allegiance recently both to the tradition of centralization and to the movement toward decentralization. This dualism is reflected in other federal court decisions as well which will be briefly mentioned. Continuing the analysis of Federal regulation, Section 3 examines the current reform efforts of the NRC. Section 4 presents an examination of State responses to nuclear plant cancellations. In this section, State administrative agency and court decisions will be examined and recent State legislation will be discussed.

  7. Neural correlates of emotion regulation in patients with schizophrenia and non-affected siblings.

    Directory of Open Access Journals (Sweden)

    Lisette van der Meer

    Full Text Available BACKGROUND: Patients with schizophrenia often experience problems regulating their emotions. Non-affected relatives show similar difficulties, although to a lesser extent, and the neural basis of such difficulties remains to be elucidated. In the current paper we investigated whether schizophrenia patients, non-affected siblings and healthy controls (HC exhibit differences in brain activation during emotion regulation. METHODS: All subjects (n = 20 per group performed an emotion regulation task while they were in an fMRI scanner. The task contained two experimental conditions for the down-regulation of emotions (reappraise and suppress, in which IAPS pictures were used to generate a negative affect. We also assessed whether the groups differed in emotion regulation strategies used in daily life by means of the emotion regulation questionnaire (ERQ. RESULTS: Though the overall negative affect was higher for patients as well as for siblings compared to HC for all conditions, all groups reported decreased negative affect after both regulation conditions. Nonetheless, neuroimaging results showed hypoactivation relative to HC in VLPFC, insula, middle temporal gyrus, caudate and thalamus for patients when reappraising negative pictures. In siblings, the same pattern was evident as in patients, but only in cortical areas. CONCLUSIONS: Given that all groups performed similarly on the emotion regulation task, but differed in overall negative affect ratings and brain activation, our findings suggest reduced levels of emotion regulation processing in neural circuits in patients with schizophrenia. Notably, this also holds for siblings, albeit to a lesser extent, indicating that it may be part and parcel of a vulnerability for psychosis.

  8. Upholding science in health, safety and environmental risk assessments and regulations

    International Nuclear Information System (INIS)

    Aschner, Michael; Autrup, Herman N.; Berry, Sir Colin L.; Boobis, Alan R.; Cohen, Samuel M.; Creppy, Edmond E.; Dekant, Wolfgang; Doull, John; Galli, Corrado L.; Goodman, Jay I.; Gori, Gio B.; Greim, Helmut A.; Joudrier, Philippe

    2016-01-01

    A public appeal has been advanced by a large group of scientists, concerned that science has been misused in attempting to quantify and regulate unmeasurable hazards and risks. The appeal recalls that science is unable to evaluate hazards that cannot be measured, and that science in such cases should not be invoked to justify risk assessments in health, safety and environmental regulations. The appeal also notes that most national and international statutes delineating the discretion of regulators are ambiguous about what rules of evidence ought to apply. Those statutes should be revised to ensure that the evidence for regulatory action is grounded on the standards of the scientific method, whenever feasible. When independent scientific evidence is not possible, policies and regulations should be informed by publicly debated trade-offs between socially desirable uses and social perceptions of affordable precaution. This article explores the premises, implications and actions supporting the appeal and its objectives.

  9. Lobbying on audit regulation at IAASB

    Directory of Open Access Journals (Sweden)

    Thiago Macedo Pereira de Matos

    2018-02-01

    Full Text Available ABSTRACT The main goal of the paper is to analyze whether the positions of auditors and regulators, and their respective coalitions, regarding the proposals of the International Auditing and Assurance Standards Board (IAASB in the last phase of the public consultation “Improving the Auditor’s Report” are significantly different, as well as the effectiveness of a lobbying strategy using comment letters. The relevance of this research lies in providing evidence on whether or not the IAASB is influenced by the lobbying strategies of different interest groups carried out via comment letters, especially auditors and regulators (both individually and in coalitions. The results show that both auditors and regulators attempeted to influence the IAASB’s decision-making process, with their coalitions taking a different position on some questions. However, none of these interest groups predominated in terms of the effectiveness of the lobbying carried out, hence the results are consistent with institutional theory, in that the IAASB seeks legitimacy in its actions and tries to accommodate several different interests, but does not let itself be captured by any specific group. We analyzed and classified the comments (from a total of 86 letters to nine questions proposed by the IAASB into a five-point Likert scale. This classification was independently cross-validated by a second researcher. We applied ANOVA tests to analyze the position of the interest groups, and chi- squared tests for the position of their coalitions. This paper addresses lobbying within the process of auditing standards settings, thus expanding the current literature on lobbying in accounting, which is mainly restricted to accounting regulations. It also contributes methodologically by using a new five-point scale for the dependent variable instead of the usual binary approach.

  10. Evidence-Based Practices in Special Education: Current Assumptions and Future Considerations

    Science.gov (United States)

    Russo-Campisi, Jacqueline

    2017-01-01

    Background: The research on evidence-based practices (EBP) in special education has shifted over the last decade from identifying efficacious interventions to exploring issues that impede implementation in the classroom. Common barriers to implementation include absence of training and resources, limited collaboration between researchers and…

  11. MicroRNAs: Key Regulators in the Central Nervous System and Their Implication in Neurological Diseases

    Directory of Open Access Journals (Sweden)

    Dan-Dan Cao

    2016-05-01

    Full Text Available MicroRNAs (miRNAs are a class of small, well-conserved noncoding RNAs that regulate gene expression post-transcriptionally. They have been demonstrated to regulate a lot of biological pathways and cellular functions. Many miRNAs are dynamically regulated during central nervous system (CNS development and are spatially expressed in adult brain indicating their essential roles in neural development and function. In addition, accumulating evidence strongly suggests that dysfunction of miRNAs contributes to neurological diseases. These observations, together with their gene regulation property, implicated miRNAs to be the key regulators in the complex genetic network of the CNS. In this review, we first focus on the ways through which miRNAs exert the regulatory function and how miRNAs are regulated in the CNS. We then summarize recent findings that highlight the versatile roles of miRNAs in normal CNS physiology and their association with several types of neurological diseases. Subsequently we discuss the limitations of miRNAs research based on current studies as well as the potential therapeutic applications and challenges of miRNAs in neurological disorders. We endeavor to provide an updated description of the regulatory roles of miRNAs in normal CNS functions and pathogenesis of neurological diseases.

  12. Modification of the Current Profile in DIII-D by Off-Axis Electron Cyclotron Current Drive

    International Nuclear Information System (INIS)

    Luce, T.C.; Lin-Liu, Y.R.; Harvey, R.W.; Giruzzi, G.; Lohr, J.M.; Petty, C.C.; Politzer, P.A.; Prater; Rice, B.W.

    1999-01-01

    Localized non-inductive currents due to electron cyclotron wave absorption have been measured on the DIII-D tokamak. Clear evidence of the non-inductive currents is seen on the internal magnetic field measurements by motional Stark effect spectroscopy. The magnitude and location of the non-inductive current is evaluated by comparing the total and Ohmic current profiles of discharges with and without electron cyclotron wave power. The measured current agrees with Fokker-Planck calculations near the magnetic axis, but exceeds the predicted value as the location of the current drive is moved to the half radius

  13. Body weight regulation and obesity: dietary strategies to improve the metabolic profile.

    Science.gov (United States)

    Munsters, M J M; Saris, W H M

    2014-01-01

    This review discusses dietary strategies that may improve the metabolic profile and body weight regulation in obesity. Recent evidence demonstrated that long-term health effects seem to be more beneficial for low-glycemic index (GI) diets compared to high-protein diets. Still, these results need to be confirmed by other prospective cohort studies and long-term clinical trials, and the discrepancy between these study designs needs to be explored in more detail. Furthermore, the current literature is mixed with regard to the efficacy of increased meal frequency (or snacking) regimens in causing metabolic alterations, particularly in relation to body weight control. In conclusion, a growing body of evidence suggests that dietary strategies with the aim to reduce postprandial insulin response and increase fat oxidation, and that tend to restore metabolic flexibility, have a place in the prevention and treatment of obesity and associated metabolic disorders.

  14. Individual Differences in Automatic Emotion Regulation Interact with Primed Emotion Regulation during an Anger Provocation

    OpenAIRE

    Zhang, Jing; Lipp, Ottmar V.; Hu, Ping

    2017-01-01

    The current study investigated the interactive effects of individual differences in automatic emotion regulation (AER) and primed emotion regulation strategy on skin conductance level (SCL) and heart rate during provoked anger. The study was a 2 × 2 [AER tendency (expression vs. control) × priming (expression vs. control)] between subject design. Participants were assigned to two groups according to their performance on an emotion regulation-IAT (differentiating automatic emotion control tend...

  15. Evidence-based Practice of Radiology.

    Science.gov (United States)

    Lavelle, Lisa P; Dunne, Ruth M; Carroll, Anne G; Malone, Dermot E

    2015-10-01

    Current health care reform in the United States is producing a shift in radiology practice from the traditional volume-based role of performing and interpreting a large number of examinations to providing a more affordable and higher-quality service centered on patient outcomes, which is described as a value-based approach to the provision of health care services. In the 1990 s, evidence-based medicine was defined as the integration of current best evidence with clinical expertise and patient values. When these methods are applied outside internal medicine, the process is called evidence-based practice (EBP). EBP facilitates understanding, interpretation, and application of the best current evidence into radiology practice, which optimizes patient care. It has been incorporated into "Practice-based Learning and Improvement" and "Systems-based Practice," which are two of the six core resident competencies of the Accreditation Council for Graduate Medical Education and two of the 12 American Board of Radiology milestones for diagnostic radiology. Noninterpretive skills, such as systems-based practice, are also formally assessed in the "Quality and Safety" section of the American Board of Radiology Core and Certifying examinations. This article describes (a) the EBP framework, with particular focus on its relevance to the American Board of Radiology certification and maintenance of certification curricula; (b) how EBP can be integrated into a residency program; and (c) the current value and likely place of EBP in the radiology information technology infrastructure. Online supplemental material is available for this article. © RSNA, 2015.

  16. Using scientific evidence to inform public policy on the long distance transportation of animals: role of the European Food Safety Authority

    Directory of Open Access Journals (Sweden)

    Oriol Ribò

    2008-03-01

    Full Text Available The authors review the work of the previous Scientific Committee on Animal Health and Animal Welfare and the current European Food Safety Authority (EFSA in providing scientific advice on the welfare aspects of animal transport and the impact of this advice on the European Union (EU regulatory framework. Through its Protocol on the Protection and Welfare of Animals, the Treaty of Amsterdam obliges European institutions to pay full regard to the welfare requirements of animals when formulating and implementing EU legislation. Regulation 1/2005 states that EU legislation should be amended to take into account new scientific evidence. Provisions for poultry, cats and dogs take into account the recommendations included in EFSA's Scientific Opinion which considers different species (poultry, deer, rabbits, dogs and cats, fish and exotic animals. Examples of the effect of the scientifically based conclusions and recommendations from the Scientific Opinion on the measures in Regulation 1/2005 are summarised and show the impact of scientific evidence on EU legislation.

  17. Using scientific evidence to inform public policy on the long distance transportation of animals: role of the European Food Safety Authority.

    Science.gov (United States)

    Ribò, Oriol; Candiani, Denise; Aiassa, Elisa; Correia, Sandra; Afonso, Ana; De Massis, Fabrizio; Serratosa, Jordi

    2008-01-01

    The authors review the work of the previous Scientific Committee on Animal Health and Animal Welfare and the current European Food Safety Authority (EFSA) in providing scientific advice on the welfare aspects of animal transport and the impact of this advice on the European Union (EU) regulatory framework. Through its Protocol on the Protection and Welfare of Animals, the Treaty of Amsterdam obliges European institutions to pay full regard to the welfare requirements of animals when formulating and implementing EU legislation. Regulation 1/2005 states that EU legislation should be amended to take into account new scientific evidence. Provisions for poultry, cats and dogs take into account the recommendations included in EFSA's Scientific Opinion which considers different species (poultry, deer, rabbits, dogs and cats, fish and exotic animals). Examples of the effect of the scientifically based conclusions and recommendations from the Scientific Opinion on the measures in Regulation 1/2005 are summarised and show the impact of scientific evidence on EU legislation.

  18. Progress toward pharmacotherapies for cannabis-use disorder: an evidence-based review

    Science.gov (United States)

    Copeland, Jan; Pokorski, Izabella

    2016-01-01

    Cannabis is the most widely used and variably regulated drug in the world, with increasing trends of use being reported in the US, Australia, Asia, and Africa. Evidence has shown a decrease in the age of commencement of cannabis use in some developed countries and a prolongation of risk of initiation to cannabis use beyond adolescence among more recent users. Cannabis use is associated with numerous health risks and long-term morbidity, as well as risk of developing cannabis-use disorders. Cannabis users infrequently seek professional treatment, and normally do so after a decade of use. Cannabis-use disorders are currently treated using a selection of psychosocial interventions. Severity of withdrawal is a factor that increases the risk of relapse, and is the target of pharmacotherapy studies. Currently, there is no approved pharmacotherapy for cannabis-use disorders. A number of approaches have been examined, and trials are continuing to find a safe and effective medication with little abuse liability. PMID:27217809

  19. Gender-Dimorphic Regulation of Skeletal Muscle Proteins in Streptozotocin-Induced Diabetic Rats

    Directory of Open Access Journals (Sweden)

    Minji Choi

    2013-03-01

    Full Text Available Background: Despite the fact that sexual differences increase diabetic risk and contribute to the need for gender-specific care, there remain contradictory results as to whether or not sexual dimorphism increases susceptibility to the development of type 1 diabetes mellitus. Methods: To examine gender-dimorphic regulation of skeletal muscle proteins between healthy control and STZ-induced diabetic rats of both genders, we performed differential proteome analysis using two-dimensional electrophoresis combined with mass spectrometry. Results: Animal experiments revealed that STZ treatment rendered female rats more susceptible to induction of diabetes than their male littermates with significantly lower plasma insulin levels due to hormonal regulation. Proteomic analysis of skeletal muscle identified a total of 21 proteins showing gender-dimorphic differential expression patterns between healthy controls and diabetic rats. Most interestingly, gender-specific proteome comparison showed that male and female rats displayed differential regulation of proteins involved in muscle contraction, carbohydrate, and lipid metabolism, as well as oxidative phosphorylation and cellular stress. Conclusion: The current proteomic study revealed that impaired protein regulation was more prominent in the muscle tissue of female diabetic rats, which were more susceptible to STZ-induced diabetes. We expect that the present proteomic data can provide valuable information for evidence-based gender-specific treatment of diabetes.

  20. Experimental and observational evidence reveals that predators in natural environments do not regulate their prey: They are passengers, not drivers

    Science.gov (United States)

    White, T. C. R.

    2013-11-01

    Among both ecologists and the wider community there is a tacit assumption that predators regulate populations of their prey. But there is evidence from a wide taxonomic and geographic range of studies that predators that are adapted to co-evolved prey generally do not regulate their prey. This is because predators either cannot reproduce as fast as their prey and/or are inefficient hunters unable to catch enough prey to sustain maximum reproduction. The greater capacity of herbivores to breed successfully is, however, normally restricted by a lack of enough food of sufficient quality to support reproduction. But whenever this shortage is alleviated by a large pulse of food, herbivores increase their numbers to outbreak levels. Their predators are unable to contain this increase, but their numbers, too, surge in response to this increase in food. Eventually both their populations will crash once the food supply runs out, first for the herbivores and then for the predators. Then an “over-run” of predators will further depress the already declining prey population, appearing to be controlling its abundance. This latter phenomenon has led many ecologists to conclude that predators are regulating the numbers of their prey. However, it is the same process that is revealed during outbreaks that limits populations of both predator and prey in “normal” times, although this is usually not readily apparent. Nevertheless, as all the diverse cases discussed here attest, the abundance of predators and their co-evolved prey are both limited by their food: the predators are passengers, not drivers.

  1. Tranexamic acid for the management of uterine fibroid tumors: A systematic review of the current evidence

    Science.gov (United States)

    Peitsidis, Panagiotis; Koukoulomati, Anna

    2014-01-01

    AIM: To conduct a detailed systematic review of the current evidence on the administration and efficacy of tranexamic acid in patients with menorrhagia due to uterine fibroids. METHODS: We conducted an electronic search on the following databases PubMed and Medline (1950-2013); (1980-2013); Cochrane library (1993-2013). RESULTS: A total of 36 articles were retrieved after the initial electronic search. Careful assessment of the retrieved studies led to the final selection of 5 articles for inclusion in the review. CONCLUSION: Tranexamic acid may reduce blood loss perioperatively in myomectomies. It may reduce the menorrhagia in patients with fibroids, however a stratification of fibroids by size and location is required to define the responses. It is safe in general, with mild adverse effects observed in some cases. More studies with a double-blind randomized design and larger numbers of participants are necessary to reach more precise and safe conclusions. PMID:25516866

  2. REGULATIONS ON PHOTOVOLTAIC MODULE DISPOSAL AND RECYCLING.

    Energy Technology Data Exchange (ETDEWEB)

    FTHENAKIS,V.

    2001-01-29

    Environmental regulations can have a significant impact on product use, disposal, and recycling. This report summarizes the basic aspects of current federal, state and international regulations which apply to end-of-life photovoltaic (PV) modules and PV manufacturing scrap destined for disposal or recycling. It also discusses proposed regulations for electronics that may set the ground of what is to be expected in this area in the near future. In the US, several states have started programs to support the recycling of electronic equipment, and materials destined for recycling often are excepted from solid waste regulations during the collection, transfer, storage and processing stages. California regulations are described separately because they are different from those of most other states. International agreements on the movement of waste between different countries may pose barriers to cross-border shipments. Currently waste moves freely among country members of the Organization of Economic Cooperation and Development (OECD), and between the US and the four countries with which the US has bilateral agreements. However, it is expected, that the US will adopt the rules of the Basel Convention (an agreement which currently applies to 128 countries but not the US) and that the Convection's waste classification system will influence the current OECD waste-handling system. Some countries adopting the Basel Convention consider end-of-life electronics to be hazardous waste, whereas the OECD countries consider them to be non-hazardous. Also, waste management regulations potentially affecting electronics in Germany and Japan are mentioned in this report.

  3. Endogenous vs. exogenous regulations in the commons

    DEFF Research Database (Denmark)

    Abatayo, Anna Lou; Lynham, John

    2016-01-01

    It is widely believed that there is strong experimental evidence to support the idea that exogenously imposed regulations crowd out the intrinsic motivations of common pool resource (CPR) users to refrain from over-harvesting. We introduce a novel experimental design that attempts to disentangle...... potential confounds in previous experiments. A key feature of our experimental design is to have the exact same regulations chosen endogenously as those that are imposed exogenously. When we compare the same regulations chosen endogenously to those externally imposed, we observe no differences in extraction...... endogenous regulations with communication and exogenous regulations without communication. Our results suggest that externally imposed regulations do not crowd out intrinsic motivations in the lab and they confirm that communication facilitates cooperation to reduce extraction....

  4. A genome-wide RNAi screen identifies regulators of cholesterol-modified hedgehog secretion in Drosophila.

    Directory of Open Access Journals (Sweden)

    Reid Aikin

    Full Text Available Hedgehog (Hh proteins are secreted molecules that function as organizers in animal development. In addition to being palmitoylated, Hh is the only metazoan protein known to possess a covalently-linked cholesterol moiety. The absence of either modification severely disrupts the organization of numerous tissues during development. It is currently not known how lipid-modified Hh is secreted and released from producing cells. We have performed a genome-wide RNAi screen in Drosophila melanogaster cells to identify regulators of Hh secretion. We found that cholesterol-modified Hh secretion is strongly dependent on coat protein complex I (COPI but not COPII vesicles, suggesting that cholesterol modification alters the movement of Hh through the early secretory pathway. We provide evidence that both proteolysis and cholesterol modification are necessary for the efficient trafficking of Hh through the ER and Golgi. Finally, we identified several putative regulators of protein secretion and demonstrate a role for some of these genes in Hh and Wingless (Wg morphogen secretion in vivo. These data open new perspectives for studying how morphogen secretion is regulated, as well as provide insight into regulation of lipid-modified protein secretion.

  5. Astrocytic actions on extrasynaptic neuronal currents

    Directory of Open Access Journals (Sweden)

    Balazs ePal

    2015-12-01

    Full Text Available In the last few decades, knowledge about astrocytic functions has significantly increased. It was demonstrated that astrocytes are not passive elements of the central nervous system, but active partners of neurons. There is a growing body of knowledge about the calcium excitability of astrocytes, the actions of different gliotransmitters and their release mechanisms, as well as the participation of astrocytes in the regulation of synaptic functions and their contribution to synaptic plasticity. However, astrocytic functions are even more complex than being a partner of the 'tripartite synapse', as they can influence extrasynaptic neuronal currents either by releasing substances or regulating ambient neurotransmitter levels. Several types of currents or changes of membrane potential with different kinetics and via different mechanisms can be elicited by astrocytic activity. Astrocyte-dependent phasic or tonic, inward or outward currents were described in several brain areas. Such currents, together with the synaptic actions of astrocytes, can contribute to neuromodulatory mechanisms, neurosensory and –secretory processes, cortical oscillatory activity, memory and learning or overall neuronal excitability. This mini-review is an attempt to give a brief summary of astrocyte-dependent extrasynaptic neuronal currents and their possible functional significance.

  6. Ribosomal S6K1 in POMC and AgRP Neurons Regulates Glucose Homeostasis but Not Feeding Behavior in Mice

    Directory of Open Access Journals (Sweden)

    Mark A. Smith

    2015-04-01

    Full Text Available Hypothalamic ribosomal S6K1 has been suggested as a point of convergence for hormonal and nutrient signals in the regulation of feeding behavior, bodyweight, and glucose metabolism. However, the long-term effects of manipulating hypothalamic S6K1 signaling on energy homeostasis and the cellular mechanisms underlying these roles are unclear. We therefore inactivated S6K1 in pro-opiomelanocortin (POMC and agouti-related protein (AgRP neurons, key regulators of energy homeostasis, but in contrast to the current view, we found no evidence that S6K1 regulates food intake and bodyweight. In contrast, S6K1 signaling in POMC neurons regulated hepatic glucose production and peripheral lipid metabolism and modulated neuronal excitability. S6K1 signaling in AgRP neurons regulated skeletal muscle insulin sensitivity and was required for glucose sensing by these neurons. Our findings suggest that S6K1 signaling is not a general integrator of energy homeostasis in the mediobasal hypothalamus but has distinct roles in the regulation of glucose homeostasis by POMC and AgRP neurons.

  7. Marketing of food and beverage in Brazil: scientific literature review on regulation and self-regulation of advertisements

    OpenAIRE

    Aline Kassahara; Flavia Mori Sarti

    2017-01-01

    The effects of marketing strategies for promotion of foods and beverages have been investigated due to its potential impacts on populations’ food choices, particularly among children and adolescents. The paper presents an academic literature review on regulation and self-regulation of food and beverage advertisements in Brazil, based on search performed in electronic databases. Majority of studies were based on law analysis or qualitative study of advertisements. There are sufficient evidence...

  8. Ranges of control in the transcriptional regulation of Escherichia coli.

    Science.gov (United States)

    Sonnenschein, Nikolaus; Hütt, Marc-Thorsten; Stoyan, Helga; Stoyan, Dietrich

    2009-12-24

    The positioning of genes in the genome is an important evolutionary degree of freedom for organizing gene regulation. Statistical properties of these distributions have been studied particularly in relation to the transcriptional regulatory network. The systematics of gene-gene distances then become important sources of information on the control, which different biological mechanisms exert on gene expression. Here we study a set of categories, which has to our knowledge not been analyzed before. We distinguish between genes that do not participate in the transcriptional regulatory network (i.e. that are according to current knowledge not producing transcription factors and do not possess binding sites for transcription factors in their regulatory region), and genes that via transcription factors either are regulated by or regulate other genes. We find that the two types of genes ("isolated" and "regulatory" genes) show a clear statistical repulsion and have different ranges of correlations. In particular we find that isolated genes have a preference for shorter intergenic distances. These findings support previous evidence from gene expression patterns for two distinct logical types of control, namely digital control (i.e. network-based control mediated by dedicated transcription factors) and analog control (i.e. control based on genome structure and mediated by neighborhood on the genome).

  9. Current Evidence regarding Prophylactic Antibiotics in Head and Neck and Maxillofacial Surgery

    Science.gov (United States)

    2014-01-01

    Antibiotic prophylaxis is commonly used to decrease the rate of infections in head and neck surgery. The aim of this paper is to present the available evidence regarding the application of antibiotic prophylaxis in surgical procedures of the head and neck region in healthy patients. A systemic literature review based on Medline and Embase databases was performed. All reviews and meta-analyses based on RCTs in English from 2000 to 2013 were included. Eight out of 532 studies fulfilled all requirements. Within those, only seven different operative procedures were analyzed. Evidence exists for the beneficial use of prophylactic antibiotics for tympanostomy, orthognathic surgery, and operative tooth extractions. Unfortunately, little high-level evidence exists regarding the use of prophylactic antibiotics in head and neck surgery. In numerous cases, no clear benefit of antibiotic prophylaxis has been shown, particularly considering their potential adverse side effects. Antibiotics are often given unnecessarily and are administered too late and for too long. Furthermore, little research has been performed on the large number of routine cases in the above-mentioned areas of specialization within the last few years, although questions arising with respect to the treatment of high-risk patients or of specific infections are discussed on a broad base. PMID:25110703

  10. Representation and Misrepresentation of Scientific Evidence in Contemporary Tobacco Regulation: A Review of Tobacco Industry Submissions to the UK Government Consultation on Standardised Packaging

    Science.gov (United States)

    Ulucanlar, Selda; Fooks, Gary J.; Hatchard, Jenny L.; Gilmore, Anna B.

    2014-01-01

    Background Standardised packaging (SP) of tobacco products is an innovative tobacco control measure opposed by transnational tobacco companies (TTCs) whose responses to the UK government's public consultation on SP argued that evidence was inadequate to support implementing the measure. The government's initial decision, announced 11 months after the consultation closed, was to wait for ‘more evidence’, but four months later a second ‘independent review’ was launched. In view of the centrality of evidence to debates over SP and TTCs' history of denying harms and manufacturing uncertainty about scientific evidence, we analysed their submissions to examine how they used evidence to oppose SP. Methods and Findings We purposively selected and analysed two TTC submissions using a verification-oriented cross-documentary method to ascertain how published studies were used and interpretive analysis with a constructivist grounded theory approach to examine the conceptual significance of TTC critiques. The companies' overall argument was that the SP evidence base was seriously flawed and did not warrant the introduction of SP. However, this argument was underpinned by three complementary techniques that misrepresented the evidence base. First, published studies were repeatedly misquoted, distorting the main messages. Second, ‘mimicked scientific critique’ was used to undermine evidence; this form of critique insisted on methodological perfection, rejected methodological pluralism, adopted a litigation (not scientific) model, and was not rigorous. Third, TTCs engaged in ‘evidential landscaping’, promoting a parallel evidence base to deflect attention from SP and excluding company-held evidence relevant to SP. The study's sample was limited to sub-sections of two out of four submissions, but leaked industry documents suggest at least one other company used a similar approach. Conclusions The TTCs' claim that SP will not lead to public health benefits is largely

  11. Dispositional mindfulness and reward motivated eating: The role of emotion regulation and mental habit.

    Science.gov (United States)

    Fisher, Naomi R; Mead, Bethan R; Lattimore, Paul; Malinowski, Peter

    2017-11-01

    Evidence regarding the effectiveness of mindfulness based interventions (MBIs) for eating disorders, weight management and food craving is emerging and further studies are required to understand the underlying mechanisms of MBIs in these domains. The current study was designed to establish the role of specific mechanisms underlying the putative relationship between mindfulness and reward motivated eating. We predicted that mindfulness would be negatively related to features of reward motivated eating and that this association would be mediated by emotion regulation and habitual negative self-thinking. A cross-sectional survey measuring uncontrolled and emotional eating, mindfulness, emotion regulation and habitual negative self-thinking was completed by female and male meditators and non-meditators (N = 632). Lower levels of dispositional mindfulness were associated with difficulties in emotion regulation, habitual negative self-thinking and both emotional and uncontrolled eating. Difficulties in emotion regulation significantly mediated the mindfulness-uncontrolled eating relationship. Habitual negative self-thinking significantly mediated the mindfulness-emotional eating relationship. Participants with meditation experience reported greater levels of dispositional mindfulness, fewer difficulties with emotion regulation and habitual negative self-thinking and reduced uncontrolled eating tendencies, compared to non-meditators. The findings suggest that MBIs designed to change reward motivated eating and weight control should focus on emotion regulation and mental habits as underlying mechanisms. Copyright © 2017. Published by Elsevier Ltd.

  12. Local health rules and building regulations: a survey on local hygiene and building regulations in Italian municipalities.

    Science.gov (United States)

    Gola, Marco; Signorelli, Carlo; Buffoli, Maddalena; Rebecchi, Andrea; Capolongo, Stefano

    2017-01-01

    WHO has highlighted the need to strengthen the relationship between health and built environment factors, such as inappropriate housing conditions. Local Health Rules (LHRs) and Building Regulations (BRs) are tools which provide safety and building hygiene in construction practices. Currently the Italian Government is considering to establish a National Building Regulation and, related to the following purpose, this paper presents a survey on the status of adoption and updating of LHRs and BRs in Italian municipalities. The current Italian state of LHRs, BRs and Municipal Development Plans (MDPs) have been examined by a survey considering a sample of about 550 cities, with different demo graphic and geographic features, starting from the previous research work by Signorelli et al. (1999). The analysis underlines a serious shortage of updated LHRs, especially in small and medium-sized municipalities whereas BRs and MDPs are widespread. Only 30% of them are previously approved and validated by Local Health Authorities. Starting from a survey, the present scenario of Building Regulations requires the introduction of further performance guidelines instead of normative ones and, therefore, the current actions to give rise to a National Building Regulation could be integrated by building hygiene contents of LHRs.

  13. Neural Regulation of Pancreatic Cancer: A Novel Target for Intervention

    International Nuclear Information System (INIS)

    Chang, Aeson; Kim-Fuchs, Corina; Le, Caroline P.; Hollande, Frédéric; Sloan, Erica K.

    2015-01-01

    The tumor microenvironment is known to play a pivotal role in driving cancer progression and governing response to therapy. This is of significance in pancreatic cancer where the unique pancreatic tumor microenvironment, characterized by its pronounced desmoplasia and fibrosis, drives early stages of tumor progression and dissemination, and contributes to its associated low survival rates. Several molecular factors that regulate interactions between pancreatic tumors and their surrounding stroma are beginning to be identified. Yet broader physiological factors that influence these interactions remain unclear. Here, we discuss a series of preclinical and mechanistic studies that highlight the important role chronic stress plays as a physiological regulator of neural-tumor interactions in driving the progression of pancreatic cancer. These studies propose several approaches to target stress signaling via the β-adrenergic signaling pathway in order to slow pancreatic tumor growth and metastasis. They also provide evidence to support the use of β-blockers as a novel therapeutic intervention to complement current clinical strategies to improve cancer outcome in patients with pancreatic cancer

  14. Neural Regulation of Pancreatic Cancer: A Novel Target for Intervention

    Energy Technology Data Exchange (ETDEWEB)

    Chang, Aeson [Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria 3052 (Australia); Kim-Fuchs, Corina [Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria 3052 (Australia); Department of Visceral Surgery and Medicine, University Hospital Bern, Bern 3010 (Switzerland); Le, Caroline P. [Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria 3052 (Australia); Hollande, Frédéric [Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria 3052 (Australia); Department of Pathology, University of Melbourne, Parkville 3010 (Australia); Sloan, Erica K., E-mail: erica.sloan@monash.edu [Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria 3052 (Australia); Cousins Center for PNI, UCLA Semel Institute, Jonsson Comprehensive Cancer Center, and UCLA AIDS Institute, University of California Los Angeles, Los Angeles, CA 90095 (United States); Peter MacCallum Cancer Centre, Division of Cancer Surgery, East Melbourne, Victoria 3002 (Australia)

    2015-07-17

    The tumor microenvironment is known to play a pivotal role in driving cancer progression and governing response to therapy. This is of significance in pancreatic cancer where the unique pancreatic tumor microenvironment, characterized by its pronounced desmoplasia and fibrosis, drives early stages of tumor progression and dissemination, and contributes to its associated low survival rates. Several molecular factors that regulate interactions between pancreatic tumors and their surrounding stroma are beginning to be identified. Yet broader physiological factors that influence these interactions remain unclear. Here, we discuss a series of preclinical and mechanistic studies that highlight the important role chronic stress plays as a physiological regulator of neural-tumor interactions in driving the progression of pancreatic cancer. These studies propose several approaches to target stress signaling via the β-adrenergic signaling pathway in order to slow pancreatic tumor growth and metastasis. They also provide evidence to support the use of β-blockers as a novel therapeutic intervention to complement current clinical strategies to improve cancer outcome in patients with pancreatic cancer.

  15. Sex chromosome-specific regulation in the Drosophila male germline but little evidence for chromosomal dosage compensation or meiotic inactivation.

    Directory of Open Access Journals (Sweden)

    Colin D Meiklejohn

    2011-08-01

    Full Text Available The evolution of heteromorphic sex chromosomes (e.g., XY in males or ZW in females has repeatedly elicited the evolution of two kinds of chromosome-specific regulation: dosage compensation--the equalization of X chromosome gene expression in males and females--and meiotic sex chromosome inactivation (MSCI--the transcriptional silencing and heterochromatinization of the X during meiosis in the male (or Z in the female germline. How the X chromosome is regulated in the Drosophila melanogaster male germline is unclear. Here we report three new findings concerning gene expression from the X in Drosophila testes. First, X chromosome-wide dosage compensation appears to be absent from most of the Drosophila male germline. Second, microarray analysis provides no evidence for X chromosome-specific inactivation during meiosis. Third, we confirm the previous discovery that the expression of transgene reporters driven by autosomal spermatogenesis-specific promoters is strongly reduced when inserted on the X chromosome versus the autosomes; but we show that this chromosomal difference in expression is established in premeiotic cells and persists in meiotic cells. The magnitude of the X-autosome difference in transgene expression cannot be explained by the absence of dosage compensation, suggesting that a previously unrecognized mechanism limits expression from the X during spermatogenesis in Drosophila. These findings help to resolve several previously conflicting reports and have implications for patterns of genome evolution and speciation in Drosophila.

  16. Structural Evidence for Regulation and Specificity of Flaviviral Proteases and Evolution of the Flaviviridae Fold

    Energy Technology Data Exchange (ETDEWEB)

    Aleshin,A.; Shiryaev, S.; Strongin, A.; Liddington, R.

    2007-01-01

    Pathogenic members of the flavivirus family, including West Nile Virus (WNV) and Dengue Virus (DV), are growing global threats for which there are no specific treatments. The two-component flaviviral enzyme NS2B-NS3 cleaves the viral polyprotein precursor within the host cell, a process that is required for viral replication. Here, we report the crystal structure of WNV NS2B-NS3pro both in a substrate-free form and in complex with the trypsin inhibitor aprotinin/BPTI. We show that aprotinin binds in a substrate-mimetic fashion in which the productive conformation of the protease is fully formed, providing evidence for an 'induced fit' mechanism of catalysis and allowing us to rationalize the distinct substrate specificities of WNV and DV proteases. We also show that the NS2B cofactor of WNV can adopt two very distinct conformations and that this is likely to be a general feature of flaviviral proteases, providing further opportunities for regulation. Finally, by comparing the flaviviral proteases with the more distantly related Hepatitis C virus, we provide insights into the evolution of the Flaviviridae fold. Our work should expedite the design of protease inhibitors to treat a range of flaviviral infections.

  17. INADMISSIBLE EVIDENCE IN CIVIL PROCEDURE

    Directory of Open Access Journals (Sweden)

    Mihajlo Dika

    2016-01-01

    Full Text Available This paper examines the exclusion of specific means of evidence as instruments for determining the object of evidence, as well as the taking of evidence in the framework of the Croatian civil procedure law. The introduction lays the grounds for classifying and qualifying exclusion of evidence (general, special; absolute, relative; removable, irremovable; direct, indirect, after which greater attention is paid to the so called absolute and relative type; exclusionary evidence of the direct relative type pertaining to the establishing of facts, and evidence dismissals. With regard to the indirect relative type, the paper examines exclusionary evidence concerning the object of evidence. The remainder of the paper focuses on illegally obtained evidence, while outlining the constitutional, statutory, judicature and doctrinaire premises of bearing for such evidence. Subsequently, the question of evidence obtained in violation of the Constitutional guarantee of respect and legal protection of private and family life, dignity, reputation and honour, as well as evidence obtained by breach of the Constitutional guarantee of freedom and secrecy of correspondence and all other forms of communication, and in violation of the right to safety and privacy of personal data, are discussed too. In addition, the paper analyses the institutions of preclusion of evidence and the so called informative evidence. Concluding, the author points to a lacking regulation of inadmissible evidence within the Croatian civil procedure law, underlining the need to determine de lege ferenda legal requirements with a view to operationalizing inadmissible evidence within the Croatian civil procedure law.

  18. "Plain packaging" regulations for tobacco products: the impact of standardizing the color and design of cigarette packs.

    Science.gov (United States)

    Hammond, David

    2010-01-01

    Tobacco packaging and labeling policies have emerged as prominent and cost-effective tobacco control measures. Although packaging policies have primarily focused on health warnings, there is growing recognition of the importance of packaging as a marketing tool for the tobacco industry. The current paper reviews evidence on the potential impact of standardizing the color and design of tobacco packages -so called "plain" packaging. The evidence indicates three primary benefits of plain packaging: increasing the effectiveness of health warnings, reducing false health beliefs about cigarettes, and reducing brand appeal especially among youth and young adults. Overall, the research to date suggests that "plain" packaging regulations would be an effective tobacco control measure, particularly in jurisdictions with comprehensive restrictions on other forms of marketing.

  19. Emotion, emotion regulation and sleep: An intimate relationship

    Directory of Open Access Journals (Sweden)

    Marie Vandekerckhove

    2017-12-01

    Full Text Available In recent years, research has witnessed an increasing interest in the bidirectional relationship between emotion and sleep. Sleep seems important for restoring daily functioning, whereas deprivation of sleep makes us more emotionally aroused and sensitive to stressful stimuli and events. Sleep appears to be essential to our ability to cope with emotional stress in everyday life. However, when daily stress is insufficiently regulated, it may result in mental health problems and sleep disturbances too. Not only does emotion impact sleep, but there is also evidence that sleep plays a key role in regulating emotion. Emotional events during waking hours affect sleep, and the quality and amount of sleep influences the way we react to these events impacting our general well-being. Although we know that daytime emotional stress affects sleep by influencing sleep physiology, dream patterns, dream content and the emotion within a dream, its exact role is still unclear. Other effects that have been found are the exaggeration of the startle response, decrease in dream recall and elevation of awakening thresholds from rapid eye movement (REM, REM-sleep, increased or decreased latency to REM-sleep, increase in percentage of REM-density, REM-sleep duration, as well as the occurrence of arousals in sleep as a marker of sleep disruption. Equally, the way an individual copes with emotional stress, or the way in which an individual regulates emotion may modulate the effects of emotional stress on sleep. The research presented here supports the idea that adaptive emotion regulation benefits our follow-up sleep. We thus conclude the current review with a call for future research in order to clarify further the precise relationship between sleep, emotion and emotion regulation, as well as to explain further how sleep dissolves our emotional stress.

  20. Regulation of bone morphogenetic proteins in early embryonic development

    Science.gov (United States)

    Yamamoto, Yukiyo; Oelgeschläger, Michael

    2004-11-01

    Bone morphogenetic proteins (BMPs), a large subgroup of the TGF-β family of secreted growth factors, control fundamental events in early embryonic development, organogenesis and adult tissue homeostasis. The plethora of dose-dependent cellular processes regulated by BMP signalling demand a tight regulation of BMP activity. Over the last decade, a number of proteins have been identified that bind BMPs in the extracellular space and regulate the interaction of BMPs with their cognate receptors, including the secreted BMP antagonist Chordin. In the early vertebrate embryo, the localized secretion of BMP antagonists from the dorsal blastopore lip establishes a functional BMP signalling gradient that is required for the determination of the dorsoventral or back to belly body axis. In particular, inhibition of BMP activity is essential for the formation of neural tissue in the development of vertebrate and invertebrate embryos. Here we review recent studies that have provided new insight into the regulation of BMP signalling in the extracellular space. In particular, we discuss the recently identified Twisted gastrulation protein that modulates, in concert with metalloproteinases of the Tolloid family, the interaction of Chordin with BMP and a family of proteins that share structural similarities with Chordin in the respective BMP binding domains. In addition, genetic and functional studies in zebrafish and frog provide compelling evidence that the secreted protein Sizzled functionally interacts with the Chd BMP pathway, despite being expressed ventrally in the early gastrula-stage embryo. These intriguing discoveries may have important implications, not only for our current concept of early embryonic patterning, but also for the regulation of BMP activity at later developmental stages and tissue homeostasis in the adult.

  1. Choosing how to feel: emotion regulation choice in bipolar disorder.

    Science.gov (United States)

    Hay, Aleena C; Sheppes, Gal; Gross, James J; Gruber, June

    2015-04-01

    Individuals with bipolar disorder experience emotion regulation difficulties, even during remission, but are able to effectively employ emotion regulation strategies when instructed. We hypothesized that this puzzling discrepancy might be due to their maladaptive emotion regulation choices. To test this hypothesis, we used a previously validated paradigm (Sheppes, Scheibe, Suri, & Gross, 2011; Sheppes et al., 2014), and asked remitted individuals with bipolar I disorder (n = 25) and healthy individuals (n = 26) to view standardized positive and negative images of high and low intensity, and choose reappraisal or distraction to decrease their emotion intensity. Replicating and extending prior results, participants across both groups showed a pattern of choosing distraction more for high versus low intensity positive and negative images, but no between-groups differences were evident. These results suggest that emotion regulation choice patterns may be robust across samples, and add to growing evidence that several basic emotion regulation elements may remain intact in bipolar disorder. (c) 2015 APA, all rights reserved).

  2. A study on the relevance and influence of the existing regulation and risk informed/performance based regulation

    Energy Technology Data Exchange (ETDEWEB)

    Cheong, B. J.; Kang, J. M.; Kim, H. S.; Koh, S. H.; Kang, D. H.; Park, C. H. [Cheju Univ., Jeju (Korea, Republic of)

    2003-02-15

    The goal of this study is to estimate the relevance and Influence of the Existing Regulation and the RI-PBR to the institutionalization of the regulatory system. This study reviews the current regulatory system and the status of the RI-PBR implementation of the US NRC and Korea based upon SECY Papers, Risk Informed Regulation Implementation Plan (RIRIP) of the US NRC and other domestic studies. In order to investigate the perceptions, knowledge level, ground for the regulatory change, a survey was performed to Korean nuclear utilities, researchers and regulators on the perception on the RIR. The questionnaire was composed of 50 questions regarding personal details on work experience, level of education and specific field of work ; level of knowledge on the risk informed performance based regulation (RI-PBR); the perception of the current regulation, the effectiveness, level of procedure, flexibility, dependency on the regulator and personal view, and the perception of the RI-PBR such as flexibility of regulation, introduction time and the effect of RI-PBR, safety improvement, public perception, parts of the existing regulatory system that should be changed, etc. 515 answered from all sectors of the nuclear field; utilities, engineering companies, research institutes, and regulatory bodies.

  3. Concussions: What a neurosurgeon should know about current scientific evidence and management strategies

    Science.gov (United States)

    Neal, Matthew T.; Wilson, Jonathan L.; Hsu, Wesley; Powers, Alexander K.

    2012-01-01

    Background: There has been a tremendous amount of interest focused on the topic of concussions over the past few decades. Neurosurgeons are frequently consulted to manage patients with mild traumatic brain injuries (mTBI) that have radiographic evidence of cerebral injury. These injuries share significant overlap with concussions, injuries that typically do not reveal radiographic evidence of structural injury, in the realms of epidemiology, pathophysiology, outcomes, and management. Further, neurosurgeons often manage patients with extracranial injuries that have concomitant concussions. In these cases, neurosurgeons are often the only “concussion experts” that patients encounter. Results: The literature has been reviewed and data have been synthesized on the topic including sections on historical background, epidemiology, pathophysiology, diagnostic advances, clinical sequelae, and treatment suggestions, with neurosurgeons as the intended target audience. Conclusions: Neurosurgeons should have a fundamental knowledge of the scientific evidence that has developed regarding concussions and be prepared to guide patients with treatment plans. PMID:22439107

  4. Circuit Regulates Speed Of dc Motor

    Science.gov (United States)

    Weaver, Charles; Padden, Robin; Brown, Floyd A., Jr.

    1990-01-01

    Driving circuit regulates speed of small dc permanent-magnet motor in tape recorder. Two nested feedback loops maintain speed within 1 percent of constant value. Inner loop provides coarse regulation, while outer loop removes most of variation in speed that remains in the presence of regulation by the inner loop. Compares speed of motor with commanded speed and adjusts current supplied to motor accordingly.

  5. Ultra-Low-Dropout Linear Regulator

    Science.gov (United States)

    Thornton, Trevor; Lepkowski, William; Wilk, Seth

    2011-01-01

    A radiation-tolerant, ultra-low-dropout linear regulator can operate between -150 and 150 C. Prototype components were demonstrated to be performing well after a total ionizing dose of 1 Mrad (Si). Unlike existing components, the linear regulator developed during this activity is unconditionally stable over all operating regimes without the need for an external compensation capacitor. The absence of an external capacitor reduces overall system mass/volume, increases reliability, and lowers cost. Linear regulators generate a precisely controlled voltage for electronic circuits regardless of fluctuations in the load current that the circuit draws from the regulator.

  6. The roles of the amygdala in the affective regulation of body, brain, and behaviour

    Science.gov (United States)

    Mirolli, Marco; Mannella, Francesco; Baldassarre, Gianluca

    2010-09-01

    Despite the great amount of knowledge produced by the neuroscientific literature on affective phenomena, current models tackling non-cognitive aspects of behaviour are often bio-inspired but rarely bio-constrained. This paper presents a theoretical account of affective systems centred on the amygdala (Amg). This account aims to furnish a general framework and specific pathways to implement models that are more closely related to biological evidence. The Amg, which receives input from brain areas encoding internal states, innately relevant stimuli, and innately neutral stimuli, plays a fundamental role in the motivational and emotional processes of organisms. This role is based on the fact that Amg implements the two associative processes at the core of Pavlovian learning (conditioned stimulus (CS)-unconditioned stimulus (US) and CS-unconditioned response (UR) associations), and that it has the capacity of modulating these associations on the basis of internal states. These functionalities allow the Amg to play an important role in the regulation of the three fundamental classes of affective responses (namely, the regulation of body states, the regulation of brain states via neuromodulators, and the triggering of a number of basic behaviours fundamental for adaptation) and in the regulation of three high-level cognitive processes (namely, the affective labelling of memories, the production of goal-directed behaviours, and the performance of planning and complex decision-making). Our analysis is conducted within a methodological approach that stresses the importance of understanding the brain within an evolutionary/adaptive framework and with the aim of isolating general principles that can potentially account for the wider possible empirical evidence in a coherent fashion.

  7. Clone of EPA Approved Regulations in the Texas SIP

    Science.gov (United States)

    changed name to EPA Approved Regulations in the Texas SIP, Add links to:Texas Read Me; Texas SIP History;Current/Previous SIP-Approved Regulations; Delete regulations--now in /node/191099, removed tables

  8. Rip current evidence by hydrodynamic simulations, bathymetric surveys and UAV observation

    Directory of Open Access Journals (Sweden)

    G. Benassai

    2017-09-01

    Full Text Available The prediction of the formation, spacing and location of rip currents is a scientific challenge that can be achieved by means of different complementary methods. In this paper the analysis of numerical and experimental data, including RPAS (remotely piloted aircraft systems observations, allowed us to detect the presence of rip currents and rip channels at the mouth of Sele River, in the Gulf of Salerno, southern Italy. The dataset used to analyze these phenomena consisted of two different bathymetric surveys, a detailed sediment analysis and a set of high-resolution wave numerical simulations, completed with Google EarthTM images and RPAS observations. The grain size trend analysis and the numerical simulations allowed us to identify the rip current occurrence, forced by topographically constrained channels incised on the seabed, which were compared with observations.

  9. Developing the skills required for evidence-based practice.

    Science.gov (United States)

    French, B

    1998-01-01

    The current health care environment requires practitioners with the skills to find and apply the best currently available evidence for effective health care, to contribute to the development of evidence-based practice protocols, and to evaluate the impact of utilizing validated research findings in practice. Current approaches to teaching research are based mainly on gaining skills by participation in the research process. Emphasis on the requirement for rigour in the process of creating new knowledge is assumed to lead to skill in the process of using research information created by others. This article reflects upon the requirements for evidence-based practice, and the degree to which current approaches to teaching research prepare practitioners who are able to find, evaluate and best use currently available research information. The potential for using the principles of systematic review as a teaching and learning strategy for research is explored, and some of the possible strengths and weakness of this approach are highlighted.

  10. LARP6 Meets Collagen mRNA: Specific Regulation of Type I Collagen Expression

    Directory of Open Access Journals (Sweden)

    Yujie Zhang

    2016-03-01

    Full Text Available Type I collagen is the most abundant structural protein in all vertebrates, but its constitutive rate of synthesis is low due to long half-life of the protein (60–70 days. However, several hundred fold increased production of type I collagen is often seen in reparative or reactive fibrosis. The mechanism which is responsible for this dramatic upregulation is complex, including multiple levels of regulation. However, posttranscriptional regulation evidently plays a predominant role. Posttranscriptional regulation comprises processing, transport, stabilization and translation of mRNAs and is executed by RNA binding proteins. There are about 800 RNA binding proteins, but only one, La ribonucleoprotein domain family member 6 (LARP6, is specifically involved in type I collagen regulation. In the 5′untranslated region (5’UTR of mRNAs encoding for type I and type III collagens there is an evolutionally conserved stem-loop (SL structure; this structure is not found in any other mRNA, including any other collagen mRNA. LARP6 binds to the 5′SL in sequence specific manner to regulate stability of collagen mRNAs and their translatability. Here, we will review current understanding of how is LARP6 involved in posttranscriptional regulation of collagen mRNAs. We will also discuss how other proteins recruited by LARP6, including nonmuscle myosin, vimentin, serine threonine kinase receptor associated protein (STRAP, 25 kD FK506 binding protein (FKBP25 and RNA helicase A (RHA, contribute to this process.

  11. LIPIDS IN REGULATED EXOCYTOSIS: WHAT ARE THEY DOING?

    Directory of Open Access Journals (Sweden)

    Mohamed Raafet Ammar

    2013-09-01

    Full Text Available TThe regulated secretory pathway in neuroendocrine cells ends with the release of hormones and neurotransmitters following a rise in cytosolic calcium. This process known as regulated exocytosis involves the assembly of soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE proteins, the synaptic vesicle VAMP (synaptobrevin and the plasma membrane proteins syntaxin and SNAP-25. Although there is much evidence suggesting that SNARE proteins play a key role in the fusion machinery, other cellular elements regulating the kinetics, the extent of fusion, and the preparation of vesicle for release have received less attention. Among those factors, lipids have also been proposed to play important functions both at the level of secretory vesicle recruitment and late membrane fusion steps. Here, we will review the latest evidence supporting the concept of the fusogenic activity of lipids, and also discuss how this may be achieved. These possibilities include the recruitment and sequestration of the components of the exocytotic machinery, regulation of protein function and direct effects on membrane topology.

  12. Power supply regulation systems installed in the Fermilab accelerators

    Energy Technology Data Exchange (ETDEWEB)

    Hays, S.; Wolff, D.; Pfeffer, H.

    1991-11-01

    A variety of current and voltage regulation systems have been installed in the Fermilab large magnet system. The four major systems employ different methods to achieve the desired degree of regulation. The methods include computer control and feedback, adaptive learning, precision (10ppm) current monitoring, and the use of feed-forward signals. This paper will explain each method used and present the measured regulation of the above systems. Also an overview of planned upgrades and improvements will be presented.

  13. Lysine Deacetylases and Regulated Glycolysis in Macrophages.

    Science.gov (United States)

    Shakespear, Melanie R; Iyer, Abishek; Cheng, Catherine Youting; Das Gupta, Kaustav; Singhal, Amit; Fairlie, David P; Sweet, Matthew J

    2018-06-01

    Regulated cellular metabolism has emerged as a fundamental process controlling macrophage functions, but there is still much to uncover about the precise signaling mechanisms involved. Lysine acetylation regulates the activity, stability, and/or localization of metabolic enzymes, as well as inflammatory responses, in macrophages. Two protein families, the classical zinc-dependent histone deacetylases (HDACs) and the NAD-dependent HDACs (sirtuins, SIRTs), mediate lysine deacetylation. We describe here mechanisms by which classical HDACs and SIRTs directly regulate specific glycolytic enzymes, as well as evidence that links these protein deacetylases to the regulation of glycolysis-related genes. In these contexts, we discuss HDACs and SIRTs as key control points for regulating immunometabolism and inflammatory outputs from macrophages. Copyright © 2018 Elsevier Ltd. All rights reserved.

  14. Vitamin A as a key regulator of obesity & its associated disorders: Evidences from an obese rat model

    Directory of Open Access Journals (Sweden)

    Shanmugam M Jeyakumar

    2015-01-01

    Full Text Available During the last century, vitamin A has evolved from its classical role as a fat-soluble vitamin and attained the status of para-/autocrine hormone. Besides its well-established role in embryogenesis, growth and development, reproduction and vision, vitamin A has also been implicated in several other physiological processes. Emerging experimental evidences emphasize adipose tissue as an active endocrine organ with great propensity to continuous growth (throughout life. Due to various genetic and lifestyle factors, excess energy accumulates in adipose tissue as fat, resulting in obesity and other complications such as type 2 diabetes, hypertension, and cardiovascular disease. Recent in vitro and in vivo studies have shed light on vitamin A metabolites; retinaldehyde and retinoic acid and participation of their pathway proteins in the regulation of adipose tissue metabolism and thus, obesity. In this context, we discuss here some of our important findings, which establish the role of vitamin A (supplementation in obesity and its associated disorders by employing an obese rat model; WNIN/Ob strain.

  15. Economic impact of potential NORM regulations

    International Nuclear Information System (INIS)

    Smith, G.E.; Fitzgibbon, T.; Karp, S.

    1995-01-01

    Oil and gas field wastes and sites contaminated with naturally occurring radioactive materials (NORM) have quickly become a focus of substantial attention by regulators both at the state and federal level. Although currently regulated in a number of states, the Environmental Protection Agency (EPA) has indicated a desire to develop federal regulations to address management and disposal of NORM-contaminated wastes. This paper provides a brief overview of current state NORM regulations, currently available technologies for managing and disposing NORM wastes, and the cost of employing these techniques. Based on these characterizations and alternative assumptions about the volume of NORM wastes, four alternative scenarios have been developed to bracket potential future NORM requirements. These scenarios have been used is the basis for an analysis of the potential economic and supply impacts of NORM requirements on the U.S. oil and gas industry. The results illustrate that a reasonable approach to regulation that focuses only on those NORM wastes that pose a risk and allows producers to use safe, low cost disposal methods (downhole or other) would have minimal economic impacts on the oil and gas industry. A very stringent regulatory approach that covered large volumes of wastes, required the use of higher cost disposal techniques, and required extensive site clean-up activities could have a substantial economic impact, resulting in a loss of up to 20 percent of U.S. oil production and 8 percent of U.S. gas production by 2000. The costs of compliance with these alternative approaches could range from $71 million to over $14 billion annually. Between these two cases lies the opportunity for regulators to develop requirements for management and disposal of NORM wastes that will address any environmental and human health risks posed at industry sites without imposing unnecessarily costly regulations on the U.S. oil and gas E ampersand P industry

  16. Interplay of oxytocin, vasopressin, and sex hormones in the regulation of social recognition.

    Science.gov (United States)

    Gabor, Christopher S; Phan, Anna; Clipperton-Allen, Amy E; Kavaliers, Martin; Choleris, Elena

    2012-02-01

    Social Recognition is a fundamental skill that forms the basis of behaviors essential to the proper functioning of pair or group living in most social species. We review here various neurobiological and genetic studies that point to an interplay of oxytocin (OT), arginine-vasopressin (AVP), and the gonadal hormones, estrogens and testosterone, in the mediation of social recognition. Results of a number of studies have shown that OT and its actions at the medial amygdala seem to be essential for social recognition in both sexes. Estrogens facilitate social recognition, possibly by regulating OT production in the hypothalamus and the OT receptors at the medial amygdala. Estrogens also affect social recognition on a rapid time scale, likely through nongenomic actions. The mechanisms of these rapid effects are currently unknown but available evidence points at the hippocampus as the possible site of action. Male rodents seem to be more dependent on AVP acting at the level of the lateral septum for social recognition than female rodents. Results of various studies suggest that testosterone and its metabolites (including estradiol) influence social recognition in males primarily through the AVP V1a receptor. Overall, it appears that gonadal hormone modulation of OT and AVP regulates and fine tunes social recognition and those behaviors that depend upon it (e.g., social bonds, social hierarchies) in a sex specific manner. This points at an important role for these neuroendocrine systems in the regulation of the sex differences that are evident in social behavior and of sociality as a whole.

  17. Regulating the unknown: Managing the occupational health risks of nanomedical technologies and nanopharmaceuticals in the research laboratory

    Science.gov (United States)

    Ersin, Ozlem Hacer

    Novel technologies and their resultant products demand fresh ways of thinking about pre-market risk analysis and post-market surveillance. A regulatory framework that is responsive to emerging knowledge about the hazards of novel technologies offers repeatable and transparent processes and remains economically and socially feasible. Workers are an especially vulnerable population who are exposed to unknown hazards of novel technologies and serve often as unwitting sentinels of impending risks. This Grounded Theory-based case study identifies gaps in our current ability to regulate novel technologies so as to minimize occupational health risks and offers necessary modifications for an environment that is conducive to proper regulation. Nanopharmaceuticals and the nano-based technologies at their base are used by way of exemplar technologies that are currently taxing the ability of the regulatory system to provide adequate oversight. Ambiguities of definition, absence of a tracking system (of who is doing nanotechnology research), and the paucity of scientific evidence to support risk management efforts are among the findings of the study and need to be addressed as ameliorative steps toward an effective regulatory structure.

  18. Planned and proposed pipeline regulations

    International Nuclear Information System (INIS)

    De Leon, C.

    1992-01-01

    The Research and Special Programs Administration administers the Natural Gas Pipeline Safety Act of 1968 (NGPSA) and the Hazardous Liquid Pipeline Safety Act of 1979 (HLPSA). The RSPA issues and enforces design, construction, operation and maintenance regulations for natural gas pipelines and hazardous liquid pipelines. This paper discusses a number of proposed and pending safety regulations and legislative initiatives currently being considered by the RSPA and the US Congress. Some new regulations have been enacted. The next few years will see a great deal of regulatory activity regarding natural gas and hazardous liquid pipelines, much of it resulting from legislative requirements. The office of Pipeline Safety is currently conducting a study to streamline its operations. This study is analyzing the office's business, social and technical operations with the goal of improving overall efficiency, effectiveness, productivity and job satisfaction to meet the challenges of the future

  19. Improvement of automatic control system for high-speed current collectors

    Science.gov (United States)

    Sidorov, O. A.; Goryunov, V. N.; Golubkov, A. S.

    2018-01-01

    The article considers the ways of regulation of pantographs to provide quality and reliability of current collection at high speeds. To assess impact of regulation was proposed integral criterion of the quality of current collection, taking into account efficiency and reliability of operation of the pantograph. The study was carried out using mathematical model of interaction of pantograph and catenary system, allowing to assess contact force and intensity of arcing at the contact zone at different movement speeds. The simulation results allowed us to estimate the efficiency of different methods of regulation of pantographs and determine the best option.

  20. Context-Dependent Modulation of GABAAR-Mediated Tonic Currents

    DEFF Research Database (Denmark)

    Patel, Bijal; Bright, Damian P; Mortensen, Martin

    2016-01-01

    UNLABELLED: Tonic GABA currents mediated by high-affinity extrasynaptic GABAA receptors, are increasingly recognized as important regulators of cell and neuronal network excitability. Dysfunctional GABAA receptor signaling that results in modified tonic GABA currents is associated with a number o...

  1. Proteomic evidences for rex regulation of metabolism in toxin-producing Bacillus cereus ATCC 14579.

    Directory of Open Access Journals (Sweden)

    Sabrina Laouami

    Full Text Available The facultative anaerobe, Bacillus cereus, causes diarrheal diseases in humans. Its ability to deal with oxygen availability is recognized to be critical for pathogenesis. The B. cereus genome comprises a gene encoding a protein with high similarities to the redox regulator, Rex, which is a central regulator of anaerobic metabolism in Bacillus subtilis and other Gram-positive bacteria. Here, we showed that B. cereus rex is monocistronic and down-regulated in the absence of oxygen. The protein encoded by rex is an authentic Rex transcriptional factor since its DNA binding activity depends on the NADH/NAD+ ratio. Rex deletion compromised the ability of B. cereus to cope with external oxidative stress under anaerobiosis while increasing B. cereus resistance against such stress under aerobiosis. The deletion of rex affects anaerobic fermentative and aerobic respiratory metabolism of B. cereus by decreasing and increasing, respectively, the carbon flux through the NADH-recycling lactate pathway. We compared both the cellular proteome and exoproteome of the wild-type and Δrex cells using a high throughput shotgun label-free quantitation approach and identified proteins that are under control of Rex-mediated regulation. Proteomics data have been deposited to the ProteomeXchange with identifier PXD000886. The data suggest that Rex regulates both the cross-talk between metabolic pathways that produce NADH and NADPH and toxinogenesis, especially in oxic conditions.

  2. Quantitative analysis of the Ca2+‐dependent regulation of delayed rectifier K+ current I Ks in rabbit ventricular myocytes

    Science.gov (United States)

    Bartos, Daniel C.; Morotti, Stefano; Ginsburg, Kenneth S.; Grandi, Eleonora

    2017-01-01

    Key points [Ca2+]i enhanced rabbit ventricular slowly activating delayed rectifier K+ current (I Ks) by negatively shifting the voltage dependence of activation and slowing deactivation, similar to perfusion of isoproterenol.Rabbit ventricular rapidly activating delayed rectifier K+ current (I Kr) amplitude and voltage dependence were unaffected by high [Ca2+]i.When measuring or simulating I Ks during an action potential, I Ks was not different during a physiological Ca2+ transient or when [Ca2+]i was buffered to 500 nm. Abstract The slowly activating delayed rectifier K+ current (I Ks) contributes to repolarization of the cardiac action potential (AP). Intracellular Ca2+ ([Ca2+]i) and β‐adrenergic receptor (β‐AR) stimulation modulate I Ks amplitude and kinetics, but details of these important I Ks regulators and their interaction are limited. We assessed the [Ca2+]i dependence of I Ks in steady‐state conditions and with dynamically changing membrane potential and [Ca2+]i during an AP. I Ks was recorded from freshly isolated rabbit ventricular myocytes using whole‐cell patch clamp. With intracellular pipette solutions that controlled free [Ca2+]i, we found that raising [Ca2+]i from 100 to 600 nm produced similar increases in I Ks as did β‐AR activation, and the effects appeared additive. Both β‐AR activation and high [Ca2+]i increased maximally activated tail I Ks, negatively shifted the voltage dependence of activation, and slowed deactivation kinetics. These data informed changes in our well‐established mathematical model of the rabbit myocyte. In both AP‐clamp experiments and simulations, I Ks recorded during a normal physiological Ca2+ transient was similar to I Ks measured with [Ca2+]i clamped at 500–600 nm. Thus, our study provides novel quantitative data as to how physiological [Ca2+]i regulates I Ks amplitude and kinetics during the normal rabbit AP. Our results suggest that micromolar [Ca2+]i, in the submembrane or junctional cleft

  3. Conceptual representations in mind and brain: theoretical developments, current evidence and future directions.

    Science.gov (United States)

    Kiefer, Markus; Pulvermüller, Friedemann

    2012-07-01

    Conceptual representations in long-term memory crucially contribute to perception and action, language and thought. However, the precise nature of these conceptual memory traces is discussed controversially. In particular, the grounding of concepts in the sensory and motor brain systems is the focus of a current debate. Here, we review theoretical accounts of the structure and neural basis of conceptual memory and evaluate them in light of recent empirical evidence. Models of conceptual processing can be distinguished along four dimensions: (i) amodal versus modality-specific, (ii) localist versus distributed, (iii) innate versus experience-dependent, and (iv) stable versus flexible. A systematic review of behavioral and neuroimaging studies in healthy participants along with brain-damaged patients will then be used to evaluate the competing theoretical approaches to conceptual representations. These findings indicate that concepts are flexible, distributed representations comprised of modality-specific conceptual features. Conceptual features are stored in distinct sensory and motor brain areas depending on specific sensory and motor experiences during concept acquisition. Three important controversial issues are highlighted, which require further clarification in future research: the existence of an amodal conceptual representation in the anterior temporal lobe, the causal role of sensory and motor activation for conceptual processing and the grounding of abstract concepts in perception and action. We argue that an embodiment view of conceptual representations realized as distributed sensory and motor cell assemblies that are complemented by supramodal integration brain circuits may serve as a theoretical framework to guide future research on concrete and abstract concepts. Copyright © 2011 Elsevier Srl. All rights reserved.

  4. The effect of taxation and regulation on cigarette smoking: Fresh evidence from Turkey.

    Science.gov (United States)

    Cetin, Tamer

    2017-12-01

    Enacting Law No 5247 in May 2008, Turkey has initiated crucial anti-tobacco policies in the last decade. This paper aims to reveal on the effect of anti-tobacco policies such as excise taxes and regulations on cigarette smoking. To this aim, I empirically investigate the long-term dynamics of demand for cigarettes in Turkey through the OLS estimation strategy under various scenarios and models. Using monthly and quarterly data that cover the pre- and post- anti-smoking policy periods, I estimate demand elasticities and compare the pre- and post- taxation and regulation terms. The results presented in the paper confirm that taxation and regulation have affected the long-term dynamics of demand for cigarettes. The price and income elasticities of demand for cigarettes are significantly higher than the previous literature on Turkey. Demand elasticities have increased on average in the anti-tobacco policies period. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Future Regulations – A Catalyst for Technology Development

    Science.gov (United States)

    Summary of current mobile source regulations and EPA mobile source regulatory authority with an emphasis on how EPA regulations are a driver for the development and introduction of automotive technology.

  6. Toddler's self-regulation strategies in a challenge context are nap-dependent.

    Science.gov (United States)

    Miller, Alison L; Seifer, Ronald; Crossin, Rebecca; Lebourgeois, Monique K

    2015-06-01

    Early childhood represents a time of developmental changes in both sleep and self-regulation, a construct reflecting the ability to control one's behaviour, attention and emotions when challenged. Links between sleep and self-regulation processes have been proposed, but experimental evidence with young children is lacking. In the current study, we tested the effects of acute sleep restriction (nap deprivation) on toddlers' self-regulation. Healthy children (n = 12; four males; aged 30-36 months (33.9 ± 1.7)) slept on a strict schedule (verified with actigraphy and sleep diaries) for 5 days before each of two afternoon assessments following a nap and a no-nap condition (~11-day protocol). Children were videotaped while attempting an unsolvable puzzle, and 10 mutually exclusive self-regulation strategies were later coded. On average, children lost ~90 min of sleep on the no-nap versus the nap day. Nap deprivation resulted in moderate-to-large effects on self-regulation strategies, with decreases in scepticism (d = 0.77; 7% change), negative self-appraisal (d = 0.92; 5% change) and increases in physical self-soothing (d = 0.68; 10% change), focus on the puzzle piece that would not fit (perseveration; d = 0.50; 9% change) and insistence on completing the unsolvable puzzle (d = 0.91; 10% change). Results suggest that sleep serves an important role in the way that toddlers respond to challenging events in their daily lives. After losing daytime sleep, toddlers were less able to engage effectively in a difficult task and reverted to less mature self-regulation strategies than when they were well rested. Over time, chronically missed sleep may impair young children's self-regulation abilities, resulting in risk for social-emotional, behavioural and school problems. © 2014 European Sleep Research Society.

  7. Regulation of Plant Microprocessor Function in Shaping microRNA Landscape

    Directory of Open Access Journals (Sweden)

    Jakub Dolata

    2018-06-01

    Full Text Available MicroRNAs are small molecules (∼21 nucleotides long that are key regulators of gene expression. They originate from long stem–loop RNAs as a product of cleavage by a protein complex called Microprocessor. The core components of the plant Microprocessor are the RNase type III enzyme Dicer-Like 1 (DCL1, the zinc finger protein Serrate (SE, and the double-stranded RNA binding protein Hyponastic Leaves 1 (HYL1. Microprocessor assembly and its processing of microRNA precursors have been reported to occur in discrete nuclear bodies called Dicing bodies. The accessibility of and modifications to Microprocessor components affect microRNA levels and may have dramatic consequences in plant development. Currently, numerous lines of evidence indicate that plant Microprocessor activity is tightly regulated. The cellular localization of HYL1 is dependent on a specific KETCH1 importin, and the E3 ubiquitin ligase COP1 indirectly protects HYL1 from degradation in a light-dependent manner. Furthermore, proper localization of HYL1 in Dicing bodies is regulated by MOS2. On the other hand, the Dicing body localization of DCL1 is regulated by NOT2b, which also interacts with SE in the nucleus. Post-translational modifications are substantial factors that contribute to protein functional diversity and provide a fine-tuning system for the regulation of protein activity. The phosphorylation status of HYL1 is crucial for its activity/stability and is a result of the interplay between kinases (MPK3 and SnRK2 and phosphatases (CPL1 and PP4. Additionally, MPK3 and SnRK2 are known to phosphorylate SE. Several other proteins (e.g., TGH, CDF2, SIC, and RCF3 that interact with Microprocessor have been found to influence its RNA-binding and processing activities. In this minireview, recent findings on the various modes of Microprocessor activity regulation are discussed.

  8. The regulatory practice of the French financial regulator, 2006-2011. From substantive to procedural financial regulation?

    Directory of Open Access Journals (Sweden)

    Thierry Kirat

    2015-11-01

    Full Text Available Fraud and misconduct in financial markets have recently become a key regulatory issue against the backdrop of the financial crisis. This paper investigates the sanctions policy and practices of the French financial regulator, Autorité des Marchés Financiers (AMF. It argues that, over time, the AMF has shifted from substantive to procedural regulation of finance. This shift consists in departing from sanctions based on observed outcomes in the market and, instead, assessing how the internal organizational schemes of financial firms actually perform. The AMF’s new policy and practice involves a process of legalization of organizations; it also evidences a tendency to delegate regulation to financial firms themselves

  9. Risk informed regulation of nuclear facilities: Overview of the current status

    International Nuclear Information System (INIS)

    2005-02-01

    This report provides guidance on the use of risk information by regulatory bodies as part of an integrated decision making process. This addresses the way in which risk information is being used in decisions about safety issues at nuclear plants, sometimes referred to as risk informed decision making, and how risk information is being used by regulatory bodies as an input into the activities that they carry out, sometimes referred to as risk informed regulation

  10. Epigenetic Regulation of Adipokines

    Directory of Open Access Journals (Sweden)

    Tho X. Pham

    2017-08-01

    Full Text Available Adipose tissue expansion in obesity leads to changes in the expression of adipokines, adipocyte-specific hormones that can regulate whole body energy metabolism. Epigenetic regulation of gene expression is a mechanism by which cells can alter gene expression through the modifications of DNA and histones. Epigenetic mechanisms, such as DNA methylation and histone modifications, are intimately tied to energy metabolism due to their dependence on metabolic intermediates such as S-adenosylmethionine and acetyl-CoA. Altered expression of adipokines in obesity may be due to epigenetic changes. The goal of this review is to highlight current knowledge of epigenetic regulation of adipokines.

  11. Smart-grid investments, regulation and organization

    International Nuclear Information System (INIS)

    Agrell, Per J.; Bogetoft, Peter; Mikkers, Misja

    2013-01-01

    Grid infrastructure managers worldwide are facing demands for reinvestments in new assets with higher on-grid and off-grid functionality in order to meet new environmental targets. The roles of the current actors will change as the vertical interfaces between regulated and unregulated tasks become blurred. In this paper, we characterize some of the effects of new asset investments policy on the network tasks, assets and costs and contrast this with the assumptions of the current economic network regulation. To provide structure, we present a model of investment provision under regulation between a distribution system operator and a potential investor–generator. The results from the model confirm the hypothesis that network regulation should find a focal point, should integrate externalities in the performance assessment and should avoid wide delegation of contracting-billing for smart-grid investments. - Highlights: ► We review regulatory solutions for smart-grid and DER investments. ► What matters more than upfront incentives is organization and delegation. ► We model regulated investment under private information by a generator or a DSO. ► Highest welfare for high-powered incentives and centralized information. ► Market approaches likely to give poor outcomes for this case.

  12. Analysis tools for the interplay between genome layout and regulation.

    Science.gov (United States)

    Bouyioukos, Costas; Elati, Mohamed; Képès, François

    2016-06-06

    Genome layout and gene regulation appear to be interdependent. Understanding this interdependence is key to exploring the dynamic nature of chromosome conformation and to engineering functional genomes. Evidence for non-random genome layout, defined as the relative positioning of either co-functional or co-regulated genes, stems from two main approaches. Firstly, the analysis of contiguous genome segments across species, has highlighted the conservation of gene arrangement (synteny) along chromosomal regions. Secondly, the study of long-range interactions along a chromosome has emphasised regularities in the positioning of microbial genes that are co-regulated, co-expressed or evolutionarily correlated. While one-dimensional pattern analysis is a mature field, it is often powerless on biological datasets which tend to be incomplete, and partly incorrect. Moreover, there is a lack of comprehensive, user-friendly tools to systematically analyse, visualise, integrate and exploit regularities along genomes. Here we present the Genome REgulatory and Architecture Tools SCAN (GREAT:SCAN) software for the systematic study of the interplay between genome layout and gene expression regulation. SCAN is a collection of related and interconnected applications currently able to perform systematic analyses of genome regularities as well as to improve transcription factor binding sites (TFBS) and gene regulatory network predictions based on gene positional information. We demonstrate the capabilities of these tools by studying on one hand the regular patterns of genome layout in the major regulons of the bacterium Escherichia coli. On the other hand, we demonstrate the capabilities to improve TFBS prediction in microbes. Finally, we highlight, by visualisation of multivariate techniques, the interplay between position and sequence information for effective transcription regulation.

  13. Managing caries: the need to close the gap between the evidence base and current practice.

    Science.gov (United States)

    Schwendicke, F; Doméjean, S; Ricketts, D; Peters, M

    2015-11-13

    Underpinned by a changing knowledge of the aetiology of caries and its sequelae, and assisted by established and advancing dental materials, there is growing evidence supporting less invasive management of dental caries based on the principles of minimal intervention dentistry. This narrative review assesses both the evidence and the adoption of less invasive caries management strategies and describes ways in which the gap between evidence and practice might be overcome. While there is increasing data supporting less invasive management of carious lesions, these are not standard in most dental practices worldwide. Usually, clinical studies focused on efficacy as outcome, and did not take into consideration the views and priorities of other stakeholders, such as primary care dentists, educators, patients and those financing services. Involving these stakeholders into study design and demonstrating the broader advantages of new management strategies might improve translation of research into practice. In theory, clinical dentists can rely on a growing evidence in cariology regarding less invasive management options. In practice, further factors seem to impede adoption of these strategies. Future research should address these factors by involving major stakeholders and investigating their prioritised outcomes to narrow or close the evidence gap.

  14. A robust low quiescent current power receiver for inductive power transmission in bio implants

    Science.gov (United States)

    Helalian, Hamid; Pasandi, Ghasem; Jafarabadi Ashtiani, Shahin

    2017-05-01

    In this paper, a robust low quiescent current complementary metal-oxide semiconductor (CMOS) power receiver for wireless power transmission is presented. This power receiver consists of three main parts including rectifier, switch capacitor DC-DC converter and low-dropout regulator (LDO) without output capacitor. The switch capacitor DC-DC converter has variable conversion ratios and synchronous controller that lets the DC-DC converter to switch among five different conversion ratios to prevent output voltage drop and LDO regulator efficiency reduction. For all ranges of output current (0-10 mA), the voltage regulator is compensated and is stable. Voltage regulator stabilisation does not need the off-chip capacitor. In addition, a novel adaptive biasing frequency compensation method for low dropout voltage regulator is proposed in this paper. This method provides essential minimum current for compensation and reduces the quiescent current more effectively. The power receiver was designed in a 180-nm industrial CMOS technology, and the voltage range of the input is from 0.8 to 2 V, while the voltage range of the output is from 1.2 to 1.75 V, with a maximum load current of 10 mA, the unregulated efficiency of 79.2%, and the regulated efficiency of 64.4%.

  15. Ribosomal S6K1 in POMC and AgRP Neurons Regulates Glucose Homeostasis but Not Feeding Behavior in Mice.

    Science.gov (United States)

    Smith, Mark A; Katsouri, Loukia; Irvine, Elaine E; Hankir, Mohammed K; Pedroni, Silvia M A; Voshol, Peter J; Gordon, Matthew W; Choudhury, Agharul I; Woods, Angela; Vidal-Puig, Antonio; Carling, David; Withers, Dominic J

    2015-04-21

    Hypothalamic ribosomal S6K1 has been suggested as a point of convergence for hormonal and nutrient signals in the regulation of feeding behavior, bodyweight, and glucose metabolism. However, the long-term effects of manipulating hypothalamic S6K1 signaling on energy homeostasis and the cellular mechanisms underlying these roles are unclear. We therefore inactivated S6K1 in pro-opiomelanocortin (POMC) and agouti-related protein (AgRP) neurons, key regulators of energy homeostasis, but in contrast to the current view, we found no evidence that S6K1 regulates food intake and bodyweight. In contrast, S6K1 signaling in POMC neurons regulated hepatic glucose production and peripheral lipid metabolism and modulated neuronal excitability. S6K1 signaling in AgRP neurons regulated skeletal muscle insulin sensitivity and was required for glucose sensing by these neurons. Our findings suggest that S6K1 signaling is not a general integrator of energy homeostasis in the mediobasal hypothalamus but has distinct roles in the regulation of glucose homeostasis by POMC and AgRP neurons. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  16. Is Current Account of Turkey Sustainable ? Evidence from Nonlinear Unit Root Tests

    Directory of Open Access Journals (Sweden)

    Serkan Taştan

    2015-09-01

    Full Text Available In this paper, current account sustainability of Turkey is analyzed in a nonlinear framework. Various nonlinear unit root tests have been used to test for structural break, sign and size nonlinearity. We have tested structural break and size nonlinearity separately and structural break-sign and size-sign nonlinearities simultaneously. Only considering the size nonlinearity, we have found that the current account of Turkey is sustainable. Thus, the size nonlinearity, in other words the speed of reversion to equilibrium, is essential for the current account sustainability of Turkey. We have also found that the speed of adjustment towards equilibrium is symmetric, while considering size and sign nonlinearities simultaneously.

  17. The fetal programming of food preferences: current clinical and experimental evidence.

    Science.gov (United States)

    Dalle Molle, R; Bischoff, A R; Portella, A K; Silveira, P P

    2015-09-28

    Increased energy consumption is one of the major factors implicated in the epidemic of obesity. There is compelling evidence, both clinical and experimental, that fetal paucity of nutrients may have programming effects on feeding preferences and behaviors that can contribute to the development of diseases. Clinical studies in different age groups show that individuals born small for their gestational age (SGA) have preferences towards highly caloric foods such as carbohydrates and fats. Some studies have also shown altered eating behaviors in SGA children. Despite an apparent discrepancy in different age groups, all studies seem to converge to an increased intake of palatable foods in SGA individuals. Small nutrient imbalances across lifespan increase the risk of noncommunicable diseases in adult life. Homeostatic factors such as altered responses to leptin and insulin and alterations in neuropeptides associated with appetite and satiety are likely involved. Imbalances between homeostatic and hedonic signaling are another proposed mechanism, with the mesocorticolimbic dopaminergic pathway having differential reward and pleasure responses when facing palatable foods. Early exposure to undernutrition also programs hypothalamic-pituitary-adrenal axis, with SGA having higher levels of cortisol in different ages, leading to chronic hyperactivity of this neuroendocrine axis. This review summarizes the clinical and experimental evidence related to fetal programming of feeding preferences by SGA.

  18. An appraisal of current regulations and recommendations in relation to proposals for the use of X-ray optics equipment

    International Nuclear Information System (INIS)

    Weatherley, E.G.

    1984-01-01

    Current regulatory requirements for the use of x-ray optics equipment in factories are compared with the 19-year-old Guidance Notes for their use in research and teaching establishments. The difficulties in drafting new legislation to cater for both areas of use are discussed and the proposed regulations and approved code of practice having a direct bearing on x-ray optics equipment are reviewed. Comment is made concerning the proposed Health and Safety Executive document, ''Radiation Safety in the use of X-ray Optics Equipment, which will give practical advice and guidance on cost effective methods of achieving the regulatory objectives. The costs involved are unlikely to be significant for the majority of users and implementation of the proposed legislation should not restrict the use of x-ray optics equipment. (author)

  19. Progress toward pharmacotherapies for cannabis-use disorder: an evidence-based review

    Directory of Open Access Journals (Sweden)

    Copel

    2016-05-01

    Full Text Available Jan Copeland, Izabella Pokorski UNSW Medicine, University of New South Wales, Sydney, NSW, Australia Abstract: Cannabis is the most widely used and variably regulated drug in the world, with increasing trends of use being reported in the US, Australia, Asia, and Africa. Evidence has shown a decrease in the age of commencement of cannabis use in some developed countries and a prolongation of risk of initiation to cannabis use beyond adolescence among more recent users. Cannabis use is associated with numerous health risks and long-term morbidity, as well as risk of developing cannabis-use disorders. Cannabis users infrequently seek professional treatment, and normally do so after a decade of use. Cannabis-use disorders are currently treated using a selection of psychosocial interventions. Severity of withdrawal is a factor that increases the risk of relapse, and is the target of pharmacotherapy studies. Currently, there is no approved pharmacotherapy for cannabis-use disorders. A number of approaches have been examined, and trials are continuing to find a safe and effective medication with little abuse liability. Keywords: marijuana, treatment, intervention, withdrawal, cannabinoid

  20. Candidate genes for COPD: current evidence and research

    Directory of Open Access Journals (Sweden)

    Kim WJ

    2015-10-01

    Full Text Available Woo Jin Kim,1 Sang Do Lee2 1Department of Internal Medicine and Environmental Health Center, Kangwon National University, Chuncheon, 2Department of Pulmonary and Critical Care Medicine, Clinical Research Center for Chronic Obstructive Airway Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea Abstract: COPD is a common complex disease characterized by progressive airflow limitation. Several genome-wide association studies (GWASs have discovered genes that are associated with COPD. Recently, candidate genes for COPD identified by GWASs include CHRNA3/5 (cholinergic nicotine receptor alpha 3/5, IREB2 (iron regulatory binding protein 2, HHIP (hedgehog-interacting protein, FAM13A (family with sequence similarity 13, member A, and AGER (advanced glycosylation end product–specific receptor. Their association with COPD susceptibility has been replicated in multiple populations. Since these candidate genes have not been considered in COPD, their pathological roles are still largely unknown. Herein, we review some evidences that they can be effective drug targets or serve as biomarkers for diagnosis or subtyping. However, more study is required to understand the functional roles of these candidate genes. Future research is needed to characterize the effect of genetic variants, validate gene function in humans and model systems, and elucidate the genes’ transcriptional and posttranscriptional regulatory mechanisms. Keywords: chronic obstructive pulmonary disease, genetics, genome-wide association study

  1. 31 CFR 363.21 - When may you require offline authentication and documentary evidence?

    Science.gov (United States)

    2010-07-01

    ... authentication and documentary evidence? 363.21 Section 363.21 Money and Finance: Treasury Regulations Relating... TreasuryDirect § 363.21 When may you require offline authentication and documentary evidence? We may require offline authentication and documentary evidence at our option. [74 FR 19419, Apr. 29, 2009] ...

  2. Discrepancy-based and anticipated emotions in behavioral self-regulation.

    Science.gov (United States)

    Brown, Christina M; McConnell, Allen R

    2011-10-01

    Discrepancies between one's current and desired states evoke negative emotions, which presumably guide self-regulation. In the current work we evaluated the function of discrepancy-based emotions in behavioral self-regulation. Contrary to classic theories of self-regulation, discrepancy-based emotions did not predict the degree to which people engaged in self-regulatory behavior. Instead, expectations about how future self-discrepancies would make one feel (i.e., anticipated emotions) predicted self-regulation. However, anticipated emotions were influenced by previous discrepancy-based emotional experiences, suggesting that the latter do not directly motivate self-regulation but rather guide expectations. These findings are consistent with the perspective that emotions do not necessarily direct immediate behavior, but rather have an indirect effect by guiding expectations, which in turn predict goal-directed action.

  3. Diagnostic utility of selective nerve root blocks in the diagnosis of lumbosacral radicular pain: systematic review and update of current evidence.

    Science.gov (United States)

    Datta, Sukdeb; Manchikanti, Laxmaiah; Falco, Frank J E; Calodney, Aaron K; Atluri, Sairam; Benyamin, Ramsin M; Buenaventura, Ricardo M; Cohen, Steven P

    2013-04-01

      Lumbosacral selective nerve root blocks and/ or transforaminal epidural injections are used for diagnosis and treatment of different disorders causing low back and lower extremity pain. A clear consensus on the use of selective nerve root injections as a diagnostic tool does not currently exist. Additionally, the validity of this procedure as a diagnostic tool is not clear. To evaluate and update the accuracy of selective nerve root injections in diagnosing lumbar spinal disorders. A systematic review of selective nerve root blocks for the diagnosis of low back and lower extremity pain. Methodological quality assessment of included studies was performed using the Quality Appraisal of Reliability Studies (QAREL) checklist. Only diagnostic accuracy studies meeting at least 50% of the designated inclusion criteria were utilized for analysis. Studies scoring less than 50% are presented descriptively and analyzed critically. The level of evidence was classified as good, fair, or limited or poor based on the quality of evidence grading scale developed by the United States Preventive Services Task Force (USPSTF). Data sources included relevant literature identified through searches of PubMed and EMBASE from 1966 to September 2012, and manual searches of the bibliographies of known primary and review articles. In this review, we evaluated studies in which controlled local anesthetic blocks were performed using at least 50% pain relief as the reference standard. There is limited evidence for the accuracy of selective nerve root injections as a diagnostic tool for lumbosacral disorders. There is limited evidence for their use in the preoperative evaluation of patients with negative or inconclusive imaging studies. The limitations of this systematic review include a paucity of literature, variations in technique, and variable criterion standards for the diagnosis of lumbar radicular pain. There is limited evidence for selective nerve root injections as a diagnostic tool in

  4. GABAB receptor phosphorylation regulates KCTD12-induced K+ current desensitization

    DEFF Research Database (Denmark)

    Adelfinger, L; Turecek, R; Ivankova, K

    2014-01-01

    released from the G-protein. Receptor-activated K+ currents desensitize in the sustained presence of agonist to avoid excessive effects on neuronal activity. Desensitization of K+ currents integrates distinct mechanistic underpinnings. GABAB receptor activity reduces protein kinase-A activity, which...... reduces phosphorylation of serine-892 in GABAB2 and promotes receptor degradation. This form of desensitization operates on the time scale of several minutes to hours. A faster form of desensitization is induced by the auxiliary subunit KCTD12, which interferes with channel activation by binding to the G......-protein βγ subunits. Here we show that the two mechanisms of desensitization influence each other. Serine-892 phosphorylation in heterologous cells rearranges KCTD12 at the receptor and slows KCTD12-induced desensitization. Likewise, protein kinase-A activation in hippocampal neurons slows fast...

  5. Temporal Regulation by Innate Type 2 Cytokines in Food Allergies.

    Science.gov (United States)

    Graham, Michelle T; Andorf, Sandra; Spergel, Jonathan M; Chatila, Talal A; Nadeau, Kari C

    2016-10-01

    Food allergies (FAs) are a growing epidemic in western countries with poorly defined etiology. Defined as an adverse immune response to common food allergens, FAs present heterogeneously as a single- or multi-organ response that ranges in severity from localized hives and angioedema to systemic anaphylaxis. Current research focusing on epithelial-derived cytokines contends that temporal regulation by these factors impact initial sensitization and persistence of FA responses upon repeated food allergen exposure. Mechanistic understanding of FA draws insight from a myriad of atopic conditions studied in humans and modeled in mice. In this review, we will highlight how epithelial-derived cytokines initiate and then potentiate FAs. We will also review existing evidence of the contribution of other atopic diseases to FA pathogenesis and whether FA symptoms overlap with other atopic diseases.

  6. Strengthening health professions regulation in Cambodia: a rapid assessment.

    Science.gov (United States)

    Clarke, David; Duke, Jan; Wuliji, Tana; Smith, Alyson; Phuong, Keat; San, Un

    2016-03-10

    This paper describes a rapid assessment of Cambodia's current system for regulating its health professions. The assessment forms part of a co-design process to set strategic priorities for strengthening health profession regulation to improve the quality and safety of health services. A health system approach for strengthening health professions' regulation is underway and aims to support the Government of Cambodia's plans for scaling up its health workforce, improving health services' safety and quality, and meeting its Association of South East Asian Nations (ASEAN) obligations to facilitate trade in health care services. The assessment used a mixed methods approach including: A desktop review of key laws, plans, reports and other documents relating to the regulation of the health professions in Cambodia (medicine, dentistry, midwifery, nursing and pharmacy); Key informant interviews with stakeholders in Cambodia (The term "stakeholders" refers to government officials, people working on health professional regulation, people working for the various health worker training institutions and health workers at the national and provincial level); Surveys and questionnaires to assess Cambodian stakeholder knowledge of regulation; Self-assessments by members of the five Cambodian regulatory councils regarding key capacities and activities of high-performing regulatory bodies; and A rapid literature review to identify: The key functions of health professional regulation; The key issues affecting the Cambodian health sector (including relevant developments in the wider ASEAN region); and "Smart" health profession regulation practices of possible relevance to Cambodia. We found that the current regulatory system only partially meets Cambodia's needs. A number of key regulatory functions are being performed, but overall, the current system was not designed with Cambodia's specific needs in mind. The existing system is also overly complex, with considerable duplication and

  7. State of play in direct-to-consumer genetic testing for lifestyle-related diseases: market, marketing content, user experiences and regulation.

    Science.gov (United States)

    Saukko, Paula

    2013-02-01

    Direct-to-consumer (DTC) genetic tests have aroused controversy. Critics have argued many of the tests are not backed by scientific evidence, misguide their customers and should be regulated more stringently. Proponents suggest that finding out genetic susceptibilities for diseases could encourage healthier behaviours and makes the results of genetics research available to the public. This paper reviews the state of play in DTC genetic testing, focusing on tests identifying susceptibilities for lifestyle-related diseases. It will start with mapping the market for the tests. The paper will review (1) research on the content of the online marketing of DTC tests, (2) studies on the effects of DTC genetic tests on customers and (3) academic and policy proposals on how to regulate the tests. Current studies suggest that the marketing of DTC genetic tests often exaggerates their predictive powers, which could misguide consumers. However, research indicates that the tests do not seem to have major negative effects (worry and confusion) but neither do they engender positive effects (lifestyle change) on current users. Research on regulation of the tests has most commonly suggested regulating the marketing claims of the companies. In conclusion, the risks and benefits of DTC genetic tests are less significant than what has been predicted by critics and proponents, which will be argued reflects broader historical trends transforming health and medicine.

  8. 76 FR 39260 - Direct Investment Surveys: Alignment of Regulations With Current Practices

    Science.gov (United States)

    2011-07-06

    ... are eliminated from the regulations are: A survey of foreign direct investment in the U.S. seafood... requirements for two surveys of new foreign direct investment in the United States. BEA suspended collection of... Enters into a Joint Venture With, a Foreign Person BE-21, Survey of Foreign Direct Investment in U.S...

  9. 76 FR 19282 - Direct Investment Surveys: Alignment of Regulations With Current Practices

    Science.gov (United States)

    2011-04-07

    ... surveys that would be eliminated from the regulations are: a survey of foreign direct investment in the U... foreign direct investment in the United States (BE-13 and BE-14). BEA suspended collection of these... a Joint Venture With, a Foreign Person BE-21, Survey of Foreign Direct Investment in U.S. Business...

  10. X-ray tube current control

    International Nuclear Information System (INIS)

    Dupuis, W.A.; Resnick, T.A.

    1982-01-01

    A closed loop feedback system for controlling the current output of an x-ray tube. The system has circuitry for improving the transient response and stability of the x-ray tube current over a substantial nonlinear portion of the tube current production characteristic. The system includes a reference generator for applying adjustable step function reference signals representing desired tube currents. The system also includes means for instantaneous sensing of actual tube current. An error detector compares the value of actual and reference tube current and produces an error signal as a function of their difference. The system feedback loop includes amplification circuitry for controlling x-ray tube filament dc voltage to regulate tube current as a function of the error signal value. The system also includes compensation circuitry, between the reference generator and the amplification circuitry, to vary the loop gain of the feedback control system as a function of the reference magnitude

  11. Impedance Based Analysis of DFIG Stator Current Unbalance and Distortion Suppression Strategies

    DEFF Research Database (Denmark)

    Song, Yipeng; Zhou, Dao; Blaabjerg, Frede

    2016-01-01

    The control strategies of Doubly Fed Induction Generator (DFIG) system output current unbalance and distortion suppression have been well investigated in detail, with the implementation of two kinds of resonant regulators, i.e., conventional Resonance (R) regulator or Vector Proportional Integral...... reshaping though the introduction of R and VPI regulator. It is pointed out that, when implemented in the DFIG system output current unbalance and distortion suppression, the VPI regulator (equivalent to the combination of virtual positive inductor and virtual positive resistor) has two advantages over R...... regulator (equivalent to the combination of virtual positive resistor and virtual negative inductor), i.e., better high order harmonic distortion suppression. The theoretical analysis and MATLAB simulation results have validated the correctness of this conclusion....

  12. Education versus regulation: The case for regulating the indoor tanning industry.

    Science.gov (United States)

    Benet, Suzeanne; Kraft, Frederic

    2016-05-01

    We examine marketing strategies for indoor tanning services that often target young adult females. Evidence of the addictive nature of indoor tanning suggests that young adults may be vulnerable to the promotion of indoor tanning and as a result deserve greater protection from the marketing of these services. As public awareness of the rising numbers of skin cancers linked to indoor tanning grows, we believe that the public will support increased regulation of this industry.

  13. Adipostatic regulation of motivation and emotion.

    Science.gov (United States)

    Davis, Jon F

    2010-05-01

    The proper maintenance of body weight and mood are two of the most prevalent health issues present in society today. Obese humans display higher levels of mood-related disorders and the causality of such an association is unknown. A common feature of obesity is the imbalance of regulatory hormones which normally act to maintain stable energy balance and body weight. The adiposity hormone leptin is one such signal elevated in obesity with the capacity to dampen feeding behavior through action on brain circuits which regulate appetite and metabolism. Recent evidence suggests that leptin may regulate motivation through its actions within brain reward circuitry. In addition, leptin signaling within central nervous system regions that regulate cognition and emotion elicits anti-depressant like effects. Together, these data indicate that leptin may regulate the decreased motivation and mood present in obesity and depression. This review describes the capacity of leptin to regulate motivation and depression through actions within brain circuits that modulate effort-based behavior and emotion, respectively.

  14. Nursing implementation science: how evidence-based nursing requires evidence-based implementation.

    NARCIS (Netherlands)

    Achterberg, T. van; Schoonhoven, L.; Grol, R.P.T.M.

    2008-01-01

    PURPOSE: Evidence is not always used in practice, and many examples of problematic implementation of research into practice exist. The aim of this paper is to provide an introduction and overview of current developments in implementation science and to apply these to nursing. METHODS: We discuss a

  15. Smart environment architecture for emotion detection and regulation.

    Science.gov (United States)

    Fernández-Caballero, Antonio; Martínez-Rodrigo, Arturo; Pastor, José Manuel; Castillo, José Carlos; Lozano-Monasor, Elena; López, María T; Zangróniz, Roberto; Latorre, José Miguel; Fernández-Sotos, Alicia

    2016-12-01

    This paper introduces an architecture as a proof-of-concept for emotion detection and regulation in smart health environments. The aim of the proposal is to detect the patient's emotional state by analysing his/her physiological signals, facial expression and behaviour. Then, the system provides the best-tailored actions in the environment to regulate these emotions towards a positive mood when possible. The current state-of-the-art in emotion regulation through music and colour/light is implemented with the final goal of enhancing the quality of life and care of the subject. The paper describes the three main parts of the architecture, namely "Emotion Detection", "Emotion Regulation" and "Emotion Feedback Control". "Emotion Detection" works with the data captured from the patient, whereas "Emotion Regulation" offers him/her different musical pieces and colour/light settings. "Emotion Feedback Control" performs as a feedback control loop to assess the effect of emotion regulation over emotion detection. We are currently testing the overall architecture and the intervention in real environments to achieve our final goal. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Self-regulation as a mediator between sibling relationship quality and early adolescents' positive and negative outcomes.

    Science.gov (United States)

    Padilla-Walker, Laura M; Harper, James M; Jensen, Alexander C

    2010-08-01

    The current study examined the role of adolescents' self-regulation as a mediator between sibling relationship quality and adolescent outcomes, after controlling for the quality of the parent-child relationship. Participants were 395 families (282 two parent; 113 single parent) with an adolescent child (M age of child at Time 1 = 11.15, SD = .96, 49% female) who took part in [project name masked for blind review] at both Time 1 and Time 2. Path analysis via structural equation modeling suggested that sibling affection was longitudinally and positively related to self-regulation and prosocial behaviors, and negatively related to externalizing behaviors; while sibling hostility was positively, and having a sister was negatively related to internalizing behaviors (in general, paths were stronger for adolescents from two- vs. single-parent families). There was also evidence that adolescents' self-regulation partially mediated the relation between sibling affection and positive and negative adolescent outcomes. The discussion focuses on the importance of continued research examining the mechanisms through which the sibling relationship influences development during adolescence.

  17. Electron emission regulator for an x-ray tube filament

    International Nuclear Information System (INIS)

    Daniels, H.E.; Randall, H.G.

    1982-01-01

    An x-ray tube ma regulator has an scr phase shift voltage regulator supplying the primary winding of a transformer whose secondary is coupled to the x-ray tube filament. Prior to initiation of an x-ray exposure, the filament is preheated to a temperature corresponding substantially to the electron emissivity needed for obtaining the desired tube ma during an exposure. During the preexposure interval, the phase shift regulator is controlled by a signal corresponding to the sum of signals representative of the voltage applied to the filament transformer, the desired filament voltage and the space charge compensation needed for the selected x-ray tube anode to cathode voltage. When an exposure is initiated, control of the voltage regulator is switched to a circuit that responds to the tube current by controlling the amount of phase shift and, hence, the voltage supplied to the transformer. Transformer leakage current compensation is provided during the exposure interval with a circuit that includes an element whose impedance is varied in accordance with the anode-to-cathode voltage setting so the element drains off tube current as required to cancel the effect of leakage current variations

  18. Regulation of heterotrimeric G-protein signaling by NDPK/NME proteins and caveolins: an update.

    Science.gov (United States)

    Abu-Taha, Issam H; Heijman, Jordi; Feng, Yuxi; Vettel, Christiane; Dobrev, Dobromir; Wieland, Thomas

    2018-02-01

    Heterotrimeric G proteins are pivotal mediators of cellular signal transduction in eukaryotic cells and abnormal G-protein signaling plays an important role in numerous diseases. During the last two decades it has become evident that the activation status of heterotrimeric G proteins is both highly localized and strongly regulated by a number of factors, including a receptor-independent activation pathway of heterotrimeric G proteins that does not involve the classical GDP/GTP exchange and relies on nucleoside diphosphate kinases (NDPKs). NDPKs are NTP/NDP transphosphorylases encoded by the nme/nm23 genes that are involved in a variety of cellular events such as proliferation, migration, and apoptosis. They therefore contribute, for example, to tumor metastasis, angiogenesis, retinopathy, and heart failure. Interestingly, NDPKs are translocated and/or upregulated in human heart failure. Here we describe recent advances in the current understanding of NDPK functions and how they have an impact on local regulation of G-protein signaling.

  19. Regulation of the muscle fiber microenvironment by activated satellite cells during hypertrophy

    Science.gov (United States)

    Fry, Christopher S.; Lee, Jonah D.; Jackson, Janna R.; Kirby, Tyler J.; Stasko, Shawn A.; Liu, Honglu; Dupont-Versteegden, Esther E.; McCarthy, John J.; Peterson, Charlotte A.

    2014-01-01

    Our aim in the current study was to determine the necessity of satellite cells for long-term muscle growth and maintenance. We utilized a transgenic Pax7-DTA mouse model, allowing for the conditional depletion of > 90% of satellite cells with tamoxifen treatment. Synergist ablation surgery, where removal of synergist muscles places functional overload on the plantaris, was used to stimulate robust hypertrophy. Following 8 wk of overload, satellite cell-depleted muscle demonstrated an accumulation of extracellular matrix (ECM) and fibroblast expansion that resulted in reduced specific force of the plantaris. Although the early growth response was normal, an attenuation of hypertrophy measured by both muscle wet weight and fiber cross-sectional area occurred in satellite cell-depleted muscle. Isolated primary myogenic progenitor cells (MPCs) negatively regulated fibroblast ECM mRNA expression in vitro, suggesting a novel role for activated satellite cells/MPCs in muscle adaptation. These results provide evidence that satellite cells regulate the muscle environment during growth.—Fry, C. S., Lee, J. D., Jackson, J. R., Kirby, T. J., Stasko, S. A., Liu, H., Dupont-Versteegden, E. E., McCarthy, J. J., Peterson, C. A. Regulation of the muscle fiber microenvironment by activated satellite cells during hypertrophy. PMID:24376025

  20. 20 CFR 219.42 - When evidence of child's dependency is required.

    Science.gov (United States)

    2010-04-01

    ... 20 Employees' Benefits 1 2010-04-01 2010-04-01 false When evidence of child's dependency is required. 219.42 Section 219.42 Employees' Benefits RAILROAD RETIREMENT BOARD REGULATIONS UNDER THE... child's dependency is required. Evidence of a child's dependency on the employee is required when— (a...