Psychological factors associated with uptake of the childhood influenza vaccine and perception of post-vaccination side-effects: A cross-sectional survey in England.

PubMed

Smith, Louise E; Webster, Rebecca K; Weinman, John; Amlôt, Richard; Yiend, Jenny; Rubin, G James

2017-04-04

To identify predictors of: uptake of the childhood influenza vaccine in the 2015-2016 influenza season, parental perceptions of side-effects from the influenza vaccine and intention to vaccinate one's child for influenza in the 2016-2017 influenza season. Cross-sectional online survey. Data were collected in England shortly after the end of the 2015-2016 immunization campaign. 1001 parents or guardians of children aged between two and seven. Self-reported uptake of the childhood influenza vaccine in the 2015-2016 influenza season, perception of side-effects from the influenza vaccine and intention to vaccinate one's child in the 2016-2017 influenza season. Self-reported uptake of the childhood influenza vaccine was 52.8%. Factors strongly positively associated with uptake included the child having previously been vaccinated against influenza, perceiving the vaccine to be effective and perceiving the child to be susceptible to flu. Factors strongly negatively associated with uptake included perceiving the vaccine to be unsafe, to cause short-term side-effects or long-term health problems and believing that yearly vaccination may overload the immune system. Predictors of intended vaccine uptake in 2016-2017 were similar. Participants who perceived side-effects after the 2015-2016 vaccination reported being less likely to vaccinate their child next year. Side-effects were more likely to be reported in first-born children, by participants who knew another child who had side-effects, those who thought that the vaccine would interact with medication that the child was currently taking, and those who believed the vaccine causes short-term side-effects. Perceptions about the childhood influenza vaccine show strong associations with uptake, intended uptake and perception of side-effects. Attempts to improve uptake rates from their current low levels must address these perceptions. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

The effects of a two-step transfer on a visuomotor adaptation task.

PubMed

Aiken, Christopher A; Pan, Zhujun; Van Gemmert, Arend W A

2017-11-01

The literature has shown robust effects of transfer-of-learning to the contralateral side and more recently transfer-of-learning effects to a new effector type on the ipsilateral side. Few studies have investigated the effects of transfer-of-learning when skills transfer to both a new effector type and the contralateral side (two-step transfer). The purpose of the current study was to investigate the effects of two-step transfer and to examine which aspects of the movement transfer and which aspects do not. Individuals practiced a 30° visual rotation task with either the dominant or non-dominant limb and with either the use of the fingers and wrist or elbow and shoulder. Following practice, participants performed the task with the untrained effector type on the contralateral side. Results showed that initial direction error and trajectory length transferred from the dominant to the non-dominant side and movement time transferred from the elbow and shoulder condition to the wrist and finger conditions irrespective of which limb was used during practice. The results offer a unique perspective on the current theoretical and practical implications for transfer-of-learning and are further discussed in this paper.

Changing HIV treatment eligibility under health system constraints in sub-Saharan Africa: investment needs, population health gains, and cost-effectiveness

PubMed Central

Hontelez, Jan A.C.; Chang, Angela Y.; Ogbuoji, Osondu; de Vlas, Sake J.; Bärnighausen, Till; Atun, Rifat

2016-01-01

Objective: We estimated the investment needs, population health gains, and cost-effectiveness of different policy options for scaling-up prevention and treatment of HIV in the 10 countries that currently comprise 80% of all people living with HIV in sub-Saharan Africa (Ethiopia, Kenya, Malawi, Mozambique, Nigeria, South Africa, Tanzania, Uganda, Zambia, and Zimbabwe). Design: We adapted the established STDSIM model to capture the health system dynamics: demand-side and supply-side constraints in the delivery of antiretroviral treatment (ART). Methods: We compared different scenarios of supply-side (i.e. health system capacity) and demand-side (i.e. health seeking behavior) constraints, and determined the impact of changing guidelines to ART eligibility at any CD4+ cell count within these constraints. Results: Continuing current scale-up would require US$178 billion by 2050. Changing guidelines to ART at any CD4+ cell count is cost-effective under all constraints tested in the model, especially in demand-side constrained health systems because earlier initiation prevents loss-to-follow-up of patients not yet eligible. Changing guidelines under current demand-side constraints would avert 1.8 million infections at US$208 per life-year saved. Conclusion: Treatment eligibility at any CD4+ cell count would be cost-effective, even under health system constraints. Excessive loss-to-follow-up and mortality in patients not eligible for treatment can be avoided by changing guidelines in demand-side constrained systems. The financial obligation for sustaining the AIDS response in sub-Saharan Africa over the next 35 years is substantial and requires strong, long-term commitment of policy-makers and donors to continue to allocate substantial parts of their budgets. PMID:27367487

Changing HIV treatment eligibility under health system constraints in sub-Saharan Africa: investment needs, population health gains, and cost-effectiveness.

PubMed

Hontelez, Jan A C; Chang, Angela Y; Ogbuoji, Osondu; de Vlas, Sake J; Bärnighausen, Till; Atun, Rifat

2016-09-24

We estimated the investment needs, population health gains, and cost-effectiveness of different policy options for scaling-up prevention and treatment of HIV in the 10 countries that currently comprise 80% of all people living with HIV in sub-Saharan Africa (Ethiopia, Kenya, Malawi, Mozambique, Nigeria, South Africa, Tanzania, Uganda, Zambia, and Zimbabwe). We adapted the established STDSIM model to capture the health system dynamics: demand-side and supply-side constraints in the delivery of antiretroviral treatment (ART). We compared different scenarios of supply-side (i.e. health system capacity) and demand-side (i.e. health seeking behavior) constraints, and determined the impact of changing guidelines to ART eligibility at any CD4 cell count within these constraints. Continuing current scale-up would require US$178 billion by 2050. Changing guidelines to ART at any CD4 cell count is cost-effective under all constraints tested in the model, especially in demand-side constrained health systems because earlier initiation prevents loss-to-follow-up of patients not yet eligible. Changing guidelines under current demand-side constraints would avert 1.8 million infections at US$208 per life-year saved. Treatment eligibility at any CD4 cell count would be cost-effective, even under health system constraints. Excessive loss-to-follow-up and mortality in patients not eligible for treatment can be avoided by changing guidelines in demand-side constrained systems. The financial obligation for sustaining the AIDS response in sub-Saharan Africa over the next 35 years is substantial and requires strong, long-term commitment of policy-makers and donors to continue to allocate substantial parts of their budgets.

The safety of tocolytics used for the inhibition of preterm labour.

PubMed

Lamont, Callum D; Jørgensen, Jan Stener; Lamont, Ronald F

2016-09-01

Preterm birth is the major cause of neonatal mortality and morbidity worldwide and a huge cost burden on healthcare. Between 22 and 26 completed weeks of gestation, for every day that delivery is delayed, survival increases by 3%. Following a systematic review of the literature, we have provided an overview of the use of tocolytics for the prevention of preterm birth and have examined the fetal and maternal adverse effects of the various tocolytic agents currently in use. No tocolytic currently in use was developed specifically to treat preterm labour so most have multi-organ side effects. β2-agonists are relatively safe for the fetus but have rare and potentially serious maternal adverse effects. In contrast, prostaglandin synthetase inhibitors have potentially serious side effects for the fetus and neonate but have mild maternal gastrointestinal side effects. In Europe, the choice of first line therapy is either atosiban or nifedipine. The evidence base for atosiban is much more robust than for nifedipine. While their efficacy is similar, atosiban has placebo level side effects and is safer than nifedipine but is much more expensive.

Research on key factors and their interaction effects of electromagnetic force of high-speed solenoid valve.

PubMed

Liu, Peng; Fan, Liyun; Hayat, Qaisar; Xu, De; Ma, Xiuzhen; Song, Enzhe

2014-01-01

Analysis consisting of numerical simulations along with lab experiments of interaction effects between key parameters on the electromagnetic force based on response surface methodology (RSM) has been also proposed to optimize the design of high-speed solenoid valve (HSV) and improve its performance. Numerical simulation model of HSV has been developed in Ansoft Maxwell environment and its accuracy has been validated through lab experiments. Effect of change of core structure, coil structure, armature structure, working air gap, and drive current on the electromagnetic force of HSV has been analyzed through simulation model and influence rules of various parameters on the electromagnetic force have been established. The response surface model of the electromagnetic force has been utilized to analyze the interaction effect between major parameters. It has been concluded that six interaction factors including working air gap with armature radius, drive current with armature thickness, coil turns with side pole radius, armature thickness with its radius, armature thickness with side pole radius, and armature radius with side pole radius have significant influence on the electromagnetic force. Optimal match values between coil turns and side pole radius; armature thickness and side pole radius; and armature radius and side pole radius have also been determined.

Research on Key Factors and Their Interaction Effects of Electromagnetic Force of High-Speed Solenoid Valve

PubMed Central

Fan, Liyun; Xu, De; Ma, Xiuzhen; Song, Enzhe

2014-01-01

Analysis consisting of numerical simulations along with lab experiments of interaction effects between key parameters on the electromagnetic force based on response surface methodology (RSM) has been also proposed to optimize the design of high-speed solenoid valve (HSV) and improve its performance. Numerical simulation model of HSV has been developed in Ansoft Maxwell environment and its accuracy has been validated through lab experiments. Effect of change of core structure, coil structure, armature structure, working air gap, and drive current on the electromagnetic force of HSV has been analyzed through simulation model and influence rules of various parameters on the electromagnetic force have been established. The response surface model of the electromagnetic force has been utilized to analyze the interaction effect between major parameters. It has been concluded that six interaction factors including working air gap with armature radius, drive current with armature thickness, coil turns with side pole radius, armature thickness with its radius, armature thickness with side pole radius, and armature radius with side pole radius have significant influence on the electromagnetic force. Optimal match values between coil turns and side pole radius; armature thickness and side pole radius; and armature radius and side pole radius have also been determined. PMID:25243217

Influence of Side Effects on ART Adherence Among PLWH in China: The Moderator Role of ART-Related Knowledge.

PubMed

Zhou, Guangyu; Li, Xiaoming; Qiao, Shan; Shen, Zhiyong; Zhou, Yuejiao

2018-03-01

Despite the medical advancements in HIV treatment, realities of side effects are faced by people living with HIV (PLWH) who receive antiretroviral therapy (ART). Mixed findings have been reported on the association between side effects and ART adherence. However, few studies have explored the combined side effects and behavior-related information on medication adherence. The aim of the current study is to examine moderator role of ART-related knowledge between side effects and ART adherence. A cross-sectional survey was conducted among 2987 PLWH from October 2012 to August 2013 in China. Of the total sample, 2095 patients had received ART and provided ART adherence. Side effects, ART-related knowledge, and ART adherence, as well as potential covariates were assessed. The results revealed that there was a negative relationship of side effects and ART adherence existed among low and medium levels of ART-related knowledge, but not among high level of knowledge. Future interventions to promote HIV medication adherence should focus on providing behavior-related information education among PLWH.

How does the side-effect information in patient information leaflets influence peoples' side-effect expectations? A cross-sectional national survey of 18- to 65-year-olds in England.

PubMed

Webster, Rebecca K; Weinman, John; Rubin, G James

2017-12-01

To establish how the terms recommended by the European Commission to describe side-effect risk in patient information leaflets (PILs) influences expectations of side-effects and to identify factors associated with these side-effect expectations. A cross-sectional online survey was carried out by a market research company. Data were collected in England between 18th March and 1st April 2016. A total of 1003 adults aged between 18 and 65. Self-reported expectation that the described side-effects would affect participants if they took the medicine, measured on a likelihood scale from 1 (very unlikely) to 5 (very likely). Participants formed high expectations of side-effects for "very common" and "common" side-effects, with 51.9% and 45.0% of participants rating these as "very likely" or "likely" to happen to them, respectively. This fell to 8.1% for "uncommon," 5.8% for "rare" and 4.1% for "very rare." For each descriptor, higher expectations of side-effects were more associated with women or being from an ethnic minority, or having less education, a household illness, high perceived sensitivity to medicines or negative beliefs about medicines. The current use of verbal descriptors to communicate side-effect risk in PILs leads to high side-effect expectations. These expectations could contribute to nocebo-induced medication side-effects experienced by patients. Additional work is required to identify ways to improve the way risk information is conveyed in PILs. © 2017 The Authors Health Expectations Published by John Wiley & Sons Ltd.

Advances in Pharmacotherapeutics of Space Motion Sickness

NASA Technical Reports Server (NTRS)

Putcha, Lakshmi

2006-01-01

Space Motion Sickness (SMS) is common occurrence in the U.S. manned space flight program and nearly 2/3 of Shuttle crewmembers experience SMS. Several drugs have been prescribed for therapeutic management of SMS. Typically, orally-administered SMS medications (scopolamine, promethazine) have poor bioavailability and often have detrimental neurocognitive side effects at recommended doses. Intramuscularly administered promethazine (PMZ) is perceived to have optimal efficacy with minimal side effects in space. However, intramuscular injections are painful and the sedating neurocognitive side effects of promethazine, significant in controlled ground testing, may be masked in orbit because injections are usually given prior to crew sleep. Currently, EVAs cannot be performed by symptomatic crew or prior to flight day three due to the lack of a consistently efficacious drug, concern about neurocognitive side effects, and because an in-suit vomiting episode is potentially fatal. NASA has long sought a fast acting, consistently effective anti-motion sickness medication which has only minor neurocognitive side effects. Development of intranasal formulations of scopolamine and promethazine, the two commonly used SMS drugs at NASA for both space and reduced gravity environment medical operations, appears to be a logical alternative to current treatment modalities for SMS. The advantages are expected to be fast absorption, reliable and high bioavailability, and probably reduced neurocognitive side effects owing to dose reduction. Results from clinical trials with intranasal scopolamine gel formulation and pre-clinical testing of a prototype microcapsule intranasal gel dosage form of PMZ (INPMZ) will be discussed. These formulations are expected to offer a dependable and effective noninvasive treatment option for SMS.

Kinin effects on electrogenic ion transport in primary cultures of pig renal papillary collecting tubule cells.

PubMed

Cuthbert, A W; George, A M; MacVinish, L

1985-09-01

Confluent monolayers of pig renal papillary collecting tubule (RPCT) cells were formed on Millipore filters coated with collagen. They were clamped in Ussing-type chambers and used to measure short-circuit current (SCC). The monolayers had low potentials (0.1 mV) with the basolateral side positive. Small inward currents flowed under short-circuit conditions. Increases in SCC were obtained following addition of a number of agents. Receptors associated with SCC changes were disposed as follows: for kinins (e.g., lysyl-bradykinin) they were present on both sides of the tissue, while those for arginine vasopressin and norepinephrine were present on the basolateral side only. Epithelia responded to PGE2 added to the apical or basolateral face of the tissue; application to one side prevented the response from the contralateral side. The tissues also responded to forskolin, an activator of adenylate cyclase, with a sustained inward current that was sensitive to furosemide. Similar sustained inward currents were recorded following exposure to 8-bromoadenosine-3',5'-cyclic monophosphate (BrcAMP). Responses to kinins were attenuated by inhibition of fatty acid cyclooxygenase with either indomethacin or piroxicam or by replacing chloride with impermeant ions. If the SCC was first increased with forskolin, BrcAMP, or norepinephrine, the kinin effects on SCC were either abolished or reversed. It is concluded that kinin can cause chloride secretion in RPCT monolayers, possibly via a prostaglandin or a prostaglandin-adenylate cyclase mechanism. Secondary effects of kinin, exposed by first raising tissue cAMP levels, are not precluded.

Analysis of series resonant converter with series-parallel connection

NASA Astrophysics Data System (ADS)

Lin, Bor-Ren; Huang, Chien-Lan

2011-02-01

In this study, a parallel inductor-inductor-capacitor (LLC) resonant converter series-connected on the primary side and parallel-connected on the secondary side is presented for server power supply systems. Based on series resonant behaviour, the power metal-oxide-semiconductor field-effect transistors are turned on at zero voltage switching and the rectifier diodes are turned off at zero current switching. Thus, the switching losses on the power semiconductors are reduced. In the proposed converter, the primary windings of the two LLC converters are connected in series. Thus, the two converters have the same primary currents to ensure that they can supply the balance load current. On the output side, two LLC converters are connected in parallel to share the load current and to reduce the current stress on the secondary windings and the rectifier diodes. In this article, the principle of operation, steady-state analysis and design considerations of the proposed converter are provided and discussed. Experiments with a laboratory prototype with a 24 V/21 A output for server power supply were performed to verify the effectiveness of the proposed converter.

Factors affecting patient's perception of anticancer treatments side-effects: an observational study.

PubMed

Russo, Stefania; Cinausero, Marika; Gerratana, Lorenzo; Bozza, Claudia; Iacono, Donatella; Driol, Pamela; Deroma, Laura; Sottile, Roberta; Fasola, Gianpiero; Puglisi, Fabio

2014-02-01

Analysis of relative importance of side effects of anticancer therapy is extremely useful in the process of clinical decision making. There is evidence that patients' perception of the side effects of anticancer treatments changes over time. Aim of this study was to evaluate the cancer patients' perceptions of physical and non-physical side effects of contemporary anticancer therapy. Four hundred and sixty-four patients entered the study (153 men and 311 women). Participants were asked to rank their side effects in order of distress by using two sets of cards naming physical and non-physical effects, respectively. Influencing factors, including treatment and patient characteristics, were also analysed. Patients ranked the non-physical side effect 'Affects my family or partner' first. 'Constantly tired' and 'Loss of hair' were ranked second and third, respectively. Significant differences from previous studies on this topic emerged. In particular, 'Vomiting', a predominant concern in previous studies, almost disappeared, whereas 'Nausea' and 'Loss of hair' remained important side effects in the patients' perception. Interestingly, marital status was predominant in driving patients' perception, being associated with several side effects ('Constantly tired', 'Loss of appetite', 'Affects my work/Home duties', 'Affects my social activities', 'Infertility'). Other significant factors influencing patient's perception of side effects included age, disease characteristics and ongoing anticancer therapy. This study provided information on current status of patients' perceptions of side effects of anticancer treatment. These results could be used in pre-treatment patient education and counselling.

Simultaneous confidence sets for several effective doses.

PubMed

Tompsett, Daniel M; Biedermann, Stefanie; Liu, Wei

2018-04-03

Construction of simultaneous confidence sets for several effective doses currently relies on inverting the Scheffé type simultaneous confidence band, which is known to be conservative. We develop novel methodology to make the simultaneous coverage closer to its nominal level, for both two-sided and one-sided simultaneous confidence sets. Our approach is shown to be considerably less conservative than the current method, and is illustrated with an example on modeling the effect of smoking status and serum triglyceride level on the probability of the recurrence of a myocardial infarction. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Effect of vacuum arc cathode spot distribution on breaking capacity of the arc-extinguishing chamber

NASA Astrophysics Data System (ADS)

Ding, Can; Yuan, Zhao; He, Junjia

2017-10-01

A DC circuit breaker performs a key function in breaking an intermediate-frequency (IF) current since breaking a pure IF current is equivalent to breaking a very small DC with a reverse IF current. In this study, it is found that cathode spots show a ring-shaped distribution at 2000 Hz. An arc with an uneven distribution of cathode spots has been simulated. The simulation results show that the distribution of cathode spots significantly affect the microparameter distribution of arc plasma. The current distribution on the anode side differs from that on the cathode side under the total radial electric field. Specifically, the anode current distribution is both uneven and concentrated. The applied axial magnetic field, which cannot reduce the concentrated anode current distribution effectively, might increase the concentration of the anode current. Finally, the uneven distribution of cathode spots reduces the breaking capacity of the arc-extinguishing chamber.

Principles of a multistack electrochemical wastewater treatment design

NASA Astrophysics Data System (ADS)

Elsahwi, Essam S.; Dawson, Francis P.; Ruda, Harry E.

2018-02-01

Electrolyzer stacks in a bipolar architecture (cells connected in series) are desirable since power provided to a stack can be transferred at high voltages and low currents and thus the losses in the power bus can be reduced. The anode electrodes (active electrodes) considered as part of this study are single sided but there are manufacturing cost advantages to implementing double side anodes in the future. One of the main concerns with a bipolar stack implementation is the existence of leakage currents (bypass currents). The leakage current is associated with current paths that are not between adjacent anode and cathode pairs. This leads to non uniform current density distributions which compromise the electrochemical conversion efficiency of the stack and can also lead to unwanted side reactions. The objective of this paper is to develop modelling tools for a bipolar architecture consisting of two single sided cells that use single sided anodes. It is assumed that chemical reactions are single electron transfer rate limited and that diffusion and convection effects can be ignored. The design process consists of the flowing two steps: development of a large signal model for the stack, and then the extraction of a small signal model from the large signal model. The small signal model facilitates the design of a controller that satisfies current or voltage regulation requirements. A model has been developed for a single cell and two cells in series but can be generalized to more than two cells in series and to incorporate double sided anode configurations in the future. The developed model is able to determine the leakage current and thus provide a quantitative assessment on the performance of the cell.

Measuring Hydrogen Concentrations in Metals

NASA Technical Reports Server (NTRS)

Danford, M. D.

1985-01-01

Commercial corrosion-measurement system adapted to electrochemical determination of hydrogen concentrations in metals. New technique based on diffusion of hydrogen through foil specimen of metal. In sample holder, hydrogen produced on one side of foil, either by corrosion reaction or by cathodic current. Hydrogen diffused through foil removed on other side by constant anode potential, which leads to oxidation of hydrogen to water. Anode current is measure of concentration of hydrogen diffusing through foil. System used to study hydrogen uptake, hydrogen elimination by baking, effect of heat treatment, and effect of electroplating on high-strength steels.

Managing side effects of JAK inhibitors for myelofibrosis in clinical practice.

PubMed

Saeed, Iram; McLornan, Donal; Harrison, Claire N

2017-07-01

Myelofibrosis (MF) is characterized by bone marrow fibrosis, abnormalities in peripheral counts, extramedullary hematopoiesis, splenomegaly and an increased risk of transformation to acute myeloid leukaemia. The disease course is often heterogeneous and management can range from observation alone through to allogeneic stem cell transplantation. As of 2017, the only approved medication for MF remains the JAK Inhibitor (JAKi), ruxolitinib (Novartis Pharmaceuticals, Basel, Switzerland; Incyte, Wilmington, Detroit, USA) although several others have reached advanced stages of clinical trials. Areas covered: In this review, we focus on the management of both common and uncommon side effects arising from the use of currently approved and clinical trial JAKi. Most of the discussion concerns ruxolitinib although we also cover both pacritinib (CTI BioPharma) and momelotinib (Gilead Sciences, Foster City, California) which have been in recent large, multinational phase III trials. The various approaches to management of JAKi-related side effects are discussed - with particular emphasis to anaemia, thrombocytopaenia and infection risk. Expert commentary: JAK inhibitors are effective in many individuals with MF and have revolutionized the current treatment paradigm. The side effect profile, in the most, is predictable and manageable with high degrees of clinical surveillance and dose modifications.

Positive Side Effects of a Job-Related Training Program for Older Adults in South Korea

ERIC Educational Resources Information Center

Lee, Minhong; Choi, Jae-Sung

2012-01-01

The objective of the current study was to evaluate empirically positive side effects of a job-related training program on older adults' self-esteem, depression, and social networks. A total of 70 older adults participated in the study after completing the Older Paraprofessional Training Program developed and provided by the Continuing Education…

Adverse mood effects of combined oral contraceptives in relation to personality traits.

PubMed

Borgström, Anna; Odlind, Viveca; Ekselius, Lisa; Sundström-Poromaa, Inger

2008-12-01

Mood symptoms, such as depressed mood, anxiety and increased irritability, remain one of the major reasons for discontinuation of combined oral contraceptive (COC) pills. The aim of this study was to compare personality traits in women with ongoing or previous use of COCs and different experiences from these compounds with respect to adverse mood symptoms. Thirty women currently on COCs with no reports of adverse mood symptoms, 28 women currently on COCs and experiencing mood-related side effects, 27 women who had discontinued COC use for reasons other than adverse mood symptoms and 33 women who had discontinued COC use due to adverse mood effects were included. All participants were asked to fill out the Swedish universities Scales of Personality (SSP) to assess different personality traits. The women who were experiencing mood-related side effects on their current COC use exhibited higher scores on the somatic anxiety and stress susceptibility traits as compared to the women who did not experience any mood-related side effects from their current COCs. Women who had discontinued COC treatment because of adverse mood effects had higher scores of detachment and mistrust compared to women who had discontinued COC for reasons unrelated to mood effects. Higher scores on specific personality traits such as somatic anxiety and stress susceptibility are found in women with ongoing experience of adverse mood symptoms from COC. Higher scores of mistrust and detachment are more common among women who have discontinued COC treatment due to adverse mood effects.

Feasibility of transcranial direct current stimulation use in children aged 5 to 12 years.

PubMed

Andrade, Agnes Carvalho; Magnavita, Guilherme Moreira; Allegro, Juleilda Valéria Brasil Nunes; Neto, Carlos Eduardo Borges Passos; Lucena, Rita de Cássia Saldanha; Fregni, Felipe

2014-10-01

Transcranial direct current stimulation is a noninvasive brain stimulation technique that has been studied for the treatment of neuropsychiatric disorders in adults, with minimal side effects. The objective of this study is to report the feasibility, tolerability, and the short-term adverse effects of transcranial direct current stimulation in children from 5 to 12 years of age. It is a naturalistic study of 14 children who underwent 10 sessions of transcranial direct current stimulation as an alternative, off-label, and open-label treatment for various languages disorders. Frequency, intensity, adverse effects, and perception of improvement reported by parents were collected. The main side effects detected were tingling (28.6%) and itching (28.6%), acute mood changes (42.9%), and irritability (35.7%). Transcranial direct current stimulation is a feasible and tolerable technique in children, although studies regarding plastic and cognitive changes in children are needed to confirm its safety. In conclusion, this is a naturalistic report in which we considered transcranial direct current stimulation as feasible in children. © The Author(s) 2013.

Effect of graded InGaN drain region and 'In' fraction in InGaN channel on performances of InGaN tunnel field-effect transistor

NASA Astrophysics Data System (ADS)

Duan, Xiaoling; Zhang, Jincheng; Wang, Shulong; Quan, Rudai; Hao, Yue

2017-12-01

An InGaN-based graded drain region tunnel field-effect transistor (GD-TFET) is proposed to suppress the ambipolar behavior. The simulation results with the trade-off between on-state current (Ion) and ambipolar current (Iambipolar) show decreased Iambipolar (1.9 × 10-14 A/μm) in comparison with that of conventional TFETs (2.0 × 10-8 A/μm). Furthermore, GD-TFET with high 'In' fraction InxGa1-xN source-side channel (SC- GD-TFET) is explored and exhibits 5.3 times Ion improvement and 60% average subthreshold swing (SSavg) reduction in comparison with GD-TFET by adjusting 'In' fraction in the InxGa1-xN source-side channel. The improvement is attributed to the confinement of BTBT in the source-side channel by the heterojunction. And then, the optimum value for source-side channel length (Lsc) is researched by DC performances results, which shows it falls into the range between Lsc = 10 nm and 20 nm.

Historical essay: electroconvulsive therapy, memory, and self in America.

PubMed

Hirshbein, Laura

2012-01-01

Electroconvulsive Therapy (ECT) practitioners and anti-ECT activists have divergent interpretations of both the treatment and its history. Despite claims by ECT opponents that practitioners do not acknowledge memory side effects, the published literature on the procedure demonstrates psychiatrists' awareness of this issue. And though current ECT practitioners claim that memory side effects were mostly the result of outmoded methods, investigators continue to publish studies that indicate ongoing memory problems. This article explores the conflict between pro- and anti-ECT groups around the issue of memory side effects in the broader context of changes in American psychiatry and society.

Impact of scaling voltage and size on the performance of Side-contacted Field Effect Diode

NASA Astrophysics Data System (ADS)

Touchaei, Behnam Jafari; Manavizadeh, Negin

2018-05-01

Side-contacted Fild Effect Diode (S-FED), with low leakage current and high Ion/Ioff ratio, has been recently introduced to suppress short channel effects in nanoscale regime. The voltage and size scalability of S-FEDs and effects on the power consumption, propagation delay time, and power delay product have been studied in this article. The most attractive properties are related to channel length to channel thickness ratio in the S-FED which reduces in comparison with MOSFET significantly, while gates control over the channel improve and the off-state current reduces dramatically. This promising advantage is not only capable to improve important S-FED's characteristics such as subthreshold slope but also eliminate Latch-up and floating body effect.

Low resistance, large dimension entrance to the inner cavity of BK channels determined by changing side-chain volume

PubMed Central

Niu, Xiaowei

2011-01-01

Large-conductance Ca2+- and voltage-activated K+ (BK) channels have the largest conductance (250–300 pS) of all K+-selective channels. Yet, the contributions of the various parts of the ion conduction pathway to the conductance are not known. Here, we examine the contribution of the entrance to the inner cavity to the large conductance. Residues at E321/E324 on each of the four α subunits encircle the entrance to the inner cavity. To determine if 321/324 is accessible from the inner conduction pathway, we measured single-channel current amplitudes before and after exposure and wash of thiol reagents to the intracellular side of E321C and E324C channels. MPA− increased currents and MTSET+ decreased currents, with no difference between positions 321 and 324, indicating that side chains at 321/324 are accessible from the inner conduction pathway and have equivalent effects on conductance. For neutral amino acids, decreasing the size of the entrance to the inner cavity by substituting large side-chain amino acids at 321/324 decreased outward single-channel conductance, whereas increasing the size of the entrance with smaller side-chain substitutions had little effect. Reductions in outward conductance were negated by high [K+]i. Substitutions had little effect on inward conductance. Fitting plots of conductance versus side-chain volume with a model consisting of one variable and one fixed resistor in series indicated an effective diameter and length of the entrance to the inner cavity for wild-type channels of 17.7 and 5.6 Å, respectively, with the resistance of the entrance ∼7% of the total resistance of the conduction pathway. The estimated dimensions are consistent with the structure of MthK, an archaeal homologue to BK channels. Our observations suggest that BK channels have a low resistance, large entrance to the inner cavity, with the entrance being as large as necessary to not limit current, but not much larger. PMID:21576375

Body-drug assemblages: theorizing the experience of side effects in the context of HIV treatment.

PubMed

Gagnon, Marilou; Holmes, Dave

2016-10-01

Each of the antiretroviral drugs that are currently used to stop the progression of HIV infection causes its own specific side effects. Despite the expansion, multiplication, and simplification of treatment options over the past decade, side effects continue to affect people living with HIV. Yet, we see a clear disconnect between the way side effects are normalized, routinized, and framed in clinical practice and the way they are experienced by people living with HIV. This paper builds on the premise that new approaches are needed to understand side effects in a manner that is more reflective of the subjective accounts of people living with HIV. Drawing on the work of Deleuze and Guattari, it offers an original application of the theory of 'assemblage'. This theory offers a new way of theorizing side effects, and ultimately the relationship between the body and antiretroviral drugs (as technologies). Combining theory with examples derived from empirical data, we examine the multiple ways in which the body connects not only to the drugs but also to people, things, and systems. Our objective is to illustrate how this theory dares us to think differently about side effects and allows us to originally (re)think the experience of taking antiretroviral drugs. © 2016 The Authors. Nursing Philosophy Published by John Wiley & Sons Ltd.

Do the frequencies of adverse events increase, decrease, or stay the same with long-term use of statins?

PubMed

Huddy, Karlyn; Dhesi, Pavittarpaul; Thompson, Paul D

2013-02-01

Statins are widely used for their cholesterol-lowering properties and proven reduction of cardiovascular disease risk. Many patients take statins as long-term treatment for a variety of conditions without a clear-cut understanding of how treatment duration affects the frequency of adverse effects. We aimed to evaluate whether the frequencies of documented adverse events increase, decrease, or remain unchanged with long-term statin use. We reviewed the established literature to define the currently known adverse effects of statin therapy, including myopathy, central nervous system effects, and the appearance of diabetes, and the frequency of these events with long-term medication use. The frequency of adverse effects associated with long-term statin therapy appears to be low. Many patients who develop side effects from statin therapy do so relatively soon after initiation of therapy, so the frequency of side effects from statin therapy when expressed as a percentage of current users decreases over time. Nevertheless, patients may develop side effects such as muscle pain and weakness years after starting statin therapy; however, the absolute number of patients affected by statin myopathy increases with treatment duration. Also, clinical trials of statin therapy rarely exceed 5 years, so it is impossible to determine with certainty the frequency of long-term side effects with these drugs.

Anxiety Sensitivity and Nicotine Replacement Therapy Side Effects: Examining the Role of Emotion Dysregulation Among Treatment-Seeking Smokers.

PubMed

Zvolensky, Michael J; Paulus, Daniel J; Garey, Lorra; Raines, Amanda M; Businelle, Michael; Shankman, Stewart A; Manning, Kara; Goodwin, Renee D; Schmidt, Norman B

2017-11-01

Nicotine replacement therapy (NRT) significantly increases the likelihood of quit success at least over the short term, yet some smokers prematurely discontinue use. NRT side effects are often cited as the primary reason for medication discontinuation. The current study examined a theoretical pathway by which two smoking-related emotional vulnerabilities (anxiety sensitivity and emotion dysregulation) were related to the number of NRT (nicotine patch) side effects reported 1 week following a scheduled quit attempt. It was hypothesized that anxiety sensitivity would have an indirect effect on NRT side effects through emotion dysregulation. A total of 179 treatment-seeking, adult daily smokers with elevated anxiety sensitivity (47.5% male; M age = 39.73 years, SD = 13.87) were enrolled in a smoking cessation trial. Covariate-adjusted analyses provided support for the hypothesized pathway, such that emotion dysregulation explained the association between anxiety sensitivity and NRT side effects (b = 0.02, SE = 0.01, 95% CI [0.002, 0.03]; completely standardized estimate = .15). The findings underscore the importance of developing cessation treatments that incorporate techniques to enhance emotion regulation, particularly among smokers higher in anxiety sensitivity, to decrease the risk of NRT side effects.

Avoiding the side effects of electric current pulse application to electroporated cells in disposable small volume cuvettes assures good cell survival.

PubMed

Grys, Maciej; Madeja, Zbigniew; Korohoda, Włodzimierz

2017-01-01

The harmful side effects of electroporation to cells due to local changes in pH, the appearance of toxic electrode products, temperature increase, and the heterogeneity of the electric field acting on cells in the cuvettes used for electroporation were observed and discussed in several laboratories. If cells are subjected to weak electric fields for prolonged periods, for example in experiments on cell electrophoresis or galvanotaxis the same effects are seen. In these experiments investigators managed to reduce or eliminate the harmful side effects of electric current application. For the experiments, disposable 20 μl cuvettes with two walls made of dialysis membranes were constructed and placed in a locally focused electric field at a considerable distance from the electrodes. Cuvettes were mounted into an apparatus for horizontal electrophoresis and the cells were subjected to direct current electric field (dcEF) pulses from a commercial pulse generator of exponentially declining pulses and from a custom-made generator of double and single rectangular pulses. More than 80% of the electroporated cells survived the dcEF pulses in both systems. Side effects related to electrodes were eliminated in both the flow through the dcEF and in the disposable cuvettes placed in the focused dcEFs. With a disposable cuvette system, we also confirmed the sensitization of cells to a dcEF using procaine by observing the loading of AT2 cells with calceine and using a square pulse generator, applying 50 ms single rectangular pulses. We suggest that the same methods of avoiding the side effects of electric current pulse application as in cell electrophoresis and galvanotaxis should also be used for electroporation. This conclusion was confirmed in our electroporation experiments performed in conditions assuring survival of over 80% of the electroporated cells. If the amplitude, duration, and shape of the dcEF pulse are known, then electroporation does not depend on the type of pulse generator. This knowledge of the characteristics of the pulse assures reproducibility of electroporation experiments using different equipment.

Image-guided preoperative prediction of pyramidal tract side effect in deep brain stimulation

NASA Astrophysics Data System (ADS)

Baumgarten, C.; Zhao, Y.; Sauleau, P.; Malrain, C.; Jannin, P.; Haegelen, C.

2016-03-01

Deep brain stimulation of the medial globus pallidus is a surgical procedure for treating patients suffering from Parkinson's disease. Its therapeutic effect may be limited by the presence of pyramidal tract side effect (PTSE). PTSE is a contraction time-locked to the stimulation when the current spreading reaches the motor fibers of the pyramidal tract within the internal capsule. The lack of side-effect predictive model leads the neurologist to secure an optimal electrode placement by iterating clinical testing on an awake patient during the surgical procedure. The objective of the study was to propose a preoperative predictive model of PTSE. A machine learning based method called PyMAN (for Pyramidal tract side effect Model based on Artificial Neural network) that accounted for the current of the stimulation, the 3D electrode coordinates and the angle of the trajectory, was designed to predict the occurrence of PTSE. Ten patients implanted in the medial globus pallidus have been tested by a clinician to create a labeled dataset of the stimulation parameters that trigger PTSE. The kappa index value between the data predicted by PyMAN and the labeled data was .78. Further evaluation studies are desirable to confirm whether PyMAN could be a reliable tool for assisting the surgeon to prevent PTSE during the preoperative planning.

Inspection of cup-shaped steel parts from the I.D. side using eddy current

NASA Astrophysics Data System (ADS)

Griffiths, Erick W.; Pearson, Lee H.

2018-04-01

An eddy current method was developed to inspect cup-shaped steel parts from the I.D. side. During the manufacturing process of these parts, a thin Al tape foil is applied to the I.D. side of the part. One of the critical process parameters is that only one foil layer can be applied. An eddy current inspection system was developed to reject parts with more than one foil layer. The Al tape foil is cut to length to fit the inner diameter, however, after application of the foil there is a gap created between the beginning and end of the foil. It was found that this gap interfered with the eddy current inspection causing a false positive indication. To solve this problem a sensor design and data analysis process were developed to overcome the effects of these gaps. The developed system incorporates simultaneous measurements from multiple eddy current sensors and signal processing to achieve a reliable inspection.

Advances in Medicinal Plants with Effects on Anxiety Behavior Associated to Mental and Health Conditions.

PubMed

Barreto, George E; Avila-Rodriguez, Marco; Foitzick, Madeline; Aliev, Gjumrakch; Echeverria, Valentina

2017-01-01

Many mental health conditions including psychiatric disorders and neurodegenerative conditions are poorly responsive for actual medications or have low patient adherence to treatment due to the side effects or costs associated with these treatments. The main goal of this review is to provide clinical providers and patients with actualized information about the efficacy of selected herbal medicines for anxiety disorders derived from mental and/or health conditions, and their associated side effects. In this review, actual scientific advances about the use of medicinal plants for anxiety disorders are presented. In recent years, the herbal therapies have reemerged as a source of efficacious natural treatments, at a lower cost and most of the time reduced side effects than currently prescribed pharmaceutical drugs. The herbs described mainly correspond to plants of traditional medicine from the American continent and near islands and Asia. Current evidence confirms the therapeutic effects of traditional medicine. Further clinical investigation is required to confirm these findings. The current understanding of the molecular mechanisms involved in psychiatric disorders, as well as the new advances in brain imaging permit a rapid and serious evaluation of anxiolytic compounds. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

The PsyLOG mobile application: development of a tool for the assessment and monitoring of side effects of psychotropic medication.

PubMed

Kuzman, Martina Rojnic; Andlauer, Olivier; Burmeister, Kai; Dvoracek, Boris; Lencer, Rebekka; Koelkebeck, Katja; Nawka, Alexander; Riese, Florian

2017-06-01

Mobile health interventions are regarded as affordable and accessible tools that can enhance standard psychiatric care. As part of the mHealth Psycho-Educational Intervention Versus Antipsychotic-Induced Side Effects (mPIVAS) project (www.psylog.eu), we developed the mobile application "PsyLOG" based on mobile "smartphone" technology to monitor antipsychotic-induced side effects. The aim of this paper is to describe the rationale and development of the PsyLOG and its clinical use. The PsyLOG application runs on smartphones with Android operating system. The application is currently available in seven languages (Croatian, Czech, English, French, German, Japanese and Serbian). It consists of several categories: "My Drug Effects", "My Life Styles", "My Charts", "My Medication", "My Strategies", "My Supporters", "Settings" and "About". The main category "My Drug Effects" includes a list of 30 side effects with the possibility to add three additional side effects. Side effects are each accompanied by an appropriate description and the possibility to rate its severity on a visual analogue scale from 0-100%. The PsyLOG application is intended to enhance the link between patients and mental health professionals, serving as a tool that more objectively monitors side-effects over certain periods of time. To the best of our knowledge, no such applications have so far been developed for patients taking antipsychotic medication or for their therapists.

Managing the oral side-effects of medications used to treat multiple sclerosis.

PubMed

Cockburn, N; Pateman, K; Taing, M W; Pradhan, A; Ford, P J

2017-09-01

Many medications used to manage multiple sclerosis (MS) affect oral health. This review aimed to identify the oral side-effects of the current drugs recommended in Australia to treat MS and make dental practitioners aware of the range of symptoms. The Australian Therapeutic Guidelines and the Australian Medicines Handbook were searched for medications used to treat MS. For each medication, the generic name, class, route of administration, dosage and drug company reported side-effects were extracted from the online Monthly Index of Medical Specialties (MIMs) database. Meyler's Side-effect of Drugs Encyclopaedia was used to identify any additional oral adverse reactions to medications used to treat MS. Fourteen drugs were identified for the treatment of MS progression and 13 drugs for the treatment of MS symptoms. For these medications, 18 oral side-effects were documented: xerostomia was the most common, followed by dysgeusia, dysphagia, mouth ulceration and sinusitis. Anticholinergic drugs caused xerostomia while immunosuppressants resulted in more infection-related side-effects. Dental practitioners should be aware of the range of symptoms likely to be reported by this population. Clinicians are encouraged to continue providing dental care for their patients who develop MS and refer complex cases to specialists. © 2017 Australian Dental Association.

Safety evaluation of lubiprostone in the treatment of constipation and irritable bowel syndrome.

PubMed

Chamberlain, Sherman M; Rao, Satish S C

2012-09-01

Lubiprostone is approved in the United States for the treatment of chronic idiopathic constipation and constipation predominant irritable bowel syndrome (IBS-C). Lubiprostone causes secretion of fluid and electrolytes in the small bowel, through the activation of chloride channels, and thereby induces laxation and improvement of bowel functions. It is generally considered to be safe and effective. Common side effects of lubiprostone include nausea, diarrhea, abdominal pain and bloating, and the rare side effect dyspnea. Likely mechanisms for these side effects may be related to lubiprostone's primary action on small bowel secretion and the associated intestinal distension, as well as smooth muscle contraction. This article reviews the pharmacokinetic and safety profile of lubiprostone, with particular relevance to the two FDA-approved dosages. Lubiprostone acts topically in the gut lumen and is almost completely metabolized in the gut lumen. Lubiprostone's M3 metabolite can be detected in low concentrations in the serum and may be responsible for some of its side effects. However, the exact mechanisms by which the side effects are produced are currently unknown.

Effect of pH on ion current through conical nanopores

NASA Astrophysics Data System (ADS)

Chander, M.; Kumar, R.; Kumar, S.; Kumar, N.

2018-05-01

Here, we examined ionic current behavior of conical nanopores at different pH and a fixed ion concentration of potassium halide (KCl). Conical shaped nanopores have been developed by chemical etching technique in polyethylene terephthalate (PET) membrane/foil of thickness 12 micron. For this we employed a self-assembled electrochemical cell having two chambers and the foil was fitted in the centre of cell. The nanopores were produced in the foil using etching and stopping solutions. The experimental results show that ionic current rectification (ICR) occurs through synthesized conical nanopores. Further, ion current increases significantly with increase of voltage from the base side of nanopores to the tip side at fixed pH of electrolyte.

Leakage and field emission in side-gate graphene field effect transistors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Di Bartolomeo, A., E-mail: dibant@sa.infn.it; Iemmo, L.; Romeo, F.

We fabricate planar graphene field-effect transistors with self-aligned side-gate at 100 nm from the 500 nm wide graphene conductive channel, using a single lithographic step. We demonstrate side-gating below 1 V with conductance modulation of 35% and transconductance up to 0.5 mS/mm at 10 mV drain bias. We measure the planar leakage along the SiO{sub 2}/vacuum gate dielectric over a wide voltage range, reporting rapidly growing current above 15 V. We unveil the microscopic mechanisms driving the leakage, as Frenkel-Poole transport through SiO{sub 2} up to the activation of Fowler-Nordheim tunneling in vacuum, which becomes dominant at higher voltages. We report a field-emission current densitymore » as high as 1 μA/μm between graphene flakes. These findings are important for the miniaturization of atomically thin devices.« less

Reirradiation on recurrent cervical cancer case: Treatment response and side effects

NASA Astrophysics Data System (ADS)

Siregar, M. F.; Supriana, N.; Nuranna, L.; Prihartono, J.

2017-08-01

Management of recurrent cervical cancer by reirradiation after radiation treatment remains controversial. In Indonesia, there is currently no data about reirradiation tumor response and side effects. This study aims to assess the tumor response to and side effects of reirradiation, the effect of time interval between first radiation treatment and cancer recurrence on the tumor response and side effects, and the effect of tumor size on tumor response. A cohort retrospective study with no comparison was done with the Radiotherapy Department at Cipto Mangunkusumo General Hospital, Jakarta. Participants were recurrent cervical cancer patients undergoing reirradiation. Data was collected from patients’ medical records and follow-up phone calls. Twenty-two patients participated in this study. Nine patients (40.9%) had complete responses, 10 patients (45.5%) had partial responses, 1 patient (4.5%) had a stable response, and 2 patients (9.1%) had tumor progressions. In general, 15 patients (68.2%) had no to light side effects (grade 0-2 RTOG) and 7 patients (31.8%) had severe side effects (grade 3-4 RTOG). Four patients (18.1%) had severe gastrointestinal acute side effects, 6 patients (27.3%) had severe gastrointestinal late side effects, 2 patients (9.1%) had severe urogenital side effects, and there were no patients had severe urogenital late side effects. There was no significant difference in tumor response between patients with time interval between first radiation treatment and recurrence of <12 months vs. ≥12 months. There was no significant difference in tumor response between patients with tumor size ≤4 cm vs. >4 cm. Reirradiation can be considered as a modality in recurrent cervical cancer management since good tumor response was achieved and the majority of patients had no to light side effects (grade 0-2 RTOG). This study found no correlation between tumor response, side effects, and time gap between first radiation treatment and recurrence of <12 months vs. ≥12 months. There was also no correlation between tumor response and tumor size of ≤4 cm vs. > 4 cm.

Understanding Statin Use in America and Gaps in Patient Education (USAGE): an internet-based survey of 10,138 current and former statin users.

PubMed

Cohen, Jerome D; Brinton, Eliot A; Ito, Matthew K; Jacobson, Terry A

2012-01-01

Statins substantially reduce the risk of cardiovascular disease and are generally well-tolerated. Despite this, many patients discontinue therapy. A better understanding of the characteristics of current and former statin users may be helpful for formulating strategies to improve long-term adherence. The Understanding Statin Use in America and Gaps in Education (USAGE) survey assessed the attitudes, beliefs, practices, and behavior of current and former statin users. Individuals 18 years or older who reported a history of high cholesterol and current or former statin use were identified within a registered consumer panel cohort in the United States and invited to participate in an Internet survey. Of the 10,138 respondents, 8918 (88%) were current statin users and 1220 (12%) were former users. Participants (mean age 61 years) were predominantly white (92%), female (61%), of middle income (median $44,504/yr), and had health insurance (93%). Among current users, 95% took a statin alone, and 70% had not missed a dose in the past month. Although ∼70% reported that their physicians had explained the importance of cholesterol levels for their heart health former users were less satisfied with the discussions (65% vs. 83%, P < .05). Muscle-related side effects were reported by 60% and 25% of former and current users, respectively (P < .05). Nearly half of all respondents switched statins at least once. The primary reason for switching by current users was cost (32%) and the primary reason for discontinuation was side effects (62%). This survey provides important insights into behavior and attitudes among current and former statin users and the results suggest that more effective dialogue between healthcare providers and patients may increase persistence of statin use, particularly when the patient has concerns about side effects and drug costs. Copyright © 2012 National Lipid Association. Published by Elsevier Inc. All rights reserved.

The effect of acute hypoxia on short-circuit current and epithelial resistivity in biopsies from human colon.

PubMed

Carra, Graciela E; Ibáñez, Jorge E; Saraví, Fernando D

2013-09-01

In isolated colonic mucosa, decreases in short-circuit current (ISC) and transepithelial resistivity (RTE) occur when hypoxia is either induced at both sides or only at the serosal side of the epithelium. We assessed in human colon biopsies the sensitivity to serosal-only hypoxia and mucosal-only hypoxia and whether Na, K-ATPase blockade with ouabain interacts with hypoxia. Biopsy material from patients undergoing colonoscopy was mounted in an Ussing chamber for small samples (1-mm2 window). In a series of experiments we assessed viability and the electrical response to the mucolytic, dithiothreitol (1 mmol/l). In a second series, we explored the effect of hypoxia without and with ouabain. In a third series, we evaluated the response to a cycle of hypoxia and reoxygenation induced at the serosal or mucosal side while keeping the oxygenation of the opposite side. 1st series: Dithiothreitol significantly decreased the unstirred layer and ISC but increased RTE. 2nd series: Both hypoxia and ouabain decreased ISC, but ouabain increased RTE and this effect on RTE prevailed even during hypoxia. 3rd series: Mucosal hypoxia caused lesser decreases of ISC and RTE than serosal hypoxia; in the former, but not in the latter, recovery was complete upon reoxygenation. In mucolytic concentration, dithiothreitol modifies ISC and RTE. Oxygen supply from the serosal side is more important to sustain ISC and RTE in biopsy samples. The different effect of hypoxia and Na, K-ATPase blockade on RTE suggests that their depressing effect on ISC involves different mechanisms.

Molecular targeted therapies for solid tumors: management of side effects.

PubMed

Grünwald, Viktor; Soltau, Jens; Ivanyi, Philipp; Rentschler, Jochen; Reuter, Christoph; Drevs, Joachim

2009-03-01

This review will provide physicians and oncologists with an overview of side effects related to targeted agents that inhibit vascular endothelial growth factor (VEGF), epidermal growth factor (EGF) and mammalian target of rapamycin (mTOR) signaling in the treatment of solid tumors. Such targeted agents can be divided into monoclonal antibodies, tyrosine kinase inhibitors, multitargeted tyrosine kinase inhibitors and serine/threonine kinase inhibitors. Molecular targeted therapies are generally well tolerated, but inhibitory effects on the biological function of the targets in healthy tissue can result in specific treatment-related side effects, particularly with multitargeted agents. We offer some guidance on how to manage adverse events in cancer patients based on the range of options currently available. Copyright 2009 S. Karger AG, Basel.

A control strategy for grid-side converter of DFIG under unbalanced condition based on Dig SILENT/Power Factory

NASA Astrophysics Data System (ADS)

Han, Pingping; Zhang, Haitian; Chen, Lingqi; Zhang, Xiaoan

2018-01-01

The models of doubly fed induction generator (DFIG) and its grid-side converter (GSC) are established under unbalanced grid condition based on DIgSILENT/PowerFactory. According to the mathematical model, the vector equations of positive and negative sequence voltage and current are deduced in the positive sequence synchronous rotating reference frame d-q-0 when the characteristics of the simulation software are considered adequately. Moreover, the reference value of current component of GSC in the positive sequence frame d-q-0 under unbalanced condition can be obtained to improve the traditional control of GSC when the national issue of unbalanced current limits is combined. The simulated results indicate that the control strategy can restrain negative sequence current and the two times frequency power wave of GSC’s ac side effectively. The voltage of DC bus can be maintained a constant to ensure the uninterrupted operation of DFIG under unbalanced grid condition eventually.

Prediction of large negative shaded-side spacecraft potentials

NASA Technical Reports Server (NTRS)

Prokopenko, S. M. L.; Laframboise, J. G.

1977-01-01

A calculation by Knott, for the floating potential of a spherically symmetric synchronous-altitude satellite in eclipse, was adapted to provide simple calculations of upper bounds on negative potentials which may be achieved by electrically isolated shaded surfaces on spacecraft in sunlight. Large (approximately 60 percent) increases in predicted negative shaded-side potentials are obtained. To investigate effective potential barrier or angular momentum selection effects due to the presence of less negative sunlit-side or adjacent surface potentials, these expressions were replaced by the ion random current, which is a lower bound for convex surfaces when such effects become very severe. Further large increases in predicted negative potentials were obtained, amounting to a doubling in some cases.

Contribution of ventral tegmental GABA receptors to cocaine self-administration in rats.

PubMed

Backes, E N; Hemby, S E

2008-03-01

Recent evidence has suggested that compounds affecting GABAergic transmission may provide useful pharmacological tools for the treatment of cocaine addiction. Using a rat model of self-administration, the present study examined the effects of GABA agonists and antagonists injected directly into the ventral tegmental area (VTA) on cocaine intake in rats trained to self-administer cocaine (0, 125, 250 and 500 microg/infusion) under an FR5 schedule of reinforcement. Separate groups of rats received bilateral intra-VTA injections of the GABA-A antagonist picrotoxin (34 ng/side, n = 7; 68 ng/side, n = 8), GABA-A agonist muscimol (14 ng/side, n = 8), GABA-B agonist baclofen (56 ng/side, n = 7; 100 ng/side, n = 6), picrotoxin (68 ng/side) co-injected with the GABA-B antagonist 2-hydroxysaclofen (100 ng/side, n = 7; 2 microg/side, n = 8) or artificial cerebrospinal fluid (aCSF, n = 6) to assess the effects of the various compounds on the cocaine self-administration dose-response curve. Both picrotoxin and baclofen reduced responding maintained by cocaine, whereas muscimol had no effect on responding. In contrast, neither picrotoxin (n = 6) nor baclofen (n = 8) affected responding maintained by food. Interestingly, 2-hydroxysaclofen effectively blocked the suppression of responding produced by picrotoxin, suggesting that both picrotoxin and baclofen exert their effects via activation of GABA-B receptors. Additionally, these effects appear to be specific to cocaine reinforcement, supporting current investigation of baclofen as a treatment for cocaine addiction.

Contribution of ventral tegmental GABA receptors to cocaine self-administration in rats

PubMed Central

Backes, E.N.; Hemby, S.E.

2008-01-01

Recent evidence has suggested that compounds affecting GABAergic transmission may provide useful pharmacological tools for the treatment of cocaine addiction. Using a rat model of self-administration, the present study examined the effects of GABA agonists and antagonists injected directly into the ventral tegmental area (VTA) on cocaine intake in rats trained to self-administer cocaine (0, 125, 250 and 500 µg/infusion) under an FR5 schedule of reinforcement. Separate groups of rats received bilateral intra-VTA injections of the GABA-A antagonist picrotoxin (34 ng/side, n=7; 68 ng/side, n=8), GABA-A agonist muscimol (14 ng/side, n=8), GABA-B agonist baclofen (56 ng/side, n=7; 100 ng/side, n=6), picrotoxin (68 ng/side) co-injected with the GABA-B antagonist 2-hydroxysaclofen (100 ng/side, n=7; 2 µg/side, n=8) or artificial cerebrospinal fluid (aCSF, n=6) to assess the effects of the various compounds on the cocaine self-administration dose-response curve. Both picrotoxin and baclofen reduced responding maintained by cocaine, whereas muscimol had no effect on responding. In contrast, neither picrotoxin (n=6) nor baclofen (n=8) affected responding maintained by food. Interestingly, 2-hydroxysaclofen effectively blocked the suppression of responding produced by picrotoxin, suggesting that both picrotoxin and baclofen exert their effects via activation of GABA-B receptors. Additionally, these effects appear to be specific to cocaine reinforcement, supporting current investigation of baclofen as a treatment for cocaine addiction. PMID:17943439

Period Prevalence and Perceived Side Effects of Hormonal Contraceptive Use and the Menstrual Cycle in Elite Athletes.

PubMed

Martin, Daniel; Sale, Craig; Cooper, Simon B; Elliott-Sale, Kirsty J

2017-12-28

To identify the period prevalence of hormonal contraceptive (HC) use and characterise the perceived side effects associated with the menstrual cycle and HC use. 430 elite female athletes completed a questionnaire to assess; the period prevalence of HC use, the reasons for initiation and discontinuation of HCs and the side effects experienced by HC and non-HC users. Descriptive statistics, between-group comparisons and associations between categorical variables were calculated. 49.5% of athletes were currently using HCs and 69.8% had used HCs at some point. Combined oral contraceptives were most commonly used (68.1%), with 30.0% using progestin-only contraceptives (implant = 13.1%; injection = 3.7%; intrauterine system = 2.8%). Perceived negative side effects were more common with progestin-only HC use (39.1%) compared to combined HC use (17.8%; P = 0.001) and were most prevalent in implant users (53.6%; P = 0.004). HC users reported perceived positive side effects relating to the ability to predict and/or manipulate the timing, frequency and amount of menstrual bleeding. Non-HC users had a menstrual cycle length of 29 ± 5 d and 77.4% reported negative side effects during their menstrual cycle, primarily during days 1-2 of menstruation (81.6%). Approximately half of elite athletes used HCs and progestin-only contraceptive users reported greater incidences of negative side effects, especially with the implant. Due to the high inter-individual variability in reported side effects, athletes and practitioners should maintain an open dialogue to pursue the best interests of the athlete.

Investigation of the novel attributes in double recessed gate SiC MESFETs at drain side

NASA Astrophysics Data System (ADS)

Orouji, Ali A.; Razavi, S. M.; Ebrahim Hosseini, Seyed; Amini Moghadam, Hamid

2011-11-01

In this paper, the potential impact of drain side-double recessed gate (DS-DRG) on silicon carbide (SiC)-based metal semiconductor field effect transistors (MESFETs) is studied. We investigate the device performance focusing on breakdown voltage, threshold voltage, drain current and dc output conductance with two-dimensional and two-carrier device simulation. Our simulation results demonstrate that the channel thickness under the gate in the drain side is an important factor in the breakdown voltage. Also, the positive shift in the threshold voltage for the DS-DRG structure is larger in comparison with that for the source side-double recessed gate (SS-DRG) SiC MESFET. The saturated drain current for the DS-DRG structure is larger compared to that for the SS-DRG structure. The maximum dc output conductance in the DS-DRG structure is smaller than that in the SS-DRG structure.

Current perspectives in NSAID-induced gastropathy.

PubMed

Sinha, Mau; Gautam, Lovely; Shukla, Prakash Kumar; Kaur, Punit; Sharma, Sujata; Singh, Tej P

2013-01-01

Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most highly prescribed drugs in the world. Their analgesic, anti-inflammatory, and antipyretic actions may be beneficial; however, they are associated with severe side effects including gastrointestinal injury and peptic ulceration. Though several approaches for limiting these side effects have been adopted, like the use of COX-2 specific drugs, comedication of acid suppressants like proton pump inhibitors and prostaglandin analogs, these alternatives have limitations in terms of efficacy and side effects. In this paper, the mechanism of action of NSAIDs and their critical gastrointestinal complications have been reviewed. This paper also provides the information on different preventive measures prescribed to minimize such adverse effects and analyses the new suggested strategies for development of novel drugs to maintain the anti-inflammatory functions of NSAIDs along with effective gastrointestinal protection.

Optimal Drug Policy in Low-Income Neighborhoods

PubMed Central

Chang, Sheng-Wen; Coulson, N. Edward; Wang, Ping

2015-01-01

The control of drug activity currently favors supply-side policies: drug suppliers in the U.S. face a higher arrest rate and longer sentences than demanders. We construct a simple model of drug activity with search and entry frictions in labor and drug markets. Our calibration analysis suggests a strong “dealer replacement effect.” As a result, given a variety of community objectives, it is beneficial to lower supplier arrests and raise the demand arrest rate from current values. A 10% shift from supply-side to demand-side arrests can reduce the population of potential drug dealers by 22–25,000 and raise aggregate local income by $380–400 million, at 2002 prices. (JEL Classification: D60, J60, K42, H70) PMID:27616878

Value of local electrogram characteristics predicting successful catheter ablation of left-versus right-sided accessory atrioventricular pathways by radiofrequency current.

PubMed

Lin, J L; Schie, J T; Tseng, C D; Chen, W J; Cheng, T F; Tsou, S S; Chen, J J; Tseng, Y Z; Lien, W P

1995-01-01

Despite similar guidance by local electrogram criteria, catheter ablation of right-sided accessory atrioventricular (AV) pathways by radiofrequency current has been less effective than that of left-sided ones. In order to elucidate the possible diversities in local electrosignal criteria, we systematically analyzed the morphological and timing characteristics of 215 bipolar local electrograms from catheter ablation sites of 65 left-sided accessory AV pathways and of 356 from those of 37 right-sided ones in 92 consecutive patients with Wolff-Parkinson-White syndrome or AV reentrant tachycardia incorporating concealed accessory AV pathways. After stepwise multivariate analysis, we selected the presence of a possible accessory pathway potential, local ventricular activation preceding QRS complex for 20 ms or more during ventricular insertion mapping, and the local retrograde ventriculoatrial (VA) continuity, local retrograde VA interval < or = 50 ms, electrogram stability (left-sided targets only), retrograde accessory pathway potential (right-sided targets only) during atrial insertion mapping, as independent local electrogram predictors for successful ablation of left- and right-sided accessory AV pathways. Combination of all local electrogram predictors could have moderate chance of success (80 and 51%) for the ventricular and atrial insertion ablation of left-sided accessory AV pathways, but only low probability of success (40% in ventricular insertion ablation) or very low sensitivity (12.5% in atrial insertion ablation) for right-sided ones. In conclusion, with the present approach, successful catheter ablation of right-sided accessory AV pathways, compared to left-sided ones, still necessitate a breakthrough in the precision mapping and the efficiency of energy delivery.

Tunneling through superlattices: the effect of anisotropy and kinematic coupling.

PubMed

Halilov, S V; Huang, X Y; Hytha, M; Stephenson, R; Yiptong, A; Takeuchi, H; Cody, N; Mears, R J

2012-12-12

The tunneling of carriers in stratified superlattice systems is analyzed in terms of the constituent effective mass tensor. The focus is on the effects on the tunneling which are caused by the side regions of an intervening barrier. Depending on the covalency and work function in the constituent layers of a superlattice, it is concluded that the kinematics in the regions on either side determined by the effective carrier mass and its interference with the band offset at heterojunctions leads to either a constructive or a destructive effect on the tunneling current. As an example, Si(1-x)Ge(x)/Si and Al(x)Ga(1-x)As/GaAs superlattices are demonstrated to reduce the tunneling current at certain fractional thicknesses and stoichiometries of the constituent slabs without affecting the lateral mobility. The findings show, in general, how manipulation of the carrier's effective mass tensor through stoichiometric/structural modulation of the heterostructure may be used to control the tunneling current through a given potential barrier, given that the characteristic de Broglie wavelength exceeds all the constituent dimensions, thus offering a method complementary to high-k technologies.

77 FR 43178 - Airworthiness Directives; The Boeing Company Airplanes

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-24

... eddy current high frequency (ETHF) inspections for cracking on the aft side of the left and right wing... NPRM proposed to require repetitive eddy current high frequency (ETHF) inspections for cracking on the...,000 flight cycles after the effective date of this AD, whichever occurs later, do an eddy current high...

Effects of 5-alpha reductase inhibitors on erectile function, sexual desire and ejaculation.

PubMed

Gur, Serap; Kadowitz, Philip J; Hellstrom, Wayne Jg

2013-01-01

Treatment with 5-alpha reductase inhibitors (5ARI) is commonly utilized for the treatment of benign prostatic hyperplasia (BPH). The true prevalence of sexual side effects with 5ARI treatment is currently unknown. The current article reviews the reported adverse effects of 5ARI in regard to erectile function, sexual desire and ejaculation. A PubMed search was performed of all articles from 1990 to present, which reported any sexual side effects with finasteride or dutasteride. Preference was given to more recent and human studies where available. Clinical trials with 5ARI report prevalence rates of de novo erectile dysfunction of 5 - 9%. Decreased circulating dihydrotestosterone (DHT) resulting from 5ARI use is associated with diminished sexual desire and/or orgasm. The presence of adverse sexual effects is associated with decreased self-esteem, quality of life and ability to maintain an intimate relationship. Inhibition of 5ARI additionally influences progesterone and deoxycorticosterone levels and may alter psychological functions, including increased depression, melancholy and loss of general well being. Ejaculatory dysfunction has not been well studied in patients using 5ARI. Patients receiving therapy with 5ARI should be counseled as to potential sexual and psychological adverse effects. Future clinical studies are needed to further investigate the sexual side effects associated with this class of drugs.

Economic study on the impact of side effects in patients taking oxycodone controlled-release for noncancer pain.

PubMed

Anastassopoulos, Kathryn P; Chow, Wing; Tapia, Crisanta I; Baik, Rebecca; Ackerman, Stacey J; Biondi, David; Kim, Myoung S

2012-10-01

Chronic pain is a prevalent condition in the United States. Musculoskeletal pain, including joint and back pain, is the most common type of chronic pain, and many patients with back pain have a neuropathic component. Pain has direct economic consequences. While oxycodone controlled-release (CR) is one of the most widely used oral long-acting opioids for pain, including pain with a neuropathic component, it is often associated with bothersome side effects, resulting in additional medical resource use (MRU) and costs. To examine the impact on MRU and costs to payers of side effects in patients taking oxycodone CR alone or in combination with other pain medications for noncancer pain (including those with neuropathic pain symptoms). A nationwide convenience sample of adults in the United States, who participated in a survey research panel and reported current use of oxycodone CR for noncancer pain, completed an online survey between November 2, 2010, and December 13, 2010. Respondents were excluded if they reported current use of other extended-release or long-acting opioid prescription medications. The survey consisted of questions on demographics, clinical characteristics, pain characteristics, experience with pain medication, and MRU associated with side effects. Payer costs were calculated based on the MRU reported by the respondents multiplied by Medicare reimbursement rates for hospitalizations and outpatient visits and average wholesale price (AWP) minus 20% for medications. A subgroup of patients who reported neuropathic pain symptoms also was examined. After applying the exclusion criteria, 432 respondents completed the survey. Approximately half of the respondents (n = 219; 50.7%) reported neuropathic pain symptoms. The majority of respondents were Caucasian (88.4%) and female (63.7%) with an average age of 41.8 years (14.89). Respondents most frequently reported low back pain (41.2%), followed by osteoarthritis/rheumatoid arthritis (20.4%), neuropathic pain (10.6%), and fibromyalgia (9.0%). Respondents reported having their pain condition for an average of 5.4 (7.42) years. On days when taken, respondents reported a mean oxycodone CR daily dose of 83.3 mg (126.93) taken in an average of 2 doses. Most respondents (82.4%) reported experiencing at least 1 side effect with 77.5% being bothered by at least 1 side effect. The most frequently reported side effects ( greater than 25%) were drowsiness (41.4%), constipation (37.0%), fatigue or daytime sleepiness (36.6%), and dizziness (27.1%). Among respondents who reported being bothered by one or more side effects in the previous month, MRU associated with side effects was reported by 39.1% of respondents and significantly increased as the level of side-effect bother increased from 19.8% among those "A little bit bothered" to 38.4% among those "Bothered" to 61.0% among those "Extremely bothered" (P less than 0.001). Additionally, total average payer costs (in 2010 dollars) per respondent in the previous month associated with side effects were $238 ($1,159) and also significantly increased as the level of side-effect bother increased from $61 ($512) among those "A little bit bothered" to $238 ($1,160) among those "Bothered" to $425 ($1,561) among those "Extremely bothered" (P less than 0.001). Results reported in the neuropathic pain subgroup were similar to results reported in the total study sample. Among adults taking oxycodone CR for chronic noncancer pain (with or without a neuropathic pain component), over three-fourths reported being bothered by side effects. Respondents who reported higher levels of side-effect bother also reported greater MRU, resulting in increased payer costs. The results of this study provide further support of the econo-mic burden to payers associated with opioid-related side effects in patients with chronic noncancer pain, with and without neuropathic pain.

Predictors of statin adherence, switching, and discontinuation in the USAGE survey: understanding the use of statins in America and gaps in patient education.

PubMed

Wei, Melissa Y; Ito, Matthew K; Cohen, Jerome D; Brinton, Eliot A; Jacobson, Terry A

2013-01-01

Although statins have been shown to reduce cardiovascular disease mortality, less than half of U.S. adults achieve their low-density lipoprotein cholesterol goal. In many patients initiated on a statin, adherence rates decrease over time. To characterize current and former statin users, identify reasons for the discontinuation or switching of statins, and identify factors associated with adherence. The USAGE survey is a cross-sectional, self-administered Internet-based survey of 10,138 U.S. adults fielded September to October 2011. The following statin users were identified and compared: adherent nonswitchers, adherent switchers, non-adherent switchers, and discontinuers. Univariate and multivariate models using a priori covariates for adherence and discontinuation were examined. Most participants were current statin users who adhered with their prescribed statin (82.5%, n = 8371). Former statin users or discontinuers (12%, n = 1220) cited muscle pain, a side effect, as the primary reason for discontinuation (60%), followed by cost (16%), and then perceived lack of efficacy (13%). Discontinuers were less satisfied with their physicians' explanation of cholesterol treatment, more likely to use the Internet to research statins, and less likely to undergo frequent cholesterol monitoring. Among adherent statin users, the primary reasons for switching were muscle side effects (33%) and cost (32%). Individuals at risk for non-adherence included those with low household income, those who experienced muscle pain as a side effect while on statin therapy, and those taking medication for cardiovascular disease. Statin-related muscle side effects are common and contribute significantly to rates of discontinuation, switching, and non-adherence. Improved physician patient communication about side effects and benefits of statins are necessary to improve both adherence and outcomes. Copyright © 2013 National Lipid Association. Published by Elsevier Inc. All rights reserved.

Current Perspectives in NSAID-Induced Gastropathy

PubMed Central

Sinha, Mau; Gautam, Lovely; Shukla, Prakash Kumar; Kaur, Punit; Sharma, Sujata; Singh, Tej P.

2013-01-01

Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most highly prescribed drugs in the world. Their analgesic, anti-inflammatory, and antipyretic actions may be beneficial; however, they are associated with severe side effects including gastrointestinal injury and peptic ulceration. Though several approaches for limiting these side effects have been adopted, like the use of COX-2 specific drugs, comedication of acid suppressants like proton pump inhibitors and prostaglandin analogs, these alternatives have limitations in terms of efficacy and side effects. In this paper, the mechanism of action of NSAIDs and their critical gastrointestinal complications have been reviewed. This paper also provides the information on different preventive measures prescribed to minimize such adverse effects and analyses the new suggested strategies for development of novel drugs to maintain the anti-inflammatory functions of NSAIDs along with effective gastrointestinal protection. PMID:23576851

Oral Versus Topical Diclofenac Sodium in the Treatment of Osteoarthritis.

PubMed

Tieppo Francio, Vinicius; Davani, Saeid; Towery, Chris; Brown, Tony L

2017-06-01

Osteoarthritis (OA) is one of the most common causes of joint pain in the United States and non-steroidal anti-inflammatories (NSAIDs), such as Diclofenac sodium, which is currently available in two main routes of administration; oral and topical distribution have been established as one of the standard treatments for OA. Generally, oral NSAIDs are well tolerated; however our narrative review suggests that the topical solution had a better tolerability property than oral Diclofenac sodium, especially due to side effects of gastrointestinal bleeding with the utilization of the oral format. In addition, the topical route may be considered a reasonable selection by clinicians for management of musculoskeletal pain in those patients with a history of potential risk and adverse side effects. Most studies reviewed comparing oral versus topical solution of Diclofenac sodium revealed comparable efficacy, with minimal side effects utilizing the topical route. The key point of this narrative review is to help clinicians that currently must decide between very inexpensive diclofenac oral presentations and expensive topical presentations especially in the elderly population and the pros and cons of such decision-making process.

Effect of Game Design, Goal Type, and Player Numbers on the Physiological and Physical Demands of Hurling-Specific Small-Sided Games.

PubMed

Malone, Shane; Collins, Kieran D

2017-06-01

The current study examined the effect that game design modification, goal type, and player numbers on the running performance and physiological demands of small-sided hurling games (SSG). Forty-eight hurling players (age, 25.5 ± 3.2 years; height, 178.9 ± 3.2 cm; body mass, 78.5 ± 4.5 kg) performed 4 types of SSG (possession [P], normal play [NP], regular goals [RG] and small goals [SG]) in 4-a-side, 5-a-side, and 6-a-side formats. Heart rate (Polar Electro Oy) and global positioning system technology (VX Sport, 4-Hz, Lower Hutt) were used to analyze the physical and physiological differences between SSG. Total distance (m), high-speed running distance (m) (≥17 km·h), very-high speed running distance (≥22 km·h) (m), peak and mean velocity (km·h) were analyzed as an indicator of the physical demands of play. The 4-a-side SSG independent of game design and goal type resulted in a significantly higher relative exercise intensity compared with 5-a-side (mean change: 6 ± 2%; p = 0.001; d = 1.9 ± 0.2; large) and 6-a-side SSG independent of game design or goal type (mean change: 12 ± 2%; p = 0.001; d = 2.9 ± 0.8; very large). The 4-a-side SG (619 ± 106-m [419-735-m]) resulted in the highest distance when compared with all PP (mean change: 141 ± 9 m; p = 0.05; d = 1.9 ± 0.3; moderate) and RG (mean change: 119 ± 39 m; p = 0.004; d = 2.1 ± 0.8; large). Similar trends were observed for 5-a-side and 6-a-side games with SG resulting in increased total running performance. In conclusion, the current observations reveal that 4-a-side NP, SG, and RG have the highest physiological demands with 4-a-side SG having increased running performance in contrast to other game design and goal-type games. Furthermore, independent of game design and goal type, 4-a-side SSG show increased relative intensity compared with 5-a-side and 6-a-side SSG.

Phytochemicals and PI3K Inhibitors in Cancer—An Insight

PubMed Central

Suvarna, Vasanti; Murahari, Manikanta; Khan, Tabassum; Chaubey, Pramila; Sangave, Preeti

2017-01-01

In today's world of modern medicine and novel therapies, cancer still remains to be one of the prime contributor to the death of people worldwide. The modern therapies improve condition of cancer patients and are effective in early stages of cancer but the advanced metastasized stage of cancer remains untreatable. Also most of the cancer therapies are expensive and are associated with adverse side effects. Thus, considering the current status of cancer treatment there is scope to search for efficient therapies which are cost-effective and are associated with lesser and milder side effects. Phytochemicals have been utilized for many decades to prevent and cure various ailments and current evidences indicate use of phytochemicals as an effective treatment for cancer. Hyperactivation of phosphoinositide 3-kinase (PI3K) signaling cascades is a common phenomenon in most types of cancers. Thus, natural substances targeting PI3K pathway can be of great therapeutic potential in the treatment of cancer patients. This chapter summarizes the updated research on plant-derived substances targeting PI3K pathway and the current status of their preclinical studies and clinical trials. PMID:29311925

Conversations between community-based neurologists and patients with epilepsy: results of an observational linguistic study.

PubMed

Gilliam, Frank; Penovich, Patricia E; Eagan, Corey A; Stern, John M; Labiner, David M; Onofrey, Meaghan; Holmes, Gregory L; Mathis, Eileen; Cramer, Joyce

2009-10-01

An in-office linguistic study was conducted to assess neurologist-patient discussions of epilepsy. Naturally occurring interactions among 20 neurologists and 60 of their patients with epilepsy were recorded. Participants were interviewed separately postvisit. Transcripts were analyzed using sociolinguistic techniques. Of 59 patients taking antiepileptic drugs previsit, 44 (75%) discussed side effects with their neurologist. Side effect discussions were most often neurologist initiated. Postvisit, patients and neurologists often disagreed about which side effects were experienced. The presence of a caregiver (e.g., spouse) usually resulted in lengthier, more detailed discussions of side effects, without drastically increasing overall visit length. Discussions of mood- and behavior-related comorbidities occurred infrequently (14 of 60 visits); postvisit, neurologists stated that they felt that management of these conditions was outside their area of expertise. Communication gaps observed in discussions of epilepsy and its treatment warrant further exploration. Additional research is currently underway to assess the efficacy of a previsit assessment tool.

Equivalent model and power flow model for electric railway traction network

NASA Astrophysics Data System (ADS)

Wang, Feng

2018-05-01

An equivalent model of the Cable Traction Network (CTN) considering the distributed capacitance effect of the cable system is proposed. The model can be divided into 110kV side and 27.5kV side two kinds. The 110kV side equivalent model can be used to calculate the power supply capacity of the CTN. The 27.5kV side equivalent model can be used to solve the voltage of the catenary. Based on the equivalent simplified model of CTN, the power flow model of CTN which involves the reactive power compensation coefficient and the interaction of voltage and current, is derived.

Individualized Low-Amplitude Seizure Therapy: Minimizing Current for Electroconvulsive Therapy and Magnetic Seizure Therapy.

PubMed

Peterchev, Angel V; Krystal, Andrew D; Rosa, Moacyr A; Lisanby, Sarah H

2015-08-01

Electroconvulsive therapy (ECT) at conventional current amplitudes (800-900 mA) is highly effective but carries the risk of cognitive side effects. Lowering and individualizing the current amplitude may reduce side effects by virtue of a less intense and more focal electric field exposure in the brain, but this aspect of ECT dosing is largely unexplored. Magnetic seizure therapy (MST) induces a weaker and more focal electric field than ECT; however, the pulse amplitude is not individualized and the minimum amplitude required to induce a seizure is unknown. We titrated the amplitude of long stimulus trains (500 pulses) as a means of determining the minimum current amplitude required to induce a seizure with ECT (bilateral, right unilateral, bifrontal, and frontomedial electrode placements) and MST (round coil on vertex) in nonhuman primates. Furthermore, we investigated a novel method of predicting this amplitude-titrated seizure threshold (ST) by a non-convulsive measurement of motor threshold (MT) using single pulses delivered through the ECT electrodes or MST coil. Average STs were substantially lower than conventional pulse amplitudes (112-174 mA for ECT and 37.4% of maximum device amplitude for MST). ST was more variable in ECT than in MST. MT explained 63% of the ST variance and is hence the strongest known predictor of ST. These results indicate that seizures can be induced with less intense electric fields than conventional ECT that may be safer; efficacy and side effects should be evaluated in clinical studies. MT measurement could be a faster and safer alternative to empirical ST titration for ECT and MST.

Disturbance of the inclined inserting-type sand fence to wind-sand flow fields and its sand control characteristics

NASA Astrophysics Data System (ADS)

Cheng, Jian-jun; Lei, Jia-qiang; Li, Sheng-yu; Wang, Hai-feng

2016-06-01

The inclined inserting-type sand fence is a novel sand retaining wall adopted along the Lanxin High-Speed Railway II in Xinjiang for controlling and blocking sand movement. To verify the effectiveness of the new fence structure for sand prevention, a wind tunnel test was used for flow field test simulation of the sand fence. The results indicate that the inclined inserting-type sand fence was able to deflect the flow of the sand and was able to easily form an upward slant acceleration zone on the leeward side of the sand fence. As shown by the percentage change in sand collection rates on the windward side and the leeward side of the sand fence, the sand flux per unit area at 4 m height in the slant upward direction increased on the leeward side of the inclined inserting-type sand fence. By comparing the flow fields, this site is an acceleration zone, which also reaffirms the correspondence of wind-sand flow fields with the spatial distribution characteristic of the wind-carried sand motion. The field sand collection data indicates that under the effects of the inclined inserting-type sand fence, the sandy air currents passing in front and behind the sand fence not only changed in quality, but the grain composition and particle size also significantly changed, suggesting that the inclined inserting-type sand fence has a sorting and filtering effect on the sandy air currents that passed through. The fence retained coarse particulates on the windward side and fine particulates within the shade of the wind on the leeward side.

Patient perceptions of glucocorticoid side effects: a cross-sectional survey of users in an online health community.

PubMed

Costello, Ruth; Patel, Rikesh; Humphreys, Jennifer; McBeth, John; Dixon, William G

2017-04-03

To identify the side effects most important to glucocorticoid (GC) users through a survey of a UK online health community (Healthunlocked.com). Online cross-sectional survey. Participants were recruited through Healthunlocked.com, an online social network for health. Adults who were currently taking GCs, or had taken GCs in the past month. Responders scored the importance of listed side effects from 1 to 10, with 10 being of high importance to them. For each side effect, histograms were plotted, and the median rating and IQR were determined. Side effects were ranked by median ranking (largest to smallest) and then IQR (smallest to largest). The scores were categorised as low (scores 1-3), medium (scores 4-7) and high (scores 8-10) importance. 604 responders completed the survey. Histograms of side effect scores showed a skew towards high importance for weight gain, a U-shaped distribution for cardiovascular disease (CVD), diabetes, eye disease and infections, and a skew towards low importance for acne. When ranked, the side effect of most importance to responders was weight gain (median score=9, IQR 6-10) followed by insomnia and moon face with equal median score (8) and IQR (5-10). Three serious side effects, CVD, diabetes and infections, were ranked of lower importance overall but had wide ranging scores (median score=8, IQR 1-10). The three most highly rated side effects were not clinically serious but remained important to patients, perhaps reflecting their impact on quality of life and high prevalence. This should be taken into consideration when discussing treatment options and planning future GC safety studies. 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/.

Image-guided preoperative prediction of pyramidal tract side effect in deep brain stimulation: proof of concept and application to the pyramidal tract side effect induced by pallidal stimulation.

PubMed

Baumgarten, Clement; Zhao, Yulong; Sauleau, Paul; Malrain, Cecile; Jannin, Pierre; Haegelen, Claire

2016-04-01

Deep brain stimulation of the medial globus pallidus (GPm) is a surgical procedure for treating patients suffering from Parkinson's disease. Its therapeutic effect may be limited by the presence of pyramidal tract side effect (PTSE). PTSE is a contraction time-locked to the stimulation when the current spreading reaches the motor fibers of the pyramidal tract within the internal capsule. The objective of the study was to propose a preoperative predictive model of PTSE. A machine learning-based method called PyMAN (PTSE model based on artificial neural network) accounting for the current used in stimulation, the three-dimensional electrode coordinates and the angle of the trajectory, was designed to predict the occurrence of PTSE. Ten patients implanted in the GPm have been tested by a clinician to create a labeled dataset of the stimulation parameters that trigger PTSE. The kappa index value between the data predicted by PyMAN and the labeled data was 0.78. Further evaluation studies are desirable to confirm whether PyMAN could be a reliable tool for assisting the surgeon to prevent PTSE during the preoperative planning.

Yohimbine-induced cutaneous drug eruption, progressive renal failure, and lupus-like syndrome.

PubMed

Sandler, B; Aronson, P

1993-04-01

Yohimbine is an indole alkaloid obtained from the yohimbe tree, a common tree in West Africa. We describe a forty-two-year black man in whom a generalized erythrodermic skin eruption, progressive renal failure, and lupus-like syndrome developed following treatment with the drug, yohimbine. A literature review failed to reveal any reported association of these side effects. We review current information on yohimbine's use in male impotence, reported side effects, and its role as a drug allergen.

Blood RNA biomarker panel detects both left- and right-sided colorectal neoplasms: a case-control study.

PubMed

Chao, Samuel; Ying, Jay; Liew, Gailina; Marshall, Wayne; Liew, Choong-Chin; Burakoff, Robert

2013-07-23

Colonoscopy is widely regarded to be the gold standard for colorectal cancer (CRC) detection. Recent studies, however, suggest that the effectiveness of colonoscopy is mostly confined to tumors on the left side of the colon (descending, sigmoid, rectum), and that the technology has poor tumor detection for right-sided (cecum, ascending, transverse) lesions. A minimally invasive test that can detect both left-sided and right-sided lesions could increase the effectiveness of screening colonoscopy by revealing the potential presence of neoplasms in the right-sided "blind spot". We previously reported on a seven-gene, blood-based biomarker panel that effectively stratifies a patient's risk of having CRC. For the current study, we assessed the effectiveness of the seven-gene panel for the detection of left- and right-sided CRC lesions. Results were evaluated for 314 patients with CRC (left-sided: TNM I, 65; TNM II, 57; TNM III, 60; TNM IV, 17; unknown, 9. right-sided: TNM I, 28; TNM II, 29; TNM III, 38; TNM IV, 12; unknown, 1 and including two samples with both left and right lesions) and 328 control samples. Blood samples were obtained prior to clinical staging and therapy. Most CRC subjects had localized disease (stages I and II, 58%); regional (stage III) and systemic (stage IV) disease represented 32% and 9%, respectively, of the study population. The panel detected left-sided (74%, 154/208) and right-sided (85%, 92/108) lesions with an overall sensitivity of 78% (215/316) at a specificity of 66% (215/328). Treatable cancer (stages I to III) was detected with left-sided lesion sensitivity of 76% (138/182) and right-sided sensitivity of 84% (80/95). This seven-gene biomarker panel detected right-sided CRC lesions across all cancer stages with a sensitivity that is at least equal to that for left-sided lesions. This study supports the use of this panel as the basis for a patient-friendly, blood-based test that can be easily incorporated into a routine physical examination in advance of colonoscopy to provide a convenient companion diagnostic and a pre-screening alert, ultimately leading to enhanced CRC screening effectiveness.

Methanol sensor operated in a passive mode

DOEpatents

Ren, Xiaoming; Gottesfeld, Shimshon

2002-01-01

A sensor outputs a signal related to a concentration of methanol in an aqueous solution adjacent the sensor. A membrane electrode assembly (MEA) is included with an anode side and a cathode side. An anode current collector supports the anode side of the MEA and has a flow channel therethrough for flowing a stream of the aqueous solution and forms a physical barrier to control access of the methanol to the anode side of the MEA. A cathode current collector supports the cathode side of the MEA and is configured for air access to the cathode side of the MEA. A current sensor is connected to measure the current in a short circuit across the sensor electrodes to provide an output signal functionally related to the concentration of methanol in the aqueous solution.

Salicylate, an aspirin metabolite, specifically inhibits the current mediated by glycine receptors containing α1-subunits

PubMed Central

Lu, Y-G; Tang, Z-Q; Ye, Z-Y; Wang, H-T; Huang, Y-N; Zhou, K-Q; Zhang, M; Xu, T-L; Chen, L

2009-01-01

Background and purpose: Aspirin or its metabolite sodium salicylate is widely prescribed and has many side effects. Previous studies suggest that targeting neuronal receptors/ion channels is one of the pathways by which salicylate causes side effects in the nervous system. The present study aimed to investigate the functional action of salicylate on glycine receptors at a molecular level. Experimental approach: Whole-cell patch-clamp and site-directed mutagenesis were deployed to examine the effects of salicylate on the currents mediated by native glycine receptors in cultured neurones of rat inferior colliculus and by glycine receptors expressed in HEK293T cells. Key results: Salicylate effectively inhibited the maximal current mediated by native glycine receptors without altering the EC50 and the Hill coefficient, demonstrating a non-competitive action of salicylate. Only when applied simultaneously with glycine and extracellularly, could salicylate produce this antagonism. In HEK293T cells transfected with either α1-, α2-, α3-, α1β-, α2β- or α3β-glycine receptors, salicylate only inhibited the current mediated by those receptors that contained the α1-subunit. A single site mutation of I240V in the α1-subunit abolished inhibition by salicylate. Conclusions and implications: Salicylate is a non-competitive antagonist specifically on glycine receptors containing α1-subunits. This action critically involves the isoleucine-240 in the first transmembrane segment of the α1-subunit. Our findings may increase our understanding of the receptors involved in the side effects of salicylate on the central nervous system, such as seizures and tinnitus. PMID:19594751

Mental health nurses' views about antipsychotic medication side effects.

PubMed

Stomski, N J; Morrison, P; Meehan, T

2016-08-01

WHAT IS KNOWN ON THE SUBJECT?: The only previous quantitative study that examined nurses' use of assessment tools to identify antipsychotic medication side effects found that about 25% of mental health nurses were using assessment tools. No previous studies have examined factors that influence the manner in which mental health nurses assess antipsychotic medication side effects. WHAT THIS PAPER ADDS TO EXISTING KNOWLEDGE?: One-third of the respondents were not aware of any antipsychotic medication side-effect assessment tool, and only one-quarter were currently using an assessment tool. 'Service responsibility' was significantly associated with ongoing use of antipsychotic medication assessment tools, indicating that respondents with more positive attitudes to their service were more likely to continue using antipsychotic medication assessment tools. WHAT ARE THE IMPLICATIONS FOR PRACTICE?: The low level of awareness and use of antipsychotic medication side-effect assessment tools indicates that nursing educational institutions should incorporate more detail about these tools in course content, and emphasize in particular the benefits that result from the use of these tools in clinical practice. Service processes contributed significantly to the use of antipsychotic medication assessment tools, which indicates that managers need to foster workplace cultures that promote routine use of these tools. Introduction Limited evidence suggests that only a minority of mental health nurses regularly use standardized assessment tools to assess antipsychotic medication side effects, but the factors that contribute to the non-routine use of these tools remain unknown. Aim To examine Australian mental health nurses' awareness of, and attitudes towards, side-effect assessment tools, and also identify factors the influence the use of these tools. Methods A cross-sectional survey was undertaken through distributing an online questionnaire via email to members of the Australian College of Mental Health Nurses. Completed questionnaires were received from 171 respondents. Linear regression was used to examine the relationship between the 'service responsibility' and 'personal confidence' scale scores, and awareness, previous use and ongoing use of antipsychotic medication assessment tools. Results Only one-quarter of the respondents (26.5%) were currently using an assessment tool. 'Service responsibility' was significantly associated with ongoing use of antipsychotic medication assessment tools (Β = 3.26; 95% CI 0.83-5.69). 'Personal confidence' did not influence the ongoing use of assessment tools (Β = -0.05; 95% CI -1.06-1.50). Implications for clinical practice Stakeholders can incorporate 'service responsibility' processes to foster increased use of assessment tools, which may enhance the identification antipsychotic medication side effects and improve the quality of care for service users. © 2016 John Wiley & Sons Ltd.

Compositional grading of InxGa1-xAs/GaAs tunnel junctions enhanced by ErAs nanoparticles

NASA Astrophysics Data System (ADS)

Salas, R.; Krivoy, E. M.; Crook, A. M.; Nair, H. P.; Bank, S. R.

2011-10-01

We investigate the electrical conductivity of GaAs-based tunnel junctions enhanced with semimetallic ErAs nanoparticles. In particular, we examine the effects of digitally-graded InGaAs alloys on the n-type side of the tunnel junction, along with different p-type doping levels. Device characteristics of the graded structures indicate that the n-type Schottky barrier may not be the limiting factor in the tunneling current as initially hypothesized. Moreover, significantly improved forward and reverse bias tunneling currents were observed with increased p-type doping, suggesting p-side limitation.

Cannabinoids: between neuroprotection and neurotoxicity.

PubMed

Sarne, Yosef; Mechoulam, Raphael

2005-12-01

Cannabinoids, such as the delta9-tetrahydrocannabinol (THC), present in the cannabis plant, as well as anandamide and 2-arachidonoyl glycerol, produced by the mammalian body, have been shown to protect the brain from various insults and to improve several neurodegenerative diseases. The current review summarizes the evidence for cannabinoid neuroprotection in vivo, and refers to recent in vitro studies, which help elucidate possible molecular mechanisms underlying this protective effect. Some of these mechanisms involve the activation of CB1 and CB2 cannabinoid receptors, while others are not dependent on them. In some cases, protection is due to a direct effect of the cannabinoids on neuronal cells, while in others, it results from their effects on non-neuronal elements within the brain. In many experimental set-ups, cannabinoid neurotoxicity, particularly by THC, resides side by side with neuroprotection. The current review attempts to shed light on this dual activity, and to dissociate between the two contradictory effects.

Details of Side Load Test Data and Analysis for a Truncated Ideal Contour Nozzle and a Parabolic Contour Nozzle

NASA Technical Reports Server (NTRS)

Ruf, Joseph H.; McDaniels, David M.; Brown, Andrew M.

2010-01-01

Two cold flow subscale nozzles were tested for side load characteristics during simulated nozzle start transients. The two test article contours were a truncated ideal and a parabolic. The current paper is an extension of a 2009 AIAA JPC paper on the test results for the same two nozzle test articles. The side load moments were measured with the strain tube approach in MSFC s Nozzle Test Facility. The processing techniques implemented to convert the strain gage signals into side load moment data are explained. Nozzle wall pressure profiles for separated nozzle flow at many NPRs are presented and discussed in detail. The effect of the test cell diffuser inlet on the parabolic nozzle s wall pressure profiles for separated flow is shown. The maximum measured side load moments for the two contours are compared. The truncated ideal contour s peak side load moment was 45% of that of the parabolic contour. The calculated side load moments, via mean-plus-three-standard-deviations at each nozzle pressure ratio, reproduced the characteristics and absolute values of measured maximums for both contours. The effect of facility vibration on the measured side load moments is quantified and the effect on uncertainty is calculated. The nozzle contour designs are discussed and the impact of a minor fabrication flaw in the nozzle contours is explained.

A T-shaped double quantum dot system as a Fano interferometer: Interplay of coherence and correlation upon spin currents

NASA Astrophysics Data System (ADS)

Fernandes, I. L.; Cabrera, G. G.

2018-05-01

Based on Keldysh non-equilibrium Green function method, we have investigated spin current production in a hybrid T-shaped device, consisting of a central quantum dot connected to the leads and a side dot which only couples to the central dot. The topology of this structure allows for quantum interference of the different paths that go across the device, yielding Fano resonances in the spin dependent transport properties. Correlation effects are taken into account at the central dot and handled within a mean field approximation. Its interplay with the Fano effect is analyzed in the strong coupling regime. Non-vanishing spin currents are only obtained when the leads are ferromagnetic, the current being strongly dependent on the relative orientation of the lead polarizations. We calculate the conductance (spin and charge) by numerically differentiating the current, and a rich structure is obtained as a manifestation of quantum coherence and correlation effects. Increase of the Coulomb interaction produces localization of states at the side dot, largely suppressing Fano resonances. The interaction is also responsible for the negative values of the spin conductance in some regions of the voltage near resonances, effect which is the spin analog of the Esaki tunnel diode. We also analyze control of the currents via gate voltages applied to the dots, possibility which is interesting for practical operations.

A systematic review of the psychiatric side-effects of efavirenz.

PubMed

Kenedi, Christopher A; Goforth, Harold W

2011-11-01

Concerns regarding the use of efavirenz in patients with a history of mental illness may predispose clinicians to not offer this agent to psychiatrically ill populations in spite of the convenience of once daily dosing, which can result in improved adherence in these at-risk populations. This systematic review examines the current data regarding the neuropsychiatric effects of efavirenz, and also attempts to provide guidance to clinicians using efavirenz to treat patients with mental illness. The review identified high rates of neuropsychiatric side effects including vivid dreams, insomnia and mood changes in approximately 50% of patients who initiate efavirenz. The effects begin quickly, commonly peak in the first 2 weeks, and are generally mild and transient in nature. Isolated case reports and uncontrolled data suggest higher rates of severe side effects; however, there is no clear evidence of a broadly increased risk of suicide or dangerous behavior for patients taking efavirenz as part of their antiretroviral regimen.

Review about gabapentin misuse, interactions, contraindications and side effects

PubMed Central

Quintero, Gabriel C

2017-01-01

The current work is targeted to review the risks of gabapentin misuse, its potential interactions with other drugs, side effects and use contraindications. This review consists of a total of 99 biographical references (from the year 1983 to 2016). A publication search of PubMed was performed from January 1983 to December 2016. It included animal studies, clinical studies, case studies and reviews related to gabapentin misuse, potential interactions, side effects and use contraindications. The search terms were gabapentin, anticonvulsant and antiepileptic. In general, it seems that gabapentin has risks of being misused based on the increased level of prescriptions, related fatalities, recreational misuse and higher doses of self-administration. The main reasons for gabapentin misuse are as follows: getting high, alleviating opioid withdrawal symptoms and potentiating methadone effects. Some of the main substances that interact with gabapentin are morphine, caffeine, losartan, ethacrynic acid, phenytoin, mefloquine and magnesium oxide. Some of the side effects caused by gabapentin are teratogenicity, hypoventilation, respiratory failure and myopathy. Finally, reports in general contraindicate the use of gabapentin in conditions such as myasthenia gravis and myoclonus. PMID:28223849

Mechanism of a-IGZO TFT device deterioration—illumination light wavelength and substrate temperature effects

NASA Astrophysics Data System (ADS)

Chen, Te-Chih; Kuo, Yue; Chang, Ting-Chang; Chen, Min-Chen; Chen, Hua-Mao

2017-10-01

Device characteristics changes in an a-IGZO thin film transistor under light illumination and at raised temperature have been investigated. Light exposure causes a large leakage current, which is more obvious with an increase in the illumination energy, power and the temperature. The increase in the leakage current is due to the trap assisted photon excitation process that generates electron-hole pairs and the mechanism is enhanced with the additional thermal energy. The leakage current comes from the source side because holes generated in the process drift to the source side and therefore lower the barrier height. The above mechanism has been further verified with experiments of drain bias induced shifts in the threshold voltage and the subthreshold slope.

Detecting and Managing Adverse Effects of Antipsychotic Medications: Current State of Play.

PubMed

Ames, Donna; Carr-Lopez, Sian M; Gutierrez, Mary A; Pierre, Joseph M; Rosen, Jennifer A; Shakib, Susan; Yudofsky, Lynn M

2016-06-01

Antipsychotics are some of the most frequently prescribed medications not only for psychotic disorders and symptoms but also for a wide range of on-label and off-label indications. Because second-generation antipsychotics have largely replaced first-generation antipsychotics as first-line options due to their substantially decreased risk of extrapyramidal side effects, attention has shifted to other clinically concerning adverse events associated with antipsychotic therapy. The focus of this article is to update the nonextrapyramidal side effects associated with second-generation antipsychotics. Issues surrounding diagnosis and monitoring as well as clinical management are addressed. Published by Elsevier Inc.

Emerging Treatment Mechanisms for Depression: Focus on Glutamate and Synaptic Plasticity

PubMed Central

Gerhard, Danielle M.; Wohleb, Eric S.; Duman, Ronald S.

2016-01-01

Major depression is a chronic and debilitating illness that effects approximately 1 in 5 people, but currently available treatments are limited by low rates of efficacy, therapeutic time lag, and undesirable side effects. Recent efforts have been directed towards investigating rapid-acting agents that reverse the behavioral and neuronal deficits of chronic stress and depression, notably the glutamate NMDA receptor antagonist ketamine. The cellular mechanisms underlying the rapid antidepressant actions of ketamine and related agents are discussed, as well as novel, selective glutamatergic receptor targets that are safer and have fewer side effects. PMID:26854424

Psychiatric effects of antiepileptic drugs in adults.

PubMed

Dussaule, Claire; Bouilleret, Viviane

2018-06-01

Epileptic and psychiatric diseases share overlaps. Indeed, anxiety and depression are common comorbidities in epilepsy, and patients with psychiatric disease are at risk of epilepsy. Some antiepileptic drugs (AED) have psychiatric side effects; conversely, some AED could be used to treat psychiatric pathologies. Based on current literature data, the aim of this study is to determine the psychiatric effects induced by the most frequently prescribed AED in epileptic adults. Some AED will have positive mood or anxiolytic effects like sodium channel blockers, valproate and benzodiazepines; conversely, others might induce negative psychiatric effect, especially depression, anxiety or aggression, like levetiracetam, perampanel, topiramate, zonisamide, and barbiturates. The main risk factor for presenting these side effects is a personal history of psychiatric pathology. We therefore recommend monitoring the occurrence of psychiatric side effects, especially when using the most at risk AED and/or in case of psychiatric history. Moreover, in this latter case, it is preferable to use AED with positive psychiatric effects. The use of anxiety and depression scales could be useful detection tools.

Mothers' Preferences and Willingness to Pay for Human Papillomavirus Vaccination for Their Daughters: A Discrete Choice Experiment in Hong Kong.

PubMed

Wong, Carlos K H; Man, Kenneth K C; Ip, Patrick; Kwan, Mike; McGhee, Sarah M

2018-05-01

To determine the preference of mothers in Hong Kong and their willingness to pay (WTP) for human papillomavirus (HPV) vaccination for their daughters. A discrete choice experiment survey with a two-alternative study design was developed. Data were collected from pediatric specialist outpatient clinics from 482 mothers with daughters aged between 8 and 17 years. Preferences of the four attributes of HPV vaccines (protection against cervical cancer, protection duration, side effects, and out-of-pocket costs) were evaluated. The marginal and overall WTP were estimated using multinomial logistic regression. A subgroup analysis was conducted to explore the impact of socioeconomic factors on mothers' WTP. Side effects, protection against cervical cancer, protection duration, and out-of-pocket cost determined the decision to receive or not receive the vaccine. All attributes had a statistically significant effect on the preference of and the WTP for the vaccine. Maximum WTP for ideal vaccines (i.e., 100% protection, lifetime protection duration, and 0% side effects) was HK$8976 (US $1129). The estimated WTP for vaccines currently available was HK$1620 (US $208), lower than the current market price. Among those who had a monthly household income of more than HK$100,000 (US $12,821), the WTP for vaccines currently offered was higher than the market price. This study provides new data on how features of the HPV vaccine are viewed and valued by mothers by determining their perception of ideal or improved and current vaccine technologies. These findings could contribute to future policies on the improvement of HPV vaccine and be useful for the immunization service in Hong Kong. Copyright © 2017 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

Individualized Low-Amplitude Seizure Therapy: Minimizing Current for Electroconvulsive Therapy and Magnetic Seizure Therapy

PubMed Central

Peterchev, Angel V; Krystal, Andrew D; Rosa, Moacyr A; Lisanby, Sarah H

2015-01-01

Electroconvulsive therapy (ECT) at conventional current amplitudes (800–900 mA) is highly effective but carries the risk of cognitive side effects. Lowering and individualizing the current amplitude may reduce side effects by virtue of a less intense and more focal electric field exposure in the brain, but this aspect of ECT dosing is largely unexplored. Magnetic seizure therapy (MST) induces a weaker and more focal electric field than ECT; however, the pulse amplitude is not individualized and the minimum amplitude required to induce a seizure is unknown. We titrated the amplitude of long stimulus trains (500 pulses) as a means of determining the minimum current amplitude required to induce a seizure with ECT (bilateral, right unilateral, bifrontal, and frontomedial electrode placements) and MST (round coil on vertex) in nonhuman primates. Furthermore, we investigated a novel method of predicting this amplitude-titrated seizure threshold (ST) by a non-convulsive measurement of motor threshold (MT) using single pulses delivered through the ECT electrodes or MST coil. Average STs were substantially lower than conventional pulse amplitudes (112–174 mA for ECT and 37.4% of maximum device amplitude for MST). ST was more variable in ECT than in MST. MT explained 63% of the ST variance and is hence the strongest known predictor of ST. These results indicate that seizures can be induced with less intense electric fields than conventional ECT that may be safer; efficacy and side effects should be evaluated in clinical studies. MT measurement could be a faster and safer alternative to empirical ST titration for ECT and MST. PMID:25920013

Therapy satisfaction and adherence in patients with relapsing–remitting multiple sclerosis: the THEPA-MS survey

PubMed Central

Haase, Rocco; Kullmann, Jennifer S.; Ziemssen, Tjalf

2016-01-01

Background: Improved clinical effectiveness and therefore positive modification of multiple sclerosis (MS) with basic therapy can be achieved by long-term regular intake of drugs as prescribed but investigations have shown that a high percentage of patients do not take their medications as prescribed. Objectives: We assessed the satisfaction and adherence of patients with MS with their current disease-modifying treatment under clinical practice conditions. We compared different facets of satisfaction as well as their internal relationship and identified predictors in an exploratory manner. Methods: Therapy satisfaction in patients with relapsing–remitting multiple sclerosis (THEPA-MS) was a noninterventional, prospective cross-sectional study performed throughout Germany in 2013 and 2014, and included patients with clinically isolated syndrome or relapsing–remitting MS. We applied a standardized approach to document satisfaction and adherence by patient-reported outcomes (Treatment Satisfaction Questionnaire for Medication) as well as by physician ratings. Results: Of 3312 patients with a mean age of 43.7 years, 73.3% were women and the mean level of disability according to the Expanded Disability Status Scale was 2.29; 13.3% did not receive any medication at the time of documentation, 21.3% received interferon β1a intramuscularly, 20.7% had interferon β1a subcutaneously, 17.0% had interferon β1b subcutaneously and 23.7% had glatiramer acetate. Adherence rates varied between 60% (lifetime) and 96.5% (current medication). Differences between current medications were found for side effects and convenience scores but not for effectiveness, satisfaction and adherence. Higher global satisfaction and effectiveness were associated with fewer relapses, longer duration of medication, lower disability score and the absence of several side effects. Conclusion: In a connected model of patient satisfaction, effectiveness, side effects, convenience and adherence, patients’ individual needs and concerns have to be addressed. Most differences were found with respect to side effects and convenience of treatment. Therefore, an improvement in these two domains seems to be the most promising proximate approach to elevate adherence levels. PMID:27366231

[High intensity focused ultrasound (HIFU) : Importance in the treatment of prostate cancer].

PubMed

Ganzer, R

2017-08-01

High intensity focused ultrasound (HIFU) has been used since the beginning of the 1990s as an alternative treatment for prostate cancer. Overview of the current status and critical review of the different indications for HIFU in the treatment of prostate cancer. Review of the current literature on the indications, side effects, oncologic results and current guideline recommendations. The principle of HIFU is based on high energy sound waves, which lead to coagulation necrosis at the focal point. It can be applied for different indications: complete ablation of prostatic tissue is attempted in whole gland HIFU in the primary treatment of localized prostate cancer. There are several case series in the current literature with a maximum median follow-up of 8.1 years. The main side effect is the formation of bladder neck sclerosis. A further indication is for salvage HIFU in patients with localized recurrent prostate cancer after radiotherapy. This is a high-risk procedure due to increased risk of incontinence and formation of rectourethral fistula. Focal therapy is an innovative field aiming at partial prostate gland ablation with HIFU thereby reducing side effects. Technical improvements in HIFU enable treatment planning with fusion of multiparametric magnetic resonance imaging (mpMRI). Due to the experimental character, this should only be carried out within clinical trials. Due to a lack of prospective randomized trials and limited long-term results, whole gland HIFU is considered differently in the guidelines of European countries. Focal therapy is still experimental and should only be carried out within clinical trials.

Central neurotoxicity of immunomodulatory drugs in multiple myeloma.

PubMed

Patel, Urmeel H; Mir, Muhammad A; Sivik, Jeffrey K; Raheja, Divisha; Pandey, Manoj K; Talamo, Giampaolo

2015-02-24

Immunomodulatory drugs (IMiDs) currently used in the treatment of multiple myeloma, are thalidomide, lenalidomide and pomalidomide. One of the most common side effects of thalidomide is neurotoxicity, predominantly in the form of peripheral neuropathy. We report 6 cases of significant central neurotoxicity associated with IMiD therapy. Treatment with thalidomide (1 patient), lenalidomide (4 patients), and pomalidomide (1 patient) was associated with various clinical manifestations of central neurotoxicity, including reversible coma, amnesia, expressive aphasia, and dysarthria. Central neurotoxicity should be recognized as an important side effect of IMiD therapy.

Central Neurotoxicity of Immunomodulatory Drugs in Multiple Myeloma

PubMed Central

Patel, Urmeel H.; Mir, Muhammad A.; Sivik, Jeffrey K.; Raheja, Divisha; Pandey, Manoj K.; Talamo, Giampaolo

2015-01-01

Immunomodulatory drugs (IMiDs) currently used in the treatment of multiple myeloma, are thalidomide, lenalidomide and pomalidomide. One of the most common side effects of thalidomide is neurotoxicity, predominantly in the form of peripheral neuropathy. We report 6 cases of significant central neurotoxicity associated with IMiD therapy. Treatment with thalidomide (1 patient), lenalidomide (4 patients), and pomalidomide (1 patient) was associated with various clinical manifestations of central neurotoxicity, including reversible coma, amnesia, expressive aphasia, and dysarthria. Central neurotoxicity should be recognized as an important side effect of IMiD therapy. PMID:25852850

β-glucans and cholesterol (Review)

PubMed Central

Sima, Petr; Vetvicka, Vaclav

2018-01-01

Hypercholesterolemia is one of primary risk factors of cardiovascular disease, together with metabolic syndrome, hypertension and diabetes. Although progress has been made, the search for novel methods of preventing and treating dyslipidemia is ongoing and current therapies for cardiovascular disease induce various side effects. β-glucans are linear unbranched polysaccharides found in various natural sources, such as mushrooms. Due to their structure they are able to interact with innate immunity receptors, however they also act as dietary fibers in the digestive tract. As there are two forms of β-glucans, insoluble and soluble forms, they are able to interact with lipids and biliary salts in the bowel and consequently reduce cholesterol levels. Therefore, they may be developed as a suitable therapeutic option to treat patients with dyslipidemia, as they are natural molecules that do not induce any significant side effects. The current review discusses the evidence supporting the effects of β-glucans on cholesterol levels. PMID:29393350

A facile electrode preparation method for accurate electrochemical measurements of double-side-coated electrode from commercial Li-ion batteries

NASA Astrophysics Data System (ADS)

Zhou, Ge; Wang, Qiyu; Wang, Shuo; Ling, Shigang; Zheng, Jieyun; Yu, Xiqian; Li, Hong

2018-04-01

The post mortem electrochemical analysis, including charge-discharge and electrochemical impedance spectroscopy (EIS) measurements, are critical steps for revealing the failure mechanisms of commercial lithium-ion batteries (LIBs). These post measurements usually require the reassembling of coin-cell with electrode which is often double-side-coated in commercial LIBs. It is difficult to use such double-side-coated electrode to perform accurate electrochemical measurements because the back side of the electrode is coated with active materials, rather than single-side-coated electrode that is often used in coin-cell measurements. In this study, we report a facile tape-covering sample preparation method, which can effectively suppress the influence of back side of the double-side-coated electrodes on capacity and EIS measurements in coin-cells. By tape-covering the unwanted side, the areal capacity of the desired investigated side of the electrode has been accurately measured with an experimental error of about 0.5% at various current densities, and accurate EIS measurements and analysis have been conducted as well.

Gene Expression in Single Cells Isolated from the CWR-R1 Prostate Cancer Cell Line and Human Prostate Tissue Based on the Side Population Phenotype.

PubMed

Gangavarapu, Kalyan J; Miller, Austin; Huss, Wendy J

2016-09-01

Defining biological signals at the single cell level can identify cancer initiating driver mutations. Techniques to isolate single cells such as microfluidics sorting and magnetic capturing systems have limitations such as: high cost, labor intense, and the requirement of a large number of cells. Therefore, the goal of our current study is to identify a cost and labor effective, reliable, and reproducible technique that allows single cell isolation for analysis to promote regular laboratory use, including standard reverse transcription PCR (RT-PCR). In the current study, we utilized single prostate cells isolated from the CWR-R1 prostate cancer cell line and human prostate clinical specimens, based on the ATP binding cassette (ABC) transporter efflux of dye cycle violet (DCV), side population assay. Expression of four genes: ABCG2; Aldehyde dehydrogenase1A1 (ALDH1A1); androgen receptor (AR); and embryonic stem cell marker, Oct-4, were determined. Results from the current study in the CWR-R1 cell line showed ABCG2 and ALDH1A1 gene expression in 67% of single side population cells and in 17% or 100% of non-side population cells respectively. Studies using single cells isolated from clinical specimens showed that the Oct-4 gene is detected in only 22% of single side population cells and in 78% of single non-side population cells. Whereas, AR gene expression is in 100% single side population and non-side population cells isolated from the same human prostate clinical specimen. These studies show that performing RT-PCR on single cells isolated by FACS can be successfully conducted to determine gene expression in single cells from cell lines and enzymatically digested tissue. While these studies provide a simple yes/no expression readout, the more sensitive quantitative RT-PCR would be able to provide even more information if necessary.

Gene Expression in Single Cells Isolated from the CWR-R1 Prostate Cancer Cell Line and Human Prostate Tissue Based on the Side Population Phenotype

PubMed Central

Gangavarapu, Kalyan J; Miller, Austin; Huss, Wendy J

2016-01-01

Defining biological signals at the single cell level can identify cancer initiating driver mutations. Techniques to isolate single cells such as microfluidics sorting and magnetic capturing systems have limitations such as: high cost, labor intense, and the requirement of a large number of cells. Therefore, the goal of our current study is to identify a cost and labor effective, reliable, and reproducible technique that allows single cell isolation for analysis to promote regular laboratory use, including standard reverse transcription PCR (RT-PCR). In the current study, we utilized single prostate cells isolated from the CWR-R1 prostate cancer cell line and human prostate clinical specimens, based on the ATP binding cassette (ABC) transporter efflux of dye cycle violet (DCV), side population assay. Expression of four genes: ABCG2; Aldehyde dehydrogenase1A1 (ALDH1A1); androgen receptor (AR); and embryonic stem cell marker, Oct-4, were determined. Results from the current study in the CWR-R1 cell line showed ABCG2 and ALDH1A1 gene expression in 67% of single side population cells and in 17% or 100% of non-side population cells respectively. Studies using single cells isolated from clinical specimens showed that the Oct-4 gene is detected in only 22% of single side population cells and in 78% of single non-side population cells. Whereas, AR gene expression is in 100% single side population and non-side population cells isolated from the same human prostate clinical specimen. These studies show that performing RT-PCR on single cells isolated by FACS can be successfully conducted to determine gene expression in single cells from cell lines and enzymatically digested tissue. While these studies provide a simple yes/no expression readout, the more sensitive quantitative RT-PCR would be able to provide even more information if necessary. PMID:27785389

The timeliness of patients reporting the side effects of chemotherapy.

PubMed

Olver, Ian; Carey, Mariko; Boyes, Allison; Hall, Alix; Noble, Natasha; Bryant, Jamie; Walsh, Justin; Sanson-Fisher, Rob

2018-05-03

To explore the actions cancer patients reported they would take in response to a range of common side effects of chemotherapy and whether these were considered appropriate based on current guidelines and evidence; and to explore the sociodemographic and cancer-related variables associated with patients selecting the appropriate action (immediate medical attention or reporting) for two potentially life-threatening side effects: fever, and unusual bleeding and bruising. Four hundred thirty-six medical oncology and haematology patients receiving chemotherapy completed two surveys to provide demographic, disease and treatment characteristics, and details on how they would respond if they experienced a range of specified side effects of chemotherapy (for example, nausea and vomiting, fatigue, and skin rash or nail changes). The proportion of patients reporting the appropriate action for each side effect was calculated. Multiple logistic regressions examined the patient demographic and cancer characteristics associated with selecting the appropriate action (seeking immediate medical attention) for two potentially life-threatening side effects of chemotherapy: high fever of 38 °C or more, and unusual bleeding or bruising. Two thirds of patients indicated that they would seek immediate medical attention for high fever (67%), but only 41% would seek immediate attention for bleeding or bruising. Cancer type and time since diagnosis were significantly associated with patients indicating that they would seek immediate medical attention for high fever; while time since diagnosis was the only variable significantly associated with patients reporting that they would seek immediate medical attention for unusual bleeding or bruising. For chronic side effects, like skin rash or nail changes, and tingling or numbness, which usually do not require urgent reporting, only between 12 and 16% would report them immediately. A significant proportion of patients reported that they would "do nothing" about fatigue or tiredness (24%). By comparison, less than 10% patients reported that they would do nothing for the other side effects investigated. Tools need to be created so that patients better understand the side effects after being treated with chemotherapy and what action they should take.

Potential climate engineering effectiveness and side effects during a high carbon dioxide-emission scenario

PubMed Central

Keller, David P.; Feng, Ellias Y.; Oschlies, Andreas

2014-01-01

The realization that mitigation efforts to reduce carbon dioxide emissions have, until now, been relatively ineffective has led to an increasing interest in climate engineering as a possible means of preventing the potentially catastrophic consequences of climate change. While many studies have addressed the potential effectiveness of individual methods there have been few attempts to compare them. Here we use an Earth system model to compare the effectiveness and side effects of afforestation, artificial ocean upwelling, ocean iron fertilization, ocean alkalinization and solar radiation management during a high carbon dioxide-emission scenario. We find that even when applied continuously and at scales as large as currently deemed possible, all methods are, individually, either relatively ineffective with limited (<8%) warming reductions, or they have potentially severe side effects and cannot be stopped without causing rapid climate change. Our simulations suggest that the potential for these types of climate engineering to make up for failed mitigation may be very limited. PMID:24569320

High temperature-induced abnormal suppression of sub-threshold swing and on-current degradations under hot-carrier stress in a-InGaZnO thin film transistors

NASA Astrophysics Data System (ADS)

Tsai, Ming-Yen; Chang, Ting-Chang; Chu, Ann-Kuo; Hsieh, Tien-Yu; Chen, Te-Chih; Lin, Kun-Yao; Tsai, Wu-Wei; Chiang, Wen-Jen; Yan, Jing-Yi

2013-07-01

This letter investigates the effect of temperature on hot-carrier stress-induced degradation behavior in InGaZnO thin film transistors. After hot-carrier stress at 25 °C, serious on-current and subthreshold swing degradations are observed due to trap state generation near the drain side. For identical stress performed at elevated temperatures, current degradation in the I-V transfer curve under reverse mode is gradually suppressed and the anomalous hump in the gate-to-drain capacitance-voltage curve becomes more severe. These suppressed degradations and the more severe hump can be both attributed to hole-trapping near the drain side due to high drain bias at high temperature.

Power Generation Evaluated on a Bismuth Telluride Unicouple Module

NASA Astrophysics Data System (ADS)

Hu, Xiaokai; Nagase, Kazuo; Jood, Priyanka; Ohta, Michihiro; Yamamoto, Atsushi

2015-06-01

The power generated by a thermoelectric unicouple module made of Bi2Te3 alloy was evaluated by use of a newly developed instrument. An electrical load was connected to the module, and the terminal voltage and output power of the module were obtained by altering electric current. Water flow was used to cool the cold side of the module and for heat flow measurement, by monitoring inlet and outlet temperatures. When the electric current was increased, heat flow was enhanced as a result of the Peltier effect and Joule heating. Voltage, power, heat flow, and efficiency as functions of current were determined for hot-side temperatures from 50 to 220°C. Maximum power output and peak conversion efficiency could thus be easily derived for each temperature.

EFFECTS OF ELECTRICAL CURRENTS ON THE ABSORPTION OF WATER BY EGGS OF NEREIS LIMBATA

PubMed Central

Osterhout, W. J. V.

1950-01-01

Unfertilized eggs of the marine worm Nereis limbata subjected to electrical currents (direct or alternating) undergo remarkable changes. Certain minute granules just inside the surface of the egg absorb water and swell to more than 300 times their original size and thereby produce a mass of jelly which surrounds the egg with a zone about as wide as the original diameter of the egg. The amount of direct current is too small to produce any change of color in eggs stained with neutral red. In direct current the jelly appears first on the side toward the anode and moves toward the anode. In alternating current it appears on opposite sides facing the electrodes. It might be thought that the current changes the chemical character of the granules so that they are able to absorb very large quantities of water but this seems unlikely. If the current is shut off after 1 minute the swelling continues. This might be explained on the ground that each jelly precursor granule is covered with a waterproof film which is removed by the current. It does not seem probable that the effect is due to heat produced by the current since the exposure is so short. It seems possible that the current may strip off micelles from the waterproof covering of the granules and allow water to penetrate. The fact that alternating current is more effective than direct current might be explained on the ground that the egg may be represented as a capacity in parallel with a resistance so constituted that relatively little direct current can enter. The non-aqueous film which covers the surface of the protoplasm appears to be liquid rather than solid. PMID:15406375

Is electroconvulsive therapy (ECT) effective and safe for treatment of depression in dementia? A short review.

PubMed

Oudman, Erik

2012-03-01

Depression is one of the most frequently diagnosed psychiatric disorders in patients with dementia with a prevalence of up to 50%. The detrimental effects of depression in dementia include disability in daily living, worse quality of life, and faster cognitive decline. Although electroconvulsive therapy (ECT) is a well-established and effective treatment for depression in the elderly, it is currently an overlooked treatment option in the elderly with dementia and depression. The aim of this review was to provide a critical analysis of the efficacy and safety of ECT in depression superimposed on dementia by reviewing the current literature on this topic. Current evidence suggests that ECT is an effective treatment for depression in dementia, although the relatively small number of controlled studies hampers the comparison of effectiveness between healthy nongeriatric patients and those with dementia. Moreover, the systematic reports on cognitive side effects are very limited in number and currently only apply to moderately mild or mild dementia of nonvascular origin. Some studies do suggest that cognitive side effects are likely in later stages of dementia and in patients with vascular dementia. It is therefore of crucial relevance to prospectively study effects of ECT in different types and phases of dementia in controlled trials. From a clinical perspective, it is essential to inform and educate patients and family about the possible risks and benefits of ECT treatment for depression in dementia.

Effect of Pin Tool Shape on Metal Flow During Friction Stir Welding

NASA Technical Reports Server (NTRS)

McClure, J. C.; Coronado, E.; Aloor, S.; Nowak, B.; Murr, L. M.; Nunes, Arthur C., Jr.; Munafo, Paul M. (Technical Monitor)

2002-01-01

It has been shown that metal moves behind the rotating Friction Stir Pin Tool in two separate currents or streams. One current, mostly on the advancing side, enters a zone of material that rotates with the pin tool for one or more revolutions and eventually is abandoned behind the pin tool in crescent-shaped pieces. The other current, largely on the retreating side of the pin tool is moved by a wiping process to the back of the pin tool and fills in between the pieces of the rotational zone that have been shed by the rotational zone. This process was studied by using a faying surface copper trace to clarify the metal flow. Welds were made with pin tools having various thread pitches. Decreasing the thread pitch causes the large scale top-to-bottorn flow to break up into multiple vortices along the pin and an unthreaded pin tool provides insufficient vertical motion for there to be a stable rotational zone and flow of material via the rotational zone is not possible leading to porosity on the advancing side of the weld.

42 CFR 484.55 - Condition of participation: Comprehensive assessment of patients.

Code of Federal Regulations, 2014 CFR

2014-10-01

...) Standard: Drug regimen review. The comprehensive assessment must include a review of all medications the patient is currently using in order to identify any potential adverse effects and drug reactions, including ineffective drug therapy, significant side effects, significant drug interactions, duplicate drug...

Herbal Medicine and Acupuncture for Breast Cancer Palliative Care and Adjuvant Therapy

PubMed Central

Liao, Guo-Shiou; Shyur, Lie-Fen

2013-01-01

Breast cancer is a life-threatening disease among women worldwide with annual rates of reported incidence and death increasing alarmingly. Chemotherapy is a recommended and effective treatment option for breast cancer; however, the narrow therapeutic indices and varied side effects of currently approved drugs present major hurdles in increasing its effectiveness. An increasing number of literature evidence indicate that complementary and alternative medicine (CAM) used in treatment-related symptom control and alleviation of side effects plays an important role in increasing survival rate and quality of life in breast cancer patients. This review focuses on the use of herbal medicines and acupuncture in palliative care and as adjuvants in the treatment of breast cancer. Herbal medicinal treatments, the correlation of clinical use with demonstrated in vitro and in vivo mechanisms of action, and the use of certain acupoints in acupuncture are summarized. The aim of this review is to facilitate an understanding of the current practice and usefulness of herbal medicine and acupuncture as adjuvants in breast cancer therapy. PMID:23840256

Prophylactic Therapy for Hereditary Angioedema.

PubMed

Longhurst, Hilary; Zinser, Emily

2017-08-01

Long-term prophylaxis is needed in many patients with hereditary angioedema and poses many challenges. Attenuated androgens are effective in many but are limited by side effect profiles. There is less evidence for efficacy of tranexamic acid and progestagens; however, the small side effect profile makes tranexamic acid an option for prophylaxis in children and progestagens an option for women. C1 inhibitor is beneficial, but at present requires intravenous delivery and may need dose titration for maximum efficacy. Short-term prophylaxis should be considered for all procedures. New therapies are promising in overcoming many problems encountered with current options for long-term prophylaxis. Copyright © 2017 Elsevier Inc. All rights reserved.

How do stroke survivors and their carers use practitioners' advice on secondary prevention medications? Qualitative study of an online forum.

PubMed

Izuka, Nkeonye J; Alexander, Matthew A W; Balasooriya-Smeekens, Chantal; Mant, Jonathan; De Simoni, Anna

2017-09-01

Secondary prevention medications reduce risk of stroke recurrence, yet many people do not receive recommended treatment, nor take medications optimally. Exploring how patients report making use of practitioners' advice on secondary prevention medicines on an online forum and what feedback was received from other participants. Thematic analysis of the archive of Talkstroke (2004-2011), UK. Posts including any secondary prevention medication terms, General Practitioner (GP) and their replies were identified. Fifity participants talked about practitioners' advice on secondary prevention medications in 43 discussion threads. Patients consulted practitioners for reassurance and dealing with side effects. Practitioners' advice varied from altering to maintaining current treatment. Three main themes emerged from the use of practitioners' advice: patients following advice (reassured, happy when side effects made tolerable, or still retaining anxiety about treatment); patients not following advice (admitting adherence on-off or stopping medications as side effects still not tolerable); asking other participants for feedback on advice received. Practitioners' advice was disregarded mainly when related to dealing with statin side effects, after one or two consultations. Themes for feedback involved sharing experience, directing back to practitioners, or to external evidence. Side effects of secondary prevention medications and statins in particular, cause anxiety and resentment in some patients, and their concerns are not always addressed by practitioners. Practitioners could consider more proactive strategies to manage such side effects. Forum feedback was appropriate and supportive of the practitioners' advice received. Our findings from peer-to-peer online conversations confirm and widen previous research. © The Author 2017. Published by Oxford University Press.

Competitive inhibition of the nondepolarizing muscle relaxant rocuronium on nicotinic acetylcholine receptor channels in the rat superior cervical ganglia.

PubMed

Zhang, Chengmi; Wang, Zhenmeng; Zhang, Jinmin; Qiu, Haibo; Sun, Yuming; Yang, Liqun; Wu, Feixiang; Zheng, Jijian; Yu, Weifeng

2014-05-01

A number of case reports now indicate that rocuronium can induce a number of serious side effects. We hypothesized that these side effects might be mediated by the inhibition of nicotinic acetylcholine receptors (nAChRs) at superior cervical ganglion (SCG) neurons. Conventional patch clamp recordings were used to study the effects of rocuronium on nAChR currents from enzymatically dissociated rat SCG neurons. We found that ACh induced a peak transient inward current in rat SCG neurons. Additionally, rocuronium suppressed the peak ACh-evoked currents in rat SCG neurons in a concentration-dependent and competitive manner, and it increased the extent of desensitization of nAChRs. The inhibitory rate of rocuronium on nAChR currents did not change significantly at membrane potentials between -70 and -20 mV, suggesting that this inhibition was voltage independent. Lastly, rocuronium preapplication enhanced its inhibitory effect, indicating that this drug might prefer to act on the closed state of nAChR channels. In conclusion, rocuronium, at clinically relevant concentrations, directly inhibits nAChRs at the SCG by interacting with both opened and closed states. This inhibition is competitive, dose dependent, and voltage independent. Blockade of synaptic transmission in the sympathetic ganglia by rocuronium might have potentially inhibitory effects on the cardiovascular system.

Loop Diuretics in the Treatment of Hypertension.

PubMed

Malha, Line; Mann, Samuel J

2016-04-01

Loop diuretics are not recommended in current hypertension guidelines largely due to the lack of outcome data. Nevertheless, they have been shown to lower blood pressure and to offer potential advantages over thiazide-type diuretics. Torsemide offers advantages of longer duration of action and once daily dosing (vs. furosemide and bumetanide) and more reliable bioavailability (vs. furosemide). Studies show that the previously employed high doses of thiazide-type diuretics lower BP more than furosemide. Loop diuretics appear to have a preferable side effect profile (less hyponatremia, hypokalemia, and possibly less glucose intolerance). Studies comparing efficacy and side effect profiles of loop diuretics with the lower, currently widely prescribed, thiazide doses are needed. Research is needed to fill gaps in knowledge and common misconceptions about loop diuretic use in hypertension and to determine their rightful place in the antihypertensive arsenal.

Laxatives Do Not Improve Symptoms of Opioid-Induced Constipation: Results of a Patient Survey

PubMed Central

Emmanuel, Anton; Johnson, Martin; McSkimming, Paula; Dickerson, Sara

2017-01-01

Abstract Introduction Laxatives are commonly used to treat opioid-induced constipation, the commonest and most bothersome complication of opioids. However, laxatives have a nonspecific action and do not target underlying mechanisms of opioid-induced constipation; their use is associated with abdominal symptoms that negatively impact quality of life. Objective To assess the effects of laxatives in patients taking opioids for chronic pain. Methods One hundred ninety-eight UK patients who had taken opioid analgesics for at least one month completed a cross-sectional online or telephone survey. Questions addressed their pain condition, medication, and laxative use (including efficacy and side effects). The survey also assessed bowel function using the Bowel Function Index. Results Since starting their current opioid, 134 of 184 patients (73%) had used laxatives at some point and 122 (91%) of these were currently taking them. The most common laxatives were osmotics and stimulants. Laxative side effects were reported in 75%, most commonly gas, bloating/fullness, and a sudden urge to defecate. Side effects were more common in patients less than 40 years of age. Approximately half of patients said laxatives interfered with work and social activities, and one-fifth needed an overnight hospital stay because of their pain condition and/or constipation. Laxatives did not improve the symptoms of constipation, as assessed by the Bowel Function Index. Constipation was not related to opioid strength, dose of opioid, or number of laxatives taken. Conclusions Use of laxatives to treat opioid-induced constipation is often ineffective and associated with side effects. Instead of relieving the burden of opioid-induced constipation, laxative use is associated with a negative impact. PMID:28339544

The Effects of Low-Dose Ketamine on Acute Pain in an Emergency Setting: A Systematic Review and Meta-Analysis.

PubMed

Lee, Eun Nam; Lee, Jae Hoon

2016-01-01

Currently ketamine is not used often as an analgesic in the emergency department (ED). Nonetheless, it can increase the efficiency of opioids and decrease their side effects. The purpose of this systematic review and meta-analysis was to evaluate whether low-dose ketamine in the ED provides better analgesia with fewer adverse effects. The PubMed, EMBASE, and Cochrane Library databases were searched by two reviewers independently (last search performed on January 2016). Data were also extracted independently. A total of 6 trials involving 438 patients were included in the current analysis. Our subgroup analysis of pain reduction indicates that the favorable effects of ketamine were similar or superior to those of placebo or opioids, although these effects were heterogeneous. However, low-dose ketamine was associated with a higher risk of neurological (relative risk [RR] = 2.17, 95% confidence interval [CI] = 1.37-3.42, P < 0.001) and psychological events (RR = 13.86, 95% CI = 4.85-39.58, P < 0.001). In contrast, the opioid group had a higher risk of major cardiopulmonary events (RR = 0.22, 95% CI = 0.05-1.01, P = 0.05). The efficiency of ketamine varies depending on the pain site, but low-dose ketamine may be a key agent for pain control in the ED, as it has no side effects. It may also help to reduce the side effects of opioids.

The Effects of Low-Dose Ketamine on Acute Pain in an Emergency Setting: A Systematic Review and Meta-Analysis

PubMed Central

2016-01-01

Objectives Currently ketamine is not used often as an analgesic in the emergency department (ED). Nonetheless, it can increase the efficiency of opioids and decrease their side effects. The purpose of this systematic review and meta-analysis was to evaluate whether low-dose ketamine in the ED provides better analgesia with fewer adverse effects. Methods The PubMed, EMBASE, and Cochrane Library databases were searched by two reviewers independently (last search performed on January 2016). Data were also extracted independently. Results A total of 6 trials involving 438 patients were included in the current analysis. Our subgroup analysis of pain reduction indicates that the favorable effects of ketamine were similar or superior to those of placebo or opioids, although these effects were heterogeneous. However, low-dose ketamine was associated with a higher risk of neurological (relative risk [RR] = 2.17, 95% confidence interval [CI] = 1.37–3.42, P < 0.001) and psychological events (RR = 13.86, 95% CI = 4.85–39.58, P < 0.001). In contrast, the opioid group had a higher risk of major cardiopulmonary events (RR = 0.22, 95% CI = 0.05–1.01, P = 0.05). Conclusions The efficiency of ketamine varies depending on the pain site, but low-dose ketamine may be a key agent for pain control in the ED, as it has no side effects. It may also help to reduce the side effects of opioids. PMID:27788221

Comparison of curative effect of 131I and antithyroid drugs in Graves' disease: a meta analysis.

PubMed

Yuan, Ju; Lu, Xiuqing; Yue, Yan

2017-03-01

Radioactive 131I is currently reported to be a potential effective intervention for Graves' Disease treatment in China. Whether 131I treatment was associated with effective outcome or reduced risk of side effects, reccurence rate remained unknown. Eligible studies were selected from Chinese VIP, Wangfang, CNKI databases using the keywords "Iodine" and "Graves Disease". Finally, 13 clinical trials met the inclusion criterion and were included this meta-analysis. Our meta-analysis included 1355 patients diagnosed of Graves' Disease with regular anti-thyroid drugs oral administration and 1320 patients with 131I therapy. The results showed that there was significant symptom improvement with radioactive iodine intervention (Odd Ratio (OR)=4.50, 95% CI [3.55, 5.71], P<0.01). 3 studies mentioned side effects, 6 mentioned reccurence rate and another 6 mentioned hypothyroidism. The ORs and 95%CIs for these subgroups were 0.12 [0.06, 0.21], 0.08 [0.05, 0.13] and 2.27 [1.77, 2.92] respectively. It means a significant reduction of side effects and reccurence rate but increased hypothyroidism after 131I intervention in Graves' Disease. Treatment with 131I was associated with better clinical outcome; it reduced side effects and reccurence rate but increased hypothyroidism in Graves' Disease.

Pharmacogenetics and outcome with antipsychotic drugs.

PubMed

Pouget, Jennie G; Shams, Tahireh A; Tiwari, Arun K; Müller, Daniel J

2014-12-01

Antipsychotic medications are the gold-standard treatment for schizophrenia, and are often prescribed for other mental conditions. However, the efficacy and side-effect profiles of these drugs are heterogeneous, with large interindividual variability. As a result, treatment selection remains a largely trial-and-error process, with many failed treatment regimens endured before finding a tolerable balance between symptom management and side effects. Much of the interindividual variability in response and side effects is due to genetic factors (heritability, h(2)~ 0.60-0.80). Pharmacogenetics is an emerging field that holds the potential to facilitate the selection of the best medication for a particular patient, based on his or her genetic information. In this review we discuss the most promising genetic markers of antipsychotic treatment outcomes, and present current translational research efforts that aim to bring these pharmacogenetic findings to the clinic in the near future.

Pharmacogenetics and outcome with antipsychotic drugs

PubMed Central

Pouget, Jennie G.; Shams, Tahireh A.; Tiwari, Arun K.; Müller, Daniel J.

2014-01-01

Antipsychotic medications are the gold-standard treatment for schizophrenia, and are often prescribed for other mental conditions. However, the efficacy and side-effect profiles of these drugs are heterogeneous, with large interindividual variability. As a result, treatment selection remains a largely trial-and-error process, with many failed treatment regimens endured before finding a tolerable balance between symptom management and side effects. Much of the interindividual variability in response and side effects is due to genetic factors (heritability, h2~ 0.60-0.80). Pharmacogenetics is an emerging field that holds the potential to facilitate the selection of the best medication for a particular patient, based on his or her genetic information. In this review we discuss the most promising genetic markers of antipsychotic treatment outcomes, and present current translational research efforts that aim to bring these pharmacogenetic findings to the clinic in the near future. PMID:25733959

Cardiac side effects of bruton tyrosine kinase (BTK) inhibitors.

PubMed

Tang, Chloe Pek Sang; McMullen, Julie; Tam, Constantine

2017-09-13

The development of bruton tyrosine kinase inhibitors (BTKi) has been a significant advancement in the treatment of chronic lymphocytic leukemia and related B-cell malignancies. As experience in using ibrutinib increased, the first drug to be licensed in its class, atrial fibrillation (AF) emerged as an important side effect. The intersection between BTKi therapy for B-cell malignancies and AF represents a complex area of management with scant evidence for guidance. Consideration needs to be taken regarding the interplay of increased bleeding risk versus thromboembolic complications of AF, drug interactions between ibrutinib and anticoagulants and antiarrhythmic agents, and the potential for other, as yet seldom reported cardiac side effects. This review describes the current knowledge regarding BTKi and potential pathophysiologic mechanisms of AF and discusses the management of BTKi-associated AF. Finally, a review of the second generation BTKi is provided and gaps in knowledge in this evolving field are highlighted.

Development of robust building energy demand-side control strategy under uncertainty

NASA Astrophysics Data System (ADS)

Kim, Sean Hay

The potential of carbon emission regulations applied to an individual building will encourage building owners to purchase utility-provided green power or to employ onsite renewable energy generation. As both cases are based on intermittent renewable energy sources, demand side control is a fundamental precondition for maximizing the effectiveness of using renewable energy sources. Such control leads to a reduction in peak demand and/or in energy demand variability, therefore, such reduction in the demand profile eventually enhances the efficiency of an erratic supply of renewable energy. The combined operation of active thermal energy storage and passive building thermal mass has shown substantial improvement in demand-side control performance when compared to current state-of-the-art demand-side control measures. Specifically, "model-based" optimal control for this operation has the potential to significantly increase performance and bring economic advantages. However, due to the uncertainty in certain operating conditions in the field its control effectiveness could be diminished and/or seriously damaged, which results in poor performance. This dissertation pursues improvements of current demand-side controls under uncertainty by proposing a robust supervisory demand-side control strategy that is designed to be immune from uncertainty and perform consistently under uncertain conditions. Uniqueness and superiority of the proposed robust demand-side controls are found as below: a. It is developed based on fundamental studies about uncertainty and a systematic approach to uncertainty analysis. b. It reduces variability of performance under varied conditions, and thus avoids the worst case scenario. c. It is reactive in cases of critical "discrepancies" observed caused by the unpredictable uncertainty that typically scenario uncertainty imposes, and thus it increases control efficiency. This is obtainable by means of i) multi-source composition of weather forecasts including both historical archive and online sources and ii) adaptive Multiple model-based controls (MMC) to mitigate detrimental impacts of varying scenario uncertainties. The proposed robust demand-side control strategy verifies its outstanding demand-side control performance in varied and non-indigenous conditions compared to the existing control strategies including deterministic optimal controls. This result reemphasizes importance of the demand-side control for a building in the global carbon economy. It also demonstrates a capability of risk management of the proposed robust demand-side controls in highly uncertain situations, which eventually attains the maximum benefit in both theoretical and practical perspectives.

Enzymatic Hydrolysis of Peanut Flour Produces Bioactive Peptides with Reduced Allergenicity

USDA-ARS?s Scientific Manuscript database

Peanut allergy is one of the most severe food allergies due to its life-threatening nature and persistency. Current immunotherapy methods, though effective, are often accompanied by allergic side-effects. Enzymatic hydrolysis of peanut flour has the potential to produce bioactive peptides with impro...

Longitudinal Proximity Effects in Superconducting Transition-Edge Sensors

NASA Technical Reports Server (NTRS)

Sadleir, John E.; Smith, Stephen J.; Bandler, SImon R.; Chervenak, James A.; Clem, John R.

2009-01-01

We have found experimentally that the critical current of a square superconducting transition-edge sensor (TES) depends exponentially upon the side length L and the square root of the temperature T. As a consequence, the effective transition temperature T(sub c) of the TES is current-dependent and at fixed current scales as 1/L(sup 2). We also have found that the critical current can show clear Fraunhofer-like oscillations in an applied magnetic field, similar to those found in Josephson junctions. The observed behavior has a natural theoretical explanation in terms of longitudinal proximity effects if the TES is regarded as a weak link between superconducting leads. We have observed the proximity effect in these devices over extraordinarily long lengths exceeding 100 microns.

Transformer coupling for transmitting direct current through a barrier

DOEpatents

Brown, Ralph L.; Guilford, Richard P.; Stichman, John H.

1988-01-01

The transmission system for transmitting direct current from an energy source on one side of an electrical and mechanical barrier to a load on the other side of the barrier utilizes a transformer comprising a primary core on one side of the transformer and a secondary core on the other side of the transformer. The cores are magnetically coupled selectively by moving a magnetic ferrite coupler in and out of alignment with the poles of the cores. The direct current from the energy source is converted to a time varying current by an oscillating circuit, which oscillating circuit is optically coupled to a secondary winding on the secondary core to interrupt oscillations upon the voltage in the secondary winding exceeding a preselected level.

Transformer coupling for transmitting direct current through a barrier

DOEpatents

Brown, R.L.; Guilford, R.P.; Stichman, J.H.

1987-06-29

The transmission system for transmitting direct current from an energy source on one side of an electrical and mechanical barrier to a load on the other side of the barrier utilizes a transformer comprising a primary core on one side of the transformer and a secondary core on the other side of the transformer. The cores are magnetically coupled selectively by moving a magnetic ferrite coupler in and out of alignment with the poles of the cores. The direct current from the energy source is converted to a time varying current by an oscillating circuit, which oscillating circuit is optically coupled to a secondary winding on the secondary core to interrupt oscillations upon the voltage in the secondary winding exceeding a preselected level. 4 figs.

Relationship among side channels, fish assemblages, and environmental gradients in the unimpounded Upper Mississippi River

USGS Publications Warehouse

Barko, V.A.; Herzog, D.P.

2003-01-01

We analyzed fish abundance and environmental data collected over nine years from six side channels of the unimpounded upper Mississippi River between river km 46.7 and 128.7. A partial canonical correspondence analysis revealed differences in fish assemblages and environmental factors correlated with the six side channels. Fishes correlated with open side channels represented large river species tolerant of current and/or turbidity. Fishes correlated with closed side channels represented assemblages preferring either moderate to low turbidity/current or pools.

Top tether effectiveness during side impacts.

PubMed

Majstorovic, Jordan; Bing, Julie; Dahle, Eric; Bolte, John; Kang, Yun-Seok

2018-02-28

Few studies have looked at the effectiveness of the top tether during side impacts. In these studies, limited anthropomorphic test device (ATD) data were collected and/or few side impact scenarios were observed. The goal of this study was to further understand the effects of the top tether on ATD responses and child restraint system (CRS) kinematics during various side impact conditions. A series of high-speed near-side and far-side sled tests were performed using the FMVSS213 side impact sled buck and Q3s ATD. Tests were performed at both 10° and 30° impacts with respect to the pure lateral direction. Two child restraints, CRS A and CRS B, were attached to the bench using flexible lower anchors. Each test scenario was performed with the presence and absence of a top tether. Instrumentation recorded Q3s responses and CRS kinematics, and the identical test scenarios with and without a top tether attachment were compared. For the far-side lateral (10°) and oblique (30°) impacts, top tether attachment increased resultant head accelerations by 8-38% and head injury criterion (HIC 15 ) values by 20-140%. However, the top tether was effective in reducing lateral head excursion by 5-25%. For near-side impacts, the top tether resulted in less than 10% increases in both resultant head acceleration and HIC 15 in the lateral impact direction. For near-side oblique impacts, the top tether increased HIC 15 by 17.3% for CRS A and decreased it by 19.5% for CRS B. However, the injury values determined from both impact conditions were below current injury assessment reference values (IARVs). Additionally, the top tether proved beneficial in preventing forward and lateral CRS rotations. The results show that the effects of the top tether on Q3s responses were dependent on impact type, impact angle, and CRS. Tether attachments that increased head accelerations and HIC 15 values were generally counterbalanced by a reduction in head excursion and CRS rotation compared to nontethered scenarios.

Algorithm for dermocosmetic use in the management of cutaneous side-effects associated with targeted therapy in oncology

PubMed Central

Dreno, B; Bensadoun, RJ; Humbert, P; Krutmann, J; Luger, T; Triller, R; Rougier, A; Seité, S

2013-01-01

Currently, numerous patients who receive targeted chemotherapy for cancer suffer from disabling skin reactions due to cutaneous toxicity, which is a significant problem for an increasing number of patients and their treating physicians. In addition, using inappropriate personal hygiene products often worsens these otherwise manageable side-effects. Cosmetic products for personal hygiene and lesion camouflage are part of a patients’ well-being and an increasing number of physicians feel that they do not have adequate information to provide effective advice on concomitant cosmetic therapy. Although ample information is available in the literature on pharmaceutical treatment for cutaneous side-effects of chemotherapy, little is available for the concomitant use of dermatological skin-care products with medical treatments. The objective of this consensus study is to provide an algorithm for the appropriate use of dermatological cosmetics in the management of cutaneous toxicities associated with targeted chemotherapy such as epidermal growth factor receptor inhibitors and other monoclonal antibodies. These guidelines were developed by a French and German expert group of dermatologists and an oncologist for oncologists and primary care physicians who manage oncology patients. The information in this report is based on published data and the expert group’s opinion. Due to the current lack of clinical evidence, only a review of published recommendations including suggestions for concomitant cosmetic use was conducted. PMID:23368717

Maximum power extraction under different vector-control schemes and grid-synchronization strategy of a wind-driven Brushless Doubly-Fed Reluctance Generator.

PubMed

Mousa, Mohamed G; Allam, S M; Rashad, Essam M

2018-01-01

This paper proposes an advanced strategy to synchronize the wind-driven Brushless Doubly-Fed Reluctance Generator (BDFRG) to the grid-side terminals. The proposed strategy depends mainly upon determining the electrical angle of the grid voltage, θ v and using the same transformation matrix of both the power winding and grid sides to ensure that the generated power-winding voltage has the same phase-sequence of the grid-side voltage. On the other hand, the paper proposes a vector-control (power-winding flux orientation) technique for maximum wind-power extraction under two schemes summarized as; unity power-factor operation and minimum converter-current. Moreover, a soft-starting method is suggested to avoid the employed converter over-current. The first control scheme is achieved by adjusting the command power-winding reactive power at zero for a unity power-factor operation. However, the second scheme depends on setting the command d-axis control-winding current at zero to maximize the ratio of the generator electromagnetic-torque per the converter current. This enables the system to get a certain command torque under minimum converter current. A sample of the obtained simulation and experimental results is presented to check the effectiveness of the proposed control strategies. Copyright © 2017 ISA. Published by Elsevier Ltd. All rights reserved.

Current concepts for chronochemotherapy of cancer.

PubMed

Laerum, O D; Smaaland, R; Abrahamsen, J F

1995-01-01

In this article, a survey on the concepts and scientific basis for applying chemotherapy against malignant tumors on a circadian schedule is given. The idea is to give the cytostatic drugs at times of the day when optimal effect on the tumor is achieved, but at the same time causing minimal toxic side effects. Following a brief description of the complexity of cancer tissue, some aspects of the present status of cancer chemotherapy in general are reviewed. Applications of chronobiology in cancer treatment are then surveyed together with possibilities to increase cytostatic doses and reduce side effects. When optimal tumor cell kill is achieved, the next step is to address the circadian aspects of normal organs, including the proliferative behavior of tissues with rapid cell renewal. Finally, the question of how regulatory mechanisms responsible for normal circadian rhythms can be interfered with is addressed. Cancer chronochemotherapy today combined with modern infusional technology is a promising field for improving cancer treatment in general and reducing side effects and is expected to make important progress in the near future.

Erythropoietin as an add-on treatment for cognitive side effects of electroconvulsive therapy: a study protocol for a randomized controlled trial.

PubMed

Schmidt, Lejla Sjanic; Petersen, Jeff Zarp; Vinberg, Maj; Hageman, Ida; Olsen, Niels Vidiendal; Kessing, Lars Vedel; Jørgensen, Martin Balslev; Miskowiak, Kamilla Woznica

2018-04-19

Electroconvulsive therapy (ECT) is the most effective treatment for severe depression, but its use is impeded by its cognitive side effects. Novel treatments that can counteract these side effects may therefore improve current treatment strategies for depression. The present randomized trial investigates (1) whether short-term add-on treatment with erythropoietin (EPO) can reduce the cognitive side -effects of ECT and (2) whether such effects are long-lasting. Further, structural and functional magnetic resonance imaging (MRI) will be used to explore the neural underpinnings of such beneficial effects of EPO. Finally, the trial examines whether potential protective effects of EPO on cognition are accompanied by changes in markers of oxidative stress, inflammation, and neuroplasticity. The trial has a double-blind, randomized, placebo-controlled, parallel group design. Patients with unipolar or bipolar disorder with current moderate to severe depression referred to ECT (N = 52) are randomized to receive four high-dose infusions of EPO (40,000 IU/ml) or placebo (saline). The first EPO/saline infusion is administered within 24 h before the first ECT. The following three infusions are administered at weekly intervals immediately after ECT sessions 1, 4, and 7. Cognition assessments are conducted at baseline, after the final EPO/saline infusion (3 days after eight ECT sessions), and at a 3 months follow-up after ECT treatment completion. The neuronal substrates for potential cognitive benefits of EPO are investigated with structural and functional MRI after the final EPO/saline infusion. The primary outcome is change from baseline to after EPO treatment (3 days after eight ECT sessions) in a cognitive composite score spanning attention, psychomotor speed, and executive functions. With a sample size of N = 52 (n = 26 per group), we have ≥ 80% power to detect a clinically relevant between-group difference in the primary outcome measure at an alpha level of 5% (two-sided test). Behavioral, mood, and blood-biomarker data will be analyzed using repeated measures analysis of covariance. Functional MRI data will be preprocessed and analyzed using the FMRIB Software Library. If EPO is found to reduce the cognitive side effects of ECT, this could have important implications for future treatment strategies for depression and for the scientific understanding of the neurobiological etiology of cognitive dysfunction in patients treated with ECT. ClinicalTrials.gov, NCT03339596 . Registered on 10 November 2017.

Elimination of resistive losses in large-area LEDs by new diffusion-driven devices

NASA Astrophysics Data System (ADS)

Kivisaari, Pyry; Kim, Iurii; Suihkonen, Sami; Oksanen, Jani

2017-02-01

High-power operation of conventional GaN-based light-emitting diodes (LEDs) is severely limited by current crowding, which increases the bias voltage of the LED, concentrates light emission close to the p-type contact edge, and aggravates the efficiency droop. Fabricating LEDs on thick n-GaN substrates alleviates current crowding but requires the use of expensive bulk GaN substrates and fairly large n-contacts, which take away a large part of the active region (AR). In this work, we demonstrate through comparative simulations how the recently introduced diffusion-driven charge transport (DDCT) concept can be used to realize lateral heterojunction (LHJ) structures, which eliminate most of the lateral current crowding. Specifically in this work, we analyze how using a single-side graded AR can both facilitate electron and hole diffusion in DDCT and increase the effective AR thickness. Our simulations show that the increased effective AR thickness allows a substantial reduction in the efficiency droop at large currents, and that unlike conventional 2D LEDs, the LHJ structure shows practically no added efficiency loss or differential resistance due to current crowding. Furthermore, as both electrons and holes enter the AR from the same side without any notable potential barriers in the LHJ structure, the LHJ structure shows an additional wall-plug efficiency gain over the conventional structures under comparison. This injection from the same side is expected to be even more interesting in multiple quantum well structures, where carriers typically need to surpass several potential barriers in conventional LEDs before recombining. In addition to simulations, we also demonstrate selective-area growth of a finger structure suitable for operation as an LHJ device with 2µm distance between n- and p-GaN regions.

Magnetopause reconnection under various space weather conditions

NASA Astrophysics Data System (ADS)

Chen, L.; Argall, M. R.; Shuster, J. R.; Li, G.; Karimabadi, H.; Daughton, W. S.; Germaschewski, K.; Torbert, R. B.; Bhattacharjee, A.

2013-12-01

In order to develop predictive capabilities for the Sun-Earth connection, the question of how various reconnection upstream conditions influence particle energization and the stability of the reconnection current layer needs to be answered. Using magnetopause reconnection events observed by the Cluster spacecraft, we address this question by comparing the observed plasma and field features in the vicinity of the magnetopause current layer for a wide range of geomagnetic conditions including nominal times and the most severe magnetic storms. Outstanding features include: 1. Plasmoid-like structures, when observed, tend to appear in series and more frequently on the magnetosheath side of the magnetopause current layer. These plasmoids contain accelerated electrons and ions up to ~100 keV, and can prevail in guide fields ranging from nearly zero to a strength approximately equal to the reconnecting field. Associated with each of these plasmoids are a bipolar DC component and intense fluctuations in the electric fields. 2. The fastest ion outflow jets occur in the magnetospheric side of the magnetopause. 3. The plasma density transition is in general removed from the magnetopause current layer to the magnetospheric side, in contrast to the predictions of a PIC simulation and THEMIS observations [1]. Feature 1 suggests that the current layer is unstable to plasmoid formation, and that the plasmoids are effective energization sites for plasmas. The above features are not sensitive functions of the degrees of upstream asymmetries. The observation results will be compared with PIC, global hybrid as well as global Hall MHD simulations to achieve fundamental understanding of asymmetric reconnection, separating two-fluid, ion kinetic and electron kinetic effects. [1] Mozer and Pritchett, JGR, 2008

Intermetallic Growth Induced Large-Scale Void Growth and Cracking Failure in Line-Type Cu/Solder/Cu Joints Under Current Stressing

NASA Astrophysics Data System (ADS)

Chen, Zhuo; Tian, Wenya; Li, Junhui; Zhu, Wenhui

2018-04-01

In order to study the electromigration (EM) behavior of solder joints in electronics packaging, especially under high-current and high-temperature working conditions, line-type Cu/solder/Cu butting samples were prepared to observe the microstructural evolution under 1.0 × 104 A/cm2 current stressing. A prominent polarity effect was found such that the Cu6Sn5 intermetallic compound (IMC) layer at the anode side, which thickened linearly with time, was much thicker than that at the cathode side. Compared to the samples subjected to thermal aging at the same temperature of 180°C, EM enhanced the Cu3Sn growth at both the anode and the cathode. Two distinct types of damage were observed after extended duration of current stressing. Back-flow of Cu into Cu3Sn was found at the Cu3Sn/Cu6Sn5 interface of the anode side, causing large voids, while strip cracks developed at the cathode solder/Cu6Sn5 interface, causing a significant increase of joint electrical resistance. With the mass transport characteristics that determine the IMC growth and vacancy accumulation analyzed in detail at each interface, formation mechanisms of the two types of damages are discussed.

Patient-Derived Antibody Targets Tumor Cells

Cancer.gov

An NCI Cancer Currents blog on an antibody derived from patients that killed tumor cells in cell lines of several cancer types and slowed tumor growth in mouse models of brain and lung cancer without evidence of side effects.

Anti-thymocyte globulins in kidney transplantation: focus on current indications and long-term immunological side effects.

PubMed

Bamoulid, Jamal; Staeck, Oliver; Crépin, Thomas; Halleck, Fabian; Saas, Philippe; Brakemeier, Susanne; Ducloux, Didier; Budde, Klemens

2017-10-01

Antithymocyte globulins (ATGs) are part of the immunosuppression arsenal currently used by clinicians to prevent or treat acute rejection in solid organ transplantation. ATG is a mixture of non-specific anti-lymphocyte immunoglobulins targeting not only T cell subsets but also several other immune and non-immune cells, rendering its precise immunoglobulin composition difficult to appreciate or to compare from one preparation to another. Furthermore, several mechanisms of action have been described. Taken together, this probably explains the efficacy and the side effects associated with this drug. Recent data suggest a long-term negative impact on allograft and patient outcomes, pointing out the need to better characterize the potential toxicity and the benefit-risk balance associated to this immunosuppressive therapy within large clinical trials. © The Author 2016. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

Urolift - minimally invasive surgical BPH management.

PubMed

Pushkaran, Anish; Stainer, Victoria; Muir, Gordon; Shergill, Iqbal S

2017-03-01

An ideal treatment option for symptomatic Benign Prostatic Hyperplasia (BPH) should relieve lower urinary tract symptoms (LUTS) and restore Quality of Life (QoL). Currently available medical therapies and surgical options for symptomatic BPH have side effects that adversely affects quality of life. Prostatic urethral lift (PUL) is a novel endourology procedure that promises to relieve LUTS without the aforementioned side effects. Areas covered: We diligently reviewed all the published literature on PUL, till July 2016 using standard search criteria. Expert commentary: There is good quality evidence to establish the efficiency of PUL in treating symptomatic BPH without adversely affecting the QoL. Based on the current literature, PUL can be considered as an option for those symptomatic BPH patients with small or medium size prostates (< 80 ml) without median lobe enlargement, who failed on medical therapy or are intolerant to it and wish to preserve their sexual function.

Thermal degradation of the solvent employed in the next-generation caustic-side solvent extraction process and its effect on the extraction, scrubbing, and stripping of cesium

DOE Office of Scientific and Technical Information (OSTI.GOV)

Roach, Benjamin D.; Williams, Neil J.; Moyer, Bruce A.

As part of the ongoing development of the Next-Generation Caustic-Side Solvent Extraction (NGS) process, the thermal stability of the process solvent was investigated and shown to be adequate for industrial application. The solvent was thermally treated at 35 C over a period of 13 months whilst in dynamic contact with each of the aqueous phases of the current NGS process, namely SRS 15 (a highly caustic waste simulant), sodium hydroxide scrub solution (0.025 M), and boric acid strip solution (0.01 M). The effect of thermal treatment was evaluated by assessing batch extract/scrub/strip performance as a function of time, by monitoringmore » the sodium extraction capacity of the solvent, and by analysis of the solvent using electrospray mass spectrometry. Current studies indicate that the NGS solvent should be thermally robust for a period of XXX months at the Modular Caustic-Side Solvent Extraction Unit (MCU) pilot plant located at Savannah River Site. Furthermore, the guanidine suppressor appears to be the solvent component most significantly impacted by thermal treatment of the solvent, showing significant degradation over time.« less

Thermal degradation of the solvent employed in the next-generation caustic-side solvent extraction process and its effect on the extraction, scrubbing, and stripping of cesium

DOE PAGES

Roach, Benjamin D.; Williams, Neil J.; Moyer, Bruce A.

2015-09-02

As part of the ongoing development of the Next-Generation Caustic-Side Solvent Extraction (NGS) process, the thermal stability of the process solvent was investigated and shown to be adequate for industrial application. The solvent was thermally treated at 35 C over a period of 13 months whilst in dynamic contact with each of the aqueous phases of the current NGS process, namely SRS 15 (a highly caustic waste simulant), sodium hydroxide scrub solution (0.025 M), and boric acid strip solution (0.01 M). The effect of thermal treatment was evaluated by assessing batch extract/scrub/strip performance as a function of time, by monitoringmore » the sodium extraction capacity of the solvent, and by analysis of the solvent using electrospray mass spectrometry. Current studies indicate that the NGS solvent should be thermally robust for a period of XXX months at the Modular Caustic-Side Solvent Extraction Unit (MCU) pilot plant located at Savannah River Site. Furthermore, the guanidine suppressor appears to be the solvent component most significantly impacted by thermal treatment of the solvent, showing significant degradation over time.« less

A Review of Indigo Naturalis as an Alternative Treatment for Nail Psoriasis.

PubMed

McDermott, Laura; Madan, Raman; Rupani, Reena; Siegel, Daniel

2016-03-01

Nail psoriasis is challenging to treat. The few currently available therapies are limited in efficacy, and often produce unfavorable side effects. A plant extract widely used in Traditional Chinese Medicine, indigo naturalis (Qing Dai), is presented in this review as an alternative topical treatment for skin and nail psoriasis. The purpose of this article is to present information on a viable alternative treatment with a favorable side effect profile for a difficult disease to treat. A PubMed search for the term "indigo naturalis" was performed, and literature from 2006 to the present relevant to indigo naturalis and treatment of psoriasis and nail psoriasis was reviewed. Indigo naturalis shares several therapeutic mechanisms with current psoriasis treatments, such as regulation of keratinocyte proliferation and differentiation, restoration of epidermal barrier function, and reduction of inflammatory processes. Clinically, it is well tolerated. Recent research of indigo naturalis suggests that it is a safe, inexpensive, and effective alternative topical treatment for skin and nail psoriasis.

Chemotherapeutic approaches to protozoa: kinetoplastida--current level of knowledge and outlook.

PubMed

Harder, A; Greif, G; Haberkorn, A

2001-09-01

The possibilities for treating haemoflagellate infections (African trypanosomiasis) are very limited (Table 1; Mehlhorn and Schrevel 1995; Croft 1997; Hunter 1997; Wang 1997; Trouiller and Olliaro 1998). All the available drugs have severe side-effects in humans and animals. Vaccination is not really an option, in view of the wide antigen variability. At present, there are several drug combinations in clinical trials: suramin/eflornithine, suramin/metronidazole, suramin/pentamidine, melarsoprol/pentamidine, melarsoprol/nifurtimox and nifurtimox/eflornithine. Some of these combinations were successful in treating resistant Trypanosoma brucei rhodesiense and/or T. b. gambiense infections (Keiser et al. 2001). In leishmaniasis, the tendency is still to resort to the old antimony compounds, with their severe side effects. At present, miltefosine is in clinical phase and is the first oral drug against visceral leishmaniasis (Jha et al. 1999). Two drugs are currently used against Chagas' disease, although these do not cure chronic effects. There is no prospect of novel drugs in this indication either (Pecoul et al. 1999; Morel 2000).

Hydrogen-terminated diamond vertical-type metal oxide semiconductor field-effect transistors with a trench gate

DOE Office of Scientific and Technical Information (OSTI.GOV)

Inaba, Masafumi, E-mail: inaba-ma@ruri.waseda.jp; Muta, Tsubasa; Kobayashi, Mikinori

2016-07-18

The hydrogen-terminated diamond surface (C-H diamond) has a two-dimensional hole gas (2DHG) layer independent of the crystal orientation. A 2DHG layer is ubiquitously formed on the C-H diamond surface covered by atomic-layer-deposited-Al{sub 2}O{sub 3}. Using Al{sub 2}O{sub 3} as a gate oxide, C-H diamond metal oxide semiconductor field-effect transistors (MOSFETs) operate in a trench gate structure where the diamond side-wall acts as a channel. MOSFETs with a side-wall channel exhibit equivalent performance to the lateral C-H diamond MOSFET without a side-wall channel. Here, a vertical-type MOSFET with a drain on the bottom is demonstrated in diamond with channel current modulationmore » by the gate and pinch off.« less

Statistical survey of day-side magnetospheric current flow using Cluster observations: magnetopause

NASA Astrophysics Data System (ADS)

Liebert, Evelyn; Nabert, Christian; Perschke, Christopher; Fornaçon, Karl-Heinz; Glassmeier, Karl-Heinz

2017-05-01

We present a statistical survey of current structures observed by the Cluster spacecraft at high-latitude day-side magnetopause encounters in the close vicinity of the polar cusps. Making use of the curlometer technique and the fluxgate magnetometer data, we calculate the 3-D current densities and investigate the magnetopause current direction, location, and magnitude during varying solar wind conditions. We find that the orientation of the day-side current structures is in accordance with existing magnetopause current models. Based on the ambient plasma properties, we distinguish five different transition regions at the magnetopause surface and observe distinctive current properties for each region. Additionally, we find that the location of currents varies with respect to the onset of the changes in the plasma environment during magnetopause crossings.

Emerging therapeutic options in GERD.

PubMed

Woodland, Philip; Amarasinghe, Gehanjali; Sifrim, Daniel

2013-06-01

Gastroesophageal reflux disease (GERD) is a prevalent problem resulting in a high level of healthcare consultation and expenditure in the Western World. Although standard medical therapy (in the form of proton pump inhibitor drugs) is effective in the majority of cases, there remains a significant proportion who are refractory to treatment. In addition, surgical therapy (in the form of laparoscopic fundoplication) is not always effective, and in some can be associated with significant side-effects, particularly gas-bloat, flatulence and dysphagia. As such there remains an unmet need in GERD to develop new therapies for refractory cases, and to develop alternatives to fundoplication with fewer side-effects. This article discusses the current state of pharmacological and non-pharmacological emerging therapies for GERD. Copyright © 2013 Elsevier Ltd. All rights reserved.

Could yoga practice improve treatment-related side effects and quality of life for women with breast cancer? A systematic review and meta-analysis.

PubMed

Pan, Yuanqing; Yang, Kehu; Wang, Yuliang; Zhang, Laiping; Liang, Haiqing

2017-04-01

To determine if yoga as a complementary and alternative therapy was associated with enhanced health and treatment-related side effects in patients with breast cancer. This systematic review examines whether yoga practice provides any measurable benefit, both physically and psychologically, for women with breast cancer. PubMed, EMBASE and the Cochrane Library for randomized controlled trials (RCTs) throughout June 2013. We evaluated the quality of the included studies by the Cochrane Handbook 5.2 standards and analyzed the data using the Stata software, version 10.0. Meta-regression and subgroup analysis were also performed to identify additional predictors of outcome and to assess heterogeneity. Sixteen RCTs with a total of 930 participants were included. Comparing yoga groups to control groups, there was a statistically significant difference in overall health-related quality of life, depression, anxiety and gastrointestinal symptoms. Meta-regression analyses revealed that the duration of yoga practice and type of control group partly explained the heterogeneity. Subgroup analyses revealed that yoga had a positive effect on anxiety only when it had been practiced for longer than 3 months. Only the wait-list control group showed an effect of yoga on physical well-being. The current evidence demonstrates that yoga practice could be effective in enhancing health and managing some treatment-related side effects for patients recovering from breast cancer. In future clinical studies, clinicians should consider the patient's wishes along with the current best evidence of the effects of yoga practice in their clinical decision-making. © 2015 Wiley Publishing Asia Pty Ltd.

Conformation of ionizable poly Para phenylene ethynylene in dilute solutions

DOE PAGES

Wijesinghe, Sidath; Maskey, Sabina; Perahia, Dvora; ...

2015-11-03

The conformation of dinonyl poly para phenylene ethynylenes (PPEs) with carboxylate side chains, equilibrated in solvents of different quality is studied using molecular dynamics simulations. PPEs are of interest because of their tunable electro-optical properties, chemical diversity, and functionality which are essential in wide range of applications. The polymer conformation determines the conjugation length and their assembly mode and affects electro-optical properties which are critical in their current and potential uses. The current study investigates the effect of carboxylate fraction on PPEs side chains on the conformation of chains in the dilute limit, in solvents of different quality. The dinonylmore » PPE chains are modeled atomistically, where the solvents are modeled both implicitly and explicitly. Dinonyl PPEs maintained a stretched out conformation up to a carboxylate fraction f of 0.7 in all solvents studied. The nonyl side chains are extended and oriented away from the PPE backbone in toluene and in implicit good solvent whereas in water and implicit poor solvent, the nonyl side chains are collapsed towards the PPE backbone. Thus, rotation around the aromatic ring is fast and no long range correlations are seen within the backbone.« less

Conformation of ionizable poly Para phenylene ethynylene in dilute solutions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wijesinghe, Sidath; Maskey, Sabina; Perahia, Dvora

The conformation of dinonyl poly para phenylene ethynylenes (PPEs) with carboxylate side chains, equilibrated in solvents of different quality is studied using molecular dynamics simulations. PPEs are of interest because of their tunable electro-optical properties, chemical diversity, and functionality which are essential in wide range of applications. The polymer conformation determines the conjugation length and their assembly mode and affects electro-optical properties which are critical in their current and potential uses. The current study investigates the effect of carboxylate fraction on PPEs side chains on the conformation of chains in the dilute limit, in solvents of different quality. The dinonylmore » PPE chains are modeled atomistically, where the solvents are modeled both implicitly and explicitly. Dinonyl PPEs maintained a stretched out conformation up to a carboxylate fraction f of 0.7 in all solvents studied. The nonyl side chains are extended and oriented away from the PPE backbone in toluene and in implicit good solvent whereas in water and implicit poor solvent, the nonyl side chains are collapsed towards the PPE backbone. Thus, rotation around the aromatic ring is fast and no long range correlations are seen within the backbone.« less

Patterns of fish assemblage structure and habitat use among main- and side-channel environments in the lower Kootenai River, Idaho

USGS Publications Warehouse

Watkins, Carson J.; Stevens, Bryan S.; Quist, Michael C.; Shepard, Bradley B.; Ireland, Susan C.

2015-01-01

The lower Kootenai River, Idaho, was sampled during the summers of 2012 and 2013 to evaluate its fish assemblage structure at seven sites within main- and side-channel habitats where large-scale habitat rehabilitation was undertaken. Understanding the current patterns of fish assemblage structure and their relationships with habitat is important for evaluating the effects of past and future rehabilitation projects on the river. Species-specific habitat associations were modeled, and the variables that best explained the occurrence and relative abundance of fish were identified in order to guide future habitat rehabilitation so that it benefits native species. The results indicated that the side-channel habitats supported higher species richness than the main-channel habitats and that nonnative fishes were closely associated with newly rehabilitated habitats. This research provides valuable insight on the current fish assemblages in the Kootenai River and the assemblage-level responses that may occur as a result of future rehabilitation activities.

Improved performance of nanoscale junctionless tunnel field-effect transistor based on gate engineering approach

NASA Astrophysics Data System (ADS)

Molaei Imen Abadi, Rouzbeh; Sedigh Ziabari, Seyed Ali

2016-11-01

In this paper, a first qualitative study on the performance characteristics of dual-work function gate junctionless TFET (DWG-JLTFET) on the basis of energy band profile modulation is investigated. A dual-work function gate technique is used in a JLTFET in order to create a downward band bending on the source side similar to PNPN structure. Compared with the single-work function gate junctionless TFET (SWG-JLTFET), the numerical simulation results demonstrated that the DWG-JLTFET simultaneously optimizes the ON-state current, the OFF-state leakage current, and the threshold voltage and also improves average subthreshold slope. It is illustrated that if appropriate work functions are selected for the gate materials on the source side and the drain side, the JLTFET exhibits a considerably improved performance. Furthermore, the optimization design of the tunnel gate length ( L Tun) for the proposed DWG-JLTFET is studied. All the simulations are done in Silvaco TCAD for a channel length of 20 nm using the nonlocal band-to-band tunneling (BTBT) model.

Longitudinal Proximity Effects in Superconducting Transition-Edge Sensors

NASA Technical Reports Server (NTRS)

Sadlier, John E.; Smith, Stephen J.; Bandler, Simon R.; Chervenak, James A.; Clem, John R.

2009-01-01

We have found experimentally that the critical current of a square thin-film superconducting transition-edge sensor (TES) depends exponentially upon the side length L and the square root of the temperature T, a behavior that has a natural theoretical explanation in terms of longitudinal proximity effects if the TES is regarded as a weak link between superconducting leads. As a consequence, the effective transition temperature T(sub c) of the TES is current-dependent and at fixed current scales as 1/L(sup 2). We also have found that the critical current can show clear Fraunhofer-like oscillations in an applied magnetic field, similar to those found in Josephson junctions. We have observed the longitudinal proximity effect in these devices over extraordinarily long lengths up to 290 micrometers, 1450 times the mean-free path.

Longitudinal Proximity Effects in Superconducting Transition-Edge Sensors

NASA Technical Reports Server (NTRS)

Sadleir, John E.; Smith, Stephen J.; Bandler, Simon R.; Chervenak, James A.; Clem, John R.

2010-01-01

We have found experimentally that the critical current of a square thin-film superconducting transition-edge sensor (TES) depends exponentially upon the side length L and the square root of the temperature T, a behavior that has a natural theoretical explanation in terms of longitudinal proximity effects if the TES is regarded as a weak link between superconducting leads. As a consequence, the effective transition temperature T(sub c) of the TES is current-dependent and at fixed current scales as 1/L(sup 2). We also have found that the critical current can show clear Fraunhofer-like oscillations in an applied magnetic field, similar to those found in Josephson junctions. We have observed the longitudinal proximity effect in these devices over extraordinarily long lengths up to 290 micrometers, 1450 times the mean-free path.

Herbs in dentistry.

PubMed

Taheri, Jamile B; Azimi, Somayyeh; Rafieian, Nasrin; Zanjani, Hosein Akhavan

2011-12-01

Herbs have been used for centuries to prevent and control disease. Herbal extracts are effective because they interact with specific chemical receptors within the body and are in a pharmacodynamic sense, drugs themselves. By using herbal medicines, patients have averted the many side effects that generally come with traditional medicines, but this does not mean that side effects do not occur. Only knowledgeable practitioners can prescribe the right herb and its proper dosage. Herbal medicines had been considered in every culture, however, pharmaceutical companies overturned this type of thinking. Now, pharmaceuticals are called traditional and herbs are libeled as the 'alternative'. The biggest challenge and problem is lack of information about the effect of herbs in oral tissues, mechanism of effect, and side effects. Several popular conventional drugs on the market are derived from herbs. These include aspirin (from white willow bark), digitalis (from foxglove), and sudafed (modelled after a component in the plant ephedra). Herbal products can vary in their potency. Therefore, care must be taken in selecting herbs, even so, herbal medicines have dramatically fewer side effects and are safer to use than conventional medications. The herbs described in this article are Bloodroot, Caraway, Chamomile, Echinacea, Myrrh, Peppermint, Rosemary, Sage, Thyme, Aloe Vera, Propolis, and a summary of other herbs that are useful in dentistry. Herbs may be good alternatives to current treatments for oral health problems but it is clear that we need more research. © 2011 FDI World Dental Federation.

Current Status of Herbal Medicines in Chronic Liver Disease Therapy: The Biological Effects, Molecular Targets and Future Prospects

PubMed Central

Hong, Ming; Li, Sha; Tan, Hor Yue; Wang, Ning; Tsao, Sai-Wah; Feng, Yibin

2015-01-01

Chronic liver dysfunction or injury is a serious health problem worldwide. Chronic liver disease involves a wide range of liver pathologies that include fatty liver, hepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma. The efficiency of current synthetic agents in treating chronic liver disease is not satisfactory and they have undesirable side effects. Thereby, numerous medicinal herbs and phytochemicals have been investigated as complementary and alternative treatments for chronic liver diseases. Since some herbal products have already been used for the management of liver diseases in some countries or regions, a systematic review on these herbal medicines for chronic liver disease is urgently needed. Herein, we conducted a review describing the potential role, pharmacological studies and molecular mechanisms of several commonly used medicinal herbs and phytochemicals for chronic liver diseases treatment. Their potential toxicity and side effects were also discussed. Several herbal formulae and their biological effects in chronic liver disease treatment as well as the underlying molecular mechanisms are also summarized in this paper. This review article is a comprehensive and systematic analysis of our current knowledge of the conventional medicinal herbs and phytochemicals in treating chronic liver diseases and on the potential pitfalls which need to be addressed in future study. PMID:26633388

New directions in the rational design of electrical and magnetic seizure therapies: individualized Low Amplitude Seizure Therapy (iLAST) and Magnetic Seizure Therapy (MST).

PubMed

Radman, Thomas; Lisanby, Sarah H

2017-04-01

Electroconvulsive therapy remains a key treatment option for severe cases of depression, but undesirable side-effects continue to limit its use. Innovations in the design of novel seizure therapies seek to improve its risk benefit ratio through enhanced control of the focality of stimulation. The design of seizure therapies with increased spatial precision is motivated by avoiding stimulation of deep brain structures implicated in memory retention, including the hippocampus. The development of two innovations in seizure therapy-individualized low-amplitude seizure therapy (iLAST) and magnetic seizure therapy (MST), are detailed. iLAST is a method of seizure titration involving reducing current spread in the brain by titrating current amplitude from the traditional fixed amplitudes. MST, which can be used in conjunction with iLAST dosing methods, involves the use of magnetic stimulation to reduce shunting and spreading of current by the scalp occurring during electrical stimulation. Evidence is presented on the rationale for increasing the focality of ECT in hopes of preserving its effectiveness, while reducing cognitive side-effects. Finally, the value of electric field and neural modelling is illustrated to explain observed clinical effects of modifications to ECT technique, and their utility in the rational design of the next generation of seizure therapies.

Current Status of Herbal Medicines in Chronic Liver Disease Therapy: The Biological Effects, Molecular Targets and Future Prospects.

PubMed

Hong, Ming; Li, Sha; Tan, Hor Yue; Wang, Ning; Tsao, Sai-Wah; Feng, Yibin

2015-12-02

Chronic liver dysfunction or injury is a serious health problem worldwide. Chronic liver disease involves a wide range of liver pathologies that include fatty liver, hepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma. The efficiency of current synthetic agents in treating chronic liver disease is not satisfactory and they have undesirable side effects. Thereby, numerous medicinal herbs and phytochemicals have been investigated as complementary and alternative treatments for chronic liver diseases. Since some herbal products have already been used for the management of liver diseases in some countries or regions, a systematic review on these herbal medicines for chronic liver disease is urgently needed. Herein, we conducted a review describing the potential role, pharmacological studies and molecular mechanisms of several commonly used medicinal herbs and phytochemicals for chronic liver diseases treatment. Their potential toxicity and side effects were also discussed. Several herbal formulae and their biological effects in chronic liver disease treatment as well as the underlying molecular mechanisms are also summarized in this paper. This review article is a comprehensive and systematic analysis of our current knowledge of the conventional medicinal herbs and phytochemicals in treating chronic liver diseases and on the potential pitfalls which need to be addressed in future study.

Effect of non-classical current paths in networks of 1-dimensional wires

NASA Astrophysics Data System (ADS)

Echternach, P. M.; Mikhalchuk, A. G.; Bozler, H. M.; Gershenson, M. E.; Bogdanov, A. L.; Nilsson, B.

1996-04-01

At low temperatures, the quantum corrections to the resistance due to weak localization and electron-electron interaction are affected by the shape and topology of samples. We observed these effects in the resistance of 2D percolation networks made from 1D wires and in a series of long 1D wires with regularly spaced side branches. Branches outside the classical current path strongly reduce the quantum corrections to the resistance and these reductions become a measure of the quantum lengths.

Effects of aging on the structural, mechanical, and thermal properties of the silicone rubber current transformer insulation bushing for a 500 kV substation.

PubMed

Wang, Zhigao; Zhang, Xinghai; Wang, Fangqiang; Lan, Xinsheng; Zhou, Yiqian

2016-01-01

In order to analyze the cracking and aging reason of the silicone rubber current transformer (CT) insulation bushing used for 8 years from a 500 kV alternating current substation, characteristics including Fourier transform infrared (FTIR) spectroscopy, mechanical properties analysis, hardness, and thermo gravimetric analysis have been carried out. The FTIR results indicated that the external surface of the silicone rubber CT insulation bushing suffered from more serious aging than the internal part, fracture of side chain Si-C bond was much more than the backbone. Mechanical properties and thermal stability results illustrated that the main aging reasons were the breakage of side chain Si-C bond and the excessive cross-linking reaction of the backbone. This study can provide valuable basis for evaluating degradation mechanism and aging state of the silicone rubber insulation bushing in electric power field.

A New Type Hi-Speed BLDC Control System Base on Indirect Current Control Strategy

NASA Astrophysics Data System (ADS)

Wang, D. P.; Wang, Y. C.; Zhang, F. G.; Jin, S.

2017-05-01

High speed BLDC has the characteristic as larger air gap smaller armature inductance, traditional PWM modulation will produce a great number of high frequency current harmonics which led problem like large torque ripple and serious motor heat. In the meantime traditional PWM modulation use the diode rectifier which cause harmonic pollution in electric power net. To solve the problem above, proposes a new motor controller topology. Using the IGBT device to replace the diode on frequency converter rectifier side, apply the power factor correction technology, reduce the pollution on the grid. Using busbar current modulation on the inverter, driving bridge-arm use 3-phase 6-state open as driving Mode, realize the control on a 10000r/min,10kw BLDC. The results of Simulation on matlab show the topological structure as proposed can effectively improve the network side power factor and reduce the motor armature winding harmonic and motor torque ripple.

Dexamethasone intravitreal implant for the treatment of noninfectious uveitis

PubMed Central

Hunter, Rebecca S; Lobo, Ann-Marie

2011-01-01

Uveitis can be a sight-threatening eye disease with significant morbidity. Corticosteroids remain the mainstay of treatment of uveitis and provide an effective treatment against ocular inflammation. However, the various modes available for corticosteroid drug delivery can carry significant ocular and systemic side effects which can limit their use in the treatment of uveitis. In an effort to avoid the damage to ocular structures that can ensue with recurrent episodes of ocular inflammation, the side effects associated with systemic steroids, and the need for repeated administration of both topical and locally injected corticosteroids, sustained-release intraocular corticosteroid implants have been developed. The dexamethasone (DEX) drug delivery system (Ozurdex®; Allergan Inc, Irvine, CA), is a biodegradable intravitreal implant. This implant has been shown to be effective in the treatment of macular edema and noninfectious posterior uveitis and has been approved by the FDA for these entities. This review will highlight the current methods available for corticosteroid delivery to the eye with a particular emphasis on the DEX intravitreal implant and the evidence currently available for its use in noninfectious uveitis. PMID:22140307

Structure-based discovery of opioid analgesics with reduced side effects.

PubMed

Manglik, Aashish; Lin, Henry; Aryal, Dipendra K; McCorvy, John D; Dengler, Daniela; Corder, Gregory; Levit, Anat; Kling, Ralf C; Bernat, Viachaslau; Hübner, Harald; Huang, Xi-Ping; Sassano, Maria F; Giguère, Patrick M; Löber, Stefan; Da Duan; Scherrer, Grégory; Kobilka, Brian K; Gmeiner, Peter; Roth, Bryan L; Shoichet, Brian K

2016-09-08

Morphine is an alkaloid from the opium poppy used to treat pain. The potentially lethal side effects of morphine and related opioids-which include fatal respiratory depression-are thought to be mediated by μ-opioid-receptor (μOR) signalling through the β-arrestin pathway or by actions at other receptors. Conversely, G-protein μOR signalling is thought to confer analgesia. Here we computationally dock over 3 million molecules against the μOR structure and identify new scaffolds unrelated to known opioids. Structure-based optimization yields PZM21-a potent G i activator with exceptional selectivity for μOR and minimal β-arrestin-2 recruitment. Unlike morphine, PZM21 is more efficacious for the affective component of analgesia versus the reflexive component and is devoid of both respiratory depression and morphine-like reinforcing activity in mice at equi-analgesic doses. PZM21 thus serves as both a probe to disentangle μOR signalling and a therapeutic lead that is devoid of many of the side effects of current opioids.

Structure–based discovery of opioid analgesics with reduced side effects

PubMed Central

Manglik, Aashish; Lin, Henry; Aryal, Dipendra K.; McCorvy, John D.; Dengler, Daniela; Corder, Gregory; Levit, Anat; Kling, Ralf C.; Bernat, Viachaslau; Hübner, Harald; Huang, Xi-Ping; Sassano, Maria F.; Giguère, Patrick M.; Löber, Stefan; Duan, Da; Scherrer, Grégory; Kobilka, Brian K.; Gmeiner, Peter; Roth, Bryan L.; Shoichet, Brian K.

2016-01-01

Morphine is an alkaloid from the opium poppy used to treat pain. The potentially lethal side effects of morphine and related opioids—which include fatal respiratory depression—are thought to be mediated by μ-opioid-receptor (μOR) signalling through the β-arrestin pathway or by actions at other receptors. Conversely, G-protein μOR signalling is thought to confer analgesia. Here we computationally dock over 3 million molecules against the μOR structure and identify new scaffolds unrelated to known opioids. Structure-based optimization yields PZM21—a potent Gi activator with exceptional selectivity for μOR and minimal β-arrestin-2 recruitment. Unlike morphine, PZM21 is more efficacious for the affective component of analgesia versus the reflexive component and is devoid of both respiratory depression and morphine-like reinforcing activity in mice at equi-analgesic doses. PZM21 thus serves as both a probe to disentangle μOR signalling and a therapeutic lead that is devoid of many of the side effects of current opioids. PMID:27533032

Nilotinib Induced Recurrent Gastric Polyps: Case Report and Review of Literature.

PubMed

Kassem, Nancy; Ismail, Omar M; Elomri, Halima; Yassin, Mohamad A

2017-07-14

BACKGROUND Tyrosine kinase inhibitors (TKIs) are currently an important targeted drug class in the treatment of chronic myeloid leukemia (CML). Imatinib was the first approved TKI for CML in 2001. Nilotinib is a second-generation TKI, approved in 2007; it inhibits BCR-ABL, PDGFR, and c-KIT, and is 30 times more potent than imatinib. Tyrosine kinase enzymes are expressed in multiple tissues and are involved in several signaling pathways; they have been shown to have several off-target side effects. CASE REPORT We report a case of an elderly male with CML and no history of gastrointestinal diseases, treated with nilotinib, and developed recurrent gastric polyps after three years of treatment. We excluded common causes of gastric polyps and therefore considered nilotinib as a probable cause of recurrent gastric polyps. CONCLUSIONS Recurrent gastric polyps could be a potential side effect of nilotinib treatment. Careful long-term monitoring of patients on TKI therapy is necessary and further long-term studies of TKI side effects are needed.

Experiments Using Local Helicity Injectors in the Lower Divertor Region as the Majority Current Drive in a Tokamak Plasma

NASA Astrophysics Data System (ADS)

Perry, Justin M.

Local helicity injection (LHI) is a non-solenoidal current drive capable of achieving high-Ip tokamak startup with a relatively compact and non-invasive array of current injectors in the plasma scrape-off layer. The choice of injector location within the edge region is flexible, but has a profound influence on the nature of the current drive in LHI discharges. Past experiments on the Pegasus ST with injection on the low-field-side near the outboard midplane produced plasmas dominated by inductive drive resulting primarily from plasma geometry evolution over the discharge. Recent experiments with injection on the high-field- side in the lower divertor region produce plasmas dominated by helicity injection current drive, with relatively static plasma geometry, and thus negligible inductive drive. Plasma current up to 200 kA is driven with helicity injection as the dominant current drive using a pair of 4 cm2 area injectors sourcing 8 kA of total injected current. Steady sustainment with LHI current drive alone is demonstrated, with 100 kA sustained for 18 ms. Maximum achievable plasma current is found to scale approximately linearly with a plasma-geometry- normalized form of the effective loop voltage from LHI, Vnorm = AinjVinj/Rinj, where A inj is the total injector area, Vinj is the injector bias voltage, and Rinj is the major radius of the injectors. A newly-discovered MHD regime for LHI-driven plasmas is described, in which the large-amplitude n = 1 fluctuations at 20-50 kHz which are generally dominant during LHI are abruptly reduced by an order of magnitude on the outboard side. High frequency fluctuations ( f > 400 kHz) increase inside the plasma edge at the same time. This regime results in improved plasma current and pervasive changes to plasma behavior, and may suggest short wavelength turbulence as a current drive mechanism during LHI.

Development of the My Medicines and Me (M3Q) side effect questionnaire for mental health patients: a qualitative study

PubMed Central

Ashoorian, Deena M.; Davidson, Rowan M.; Rock, Daniel J. T.; Seubert, Liza J.; Clifford, Rhonda M.

2015-01-01

Objective: The objective of this study was to assess the acceptability, content validity and usability of the My Medicines and Me (M3Q) self-report side effect questionnaire. Methods: Eight focus groups consisting of mental health patients, carers, general practitioners, psychiatrists, mental health nurses and pharmacists were conducted, involving 78 participants. Two researchers independently examined the transcriptions and analysed the data thematically using an inductive method. Results: The findings supported changes to the formatting, length and phrasing of questions in the original version of the questionnaire. Although the groups provided differing views on the usability of the M3Q in clinical practice, the patient and carer groups were unconditionally in favour of such a tool to be used systematically to describe patients’ subjective experiences with side effects. Conclusion: The differing contribution made by all groups involved in the administration and completion of the M3Q assisted with content validity of the questionnaire. The acceptability and usability of this novel side effect questionnaire was also explored, with many participants agreeing it was a necessary tool for a patient centred approach to treatment. Following implementation of the changes to the current format of the questionnaire, investigation into the uptake and use in clinical practice should be carried out. PMID:26557985

Classics in Chemical Neuroscience: Aripiprazole.

PubMed

Casey, Austen B; Canal, Clinton E

2017-06-21

Aripiprazole was the first antipsychotic developed to possess agonist properties at dopamine D 2 autoreceptors, a groundbreaking strategy that presented a new vista for schizophrenia drug discovery. The dopamine D 2 receptor is the crucial target of all extant antipsychotics, and all developed prior to aripiprazole were D 2 receptor antagonists. Extensive blockade of these receptors, however, typically produces extrapyramidal (movement) side effects, which plagued first-generation antipsychotics, such as haloperidol. Second-generation antipsychotics, such as clozapine, with unique polypharmacology and D 2 receptor binding kinetics, have significantly lower risk of movement side effects but can cause myriad additional ones, such as severe weight gain and metabolic dysfunction. Aripiprazole's polypharmacology, characterized by its unique agonist activity at dopamine D 2 and D 3 and serotonin 5-HT 1A receptors, as well as antagonist activity at serotonin 5-HT 2A receptors, translates to successful reduction of positive, negative, and cognitive symptoms of schizophrenia, while also mitigating risk of weight gain and movement side effects. New observations, however, link aripiprazole to compulsive behaviors in a small group of patients, an unusual side effect for antipsychotics. In this review, we discuss the chemical synthesis, pharmacology, pharmacogenomics, drug metabolism, and adverse events of aripiprazole, and we present a current understanding of aripiprazole's neurotherapeutic mechanisms, as well as the history and importance of aripiprazole to neuroscience.

Adolescents' attitudes and experiences regarding levonorgestrel 100 mcg/ethinyl estradiol 20 mcg.

PubMed

Rosenthal, S L; Cotton, S; Ready, J N; Potter, L S; Succop, P A

2002-12-01

Oral contraceptive pills (OCs) are a commonly prescribed method of birth control for sexually experienced adolescents. The purpose of the current study was to describe anticipated parental involvement and adolescent compliance with pill taking, and to describe experiences with a 20-mcg OC regarding satisfaction and side effects after six cycles. Anticipated parental involvement and anticipated compliance, and experiences with an OC, were assessed at baseline, and after the first and sixth cycles during a clinical trial of oral contraceptives, which required parental consent. Three adolescent medicine clinics in New York, NY; Cincinnati, OH; and San Juan, Puerto Rico. The sample consisted of 43 female adolescents with a mean age of 17 years. The majority of adolescents living with a parent anticipated parental involvement, and few adolescents anticipated difficulties with consistent pill taking. For two side effects (weight and mood changes), more than 30% of the adolescents anticipated the occurrence or worsening of side effects. However, few adolescents actually experienced increases in any of the nine side effects assessed. Ninety-seven percent of adolescents in this trial reported being satisfied with a 20-mcg OC. Health care providers can assess adolescents' anticipated difficulties with compliance with daily pill taking, and desire for help from their parents. This information can be incorporated into counseling to promote consistent and correct use.

cAMP Stimulates Transepithelial Short-Circuit Current and Fluid Transport Across Porcine Ciliary Epithelium.

PubMed

Cheng, Angela King-Wah; Civan, Mortimer M; To, Chi-Ho; Do, Chi-Wai

2016-12-01

To investigate the effects of cAMP on transepithelial electrical parameters and fluid transport across porcine ciliary epithelium. Transepithelial electrical parameters were determined by mounting freshly isolated porcine ciliary epithelium in a modified Ussing chamber. Similarly, fluid movement across intact ciliary body was measured with a custom-made fluid flow chamber. Addition of 1, 10, and 100 μM 8-Br-cAMP (cAMP) to the aqueous side (nonpigmented ciliary epithelium, NPE) induced a sustained increase in short-circuit current (Isc). Addition of niflumic acid (NFA) to the aqueous surface effectively blocked the cAMP-induced Isc stimulation. The administration of cAMP to the stromal side (pigmented ciliary epithelium, PE) triggered a significant stimulation of Isc only at 100 μM. No additive effect was observed with bilateral application of cAMP. Likewise, forskolin caused a significant stimulation of Isc when applied to the aqueous side. Concomitantly, cAMP and forskolin increased fluid transport across porcine ciliary epithelium, and this stimulation was effectively inhibited by aqueous NFA. Depleting Cl- in the bathing solution abolished the baseline Isc and inhibited the subsequent stimulation by cAMP. Pretreatment with protein kinase A (PKA) blockers (H89/KT5720) significantly inhibited the cAMP- and forskolin-induced Isc responses. Our results suggest that cAMP triggers a sustained stimulation of Cl- and fluid transport across porcine ciliary epithelium; Cl- channels in the NPE cells are potentially a cellular site for this PKA-sensitive cAMP-mediated response.

Ablative skin resurfacing.

PubMed

Agrawal, Nidhi; Smith, Greg; Heffelfinger, Ryan

2014-02-01

Ablative laser resurfacing has evolved as a safe and effective treatment for skin rejuvenation. Although traditional lasers were associated with significant thermal damage and lengthy recovery, advances in laser technology have improved safety profiles and reduced social downtime. CO2 lasers remain the gold standard of treatment, and fractional ablative devices capable of achieving remarkable clinical improvement with fewer side effects and shorter recovery times have made it a more practical option for patients. Although ablative resurfacing has become safer, careful patient selection and choice of suitable laser parameters are essential to minimize complications and optimize outcomes. This article describes the current modalities used in ablative laser skin resurfacing and examines their efficacy, indications, and possible side effects. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

From idea to implementation: creation of an educational picture book for radiation therapy patients.

PubMed

Osmar, Kari; Webb, Deborah

2015-03-01

Patient education is an integral part of the cancer patient's journey. Radiation therapists strive to provide timely, effective, and evidence-based information on care processes, side effects, and side effect management treatment strategies. Patient satisfaction surveys in health-care settings can guide new interventions and strategies to provide the right education to patients at the right time. Courses offered in adult education and patient education to practicing health-care providers allow for a unique opportunity to look at the current provision of health-care education to patients. This paper explores the development and implementation of a new visual aid for radiation therapy patients in an acute health-care setting with a diversity of languages spoken using principles of adult education.

Classical Hall Effect without Magnetic Field

NASA Astrophysics Data System (ADS)

Schade, Nicholas; Tao, Chiao-Yu; Schuster, David; Nagel, Sidney

We show that the sign and density of charge carriers in a material can be obtained without the presence of a magnetic field. This effect, analogous to the classical Hall effect, is due solely to the geometry of the current-carrying wire. When current flows, surface charges along the wire create small electric fields that direct the current to follow the path of the conductor. In a curved wire, the charge carriers must experience a centripetal force, which arises from an electric field perpendicular to the drift velocity. This electric field produces a potential difference between the sides of the wire that depends on the sign and density of the charge carriers. We experimentally investigate circuits made from superconductors or graphene to find evidence for this effect.

Management of side effects during and post-treatment in breast cancer survivors.

PubMed

Palesh, Oxana; Scheiber, Caroline; Kesler, Shelli; Mustian, Karen; Koopman, Cheryl; Schapira, Lidia

2018-03-01

Cancer-related fatigue, insomnia, and cancer-related cognitive impairment are commonly experienced symptoms that share psychological and physical manifestations. One or more of these symptoms will affect nearly all patients at some point during their course of treatment or survivorship. These side effects are burdensome and reduce patients' quality of life well beyond their cancer diagnosis and associated care treatments. Cancer-related fatigue, insomnia, and cancer-related cognitive impairment are likely to have multiple etiologies that make it difficult to identify the most effective method to manage them. In this review, we summarized the information on cancer-related fatigue, insomnia, and cancer-related cognitive impairment incidence and prevalence among breast cancer patients and survivors as well as recent research findings on pharmaceutical, psychological, and exercise interventions that have shown effectiveness in the treatment of these side effects. Our review revealed that most current pharmaceutical interventions tend to ameliorate symptoms only temporarily without addressing the underlying causes. Exercise and behavioral interventions are consistently more effective at managing chronic symptoms and possibly address an underlying etiology. Future research is needed to investigate effective interventions that can be delivered directly in clinic to a large portion of patients and survivors. © 2017 Wiley Periodicals, Inc.

Practice Patterns Compared with Evidence-based Strategies for the Management of Androgen Deprivation Therapy-Induced Side Effects in Prostate Cancer Patients: Results of a European Web-based Survey.

PubMed

Bultijnck, Renée; Surcel, Cristian; Ploussard, Guillaume; Briganti, Alberto; De Visschere, Pieter; Fütterer, Jurgen; Ghadjar, Pirus; Giannarini, Gianluca; Isbarn, Hendrik; Massard, Christophe; Sooriakumaran, Prasanna; Valerio, Massimo; van den Bergh, Roderick; Ost, Piet

2016-12-01

Evidence-based recommendations are available for the management of androgen deprivation therapy (ADT)-induced side effects; however, there are no data on the implementation of the recommendations into daily practice patterns. To compare practice patterns in the management of ADT-induced side effects with evidence-based strategies. A European Web-based survey was conducted from January 16, 2015, to June 24, 2015. The 25-item questionnaire was designed with the aid of expert opinion and covered general respondent information, ADT preference per disease stage, patient communication on ADT-induced side effects, and strategies to mitigate side effects. All questions referred to patients with long-term ADT use. Reported practice patterns were compared with available evidence-based strategies. Following data collection, descriptive statistics were used for analysis. Frequency distributions were compiled and compared using a generalised chi-square test. In total, 489 eligible respondents completed the survey. Luteinising hormone-releasing hormone-agonist with or without an antiandrogen was the preferred method of ADT in different settings. Patients were well informed about loss of libido (90%), hot flushes (85%), fatigue (67%), and osteoporosis (63%). An osteoporotic and metabolic risk assessment prior to commencing ADT was done by one-quarter of physicians. The majority (85%) took preventive measures and applied at least one evidence-based strategy. Exercise was recommended by three-quarters of physicians who advocate its positive effects; however, only 25% of physicians had access to exercise programmes. Although the minimum sample size was set at 400 participants, the current survey remains susceptible to volunteer and nonresponder bias. Patients were well informed about several ADT-induced complications but uncommonly underwent an osteoporotic and metabolic risk assessment. Nevertheless, physicians partially provided evidence-based strategies for the management of the complications. Physicians often advised exercise to reduce ADT-induced side effects, but programmes were not widely available. Implementation of evidence-based strategies for androgen deprivation therapy-induced side effects in real-life practice patterns should be improved. Copyright © 2016 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Treatment of pseudofolliculitis barbae in very dark skin with a long pulse Nd:YAG laser.

PubMed Central

Ross, E. Victor; Cooke, Linda M.; Overstreet, Kristen A.; Buttolph, Greg D.; Blair, Mark A.

2002-01-01

BACKGROUND: Pseudofolliculitis barbae affects some individuals with coarse curly hair. Currently available treatment modalities are often ineffective. In some studies, lasers have been shown to be potentially helpful in mitigating disease severity by reducing the number and/or thickness of hair shafts. METHODS: This was a side-by-side interventional study conducted at a military tertiary medical facility. The study group included 26 patients (skin types IV, V, and VI) referred from primary care physicians with a diagnosis of pseudofolliculitis barbae refractory to medical therapy. A neodymium YAG laser was used to treat one half of the neck. One month later, shaving bumps were counted and compared to their preoperative levels on both sides. RESULTS: Mean postoperative papule counts were 11.6 +/- 6 (SD) and 30.1 +/- 19 (SD) on the treated side and untreated sides, respectively. CONCLUSION: Neodymium YAG laser treatment represents a safe and effective option for reducing papule formation in patients with pseudofolliculitis barbae. Images Figure 1 PMID:12408693

Aerodynamic Inner Workings of Circumferential Grooves in a Transonic Axial Compressor

NASA Technical Reports Server (NTRS)

Hah, Chunill; Mueller, Martin; Schiffer, Heinz-Peter

2007-01-01

The current paper reports on investigations of the fundamental flow mechanisms of circumferential grooves applied to a transonic axial compressor. Experimental results show that the compressor stall margin is significantly improved with the current set of circumferential grooves. The primary focus of the current investigation is to advance understanding of basic flow mechanics behind the observed improvement of stall margin. Experimental data and numerical simulations of a circumferential groove were analyzed in detail to unlock the inner workings of the circumferential grooves in the current transonic compressor rotor. A short length scale stall inception occurs when a large flow blockage is built on the pressure side of the blade near the leading edge and incoming flow spills over to the adjacent blade passage due to this blockage. The current study reveals that a large portion of this blockage is created by the tip clearance flow originating from 20% to 50% chord of the blade from the leading edge. Tip clearance flows originating from the leading edge up to 20% chord form a tip clearance core vortex and this tip clearance core vortex travels radially inward. The tip clearance flows originating from 20% to 50% chord travels over this tip clearance core vortex and reaches to the pressure side. This part of tip clearance flow is of low momentum as it is coming from the casing boundary layer and the blade suction surface boundary layer. The circumferential grooves disturb this part of the tip clearance flow close to the casing. Consequently the buildup of the induced vortex and the blockage near the pressure side of the passage is reduced. This is the main mechanism of the circumferential grooves that delays the formation of blockage near the pressure side of the passage and delays the onset of short length scale stall inception. The primary effect of the circumferential grooves is preventing local blockage near the pressure side of the blade leading edge that directly determines flow spillage around the leading edge. The circumferential grooves do not necessarily reduce the over all blockage built up at the rotor tip section.

Fat, demented and stupid: An unrecognized legacy of pediatric urology?

PubMed

Cooper, Christopher S

2017-08-01

The human body is an unfathomably intricate structure consisting of many connected and intertwined systems. This makes it impossible for therapeutic interventions to selectively target only one physiologic system without some impact or side effects on all the other systems. The resiliency of the human body modifies and disguises side effects, some of which may be undetectable for years and not apparent without scientific investigation. Pediatric urologists employ relatively few medications for the common conditions they treat and in general these consist of antibiotics, anticholinergics, and anesthetics. Although harm from early side effects is well recognized, recent medical literature suggests there may be other side effects of these common interventions that aren't as well recognized. Antibiotics have been added to livestock feed as growth promoters for three-quarters of a century. Antibiotics alter the microbiota of the intestinal tract and these alterations have been demonstrated to impact growth, metabolism, and the risk of obesity in animals and humans. To date, the long-term impact of daily antibiotic prophylaxis in children with such pediatric urology conditions as vesicoureteral reflux or prenatal hydronephrosis have not been published. Similarly, there are no studies assessing long-term effects of anticholinergic use on cognition in children despite research demonstrating an increased risk of dementia in adults using anticholinergics. Research in animals and children recently led the FDA to issue a warning regarding the risk of lengthy use of general anesthesia on cognitive development in children. This review raises the possibility that antibiotics in children may alter growth, anticholinergics may increase their risk of dementia later in life, and anesthetics may impair their cognitive development. The possibility of such an unrecognized legacy from current therapeutic interventions should give all physicians, including pediatric urologists, pause for consideration before electing any intervention, no matter how routine or currently well accepted. Copyright © 2017 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.

New developments in the management of periocular capillary hemangioma in children.

PubMed

Ni, Nina; Wagner, Rudolph S; Langer, Paul; Guo, Suqin

2011-01-01

The authors describe the theories of pathogenesis for capillary hemangioma and discuss the benefits and side effects of current treatment options, such as systemic and intralesional corticosteroids, laser therapy, and surgical excision. They also evaluate the recent systemic and topical applications of beta-blockers to treat infantile hemangioma. Although no major adverse events from beta-blocker treatment have been reported, the incidence of potential side effects such as bronchospasm, hypoglycemia, heart block, bradycardia, and congestive heart failure is unknown due to the novelty of the treatment. It has been postulated that topical application for localized superficial tumor may reduce systemic effects. Further research is necessary to compare the effectiveness of different treatments and to find the optimal dosing and delivery methods to minimize adverse effects in the treatment of this disorder. Copyright 2011, SLACK Incorporated.

Increased cognitive problem reporting after information about chemotherapy-induced cognitive decline: The moderating role of stigma consciousness.

PubMed

Jacobs, W; Das, E; Schagen, S B

2017-01-01

Information about treatment side effects can increase their occurrence; breast cancer (BC) patients showed increased cognitive problem reporting (CPR) and decreased memory performance after information about cognitive side effects. The current study extends previous research on adverse information effects (AIE) by investigating (a) risk factors, (b) underlying mechanisms and (c) an intervention to reduce AIE. In an online experiment, 175 female BC patients were randomly assigned to one of three conditions. In the two experimental groups, patients were informed about the possible occurrence of cognitive problems after chemotherapy with (intervention group) or without (experimental group) reassuring information that 'there are still patients who score well on memory tests'. In the control group, no reference to chemotherapy-related cognitive problems was made. Main dependent measure was CPR. Four moderating and five mediating processes were examined. CPR increased with higher levels of stigma consciousness in the two experimental groups, but not in the no-information control group. Merely informing patients about cognitive side effects may increase their occurrence, especially among individuals vulnerable to patient stereotypes. Adding reassuring information is not sufficient to reduce AIE.

Use of Biologics in Private Practice: Nine Years of Lessons and Learning.

PubMed

Correa-Selm, Lilia M; Alamgir, Mahin; Rao, Babar K

2017-03-01

Over a decade ago, the FDA approved biologics for psoriasis, which changed how the disease is treated and, in most cases, has a significant positive impact on the lives of patients. Side effects primarily identified during the investigational and research phase led to the development of specific guidelines for treatment. The treatment guidelines have been amended to incorporate better understandings of side-effects over the years that the disease has been treated. In this study, we focused on a chart review that included assessing the current guidelines and their alignment with modern patient management and the recent side effects presented. This life-cycle evaluation included over 100 patients, management of their treatment, laboratory abnormalities, criteria for choosing or changing to a different biologic, and the effects of the treatments management throughout the years. The review identified some recommended changes in the application and treatment of psoriasis with biologics. To further evidence our findings, we hope to expand this study to a larger scale with more patients.

J Drugs Dermatol. 2017;16(3):215-217.

Mining adverse drug reactions from online healthcare forums using hidden Markov model.

PubMed

Sampathkumar, Hariprasad; Chen, Xue-wen; Luo, Bo

2014-10-23

Adverse Drug Reactions are one of the leading causes of injury or death among patients undergoing medical treatments. Not all Adverse Drug Reactions are identified before a drug is made available in the market. Current post-marketing drug surveillance methods, which are based purely on voluntary spontaneous reports, are unable to provide the early indications necessary to prevent the occurrence of such injuries or fatalities. The objective of this research is to extract reports of adverse drug side-effects from messages in online healthcare forums and use them as early indicators to assist in post-marketing drug surveillance. We treat the task of extracting adverse side-effects of drugs from healthcare forum messages as a sequence labeling problem and present a Hidden Markov Model(HMM) based Text Mining system that can be used to classify a message as containing drug side-effect information and then extract the adverse side-effect mentions from it. A manually annotated dataset from http://www.medications.com is used in the training and validation of the HMM based Text Mining system. A 10-fold cross-validation on the manually annotated dataset yielded on average an F-Score of 0.76 from the HMM Classifier, in comparison to 0.575 from the Baseline classifier. Without the Plain Text Filter component as a part of the Text Processing module, the F-Score of the HMM Classifier was reduced to 0.378 on average, while absence of the HTML Filter component was found to have no impact. Reducing the Drug names dictionary size by half, on average reduced the F-Score of the HMM Classifier to 0.359, while a similar reduction to the side-effects dictionary yielded an F-Score of 0.651 on average. Adverse side-effects mined from http://www.medications.com and http://www.steadyhealth.com were found to match the Adverse Drug Reactions on the Drug Package Labels of several drugs. In addition, some novel adverse side-effects, which can be potential Adverse Drug Reactions, were also identified. The results from the HMM based Text Miner are encouraging to pursue further enhancements to this approach. The mined novel side-effects can act as early indicators for health authorities to help focus their efforts in post-marketing drug surveillance.

A novel photoactive and three-dimensional stainless steel anode dramatically enhances the current density of bioelectrochemical systems.

PubMed

Feng, Huajun; Tang, Chenyi; Wang, Qing; Liang, Yuxiang; Shen, Dongsheng; Guo, Kun; He, Qiaoqiao; Jayaprada, Thilini; Zhou, Yuyang; Chen, Ting; Ying, Xianbin; Wang, Meizhen

2018-04-01

This study reports a high-performance 3D stainless-steel photoanode (3D SS photoanode) for bioelectrochemical systems (BESs). The 3D SS photoanode consists of 3D carbon-coated SS felt bioactive side and a flat α-Fe 2 O 3 -coated SS plate photoactive side. Without light illumination, the electrode reached a current density of 26.2 ± 1.9 A m -2 , which was already one of the highest current densities reported thus far. Under illumination, the current density of the electrode was further increased to 46.5 ± 2.9 A m -2 . The mechanism of the photo-enhanced current production can be attributed to the reduced charge-transfer resistance between electrode surface and the biofilm with illumination. It was also found that long-term light illumination can enhance the biofilm formation on the 3D SS photoanode. These findings demonstrate that using the synergistic effect of photocatalysis and microbial electrocatalysis is an efficient way to boost the current production of the existing high-performance 3D anodes for BESs. Copyright © 2017 Elsevier Ltd. All rights reserved.

Comparison of the discontinuation rates and side-effect profiles of pilocarpine and cevimeline for xerostomia in primary Sjögren's syndrome.

PubMed

Noaiseh, Ghaith; Baker, Joshua F; Vivino, Frederick B

2014-01-01

There are currently no head-to-head comparisons of sialagogues for Primary Sjögren's syndrome (pSS). We compared the tolerability and side effect profile of pilocarpine and cevimeline in patients with pSS and determined clinical, laboratory and pathological variables associated with therapeutic failure. We retrospectively reviewed the use of pilocarpine and cevimeline in 118 patients with pSS who fulfilled the 2002 American European Consensus Group criteria in a University-based setting. Clinical, laboratory and pathological baseline variables were collected. Failure of therapy was defined as the clinician or patient's decision to stop treatment either due to lack of efficacy or side effects. Cevimeline was associated with lower failure rates compared to pilocarpine among first-time users: 27% vs. 47% (p=0.02), and all users: 32% vs. 61% (p<0.001). Severe sweating was the most frequent side effect leading to cessation of therapy and occurred more frequently in pilocarpine (25%) than cevimeline (11%) users (p=0.02). Patients who previously failed one secretagogue were less likely to discontinue treatment with the other agent, 52% of first-time users vs. 27% of second-time users (p=0.004). Only ANA positivity was associated with failure: [59% vs. 38%] (p=0.03). pSS patients were more likely to continue cevimeline than pilocarpine long-term due to fewer reported side effects with cevimeline. Therapeutic failure of one secretagogue did not predict similar results with the other since second time users were more likely to continue long-term treatment.

Shields for protecting cables from the effects of electromagnetic noise and interference

NASA Astrophysics Data System (ADS)

Hoeft, L. O.; Hofstra, J. S.; Karaskiewicz, R. J.; Torres, B. W.

1988-12-01

The intrinsic electromagnetic property of a cable or connector shield is its surface transfer impedance. This is the ratio of the longitudinal open circuit voltage measured on one side of the shield (normally the inside) to the axial current on the other side (normally the outside). In cases where a high electric field is present at the surface of the shield, the transfer admittance or charge transfer elastance is also important. Measurements of typical cables, connectors, backshells and cable terminations are presented and explained in terms of simple models.

Skin Color, Cultural Capital, and Beauty Products: An Investigation of the Use of Skin Fairness Products in Mumbai, India

PubMed Central

Shroff, Hemal; Diedrichs, Phillippa C.; Craddock, Nadia

2018-01-01

The use of skin fairness products that frequently contain toxic ingredients is associated with significant adverse health side effects. Due to the high prevalence of use in Asian and African countries, skin fairness product use is recognized as a growing public health concern. The multi-million-dollar skin fairness product industry has also been criticized for perpetuating racism and social inequalities by reinforcing beliefs about the benefits of skin fairness for cultural capital. No quantitative studies have assessed people’s beliefs about fairness and reasons for using or not using these products in India, one of the largest global markets for skin fairness products. The current study explored skin fairness product use among 1,992 women and men aged 16–60 years in the city of Mumbai, India using a self-report questionnaire. A total of 37.6% of the sample reported currently using skin fairness products, with women being two times more likely to use these products. Among current users, 17% reported past experiences of adverse side effects, and “Media/TV/Adverts” were the most common prompts for using fairness products, followed by “Friends” and “Family.” Men were significantly more likely than women to endorse beliefs about fairness being more attractive and were more likely to perceive family and peers as viewing fairness as beneficial for cultural capital. There were no differences between women and men currently using products in their desire to look as fair as media celebrities. Among non-users, women were significantly more likely than men to report concerns about product efficacy and side effects as reasons for non-use, while men were significantly more likely to report socioeconomic reasons for non-use. Implications of these findings are discussed in light of growing public health concerns about the use of fairness products, and potential for advocacy and public health interventions to address the use of skin fairness products. PMID:29410952

Skin Color, Cultural Capital, and Beauty Products: An Investigation of the Use of Skin Fairness Products in Mumbai, India.

PubMed

Shroff, Hemal; Diedrichs, Phillippa C; Craddock, Nadia

2017-01-01

The use of skin fairness products that frequently contain toxic ingredients is associated with significant adverse health side effects. Due to the high prevalence of use in Asian and African countries, skin fairness product use is recognized as a growing public health concern. The multi-million-dollar skin fairness product industry has also been criticized for perpetuating racism and social inequalities by reinforcing beliefs about the benefits of skin fairness for cultural capital. No quantitative studies have assessed people's beliefs about fairness and reasons for using or not using these products in India, one of the largest global markets for skin fairness products. The current study explored skin fairness product use among 1,992 women and men aged 16-60 years in the city of Mumbai, India using a self-report questionnaire. A total of 37.6% of the sample reported currently using skin fairness products, with women being two times more likely to use these products. Among current users, 17% reported past experiences of adverse side effects, and "Media/TV/Adverts" were the most common prompts for using fairness products, followed by "Friends" and "Family." Men were significantly more likely than women to endorse beliefs about fairness being more attractive and were more likely to perceive family and peers as viewing fairness as beneficial for cultural capital. There were no differences between women and men currently using products in their desire to look as fair as media celebrities. Among non-users, women were significantly more likely than men to report concerns about product efficacy and side effects as reasons for non-use, while men were significantly more likely to report socioeconomic reasons for non-use. Implications of these findings are discussed in light of growing public health concerns about the use of fairness products, and potential for advocacy and public health interventions to address the use of skin fairness products.

Amorfrutins are potent antidiabetic dietary natural products

PubMed Central

Weidner, Christopher; de Groot, Jens C.; Prasad, Aman; Freiwald, Anja; Quedenau, Claudia; Kliem, Magdalena; Witzke, Annabell; Kodelja, Vitam; Han, Chung-Ting; Giegold, Sascha; Baumann, Matthias; Klebl, Bert; Siems, Karsten; Müller-Kuhrt, Lutz; Schürmann, Annette; Schüler, Rita; Pfeiffer, Andreas F. H.; Schroeder, Frank C.; Büssow, Konrad; Sauer, Sascha

2012-01-01

Given worldwide increases in the incidence of obesity and type 2 diabetes, new strategies for preventing and treating metabolic diseases are needed. The nuclear receptor PPARγ (peroxisome proliferator-activated receptor gamma) plays a central role in lipid and glucose metabolism; however, current PPARγ-targeting drugs are characterized by undesirable side effects. Natural products from edible biomaterial provide a structurally diverse resource to alleviate complex disorders via tailored nutritional intervention. We identified a family of natural products, the amorfrutins, from edible parts of two legumes, Glycyrrhiza foetida and Amorpha fruticosa, as structurally new and powerful antidiabetics with unprecedented effects for a dietary molecule. Amorfrutins bind to and activate PPARγ, which results in selective gene expression and physiological profiles markedly different from activation by current synthetic PPARγ drugs. In diet-induced obese and db/db mice, amorfrutin treatment strongly improves insulin resistance and other metabolic and inflammatory parameters without concomitant increase of fat storage or other unwanted side effects such as hepatoxicity. These results show that selective PPARγ-activation by diet-derived ligands may constitute a promising approach to combat metabolic disease. PMID:22509006

Controlling the mode of operation of organic transistors through side-chain engineering.

PubMed

Giovannitti, Alexander; Sbircea, Dan-Tiberiu; Inal, Sahika; Nielsen, Christian B; Bandiello, Enrico; Hanifi, David A; Sessolo, Michele; Malliaras, George G; McCulloch, Iain; Rivnay, Jonathan

2016-10-25

Electrolyte-gated organic transistors offer low bias operation facilitated by direct contact of the transistor channel with an electrolyte. Their operation mode is generally defined by the dimensionality of charge transport, where a field-effect transistor allows for electrostatic charge accumulation at the electrolyte/semiconductor interface, whereas an organic electrochemical transistor (OECT) facilitates penetration of ions into the bulk of the channel, considered a slow process, leading to volumetric doping and electronic transport. Conducting polymer OECTs allow for fast switching and high currents through incorporation of excess, hygroscopic ionic phases, but operate in depletion mode. Here, we show that the use of glycolated side chains on a thiophene backbone can result in accumulation mode OECTs with high currents, transconductance, and sharp subthreshold switching, while maintaining fast switching speeds. Compared with alkylated analogs of the same backbone, the triethylene glycol side chains shift the mode of operation of aqueous electrolyte-gated transistors from interfacial to bulk doping/transport and show complete and reversible electrochromism and high volumetric capacitance at low operating biases. We propose that the glycol side chains facilitate hydration and ion penetration, without compromising electronic mobility, and suggest that this synthetic approach can be used to guide the design of organic mixed conductors.

Controlling the mode of operation of organic transistors through side-chain engineering

PubMed Central

Giovannitti, Alexander; Sbircea, Dan-Tiberiu; Inal, Sahika; Nielsen, Christian B.; Bandiello, Enrico; Hanifi, David A.; Sessolo, Michele; Malliaras, George G.; McCulloch, Iain; Rivnay, Jonathan

2016-01-01

Electrolyte-gated organic transistors offer low bias operation facilitated by direct contact of the transistor channel with an electrolyte. Their operation mode is generally defined by the dimensionality of charge transport, where a field-effect transistor allows for electrostatic charge accumulation at the electrolyte/semiconductor interface, whereas an organic electrochemical transistor (OECT) facilitates penetration of ions into the bulk of the channel, considered a slow process, leading to volumetric doping and electronic transport. Conducting polymer OECTs allow for fast switching and high currents through incorporation of excess, hygroscopic ionic phases, but operate in depletion mode. Here, we show that the use of glycolated side chains on a thiophene backbone can result in accumulation mode OECTs with high currents, transconductance, and sharp subthreshold switching, while maintaining fast switching speeds. Compared with alkylated analogs of the same backbone, the triethylene glycol side chains shift the mode of operation of aqueous electrolyte-gated transistors from interfacial to bulk doping/transport and show complete and reversible electrochromism and high volumetric capacitance at low operating biases. We propose that the glycol side chains facilitate hydration and ion penetration, without compromising electronic mobility, and suggest that this synthetic approach can be used to guide the design of organic mixed conductors. PMID:27790983

The Effect of a Guide Field on the Structures of Magnetic Islands: 2D PIC Simulations

NASA Astrophysics Data System (ADS)

Huang, C.; Lu, Q.; Lu, S.; Wang, P.; Wang, S.

2014-12-01

Magnetic island plays an important role in magnetic reconnection. Using a series of 2D PIC simulations, we investigate the magnetic structures of a magnetic island formed during multiple X-line magnetic reconnection, considering the effects of the guide field in symmetric and asymmetric current sheets. In a symmetric current sheet, the current in the direction forms a tripolar structure inside a magnetic island during anti-parallel reconnection, which results in a quadrupole structure of the out-of-plane magnetic field. With the increase of the guide field, the symmetry of both the current system and out-of-plane magnetic field inside the magnetic island is distorted. When the guide field is sufficiently strong, the current forms a ring along the magnetic field lines inside magnetic island. At the same time, the current carried by the energetic electrons accelerated in the vicinity of the X lines forms another ring at the edge of the magnetic island. Such a dual-ring current system enhance the out-of-plane magnetic field inside the magnetic island with a dip in the center of the magnetic island. In an asymmetric current sheet, when there is no guide field, electrons flows toward the X lines along the separatrices from the side with a higher density, and are then directed away from the X lines along the separatrices to the side with a lower density. The formed current results in the enhancement of the out-of-plane magnetic field at one end of the magnetic island, and the attenuation at the other end. With the increase of the guide field, the structures of both the current system and the out-of-plane magnetic field are distorted.

The effect of a guide field on the structures of magnetic islands formed during multiple X line reconnections: Two-dimensional particle-in-cell simulations

NASA Astrophysics Data System (ADS)

Huang, Can; Lu, Quanming; Lu, San; Wang, Peiran; Wang, Shui

2014-02-01

A magnetic island plays an important role in magnetic reconnection. In this paper, using a series of two-dimensional particle-in-cell simulations, we investigate the magnetic structures of a magnetic island formed during multiple X line magnetic reconnections, considering the effects of the guide field in symmetric and asymmetric current sheets. In a symmetric current sheet, the current in the x direction forms a tripolar structure inside a magnetic island during antiparallel reconnection, which results in a quadrupole structure of the out-of-plane magnetic field. With the increase of the guide field, the symmetry of both the current system and out-of-plane magnetic field inside the magnetic island is distorted. When the guide field is sufficiently strong, the current forms a ring along the magnetic field lines inside a magnetic island. At the same time, the current carried by the energetic electrons accelerated in the vicinity of the X lines forms another ring at the edge of the magnetic island. Such a dual-ring current system enhances the out-of-plane magnetic field inside the magnetic island with a dip in the center of the magnetic island. In an asymmetric current sheet, when there is no guide field, electrons flow toward the X lines along the separatrices from the side with a higher density and are then directed away from the X lines along the separatrices to the side with a lower density. The formed current results in the enhancement of the out-of-plane magnetic field at one end of the magnetic island and the attenuation at the other end. With the increase of the guide field, the structures of both the current system and the out-of-plane magnetic field are distorted.

Pathogen reduction in human plasma using an ultrashort pulsed laser

USDA-ARS?s Scientific Manuscript database

Pathogen reduction is an ideal approach to ensure the continued safety of the blood supply against emerging pathogens. However, the currently licensed pathogen reduction techniques are ineffective against non-enveloped viruses, and they introduce chemicals with concerns of side effects which prevent...

Deficiency of the bulk spin Hall effect model for spin-orbit torques in magnetic-insulator/heavy-metal heterostructures

NASA Astrophysics Data System (ADS)

Li, Junxue; Yu, Guoqiang; Tang, Chi; Liu, Yizhou; Shi, Zhong; Liu, Yawen; Navabi, Aryan; Aldosary, Mohammed; Shao, Qiming; Wang, Kang L.; Lake, Roger; Shi, Jing

2017-06-01

Electrical currents in a magnetic-insulator/heavy-metal heterostructure can induce two simultaneous effects, namely, spin Hall magnetoresistance (SMR) on the heavy-metal side and spin-orbit torques (SOTs) on the magnetic-insulator side. Within the framework of a pure spin current model based on the bulk spin Hall effect (SHE), the ratio of the spin Hall-induced anomalous Hall effect (SH-AHE) to SMR should be equal to the ratio of the fieldlike torque (FLT) to the dampinglike torque (DLT). We perform a quantitative study of SMR, SH-AHE, and SOTs in a series of thulium iron garnet/platinum or T m3F e5O12/Pt heterostructures with different T m3F e5O12 thicknesses, where T m3F e5O12 is a ferrimagnetic insulator with perpendicular magnetic anisotropy. We find the ratio between the measured effective fields of FLT and DLT is at least two times larger than the ratio of the SH-AHE to SMR. In addition, the bulk SHE model grossly underestimates the spin-torque efficiency of FLT. Our results reveal deficiencies of the bulk SHE model and also address the importance of interfacial effects such as the Rashba and magnetic proximity effects in magnetic-insulator/heavy-metal heterostructures.

Extended score interval in the assessment of basic surgical skills.

PubMed

Acosta, Stefan; Sevonius, Dan; Beckman, Anders

2015-01-01

The Basic Surgical Skills course uses an assessment score interval of 0-3. An extended score interval, 1-6, was proposed by the Swedish steering committee of the course. The aim of this study was to analyze the trainee scores in the current 0-3 scored version compared to a proposed 1-6 scored version. Sixteen participants, seven females and nine males, were evaluated in the current and proposed assessment forms by instructors, observers, and learners themselves during the first and second day. In each assessment form, 17 tasks were assessed. The inter-rater reliability between the current and the proposed score sheets were evaluated with intraclass correlation (ICC) with 95% confidence intervals (CI). The distribution of scores for 'knot tying' at the last time point and 'bowel anastomosis side to side' given by the instructors in the current assessment form showed that the highest score was given in 31 and 62%, respectively. No ceiling effects were found in the proposed assessment form. The overall ICC between the current and proposed score sheets after assessment by the instructors increased from 0.38 (95% CI 0.77-0.78) on Day 1 to 0.83 (95% CI 0.51-0.94) on Day 2. A clear ceiling effect of scores was demonstrated in the current assessment form, questioning its validity. The proposed score sheet provides more accurate scores and seems to be a better feedback instrument for learning technical surgical skills in the Basic Surgical Skills course.

Extended score interval in the assessment of basic surgical skills.

PubMed

Acosta, Stefan; Sevonius, Dan; Beckman, Anders

2015-01-01

Introduction The Basic Surgical Skills course uses an assessment score interval of 0-3. An extended score interval, 1-6, was proposed by the Swedish steering committee of the course. The aim of this study was to analyze the trainee scores in the current 0-3 scored version compared to a proposed 1-6 scored version. Methods Sixteen participants, seven females and nine males, were evaluated in the current and proposed assessment forms by instructors, observers, and learners themselves during the first and second day. In each assessment form, 17 tasks were assessed. The inter-rater reliability between the current and the proposed score sheets were evaluated with intraclass correlation (ICC) with 95% confidence intervals (CI). Results The distribution of scores for 'knot tying' at the last time point and 'bowel anastomosis side to side' given by the instructors in the current assessment form showed that the highest score was given in 31 and 62%, respectively. No ceiling effects were found in the proposed assessment form. The overall ICC between the current and proposed score sheets after assessment by the instructors increased from 0.38 (95% CI 0.77-0.78) on Day 1 to 0.83 (95% CI 0.51-0.94) on Day 2. Discussion A clear ceiling effect of scores was demonstrated in the current assessment form, questioning its validity. The proposed score sheet provides more accurate scores and seems to be a better feedback instrument for learning technical surgical skills in the Basic Surgical Skills course.

Optimal Load-Side Control for Frequency Regulation in Smart Grids

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhao, Changhong; Mallada, Enrique; Low, Steven

Frequency control rebalances supply and demand while maintaining the network state within operational margins. It is implemented using fast ramping reserves that are expensive and wasteful, and which are expected to become increasingly necessary with the current acceleration of renewable penetration. The most promising solution to this problem is the use of demand response, i.e., load participation in frequency control. Yet it is still unclear how to efficiently integrate load participation without introducing instabilities and violating operational constraints. In this paper, we present a comprehensive load-side frequency control mechanism that can maintain the grid within operational constraints. In particular, ourmore » controllers can rebalance supply and demand after disturbances, restore the frequency to its nominal value, and preserve interarea power flows. Furthermore, our controllers are distributed (unlike the currently implemented frequency control), can allocate load updates optimally, and can maintain line flows within thermal limits. We prove that such a distributed load-side control is globally asymptotically stable and robust to unknown load parameters. We illustrate its effectiveness through simulations.« less

Healthier side dishes at restaurants: an analysis of children's perspectives, menu content, and energy impacts.

PubMed

Anzman-Frasca, Stephanie; Dawes, Franciel; Sliwa, Sarah; Dolan, Peter R; Nelson, Miriam E; Washburn, Kyle; Economos, Christina D

2014-07-04

Children consume restaurant-prepared foods at high rates, suggesting that interventions and policies targeting consumption of these foods have the potential to improve diet quality and attenuate excess energy intake. One approach to encouraging healthier dietary intake in restaurants is to offer fruits and vegetables (FV) as side dishes, as opposed to traditional, energy-dense accompaniments like French fries. The aims of the current study were to examine: children's views about healthier side dishes at restaurants; current side dish offerings on children's menus at leading restaurants; and potential energy reductions when substituting FV side dishes in place of French fries. To investigate children's attitudes, a survey was administered to a nationally representative sample of U.S. 8- to 18-year-olds (n = 1178). To examine current side dish offerings, children's menus from leading quick service (QSR; n = 10) and full service restaurant chains (FSR; n = 10) were analyzed. Energy reductions that could result from substituting commonly-offered FV side dishes for French fries were estimated using nutrition information corresponding to the children's menu items. Two-thirds of children reported that they would not feel negatively about receiving FV sides instead of French fries with kids' meals. Liking/taste was the most common reason that children gave to explain their attitudes about FV side dishes. Nearly all restaurants offered at least 1 FV side dish option, but at most restaurants (60% of QSR; 70% of FSR), FV sides were never served by default. Substituting FV side dishes for French fries yielded an average estimated energy reduction of at least 170 calories. Results highlight some healthy trends in the restaurant context, including the majority of children reporting non-negative attitudes about FV side dishes and the consistent availability of FV side dish options at leading QSR and FSR. Yet the minority of restaurants offer these FV sides by default. Promoting creative, appealing FV side dishes can result in healthier, less energy-dense meals for children. Substituting or displacing energy-dense default side dishes with such FV dishes show promise as part of continued, comprehensive efforts to increase the healthfulness of meals consumed by children in restaurant settings.

Use of probiotics in the fight against Helicobacter pylori

PubMed Central

Ruggiero, Paolo

2014-01-01

After the discovery of Helicobacter pylori (H. pylori), and the evidence of its relationship with gastric diseases, antibiotic-based therapies were developed, which efficacy was however limited by antibiotic resistance and lack of patient compliance. A vaccine would overcome these drawbacks, but currently there is not any H. pylori vaccine licensed. In the frame of the studies aimed at finding alternative therapies or at increasing the efficacy of the current ones and/or reducing their side effects, the investigation on the use of probiotics plays an interesting role. In vitro and preclinical studies have shown the feasibility of this approach. Several clinical trials indicated that administration of probiotics can reduce the side effects of H. pylori eradication treatment, increasing tolerability, and often increases the overall efficacy. The results of these trials vary, likely reflecting the variety of probiotics assessed and that of the eradication treatment, as well as the differences in the geographic area that imply different H. pylori strains distribution, host susceptibility, and therapy efficacy. In conclusion, the use of probiotics appears promising as an adjuvant for the current H. pylori eradication treatment, though it still requires optimization. PMID:25400981

Maternal and congenital toxoplasmosis, currently available and novel therapies in horizon

PubMed Central

Oz, Helieh S.

2014-01-01

Over one billion people worldwide are predicted to harbor Toxoplasma infection frequently with unknown lifelong health consequences. Toxoplasmosis is an important cause of foodborne, inflammatory illnesses, as well as congenital abnormalities. Ubiquitous Toxoplasma has a unique tropism for central nervous system with a mind-bugging effect and is transmitted sexually through semen. Currently available therapies are ineffective for persistent chronic disease and congenital toxoplasmosis or have severe side effects which may result in life-threatening complications. There is an urgent need for safe and effective therapies to eliminate or treat this cosmopolitan infectious and inflammatory disease. This investigation discusses pathogenesis of maternal and congenital toxoplasmosis, the currently available therapies in practice, and the experimental therapeutic modalities for promising future trials. PMID:25104952

[Interferons--its method of administration and adverse effect related to pharmacokinetics ].

PubMed

Furue, H

1984-02-01

The potential role of interferons in the treatment of malignant diseases is currently being evaluated. This paper reviews experimental and clinical findings regarding pharmacokinetics, method of administration, and side reactions of interferons. Interferon in the blood is rapidly cleared from the circulation. Intramuscular injection of alpha-interferon causes low but stable interferon levels in the blood. However, in the case of beta-interferon, interferon is never detected consistently in the blood after intramuscular or subcutaneous administration. The studies with animal models suggest that doses higher than those given in current clinical trials will be necessary to obtain clearly beneficial effects in human. The maximum safely tolerated daily dose is appreciably higher than that used in most previous studies, although even at this level, considerable toxicity may be encountered. Adequate method of administration, route, dose and interval are not yet established at all. Exact mechanism of anticancer activity is not yet well defined. The most frequent side reaction is fever. However, the exact mechanism to cause these side reactions is also not yet clarified. Dose limiting central nervous system toxicities, hypotension, hypocalcaemia etc. are occasionally encountered in some instances. Antibody to interferon is demonstrated in some cases. Purification of interferon does not always causes reduction of side reactions. The treatment of cancer cases with interferon has just started and there are many problems to be solved. However, therapeutic beneficial may be achieved in the treatment of malignant tumors by appropriate combinations of interferon with conventional treatment. More laboratory studies as well as carefully controlled clinical observations are warranted.

Cutaneous Side-effects of Immunomodulators in MS.

PubMed

Lebrun, C; Bertagna, M; Cohen, M

2011-09-01

Local skin reactions to subcutaneous injections of interferon beta (IFNB) or glatiramer acetate (GA) in multiple sclerosis (MS) are frequent, while severe cutaneous toxicity is rare. Both IFNB and GA are immunomodulatory drugs that have excellent safety profiles and are currently used for treatment of MS. They are administered by SC injection every other day for IFNB-1b, three times a week for IFNB-1a or daily for 20 mg for GA. The most common adverse effects, which occur in approximately 20-60% of patients, include pain, inflammation and induration at the injection sites. Another adverse effect is frank panniculitis followed by localized lipoatrophy at the injection sites, which has been described in half of the patients receiving GA injections but is also described with Subcutaneous IFNB-1b. No guidelines have yet been established for the treatment of skin reactions, which is a frequent point for discussion between neurologists and dermatologists. In addition, no treatment has been found for established lipoatrophy. The prevention and management of cutaneous side-effects include patient education, regular examination and manual palpation of all injection sites. Non-steroid antiinflammatory gels, local corticosteroids or endermology can help patients to resolve side-effects and to continue immunomodulatory treatment.

Experimental treatment of antipsychotic-induced movement disorders

PubMed Central

Shireen, Erum

2016-01-01

Antipsychotic drugs are extensively prescribed for the treatment of schizophrenia and other related psychiatric disorders. These drugs produced their action by blocking dopamine (DA) receptors, and these receptors are widely present throughout the brain. Therefore, extended antipsychotic use also leads to severe extrapyramidal side effects. The short-term effects include parkinsonism and the later appearing tardive dyskinesia. Currently available treatments for these disorders are mostly symptomatic and insufficient, and are often linked with a number of detrimental side effects. Antipsychotic-drug-induced tardive dyskinesia prompted researchers to explore novel drugs with fewer undesirable extrapyramidal side effects. Preclinical studies suggest a role of 5-hydroxytryptamine (serotonin)-1A and 2A/2C receptors in the modulation of dopaminergic neurotransmission and motivating a search for better therapeutic strategies for schizophrenia and related disorders. In addition, adjunctive treatment with antioxidants such as vitamin E, red rice bran oil, and curcumin in the early phases of illness may prevent additional oxidative injury, and thus improve and prevent further possible worsening of related neurological and behavioral deficits in schizophrenia. This review explains the role of serotonergic receptors and oxidative stress, with the aim of providing principles for prospect development of compounds to improve therapeutic effects of antischizophrenic drugs. PMID:27540314

Cancer preventive and curative attributes of plants of the Cactaceae family: a review.

PubMed

Harlev, Eli; Nevo, Eviatar; Solowey, Elaine; Bishayee, Anupam

2013-06-01

The ever-increasing occurrence of cancer and the severe side effects and limited efficacy of current cancer chemotherapy based on chemical drugs shift the attention toward drugs of plant origin. The Cactaceae family comprises more than 1500 species, but until recently only a few of them have been tested for their chemopreventive and anticancer attributes, leaving a wide unexplored area still waiting for researchers to investigate. Considering this fact, and also the promising results obtained with the relatively few plants of this family already tested, it should justly be expected that some plants of the Cactaceae family yet unexplored might possess outstanding anticancer attributes, exceeding those displayed by the plants already tested. This review presents in vitro and in vivo experimental evidence on cancer chemopreventive and therapeutic potential of bioactive phytoconstituents and extracts derived from cactus plants. It also examines the underlying biochemical and molecular mechanisms involved in the antineoplastic effects of plants of the Cactaceae family. Current limitation and future directions of research towards effective use of cacti to develop efficient and side effect-free future cancer-preventive and anticancer drugs are also discussed. Georg Thieme Verlag KG Stuttgart · New York.

Vertically aligned P(VDF-TrFE) core-shell structures on flexible pillar arrays

PubMed Central

Choi, Yoon-Young; Yun, Tae Gwang; Qaiser, Nadeem; Paik, Haemin; Roh, Hee Seok; Hong, Jongin; Hong, Seungbum; Han, Seung Min; No, Kwangsoo

2015-01-01

PVDF and P(VDF-TrFE) nano- and micro- structures have been widely used due to their potential applications in several fields, including sensors, actuators, vital sign transducers, and energy harvesters. In this study, we developed vertically aligned P(VDF-TrFE) core-shell structures using high modulus polyurethane acrylate (PUA) pillars as the support structure to maintain the structural integrity. In addition, we were able to improve the piezoelectric effect by 1.85 times from 40 ± 2 to 74 ± 2 pm/V when compared to the thin film counterpart, which contributes to the more efficient current generation under a given stress, by making an effective use of the P(VDF-TrFE) thin top layer as well as the side walls. We attribute the enhancement of piezoelectric effects to the contributions from the shell component and the strain confinement effect, which was supported by our modeling results. We envision that these organic-based P(VDF-TrFE) core-shell structures will be used widely as 3D sensors and power generators because they are optimized for current generations by utilizing all surface areas, including the side walls of core-shell structures. PMID:26040539

Vertically aligned P(VDF-TrFE) core-shell structures on flexible pillar arrays

DOE PAGES

Choi, Yoon-Young; Yun, Tae Gwang; Qaiser, Nadeem; ...

2015-06-04

PVDF and P(VDF-TrFE) nano- and micro- structures are widely used due to their potential applications in several fields, including sensors, actuators, vital sign transducers, and energy harvesters. In this study, we developed vertically aligned P(VDF-TrFE) core-shell structures using high modulus polyurethane acrylate (PUA) pillars as the support structure to maintain the structural integrity. In addition, we were able to improve the piezoelectric effect by 1.85 times from 40 ± 2 to 74 ± 2 pm/V when compared to the thin film counterpart, which contributes to the more efficient current generation under a given stress, by making an effective use ofmore » the P(VDF-TrFE) thin top layer as well as the side walls. We attribute the enhancement of piezoelectric effects to the contributions from the shell component and the strain confinement effect, which was supported by our modeling results. We envision that these organic-based P(VDF-TrFE) core-shell structures will be used widely as 3D sensors and power generators because they are optimized for current generations by utilizing all surface areas, including the side walls of core-shell structures.« less

Novel pharmacological approaches for the treatment of acne vulgaris.

PubMed

Valente Duarte de Sousa, Isabel Cristina

2014-10-01

Acne vulgaris is the most common skin disease worldwide; yet, current treatment options, although effective, are associated with unwanted side effects, chronicity, relapses and recurrences. The adequate control of the four pathogenic mechanisms, involved in the appearance of acne lesions, is paramount to treatment success. The authors discuss and evaluate the pathogenic pathways related to the mechanisms of action of novel molecules, which are currently under investigation for the treatment of acne vulgaris. The manuscript is based on comprehensive searches made through PubMed, GoogleScholar and ClinicalTrial.gov, using different combination of key words, which include acne vulgaris, pathogenesis, treatment, sebogenesis and Propionibacterium acnes. In the near future, more effective treatments with fewer side effects are expected. The use of topical antiandrogens, acetylcholine inhibitors and PPAR modulators seem to be promising options for controlling sebum production. Retinoic acid metabolism-blocking agents and IL-1α inhibitors have the potential to become legitimate alternative options to retinoid therapy in the management of infundibular dyskeratosis. Indeed, the authors believe that there will likely be a decline in the use of antibiotics for controlling P. acnes colonization and targeting the inflammation cascade.

Ocular toxoplasmosis: background and evidence for an antibiotic prophylaxis.

PubMed

Reich, Michael; Mackensen, Friederike

2015-11-01

The purpose of this review was to provide an overview of current data on antibiotic prophylaxis in ocular toxoplasmosis. Studies showing the prophylactic effect of long-term antibiotics are discussed. Prophylaxis seems to be justified in patients with a high risk of recurrence because of antibiotic's potential side-effects. Therefore, predisposing factors leading to a higher risk of recurrence and the time period during which an antibiotic prophylaxis is most appropriate are reviewed. Finally, a patient-individualized treatment recommendation is summarized. In the current literature, two prospective, randomized case-control studies exist, which show the protective effect of an antibiotic prophylaxis. Hematologic, gastrointestinal and dermatologic complications are potential side-effects. Especially during the first year after suffering a recurrence, an antibiotic prophylaxis seems to be justified. The risk of a recurrence is inter alia influenced by the duration of the disease, the immune status of the host and the patient's age. Therefore, an antibiotic prophylaxis should be considered for patients who have recently been infected with ocular toxoplasmosis, for middle-aged and elderly patients and patients with a compromised immune system. This should be discussed with each patient individually, especially if the lesion is close to the macula.

Mutagenic and genotoxic potential of direct electric current in Escherichia coli and Salmonella thyphimurium strains.

PubMed

Gomes, Marina das Neves; Cardoso, Janine Simas; Leitão, Alvaro Costa; Quaresma, Carla Holandino

2016-05-01

Direct electric current has several therapeutic uses such as antibacterial and antiprotozoal action, tissues scarring and regeneration, as well as tumor treatment. This method has shown promising results in vivo and in vitro, with significant efficacy and almost no side effects. Considering lack of studies regarding direct electric current mutagenic and/or genotoxic effects, the present work evaluated both aspects by using five different bacterial experimental assays: survival of repair-deficient mutants, Salmonella-histidine reversion mutagenesis (Ames test), forward mutations to rifampicin resistance, phage reactivation, and lysogenic induction. In these experimental conditions, cells were submitted to an approach that allows evaluation of anodic, cathodic, and electro-ionic effects generated by 2 mA of direct electric current, with doses ranging from 0.36 to 3.60 Coulombs. Our results showed these doses did not induce mutagenic or genotoxic effects. © 2016 Wiley Periodicals, Inc.

GLYX-13, a NMDA Receptor Glycine-Site Functional Partial Agonist, Induces Antidepressant-Like Effects Without Ketamine-Like Side Effects

PubMed Central

Burgdorf, Jeffrey; Zhang, Xiao-lei; Nicholson, Katherine L; Balster, Robert L; David Leander, J; Stanton, Patric K; Gross, Amanda L; Kroes, Roger A; Moskal, Joseph R

2013-01-01

Recent human clinical studies with the NMDA receptor (NMDAR) antagonist ketamine have revealed profound and long-lasting antidepressant effects with rapid onset in several clinical trials, but antidepressant effects were preceded by dissociative side effects. Here we show that GLYX-13, a novel NMDAR glycine-site functional partial agonist, produces an antidepressant-like effect in the Porsolt, novelty induced hypophagia, and learned helplessness tests in rats without exhibiting substance abuse-related, gating, and sedative side effects of ketamine in the drug discrimination, conditioned place preference, pre-pulse inhibition and open-field tests. Like ketamine, the GLYX-13-induced antidepressant-like effects required AMPA/kainate receptor activation, as evidenced by the ability of NBQX to abolish the antidepressant-like effect. Both GLYX-13 and ketamine persistently (24 h) enhanced the induction of long-term potentiation of synaptic transmission and the magnitude of NMDAR-NR2B conductance at rat Schaffer collateral-CA1 synapses in vitro. Cell surface biotinylation studies showed that both GLYX-13 and ketamine led to increases in both NR2B and GluR1 protein levels, as measured by Western analysis, whereas no changes were seen in mRNA expression (microarray and qRT-PCR). GLYX-13, unlike ketamine, produced its antidepressant-like effect when injected directly into the medial prefrontal cortex (MPFC). These results suggest that GLYX-13 produces an antidepressant-like effect without the side effects seen with ketamine at least in part by directly modulating NR2B-containing NMDARs in the MPFC. Furthermore, the enhancement of ‘metaplasticity' by both GLYX-13 and ketamine may help explain the long-lasting antidepressant effects of these NMDAR modulators. GLYX-13 is currently in a Phase II clinical development program for treatment-resistant depression. PMID:23303054

Does transcranial electrical stimulation enhance corticospinal excitability of the motor cortex in healthy individuals? A systematic review and meta-analysis.

PubMed

Dissanayaka, Thusharika; Zoghi, Maryam; Farrell, Michael; Egan, Gary F; Jaberzadeh, Shapour

2017-08-01

Numerous studies have explored the effects of transcranial electrical stimulation (tES) - including anodal transcranial direct current stimulation (a-tDCS), cathodal transcranial direct current stimulation (c-tDCS), transcranial alternative current stimulation (tACS), transcranial random noise stimulation (tRNS) and transcranial pulsed current stimulation (tPCS) - on corticospinal excitability (CSE) in healthy populations. However, the efficacy of these techniques and their optimal parameters for producing robust results has not been studied. Thus, the aim of this systematic review was to consolidate current knowledge about the effects of various parameters of a-tDCS, c-tDCS, tACS, tRNS and tPCS on the CSE of the primary motor cortex (M1) in healthy people. Leading electronic databases were searched for relevant studies published between January 1990 and February 2017; 126 articles were identified, and their results were extracted and analysed using RevMan software. The meta-analysis showed that a-tDCS application on the dominant side significantly increases CSE (P < 0.01) and that the efficacy of a-tDCS is dependent on current density and duration of application. Similar results were obtained for stimulation of M1 on the non-dominant side (P = 0.003). The effects of a-tDCS reduce significantly after 24 h (P = 0.006). Meta-analysis also revealed significant reduction in CSE following c-tDCS (P < 0.001) and significant increases after tRNS (P = 0.03) and tPCS (P = 0.01). However, tACS effects on CSE were only significant when the stimulation frequency was ≥140 Hz. This review provides evidence that tES has substantial effects on CSE in healthy individuals for a range of stimulus parameters. © 2017 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Civil & Military Operations: Evolutionary Prep Steps to Pass Smart Power Current Limitations

DTIC Science & Technology

2011-06-01

and outcomes – Identifying the best time, place, and method for action – Reduced ambiguity for action application, reduced side effects – Find the...improvements to arrive at increased accuracy, precision, and reduction of un-intended effects . The examples of these streams will demonstrate the...DIME – Diplomatic, Intelligence, Military, and Economic; EBO – Effects Based Operations. 16th International Command and Control Research and

Wavelet analysis of near-inertial currents at the East Flower Garden Bank

NASA Astrophysics Data System (ADS)

Teague, W. J.; Wijesekera, H. W.; Jarosz, E.; Lugo-Fernández, A.; Hallock, Z. R.

2014-10-01

Near-inertial currents (NICs) often dominate the mean circulation at the East Flower Garden Bank (EFGB), part of the Flower Garden Banks National Marine Sanctuary. The EFGB, one of several submerged coral reefs, is located in the northwestern Gulf of Mexico, about 190 km southeast of Galveston, Texas. The bank is about 6 km wide in the east-west direction and rises to within about 20 m from the surface. NICs near the EFGB are described using current data from 5 acoustic Doppler current profilers that were moored at the edges of the bank and on top of the bank for about a year. A wavelet analysis was used in order to better describe the nonstationarity of the NICs. NICs were strongest during spring and summer due to their near resonant response with sea breeze and the shallowness of the mixed layer, and exhibited a first-baroclinic-mode vertical structure. NICS were generally larger near the surface and extended to the bottom on the west side of the EFGB but only to within about 20 m of the bottom on the eastern side of the bank. NIC ellipses were nearly circular and rotated clockwise above the top of the EFGB but became flatter and aligned with the bathymetry with increasing depth; occasionally, on the eastern side of the bank, the NIC vectors rotated counterclockwise due to probable effects of lee vortices arising from the mean flow interacting with the bank. Most energy input by the wind at the surface was likely transferred downward through divergence of the meridional flow against the coastal boundary. The inertial currents were at times more energetic than the mean flow, and often accounted for more than 50% of the total current energy.

Building a better hormone therapy?: How understanding the rapid effects of sex steroid hormones could lead to new therapeutics for age-related memory decline

PubMed Central

Frick, Karyn M.

2012-01-01

A wealth of data collected in recent decades has demonstrated that ovarian sex-steroid hormones, particularly 17β-estradiol (E2), are important trophic factors that regulate the function of cognitive regions of the brain such as the hippocampus. The loss of hormone cycling at menopause is associated with cognitive decline and dementia in women, and the onset of memory decline in animal models. However, hormone therapy is not currently recommended to prevent or treat cognitive decline, in part because of its detrimental side effects. In this article, it is proposed that investigations of the rapid effects of E2 on hippocampal function be used to further the design of new drugs that mimic the beneficial effects of E2 on memory without the side effects of current therapies. A conceptual model is presented for elucidating the molecular and biochemical mechanisms through which sex-steroid hormones modulate memory, and a specific hypothesis is proposed to account for the rapid memory-enhancing effects of E2. Empirical support for this hypothesis is discussed as a means of stimulating the consideration of new directions for the development of hormone-based therapies to preserve memory function in menopausal women. PMID:22289043

Implicit Goalkeeper Influences on Goal Side Selection in Representative Penalty Kicking Tasks

PubMed Central

Noël, Benjamin; van der Kamp, John; Memmert, Daniel

2015-01-01

In well-controlled lab situations, marginal displacements of the goalkeeper on the goal line affect goal side selection of penalty takers implicitly, that is, without the penalty takers being consciously aware of the displacement. Whether this effect is retained in more representative real-life situations with competing goalkeepers and penalty takers has not been verified. In the current study, penalty takers were instructed to position the goalkeepers at the centre of the goal. They then performed penalty kicks adopting either a keeper independent or a keeper dependent strategy, while goalkeepers actually attempted to save the ball by strategically diving early or late. Analyses of trials in which penalty takers failed to place the goalkeeper in the centre of the goal (although they incorrectly believed they placed the goalkeeper at the centre of the goal) showed that implicit influences of the goalkeeper’s position on goal side selection were overridden by the (conscious) perception of the direction of the goalkeeper’s dive, but only if the penalty takers deliberately monitored the goalkeeper’s action and the goalkeeper committed early enough for penalty takers to respond. In all other combinations of penalty kick and goalkeeper strategies more than 60% of the kicks were directed to the side of the goal with more space. Most importantly, however, the current study shows that influences of implicit perception on the penalty takers’ decision making are rather pervasive considering that many supraliminal sources of information were available. That is, the current study demonstrates that implicit perception retains its influence on decision-making even if other (stronger) stimuli are also present. PMID:26267378

Current applications and future potential for bioinorganic chemistry in the development of anticancer drugs

PubMed Central

van Rijt, Sabine H.; Sadler, Peter J.

2010-01-01

This review illustrates notable recent progress in the field of medicinal bioinorganic chemistry with many new approaches to the design of innovative metal-based anticancer drugs emerging. Current research addressing the problems associated with platinum drugs has focused on other metal-based therapeutics that have different modes of action, and on prodrug and targeting strategies in an effort to diminish the side-effects of cisplatin chemotherapy. PMID:19782150

Free radical mediated oxidative stress and toxic side effects in brain induced by the anti cancer drug adriamycin: insight into chemobrain.

PubMed

Joshi, Gururaj; Sultana, Rukhsana; Tangpong, Jitbanjong; Cole, Marsha Paulette; St Clair, Daret K; Vore, Mary; Estus, Steven; Butterfield, D Allan

2005-11-01

Adriamycin (ADR) is a chemotherapeutic agent useful in treating various cancers. ADR is a quinone-containing anthracycline chemotherapeutic and is known to produce reactive oxygen species (ROS) in heart. Application of this drug can have serious side effects in various tissues, including brain, apart from the known cardiotoxic side effects, which limit the successful use of this drug in treatment of cancer. Neurons treated with ADR demonstrate significant protein oxidation and lipid peroxidation. Patients under treatment with this drug often complain of forgetfulness, lack of concentration, dizziness (collectively called somnolence or sometimes called chemobrain). In this study, we tested the hypothesis that ADR induces oxidative stress in brain. Accordingly, we examined the in vivo levels of brain protein oxidation and lipid peroxidation induced by i.p. injection of ADR. We also measured levels of the multidrug resistance-associated protein (MRP1) in brain isolated from ADR- or saline-injected mice. MRP1 mediates ATP-dependent export of cytotoxic organic anions, glutathione S-conjugates and sulphates. The current results demonstrated a significant increase in levels of protein oxidation and lipid peroxidation and increased expression of MRP1 in brain isolated from mice, 72 h post i.p injection of ADR. These results are discussed with reference to potential use of this redox cycling chemotheraputic agent in the treatement of cancer and its chemobrain side effect in brain.

Suitability of the adenosine antagonist istradefylline for the treatment of Parkinson's disease: pharmacokinetic and clinical considerations.

PubMed

Müller, Thomas

2013-08-01

Recent experimental and clinical research has shown that A2A adenosine receptor antagonism can bring about an improvement in the motor behavior of patients with Parkinson's disease. Istradefylline , a xanthine derivative, has the longest half-life of all the currently available A2A adenosine receptor antagonists; it can successfully permeate through the blood-brain barrier and has a high human A2A adenosine receptor affinity. In this article, the author discusses the potential role of A2A adenosine receptor antagonists in the treatment of Parkinson's disease through the evaluation of istradefylline. Specifically, the article reviews the clinical and pharmacokinetic information available to elucidate its therapeutic potential. A2A adenosine receptor antagonists are efficacious in combination with l-dopa. l-dopa has a complex pharmacokinetic behavior and causes long-term behavioral and metabolic side effects. Future research on A2A adenosine receptor antagonism should consider compounds like istradefylline as l-dopa and/or dopamine agonist-sparing treatment alternatives, since their clinical handling, safety and side-effect profile are superior to l-dopa and/or dopamine agonists. The current focus to demonstrate a specific dyskinesia-ameliorating efficacy of A2A adenosine receptor antagonism in clinical trials is risky, since the presentation of dyskinesia varies on a day-to-day basis and is considerably influenced by peripheral l-dopa metabolism. The demonstration of an antidyskinetic effect may convince authorities, but this is far less relevant in clinical practice as patients generally better tolerate dyskinesia than other phenomena and dopaminergic side effects.

Assessment of the efficacy and tolerance of a new combination of retinoids and depigmenting agents in the treatment of melasma.

PubMed

Truchuelo, Maria Teresa; Jiménez, Natalia; Jaén, Pedro

2014-12-01

Melasma is a dermatosis with significant repercussions on patients' quality of life, and there is currently no standard treatment. Hydroquinone is deemed the treatment of choice, but its safety has been questioned in certain cases. To determine the efficacy and safety of a new combination of retinoids in the improvement of melasma. Prospective, double-blind, vehicle-controlled, and randomized study in 30 patients with melasma. The product was applied on one side of the face and the vehicle on the other, twice daily during 3 months. Standardized photographs were taken using RBX technology on the three visits (basal, at one and a half months and at 3 months). The main variable to determine the efficacy was the improvement of the hemifacial Melasma Area Severity Index (MASI). Other variables were determined such as improvement perceived by the investigator, improvement perceived by the patient, impact on quality of life or side effects. The MASI improvement at 3 months of treatment was significant on the treated side vs. the vehicle side, reaching an improvement of 70%, which is comparable to the percentage of improvement described with hydroquinone. No notable side effects were detected, in spite of a significant percentage of patients included in the study citing a history that could be compatible with sensitive skin. This new combination of retinoids and depigmenting agents proved to be effective and safe in the treatment of melasma. © 2014 Wiley Periodicals, Inc.

Quaternary sedimentary processes on the northwestern African continental margin - An integrated study using side-scan sonar, high-resolution profiling, and core data

DOE Office of Scientific and Technical Information (OSTI.GOV)

Masson, D.G.; Huggett, Q.J.; Weaver, P.P.E.

1991-08-01

Side-scan sonar data, cores, and high-resolution profiles have been used to produce an integrated model of sedimentation for the continental margin west of the Canary Islands. Long-range side-scan sonar (GLORIA) data and a grid of 3.5-kHz profiles, covering some 200,000 km{sup 2} allow a regional appraisal of sedimentation. More detailed studies of selected areas have been undertaken using a new 30 kHz deep-towed side-scan sonar (TOBI) developed by the U.K. Institute of Oceanographic Sciences. Sediment cores have been used both to calibrate acoustic facies identified on sonographs and for detailed stratigraphic studies. The most recent significant sedimentation event in themore » area is to Saharan Sediment Slide, which carried material from the upper continental slope off West Africa to the edge of the Madeira Abyssal Plain, a distance of some 1000 km. The authors data shows the downslope evolution of the debris flow. Near the Canaries, it is a 20-m-thick deposit rafting coherent blocks of more than 1 km diameter; side-scan records show a strong flow-parallel fabric on a scale of tens of meters. On the lower slope, the debris flow thins to a few meters, the flow fabric disappears, and the rafted blocks decrease to meters in diameter. Side-scan data from the lower slope show that the Saharan Slide buries an older landscape of turbidity current channels, typically 1 km wide and 50 m deep. Evidence from the Madeiran Abyssal Plain indicates a history of large but infrequent turbidity currents, the emplacement of which is related to the effects of sea level changes on the northwest African margin.« less

D-Side: A Facility and Workforce Planning Group Multi-criteria Decision Support System for Johnson Space Center

NASA Technical Reports Server (NTRS)

Tavana, Madjid

2005-01-01

"To understand and protect our home planet, to explore the universe and search for life, and to inspire the next generation of explorers" is NASA's mission. The Systems Management Office at Johnson Space Center (JSC) is searching for methods to effectively manage the Center's resources to meet NASA's mission. D-Side is a group multi-criteria decision support system (GMDSS) developed to support facility decisions at JSC. D-Side uses a series of sequential and structured processes to plot facilities in a three-dimensional (3-D) graph on the basis of each facility alignment with NASA's mission and goals, the extent to which other facilities are dependent on the facility, and the dollar value of capital investments that have been postponed at the facility relative to the facility replacement value. A similarity factor rank orders facilities based on their Euclidean distance from Ideal and Nadir points. These similarity factors are then used to allocate capital improvement resources across facilities. We also present a parallel model that can be used to support decisions concerning allocation of human resources investments across workforce units. Finally, we present results from a pilot study where 12 experienced facility managers from NASA used D-Side and the organization's current approach to rank order and allocate funds for capital improvement across 20 facilities. Users evaluated D-Side favorably in terms of ease of use, the quality of the decision-making process, decision quality, and overall value-added. Their evaluations of D-Side were significantly more favorable than their evaluations of the current approach. Keywords: NASA, Multi-Criteria Decision Making, Decision Support System, AHP, Euclidean Distance, 3-D Modeling, Facility Planning, Workforce Planning.

The toxicology of cannabis and cannabis prohibition.

PubMed

Grotenhermen, Franjo

2007-08-01

The acute side effects caused by cannabis use are mainly related to psyche and cognition, and to circulation. Euphoria, anxiety, changes in sensory perception, impairment of memory and psychomotor performance are common effects after a dose is taken that exceeds an individually variable threshold. Cannabis consumption may increase heart rate and change blood pressure, which may have serious consequences in people with heart disease. Effects of chronic use may be induction of psychosis and development of dependency to the drug. Effects on cognitive abilities seem to be reversible after abstinence, except possibly in very heavy users. Cannabis exposure in utero may have negative consequences on brain development with subtle impairment of cognitive abilities in later life. Consequences of cannabis smoking may be similar to those of tobacco smoking and should be avoided. Use by young people has more detrimental effects than use by adults. There appear to be promising therapeutic uses of cannabis for a range of indications. Use of moderate doses in a therapeutic context is usually not associated with severe side effects. Current prohibition on cannabis use may also have harmful side effects for the individual and the society, while having little influence on prevalence of use. Harm is greatest for seriously ill people who may benefit from a treatment with cannabis. This makes it difficult to justify criminal penalties against patients.

Tranexamic Acid in the Treatment of Melasma: A Review of the Literature.

PubMed

Perper, Marina; Eber, Ariel Eva; Fayne, Rachel; Verne, Sebastian Hugo; Magno, Robert James; Cervantes, Jessica; ALharbi, Mana; ALOmair, Ibrahim; Alfuraih, Abdulkarem; Nouri, Keyvan

2017-06-01

Melasma is a common acquired pigmentary disorder marked by irregular hyperpigmented macules or patches and most commonly occurs in women of darker skin color. It is a chronic often-relapsing condition that causes negative psychosocial effects in those affected. Current treatments such as hydroquinone, kojic acid, and retinoids, among others, demonstrate variable efficacy and side-effect profiles. We conducted a comprehensive literature review examining the use of tranexamic acid (TA), a well-known anti-fibrinolytic agent, in the treatment of melasma. TA delivered orally, topically, and through physical methods works via the inhibition of ultraviolet (UV)-induced plasmin activity in keratinocytes. Predefined search terms were entered into PubMed. Articles were then independently screened by two authors to include only those written in the English language and relating to human subjects with at least mild melasma. The search identified 28 articles, 15 of which met the criteria for full review. The review revealed that TA treatment for melasma is equally effective or more effective than other standard therapies and may induce fewer side effects. Our comprehensive review suggests that TA may be a promising treatment option for melasma because of its demonstrated effectiveness alone and in combination with other modalities as well as its limited side-effect profile.

Integrated main rail, feed rail, and current collector

DOEpatents

Petri, Randy J.; Meek, John; Bachta, Robert P.; Marianowski, Leonard G.

1994-01-01

A separator plate for a fuel cell comprising an anode current collector, a cathode current collector and a main plate, the main plate disposed between the anode current collector and the cathode current collector. The anode current collector forms a flattened peripheral wet seal structure and manifold wet seal structure on the anode side of the separator plate and the cathode current collector forms a flattened peripheral wet seal structure and manifold wet seal structure on the cathode side of the separator plate. In this manner, the number of components required to manufacture and assemble a fuel cell stack is reduced.

Increasing AR by HIF-2α inhibitor (PT-2385) overcomes the side-effects of sorafenib by suppressing hepatocellular carcinoma invasion via alteration of pSTAT3, pAKT and pERK signals

PubMed Central

Xu, Junjie; Zheng, Longbo; Chen, Jiang; Sun, Yin; Lin, Hui; Jin, Ren-an; Tang, Minyue; Liang, Xiao; Cai, Xiujun

2017-01-01

Although sorafenib is currently used as a standard treatment for advanced hepatocellular carcinoma, low response rate, transient and limited efficacy, primary and acquired resistance and negative side-effects gain increasing attentions, suggesting the need for better efficacious combination therapy. Here, we demonstrated that the sorafenib-induced or hypoxia-induced hypoxia inducible factor (HIF)-2α could bind to an hypoxia responsive element within 500 bp region of androgen receptor (AR) promoter and thus transcriptionally suppress AR. Importantly, In vitro and In vivo studies suggested a specific and potent HIF-2α inhibitor, PT-2385, could significantly enhance sorafenib efficacy by suppressing HIF-2α, increasing AR and suppressing downstream pSTAT3/pAKT/pERK pathways. Clinical samples further confirmed the role of HIF-2α and AR. It is promising that PT-2385 could alleviate the undesirable side-effects of sorafenib treatment by sorafenib-PT-2385 combination therapy, which may shed light for late-stage HCC patients. PMID:29022906

Increasing AR by HIF-2α inhibitor (PT-2385) overcomes the side-effects of sorafenib by suppressing hepatocellular carcinoma invasion via alteration of pSTAT3, pAKT and pERK signals.

PubMed

Xu, Junjie; Zheng, Longbo; Chen, Jiang; Sun, Yin; Lin, Hui; Jin, Ren-An; Tang, Minyue; Liang, Xiao; Cai, Xiujun

2017-10-12

Although sorafenib is currently used as a standard treatment for advanced hepatocellular carcinoma, low response rate, transient and limited efficacy, primary and acquired resistance and negative side-effects gain increasing attentions, suggesting the need for better efficacious combination therapy. Here, we demonstrated that the sorafenib-induced or hypoxia-induced hypoxia inducible factor (HIF)-2α could bind to an hypoxia responsive element within 500 bp region of androgen receptor (AR) promoter and thus transcriptionally suppress AR. Importantly, In vitro and In vivo studies suggested a specific and potent HIF-2α inhibitor, PT-2385, could significantly enhance sorafenib efficacy by suppressing HIF-2α, increasing AR and suppressing downstream pSTAT3/pAKT/pERK pathways. Clinical samples further confirmed the role of HIF-2α and AR. It is promising that PT-2385 could alleviate the undesirable side-effects of sorafenib treatment by sorafenib-PT-2385 combination therapy, which may shed light for late-stage HCC patients.

Mining Archived HYSPEC User Data to Analyze the Prompt Pulse at the SNS

DOE Office of Scientific and Technical Information (OSTI.GOV)

Smith, Michael B.; Iverson, Erik B.; Gallmeier, Franz X.

The Hybrid-Spectrometer (HYSPEC) is one of 17 instruments currently operated at the Spallation Neutron Source (SNS) at Oak Ridge National Laboratories (ORNL). The secondary spectrometer of this instrument is located inside an out-building off the north side of the SNS instrument hall. HYSPEC has experienced a larger background feature than similar inelastic instruments since its commissioning in 2011. This background feature is caused by a phenomenon known as the “prompt pulse” which is an essential part of neutron production in a pulsed spallation source but comes with unfortunate side effects.

Free Energy Perturbation Calculations of the Thermodynamics of Protein Side-Chain Mutations.

PubMed

Steinbrecher, Thomas; Abel, Robert; Clark, Anthony; Friesner, Richard

2017-04-07

Protein side-chain mutation is fundamental both to natural evolutionary processes and to the engineering of protein therapeutics, which constitute an increasing fraction of important medications. Molecular simulation enables the prediction of the effects of mutation on properties such as binding affinity, secondary and tertiary structure, conformational dynamics, and thermal stability. A number of widely differing approaches have been applied to these predictions, including sequence-based algorithms, knowledge-based potential functions, and all-atom molecular mechanics calculations. Free energy perturbation theory, employing all-atom and explicit-solvent molecular dynamics simulations, is a rigorous physics-based approach for calculating thermodynamic effects of, for example, protein side-chain mutations. Over the past several years, we have initiated an investigation of the ability of our most recent free energy perturbation methodology to model the thermodynamics of protein mutation for two specific problems: protein-protein binding affinities and protein thermal stability. We highlight recent advances in the field and outline current and future challenges. Copyright © 2017 Elsevier Ltd. All rights reserved.

The Oxford Questionnaire on the Emotional Side-effects of Antidepressants (OQuESA): development, validity, reliability and sensitivity to change.

PubMed

Price, Jonathan; Cole, Victoria; Doll, Helen; Goodwin, Guy M

2012-09-01

Some patients with major depression report a restricted range of emotions that may appear to arise as a side-effect of treatment with antidepressants. It is uncertain whether this phenomenon, sometimes called emotional blunting, represents residual symptoms of depression or side-effects of antidepressant treatment. There is currently no adequate instrument to measure this phenomenon. A draft questionnaire was developed from patient-derived qualitative data, refined using cognitive interviewing, and administered on three occasions to patients taking antidepressants. Statistical methods including factor analysis were used to reduce the size of the draft questionnaire, and to assess the performance of the resulting Oxford Questionnaire on the Emotional Side-effects of Antidepressants (OQuESA). 207 patients completed the OQuESA on at least one occasion. Their BDI-II scores and self-reported emotional blunting were spread across the possible range. The factor analysis resulted in four dimensions: 'not caring', 'emotional detachment', 'reduction in positive emotions', and 'general reduction in emotions'. The OQuESA appears to be acceptable, valid, and reliable, with sensitivity to change. The OQuESA offers promise as an effective self-report measure of the symptoms of emotional blunting in patients with depression. It can be used as a clinical tool, to facilitate the identification of patients with the syndrome of emotional blunting. It should also be used in research studies, to advance our understanding of the nature, causes and treatment of this phenomenon. Copyright © 2012 Elsevier B.V. All rights reserved.

Prevalence of anabolic steroid use and associated factors among body-builders in Hamadan, West province of Iran.

PubMed

Razavi, Zahra; Moeini, Babak; Shafiei, Yones; Bazmamoun, Hassan

2014-01-01

Androgenic-anabolic steroids (AAS) are abused by a growing number of bodybuilders. This descriptive cross-sectional study was conducted to determine prevalence and patterns of AAS use by bodybuilders in Hamadan, western Iran. In this cross-sectional study, participants were recruited from five gym clubs in two area of Hamadan (a total of 10 clubs). Twenty-five bodybuilders from each club were administered. Questions investigating demographic information, sport history, education level, general knowledge about AAS, and their side effects were asked. Statistical analysis was performed using SPSS 16. The frequency of AAS use was 28.8% (72/250). Fifty-four percent of users were 25 years or younger. AAS abuse showed a significant association with duration of exercise. The drugs were suggested mostly from peers (43.1%) and coaches (36.1%). The most commonly consumed anabolic steroid was testosterone (66.7%). The most commonly reported AAS side effect was acne (18.1%). There was not significant association between general knowledge about side effects of ASS and their use. The results of current survey indicate that frequency of ASS use is high in adolescents and young adult bodybuilders. Well educated bodybuilders have a higher prevalence of abuse. Awareness about the side effects of drugs is not deterrent factor for their abuse. Iranian Ministry of Sport and the Youth, and the National Council for Youth, should be urged to conduct more effective prevention strategies.

75 FR 35611 - Airworthiness Directives; McDonnell Douglas Corporation Model DC-10-10, DC-10-10F, and MD-10-10F...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-23

... one-time high frequency eddy current inspection of fastener holes for cracks at the left and right... frequency eddy current inspection of fastener holes for cracks at the left and right side wing rear spar... frequency eddy current inspection for cracking of fastener holes at the left and right side wing rear spar...

Effects of electroconvulsive therapy and magnetic seizure therapy on acute memory retrieval.

PubMed

Polster, Julia D; Kayser, Sarah; Bewernick, Bettina H; Hurlemann, René; Schlaepfer, Thomas E

2015-03-01

Electroconvulsive therapy (ECT) is currently the most effective treatment for severe depression. However, it is frequently associated with negative cognitive side effects. Magnetic seizure therapy (MST) depicts an alternative, although experimental, convulsive treatment for major depression. Initial results suggest comparable antidepressant effects accompanied by a better side effect profile. However, no studies up to now have addressed acute retrieval disruption after MST in comparison to ECT. Therefore, we intended to broaden insight into the side effect profile of MST compared to ECT by examining the disruption of acute verbal memory processes after treatment. Twenty depressed patients were randomly assigned to either MST (10 patients) or ECT (10 patients) treatment. On 2 treatment days and 2 treatment-free days, the patients memorized words using a controlled learning paradigm derived from the Batchelder and Riefer storage retrieval model. Four hours after memorization, the patients were asked to retrieve words freely (delayed recall) and a second time with the help of an additional cue constructed out of a hypernymic category (cued recall). By comparing memory performance on treatment days to control days, treatment-induced memory disruption was evaluated. After ECT, delayed recall was disturbed, whereas after MST, it was not. However, this difference in performance was no longer apparent upon cue application (cued recall). This study demonstrates that ECT-induced acute memory disruption measured by delayed recall is absent after MST, confirming its superior side effect profile. We hope that confirming advantages of MST over ECT will improve therapy options for patients with severe depression.

No blank slates: Pre-existing schemas about pharmaceuticals predict memory for side effects.

PubMed

Heller, Monika K; Chapman, Sarah C E; Horne, Rob

2017-04-01

Attribution of symptoms as medication side effects is informed by pre-existing beliefs about medicines and perceptions of personal sensitivity to their effects (pharmaceutical schemas). We tested whether (1) pharmaceutical schemas were associated with memory (recall/recognition) for side effect information (2) memory explained the attribution of a common unrelated symptom as a side effect. In this analogue study participants saw the patient leaflet of a fictitious asthma drug listing eight side effects. We measured recall and recognition memory for side effects and used a vignette to test whether participants attributed an unlisted common symptom (headache) as a side effect. Participants who perceived pharmaceuticals as more harmful in general recalled fewer side effects correctly (r Correct Recall  = -.273), were less able to differentiate between listed and unlisted side effects (r Recognition Sensitivity  = -.256) and were more likely to attribute the unlisted headache symptom as a side effect (r side effect attribution  = .381, ps < .01). The effect of harm beliefs on side effect attribution was partially mediated by correct recall of side effects. Pharmaceutical schemas are associated with memory for side effect information. Memory may explain part of the association between pharmaceutical schemas and the attribution of unrelated symptoms as side effects.

77 FR 65810 - Airworthiness Directives; Bombardier, Inc. Airplanes

Federal Register 2010, 2011, 2012, 2013, 2014

2012-10-31

... directive (AD) for certain Bombardier, Inc. Model CL-600-2B19 (Regional Jet Series 100 & 440) airplanes. That AD currently requires a one-time inspection of the shafts of the main landing gear (MLG) side... MLG side-brace fitting, and replacing the side-brace fitting shaft with the re-designed side-brace...

Colonic stenting as bridge to surgery versus emergency surgery for management of acute left-sided malignant colonic obstruction: a multicenter randomized trial (Stent-in 2 study)

PubMed Central

van Hooft, Jeanin E; Bemelman, Willem A; Breumelhof, Ronald; Siersema, Peter D; Kruyt, Philip M; van der Linde, Klaas; Veenendaal, Roeland A; Verhulst, Marie-Louise; Marinelli, Andreas W; Gerritsen, Josephus JGM; van Berkel, Anne-Marie; Timmer, Robin; Grubben, Marina JAL; Scholten, Pieter; Geraedts, Alfons AM; Oldenburg, Bas; Sprangers, Mirjam AG; Bossuyt, Patrick MM; Fockens, Paul

2007-01-01

Background Acute left-sided colonic obstruction is most often caused by malignancy and the surgical treatment is associated with a high mortality and morbidity rate. Moreover, these operated patients end up with a temporary or permanent stoma. Initial insertion of an enteral stent to decompress the obstructed colon, allowing for surgery to be performed electively, is gaining popularity. In uncontrolled studies stent placement before elective surgery has been suggested to decrease mortality, morbidity and number of colostomies. However stent perforation can lead to peritoneal tumor spill, changing a potentially curable disease in an incurable one. Therefore it is of paramount importance to compare the outcomes of colonic stenting followed by elective surgery with emergency surgery for the management of acute left-sided malignant colonic obstruction in a randomized multicenter fashion. Methods/design Patients with acute left-sided malignant colonic obstruction eligible for this study will be randomized to either emergency surgery (current standard treatment) or colonic stenting as bridge to elective surgery. Outcome measurements are effectiveness and costs of both strategies. Effectiveness will be evaluated in terms of quality of life, morbidity and mortality. Quality of life will be measured with standardized questionnaires (EORTC QLQ-C30, EORTC QLQ-CR38, EQ-5D and EQ-VAS). Morbidity is defined as every event leading to hospital admission or prolonging hospital stay. Mortality will be analyzed as total mortality as well as procedure-related mortality. The total costs of treatment will be evaluated by counting volumes and calculating unit prices. Including 120 patients on a 1:1 basis will have 80% power to detect an effect size of 0.5 on the EORTC QLQ-C30 global health scale, using a two group t-test with a 0.05 two-sided significance level. Differences in quality of life and morbidity will be analyzed using mixed-models repeated measures analysis of variance. Mortality will be compared using Kaplan-Meier curves and log-rank statistics. Discussion The Stent-in 2 study is a randomized controlled multicenter trial that will provide evidence whether or not colonic stenting as bridge to surgery is to be performed in patients with acute left-sided colonic obstruction. Trial registration Current Controlled Trials ISRCTN46462267. PMID:17608947

The Effect of Hock Injury Laterality and Lameness on Lying Behaviors and Lying Laterality in Holstein Dairy Cows

PubMed Central

Krawczel, Peter D.

2017-01-01

Simple Summary Dairy cattle may experience discomfort in a myriad of ways throughout their life cycle, particularly when sustaining hock injuries or suboptimal locomotion. Lactating dairy cattle divide their lying time equally between left and right sides; however, discomfort experienced during pregnancy or following cannulation can cause a shift in the normal lying laterality. The objective of this study was to determine the effect of hock injuries and lameness on the lying behaviors of dairy cattle, particularly lying laterality. Lying laterality did not differ from the expected 50% (left side lying time) in cattle with hock injuries, lameness, or both. The current results suggest that lying laterality does not differ between varying levels of hock injury or lameness severity. Going forward, further research could determine if lying laterality shifts over the course of the animal developing a hock injury or lameness. Abstract Lactating dairy cattle divide their lying equally between their left side and their right side. However, discomfort, such as pregnancy and cannulation, can cause a cow to shift lying side preference. The objective of this study was to determine the effect of lameness and hock injuries on lying behaviors, particularly lying laterality, of lactating dairy cows. Cows from four commercial farms in eastern Croatia that had lying behavior data, health score data, and production records were used in the study. Health scores including hock injuries and locomotion were collected once per cow. Severely lame cows had greater daily lying time compared to sound cows and moderately lame cows. Overall, cows spent 51.3 ± 1.2% of their daily lying time on the left side. Maximum hock score, locomotion score, hock injury laterality, or parity did not result in lying laterality differing from 50%. PMID:29149044

Inauhzin sensitizes p53-dependent cytotoxicity and tumor suppression of chemotherapeutic agents.

PubMed

Zhang, Yiwei; Zhang, Qi; Zeng, Shelya X; Hao, Qian; Lu, Hua

2013-05-01

Toxicity and chemoresistance are two major issues to hamper the success of current standard tumor chemotherapy. Combined therapy of agents with different mechanisms of action is a feasible and effective means to minimize the side effects and avoid the resistance to chemotherapeutic drugs while improving the antitumor effects. As the most essential tumor suppressor, p53 or its pathway has been an attractive target to develop a new type of molecule-targeting anticancer therapy. Recently, we identified a small molecule, Inauhzin (INZ), which can specifically activate p53 by inducing its deacetylation. In this study, we tested if combination with INZ could sensitize tumor cells to the current chemotherapeutic drugs, cisplatin (CIS) and doxorubicin (DOX). We found that compared with any single treatment, combination of lower doses of INZ and CIS or DOX significantly promoted apoptosis and cell growth inhibition in human non-small lung cancer and colon cancer cell lines in a p53-dependent fashion. This cooperative effect between INZ and CIS on tumor suppression was also confirmed in a xenograft tumor model. Therefore, this study suggests that specifically targeting the p53 pathway could enhance the sensitivity of cancer cells to chemotherapeutic agents and markedly reduce the doses of the chemotherapy, possibly decreasing its adverse side effects.

Informing the introduction of contraceptive implants in the Pacific: a mixed methods study of contraceptive beliefs and behaviours in Tonga.

PubMed

Winn-Dix, Edward A; Nathan, Sally A; Rawstorne, Patrick

2016-04-01

To explore the knowledge and attitudes underlying contraceptive use and non-use among Tongan adults and investigate the potential acceptability of contraceptive implants. A mixed methods study was conducted that used two focus groups and a short self-completed survey (n=109). Participants were recruited from a Tongan non-governmental sexual and reproductive health clinic. Contraceptive method discontinuation was high among the study group, with reasons for discontinuation often relating to misconceptions circulating in the community about the side effects of contraceptives. A high proportion (38%) reported using 'natural' contraceptive methods. A total of 47% of survey participants reported having heard of implants and 37% indicated they would be willing to try them. Current Tongan contraceptive uptake and continuation is hampered by misconceptions about side effects of methods and their risks, particularly among long-acting and reversible methods. Contraceptive implants may be acceptable to Tongans given their arm placement, reversibility and long-lasting effect. Efforts to improve contraceptive continuation in Tonga should focus on improving counselling on potential side effects for all methods. The introduction of contraceptive implants as an additional long-acting reversible method should be considered. © 2015 Public Health Association of Australia.

Psychodermatology: A Guide to Understanding Common Psychocutaneous Disorders

PubMed Central

Jafferany, Mohammad

2007-01-01

Objective: This review focuses on classification and description of and current treatment recommendations for psychocutaneous disorders. Medication side effects of both psychotropic and dermatologic drugs are also considered. Data Sources: A search of the literature from 1951 to 2004 was performed using the MEDLINE search engine. English-language articles were identified using the following search terms: skin and psyche, psychiatry and dermatology, mind and skin, psychocutaneous, and stress and skin. Data Synthesis: The psychotropic agents most frequently used in patients with psychocutaneous disorders are those that target anxiety, depression, and psychosis. Psychiatric side effects of dermatologic drugs can be significant but can occur less frequently than the cutaneous side effects of psychiatric medications. In a majority of patients presenting to dermatologists, effective management of skin conditions requires consideration of associated psychosocial factors. For some dermatologic conditions, there are specific demographic and personality features that commonly associate with disease onset or exacerbation. Conclusions: More than just a cosmetic disfigurement, dermatologic disorders are associated with a variety of psychopathologic problems that can affect the patient, his or her family, and society together. Increased understanding of biopsychosocial approaches and liaison among primary care physicians, psychiatrists, and dermatologists could be very useful and highly beneficial. PMID:17632653

Do the emotional side-effects of hormonal contraceptives come from pharmacologic or psychological mechanisms?

PubMed

Robinson, Stephen A; Dowell, Matt; Pedulla, Dominic; McCauley, Larry

2004-01-01

Hormonal preparations have become one of the most popular methods used for controlling fertility. The literature over the last 40 years continues to reveal how their numerous side effects negatively impact many users and even society at large. Three large cohort trials were the first to demonstrate, on a grand scale, certain emotional and behavioral associations with contraceptive use. Current contraceptive use was associated with an increase rate in depression, divorce, tranquilizer use, sexual dysfunction, and suicide and other violent and accidental deaths. Despite the advent of more "user friendly" contraceptives, the discontinuation rate secondary to side effects has changed little through the years. While in rare cases hormonal preparations can be deadly to the user, there is substantial evidence that their negative effect issues more from their emotional and behavioral properties. This paper reviews the results of over seven studies which further characterize these prominent associations, particularly with hormonal contraception, in an attempt to demonstrate their association with the intrinsic pharmacologic properties of hormonal preparations. Hormonal contraceptive users, in contrast with non users, were found to have higher rates of depression, anxiety, fatigue, neurotic symptoms, sexual disturbances, compulsion, anger, and negative menstrual effects. The question of whether the association of these maladies is directly due to the effect of taking exogenous hormones versus the psychological impact of the contraceptive behavior itself had yet to be studied. Seven small randomized-controlled trials were found in a review of the literature which studied this hypothesis in a direct way. They do not support the origination of these side effects being from the pharmacological properties of hormones. No association was found between hormone levels and emotional functioning in females. Psychiatric evaluations among IUD and oral contraceptive pill (OCP) users reveal no significant differences. Women who were given an OCP placebo experienced a similar side effect profile of OCP users. Different hormonal concentrations and combinations made no significant difference in the side effect profile. A study of women who were given either "weak female hormones" or a placebo failed to duplicate the side effect profile found in all of the other studies where the hormones were labeled as contraceptives. The evidence suggests that most of the side effects of hormonal contraception are a result of a psychological response to the practice of contraception. More study is warranted to further understand this psychological phenomenon, especially now that an effective non-contraceptive method of fertility regulation and more reliable psychological instruments are available. Furthermore, it is reasonable to hypothesize, given the present data, that contraceptive activity itself is inherently damaging to women.

Numerical investigation of flow and heat transfer in a novel configuration multi-tubular fixed bed reactor for propylene to acrolein process

NASA Astrophysics Data System (ADS)

Jiang, Bin; Hao, Li; Zhang, Luhong; Sun, Yongli; Xiao, Xiaoming

2015-01-01

In the present contribution, a numerical study of fluid flow and heat transfer performance in a pilot-scale multi-tubular fixed bed reactor for propylene to acrolein oxidation reaction is presented using computational fluid dynamics (CFD) method. Firstly, a two-dimensional CFD model is developed to simulate flow behaviors, catalytic oxidation reaction, heat and mass transfer adopting porous medium model on tube side to achieve the temperature distribution and investigate the effect of operation parameters on hot spot temperature. Secondly, based on the conclusions of tube-side, a novel configuration multi-tubular fixed-bed reactor comprising 790 tubes design with disk-and-doughnut baffles is proposed by comparing with segmental baffles reactor and their performance of fluid flow and heat transfer is analyzed to ensure the uniformity condition using molten salt as heat carrier medium on shell-side by three-dimensional CFD method. The results reveal that comprehensive performance of the reactor with disk-and-doughnut baffles is better than that of with segmental baffles. Finally, the effects of operating conditions to control the hot spots are investigated. The results show that the flow velocity range about 0.65 m/s is applicable and the co-current cooling system flow direction is better than counter-current flow to control the hottest temperature.

Effect of laryngotracheal topical anesthesia on recurrent laryngeal nerve monitoring during thyroid Surgery.

PubMed

Pachuski, Justin; Vaida, Sonia; Donahue, Kathleen; Roberts, John; Kunselman, Allen; Oberman, Benjamin; Patel, Hetal; Goldenberg, David

2016-03-01

Intraoperative neuromonitoring of the recurrent laryngeal nerve (RLN) is often used as an adjunct for RLN identification and preservation during thyroidectomies. Laryngotracheal anesthesia (LTA) with topical lidocaine reduces coughing upon emergence from anesthesia and in the immediate postoperative period; however, its use is prohibited with concerns that it could decrease the sensitivity of the intraoperative neuromonitoring. We hypothesize that there is no difference in measurements of nerve conduction made before and after LTA administration. An observational study in which all patients were subjected to LTA administration was conducted. Recurrent laryngeal nerve threshold currents were measured before and after the intervention. Tertiary medical center operating room. Eighteen patients (total of 25 nerves at risk) with American Society of Anesthesiologists classes 1 to 3 undergoing thyroid surgery. After the thyroid was removed and threshold currents at the RLN were obtained, LTA with endotracheal lidocaine was applied on the left and right side of the in situ endotracheal tube (2 cc of 4% lidocaine per side). Threshold currents were reassessed at 5 and 10 minutes after LTA administration. Threshold currents (minimum stimulus current applied to the RLN required to generate a discernible electromyographic response at the vocal cords) were recorded along the RLN for a baseline at 5 and 10 mm from the insertion point of the RLN into the larynx. Threshold currents were reassessed at the same 2 positions on the RLN at 5 and 10 minutes after LTA administration. Differences in mean values, between threshold currents recorded at the 3 different times, at 2 positions on the RLN, were used to compare effects of LTA on nerve conduction. There were no statistically significant differences when comparing threshold currents before and after LTA administration. Laryngotracheal anesthesia had no significant effect on RLN nerve conduction in the period assessed. Copyright © 2016 Elsevier Inc. All rights reserved.

49 CFR 563.9 - Data capture.

Code of Federal Regulations, 2013 CFR

2013-10-01

... frontal air bag deployment crash, capture and record the current deployment data. In a side or side curtain/tube air bag deployment crash, where lateral delta-V is recorded by the EDR, capture and record the current deployment data. The memory for the air bag deployment event must be locked to prevent any...

49 CFR 563.9 - Data capture.

Code of Federal Regulations, 2014 CFR

2014-10-01

... frontal air bag deployment crash, capture and record the current deployment data. In a side or side curtain/tube air bag deployment crash, where lateral delta-V is recorded by the EDR, capture and record the current deployment data. The memory for the air bag deployment event must be locked to prevent any...

49 CFR 563.9 - Data capture.

Code of Federal Regulations, 2012 CFR

2012-10-01

... frontal air bag deployment crash, capture and record the current deployment data. In a side or side curtain/tube air bag deployment crash, where lateral delta-V is recorded by the EDR, capture and record the current deployment data. The memory for the air bag deployment event must be locked to prevent any...

Effect of quantum tunneling on spin Hall magnetoresistance

NASA Astrophysics Data System (ADS)

Ok, Seulgi; Chen, Wei; Sigrist, Manfred; Manske, Dirk

2017-02-01

We present a formalism that simultaneously incorporates the effect of quantum tunneling and spin diffusion on the spin Hall magnetoresistance observed in normal metal/ferromagnetic insulator bilayers (such as Pt/Y3Fe5O12) and normal metal/ferromagnetic metal bilayers (such as Pt/Co), in which the angle of magnetization influences the magnetoresistance of the normal metal. In the normal metal side the spin diffusion is known to affect the landscape of the spin accumulation caused by spin Hall effect and subsequently the magnetoresistance, while on the ferromagnet side the quantum tunneling effect is detrimental to the interface spin current which also affects the spin accumulation. The influence of generic material properties such as spin diffusion length, layer thickness, interface coupling, and insulating gap can be quantified in a unified manner, and experiments that reveal the quantum feature of the magnetoresistance are suggested.

Separator plate for a fuel cell

DOEpatents

Petri, R.J.; Meek, J.; Bachta, R.P.; Marianowski, L.G.

1996-04-02

A separator plate is described for a fuel cell comprising an anode current collector, a cathode current collector and a main plate, the main plate disposed between the anode current collector and the cathode current collector. The anode current collector forms a flattened peripheral wet seal structure and manifold wet seal structure on the anode side of the separator plate and the cathode current collector forms a flattened peripheral wet seal structure and manifold wet seal structure on the cathode side of the separator plate. In this manner, the number of components required to manufacture and assemble a fuel cell stack is reduced. 9 figs.

Separator plate for a fuel cell

DOEpatents

Petri, Randy J.; Meek, John; Bachta, Robert P.; Marianowski, Leonard G.

1996-01-01

A separator plate for a fuel cell comprising an anode current collector, a cathode current collector and a main plate, the main plate disposed between the anode current collector and the cathode current collector. The anode current collector forms a flattened peripheral wet seal structure and manifold wet seal structure on the anode side of the separator plate and the cathode current collector forms a flattened peripheral wet seal structure and manifold wet seal structure on the cathode side of the separator plate. In this manner, the number of components required to manufacture and assemble a fuel cell stack is reduced.

Telluric currents: A meeting of theory and observation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Boteler, D.H.; Seager, W.H.

Pipe-to-soil (P/S) potential variations resulting from telluric currents have been observed on pipelines in many locations. However, it has never teen clear which parts of a pipeline will experience the worst effects. Two studies were conducted to answer this question. Distributed-source transmission line (DSTL) theory was applied to the problem of modeling geomagnetic induction in pipelines. This theory predicted that the largest P/S potential variations would occur at the ends of the pipeline. The theory also predicted that large P/S potential variations, of opposite sign, should occur on either side of an insulating flange. Independently, an observation program was conductedmore » to determine the change in telluric current P/S potential variations and to design counteractive measures along a pipeline in northern Canada. Observations showed that the amplitude of P/S potential fluctuations had maxima at the northern and southern ends of the pipeline. A further set of recordings around an insulating flange showed large P/S potential variations, of opposite sign, on either side of the flange. Agreement between the observations and theoretical predictions was remarkable. While the observations confirmed the theory, the theory explains how P/S potential variations are produced by telluric currents and provides the basis for design of cathodic protection systems for pipelines that can counteract any adverse telluric effects.« less

Healthier side dishes at restaurants: an analysis of children’s perspectives, menu content, and energy impacts

PubMed Central

2014-01-01

Background Children consume restaurant-prepared foods at high rates, suggesting that interventions and policies targeting consumption of these foods have the potential to improve diet quality and attenuate excess energy intake. One approach to encouraging healthier dietary intake in restaurants is to offer fruits and vegetables (FV) as side dishes, as opposed to traditional, energy-dense accompaniments like French fries. The aims of the current study were to examine: children's views about healthier side dishes at restaurants; current side dish offerings on children's menus at leading restaurants; and potential energy reductions when substituting FV side dishes in place of French fries. Methods To investigate children’s attitudes, a survey was administered to a nationally representative sample of U.S. 8- to 18-year-olds (n = 1178). To examine current side dish offerings, children's menus from leading quick service (QSR; n = 10) and full service restaurant chains (FSR; n = 10) were analyzed. Energy reductions that could result from substituting commonly-offered FV side dishes for French fries were estimated using nutrition information corresponding to the children's menu items. Results Two-thirds of children reported that they would not feel negatively about receiving FV sides instead of French fries with kids' meals. Liking/taste was the most common reason that children gave to explain their attitudes about FV side dishes. Nearly all restaurants offered at least 1 FV side dish option, but at most restaurants (60% of QSR; 70% of FSR), FV sides were never served by default. Substituting FV side dishes for French fries yielded an average estimated energy reduction of at least 170 calories. Conclusions Results highlight some healthy trends in the restaurant context, including the majority of children reporting non-negative attitudes about FV side dishes and the consistent availability of FV side dish options at leading QSR and FSR. Yet the minority of restaurants offer these FV sides by default. Promoting creative, appealing FV side dishes can result in healthier, less energy-dense meals for children. Substituting or displacing energy-dense default side dishes with such FV dishes show promise as part of continued, comprehensive efforts to increase the healthfulness of meals consumed by children in restaurant settings. PMID:24996545

Imidazenil prevention of alprazolam-induced acquisition deficit in patas monkeys is devoid of tolerance

PubMed Central

Auta, James; Guidotti, Alessandro; Costa, Erminio

2000-01-01

The partial allosteric modulators (PAMs) of γ-aminobutyric acid-gated Cl− current intensities at γ-aminobutyric acid type A receptors have high affinity but low intrinsic efficacy on benzodiazepine recognition sites. Unlike the full allosteric modulators (FAM), like alprazolam, triazolam, and diazepam, PAMs are virtually devoid of unwanted side effects, including tolerance. Imidazenil (IMD) is a PAM that elicits potent anxiolytic and anticonvulsant actions in rodents and nonhuman primates and retains its anticonvulsant and anxiolytic effects, even in rodents that are tolerant to FAMs. IMD antagonizes the side effects of FAMs in rodents and nonhuman primates. Using patas monkeys and a multiple schedule with repeated acquisition and performance of chain responses, we report that IMD administration for 17 days antagonized without showing tolerance ALP-induced disruption of acquisition. PMID:10696114

Drug profile: transdermal rivastigmine patch in the treatment of Alzheimer disease.

PubMed

Emre, Murat; Bernabei, Roberto; Blesa, Rafael; Bullock, Roger; Cunha, Luis; Daniëls, Hugo; Dziadulewicz, Edward; Förstl, Hans; Frölich, Lutz; Gabryelewicz, Tomasz; Levin, Oleg; Lindesay, James; Martínez-Lage, Pablo; Monsch, Andreas; Tsolaki, Magda; van Laar, Teus

2010-08-01

Cholinesterase inhibitors constitute one of the mainstays of treatment of Alzheimer disease (AD). Gastrointestinal side effects, difficulty accessing therapeutic doses and poor patient compliance have been identified as barriers to effective treatment with these substances. The rivastigmine transdermal patch provides continuous delivery of drug through the skin into the bloodstream, avoiding the fluctuations in plasma concentration associated with oral administration. This pharmacokinetic profile is associated with reduced side effects, resulting in easier access to expected target doses. These benefits, along with other practical advantages of the transdermal patch, may contribute to enhanced patient compliance. Here, we present a review of the current literature on rivastigmine patch, and offer advice based on our own collective clinical experience. Rivastigmine patch provides an efficient option for managing patients with AD, to be considered among the first line therapies for the disease.

Strategies to minimize cognitive side effects with ECT: aspects of ECT technique.

PubMed

Prudic, Joan

2008-03-01

The adverse cognitive effects of electroconvulsive therapy are important limitations in the use of this treatment that continues to be a significant therapeutic strategy after 7 decades of use. Among the approaches to mitigation of these side effects are considerations involving the prescription and manipulation of the electrical stimulus itself. The impact of the following electrical factors on the cognitive outcomes of electroconvulsive therapy are surveyed: efficiency of the stimulus as expressed in electrical waveform; targeting of the stimulus, the major concept underlying electrode placement; stimulus dosing; and frequency and number of treatments. The current state of development of knowledge in these areas is summarized, and methods to achieve the best cognitive outcomes without sacrificing clinical efficacy are discussed. Future trends in the further optimization of the electrical stimulus are briefly mentioned.

Tailoring the Employment of Offshore Wind Turbine Support Structure Load Mitigation Controllers

NASA Astrophysics Data System (ADS)

Shrestha, Binita; Kühn, Martin

2016-09-01

The currently available control concepts to mitigate aerodynamic and hydrodynamic induced support structure loads reduce either fore-aft or side-to-side damage under certain operational conditions. The load reduction is achieved together with an increase in loads in other components of the turbine e.g. pitch actuators or drive train, increasing the risk of unscheduled maintenance. The main objective of this paper is to demonstrate a methodology for reduction of support structure damage equivalent loads (DEL) in fore-aft and side-to-side directions using already available control concepts. A multi-objective optimization problem is formulated to minimize the DELs, while limiting the collateral effects of the control algorithms for load reduction. The optimization gives trigger values of sea state condition for the activation or deactivation of certain control concepts. As a result, by accepting the consumption of a small fraction of the load reserve in the design load envelope of other turbine components, a considerable reduction of the support structure loads is facilitated.

Skyrmion based universal memory operated by electric current

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zang, Jiadong; Chien, Chia-Ling; Li, Yufan

2017-09-26

A method for generating a skyrmion, comprising: depositing a vertical metallic nanopillar electrode on a first side of a helimagnetic thin film, the helimagnetic thin film having a contact on a second side to provide a current drain; injecting a current through the vertical metallic nanopillar electrode to generate a rotating field; and applying a static upward magnetic field perpendicular to the helimagnetic thin film to maintain an FM phase background.

Integrated main rail, feed rail, and current collector

DOEpatents

Petri, R.J.; Meek, J.; Bachta, R.P.; Marianowski, L.G.

1994-11-08

A separator plate is described for a fuel cell comprising an anode current collector, a cathode current collector and a main plate, the main plate disposed between the anode current collector and the cathode current collector. The anode current collector forms a flattened peripheral wet seal structure and manifold wet seal structure on the anode side of the separator plate and the cathode current collector forms a flattened peripheral wet seal structure and manifold wet seal structure on the cathode side of the separator plate. In this manner, the number of components required to manufacture and assemble a fuel cell stack is reduced. 9 figs.

A rugged 650 V SOI-based high-voltage half-bridge IGBT gate driver IC for motor drive applications

NASA Astrophysics Data System (ADS)

Hua, Qing; Li, Zehong; Zhang, Bo; Chen, Weizhong; Huang, Xiangjun; Feng, Yuxiang

2015-05-01

This paper proposes a rugged high-voltage N-channel insulated gate bipolar transistor (IGBT) gate driver integrated circuit. The device integrates a high-side and a low-side output stages on a single chip, which is designed specifically for motor drive applications. High-voltage level shift technology enables the high-side stage of this device to operate up to 650 V. The logic inputs are complementary metal oxide semiconductor (CMOS)/transistor transistor logic compatible down to 3.3 V. Undervoltage protection functionality with hysteresis characteristic has also been integrated to enhance the device reliability. The device is fabricated in a 1.0 μm, 650 V high-voltage bipolar CMOS double-diffused metal oxide semiconductor (BCD) on silicon-on-insulator (SOI) process. Deep trench dielectric isolation technology is employed to provide complete electrical isolation with advantages such as reduced parasitic effects, excellent noise immunity and low leakage current. Experimental results show that the isolation voltage of this device can be up to approximately 779 V at 25°C, and the leakage current is only 5 nA at 650 V, which is 15% higher and 67% lower than the conventional ones. In addition, it delivers an excellent thermal stability and needs very low quiescent current and offers a high gate driver capability which is needed to adequately drive IGBTs that have large input capacitances.

Anodal transcranial direct current stimulation over the right hemisphere improves auditory comprehension in a case of dementia.

PubMed

Costa, Vanessa; Brighina, Filippo; Piccoli, Tommaso; Realmuto, Sabrina; Fierro, Brigida

2017-01-01

Noninvasive transcranial stimulation methods have been increasingly employed in order to improve cognitive performance in neurological patients. In previous studies with both stroke patients and healthy subjects, noninvasive stimulation of temporal-parietal regions and their homologue produced an improvement in linguistic tasks. The aim of the current study was to evaluate if anodal transcranial direct current stimulation (tDCS) over Brodmann areas 39/40 (angular and supramarginal gyri) could promote the recovery of linguistic functions, in particular comprehension and naming, in a single patient affected by dementia. Three preliminary explorative single sessions (right-side anodal, left-side anodal and sham tDCS) were carried out (Experiment 1). This procedure allows targeting the more effective site of stimulation for the treatment. Subsequently, we carried out a five-days tDCS treatment on the selected hemisphere (Experiment 2). We report verb comprehension amelioration after 5 days of anodal tDCS over the right BAs 39/40 compared with the placebo tDCS. This result is maintained until two weeks after the end of the 5-days treatment. Our findings provide new evidence for the therapeutic use of tDCS in degenerative diseases, suggesting that an explorative study can be useful for targeting the more appropriate stimulation site, and confirm the involvement of right-sided areas associated with language activities.

Lipid-Based Drug Delivery Systems in Cancer Therapy: What Is Available and What Is Yet to Come

PubMed Central

Yingchoncharoen, Phatsapong; Kalinowski, Danuta S.

2016-01-01

Cancer is a leading cause of death in many countries around the world. However, the efficacy of current standard treatments for a variety of cancers is suboptimal. First, most cancer treatments lack specificity, meaning that these treatments affect both cancer cells and their normal counterparts. Second, many anticancer agents are highly toxic, and thus, limit their use in treatment. Third, a number of cytotoxic chemotherapeutics are highly hydrophobic, which limits their utility in cancer therapy. Finally, many chemotherapeutic agents exhibit short half-lives that curtail their efficacy. As a result of these deficiencies, many current treatments lead to side effects, noncompliance, and patient inconvenience due to difficulties in administration. However, the application of nanotechnology has led to the development of effective nanosized drug delivery systems known commonly as nanoparticles. Among these delivery systems, lipid-based nanoparticles, particularly liposomes, have shown to be quite effective at exhibiting the ability to: 1) improve the selectivity of cancer chemotherapeutic agents; 2) lower the cytotoxicity of anticancer drugs to normal tissues, and thus, reduce their toxic side effects; 3) increase the solubility of hydrophobic drugs; and 4) offer a prolonged and controlled release of agents. This review will discuss the current state of lipid-based nanoparticle research, including the development of liposomes for cancer therapy, different strategies for tumor targeting, liposomal formulation of various anticancer drugs that are commercially available, recent progress in liposome technology for the treatment of cancer, and the next generation of lipid-based nanoparticles. PMID:27363439

Impact of adherence on the outcome of antiviral therapy for chronic hepatitis C.

PubMed

Mulhall, Brian P; Younossi, Zobair

2005-01-01

Nearly 4 million people in the United States have evidence of hepatitis C infection (HCV), representing a significant cause of cirrhosis and liver cancer as well a major burden to our healthcare systems and society. Antiviral therapy can successfully eradicate HCV over the long term, potentially reducing the risk of progression and improving patients' quality of life. The currently preferred HCV treatment is a combination of pegylated interferon alfa and ribavirin, which can achieve an overall sustained viral eradication rate of 55%. The duration of this treatment is typically determined by HCV genotype and the patient's early virologic response to the antiviral regimen. Evidence has accumulated over the past few years to indicate that close adherence to the optimal antiviral regimen can enhance sustained virologic response. But optimal treatment outcomes require diligence and careful management of side effects related to combination therapy. Although reducing the dose of pegylated interferon alfa, ribavirin, or both can effectively treat side effects, suboptimal doses of this regimen, especially ribavirin, may negatively affect virologic response. An alternative strategy is to use growth factors to treat cytopenias. This strategy can obviate dose reductions while potentially improving patients' quality of life. Patient support seems especially important early after the initiation of antiviral therapy. Encouraging study findings involving the growth factors, epoetin alfa and darbepoetin alfa, suggest improved anemia and quality of life while maintaining the optimal ribavirin dose. Future work should be aimed at providing stronger evidence for the use of these "supportive products" during anti-HCV therapy. As we strive to develop better treatment options for our HCV patients, the importance of adhering to the treatment regimen continues to play a central role. Effective side effect management is crucial for the success of this treatment because adherence is negatively affected by side effects related to the antiviral regimen. By identifying and addressing the important side effects of combination therapy for HCV, adherence to treatment can be improved and optimal outcomes can be achieved.

Sea-floor observations in the tongue of the ocean, Bahamas: An Argo/SeaMARC survey

USGS Publications Warehouse

Schwab, W.C.; Uchupi, E.; Ballard, Richard D.; Dettweiler, T.K.

1989-01-01

SeaMARC side-scan sonographs and Argo video and photographic data suggest that the recent sedimentary environment of the floor of the Tongue of the Ocean is controlled by an interplay of turbidity current flow from the south, sediment spill-over from the carbonate platform to the east (windward side), and rock falls from the west carbonate escarpment (lee side). The spill-over forms a sandy sedimentary deposit that acts as a topographic obstruction to the turbidity current flow from the south. This obstruction is expressed by the westward migration of a northwest-southeast oriented turbidity-current-cut channel. ?? 1989 Springer-Verlag New York Inc.

Pharmacotherapy for chronic non-specific low back pain: current and future options.

PubMed

Koes, Bart W; Backes, Daan; Bindels, Patrick J E

2018-04-01

Low back pain is associated with a large burden-of-illness. It is responsible for the most years lived with disability as compared with any other medical condition. A comprehensive overview of the evidence on pharmacological treatment options for chronic low back pain is lacking. This review evaluates the evidence for the benefits and risks of currently available pharmacological treatments for chronic low back pain. Areas covered: The authors focus on the recent (Cochrane) systematic reviews and meta-analyses of randomized clinical trials covering paracetamol (acetaminophen), NSAIDs, muscle relaxants, antidepressants, anticonvulsants, opioids, and other (new) drugs. Expert opinion: The overall impression of the efficacy of pharmacological treatments for patients with chronic low back pain is rather sobering. The effects on pain reduction and improvement of function are commonly small to moderate and short lasting when compared to placebo. At the same time, the various types of drugs are not without side-effects. This holds especially true for serious side-effects associated with (prolonged) use of strong opioids. Future studies on patients with chronic back pain should aim to identify subgroups of patients with good response to specific pharmacological treatment to facilitate personalized care.

Dual-gate operation and carrier transport in SiGe p–n junction nanowires

DOE PAGES

Delker, Collin James; Yoo, Jink Young; Bussmann, Ezra; ...

2017-10-23

Here, we investigate carrier transport in silicon–germanium nanowires with an axial p–n junction doping profile by fabricating these wires into transistors that feature separate top gates over each doping segment. By independently biasing each gate, carrier concentrations in the n- and p-side of the wire can be modulated. For these devices, which were fabricated with nickel source–drain electrical contacts, holes are the dominant charge carrier, with more favorable hole injection occurring on the p-side contact. Channel current exhibits greater sensitivity to the n-side gate, and in the reverse biased source–drain configuration, current is limited by the nickel/n-side Schottky contact.

Novel technique of source and drain engineering for dual-material double-gate (DMDG) SOI MOSFETS

NASA Astrophysics Data System (ADS)

Yadav, Himanshu; Malviya, Abhishek Kumar; Chauhan, R. K.

2018-04-01

The dual-metal dual-gate (DMDG) SOI has been used with Dual Sided Source and Drain Engineered 50nm SOI MOSFET with various high-k gate oxide. It has been scrutinized in this work to enhance its electrical performance. The proposed structure is designed by creating Dual Sided Source and Drain Modification and its characteristics are evaluated on ATLAS device simulator. The consequence of this dual sided assorted doping on source and drain side of the DMDG transistor has better leakage current immunity and heightened ION current with higher ION to IOFF Ratio. Which thereby vesting the proposed device appropriate for low power digital applications.

Dual-gate operation and carrier transport in SiGe p-n junction nanowires

NASA Astrophysics Data System (ADS)

Delker, C. J.; Yoo, J. Y.; Bussmann, E.; Swartzentruber, B. S.; Harris, C. T.

2017-11-01

We investigate carrier transport in silicon-germanium nanowires with an axial p-n junction doping profile by fabricating these wires into transistors that feature separate top gates over each doping segment. By independently biasing each gate, carrier concentrations in the n- and p-side of the wire can be modulated. For these devices, which were fabricated with nickel source-drain electrical contacts, holes are the dominant charge carrier, with more favorable hole injection occurring on the p-side contact. Channel current exhibits greater sensitivity to the n-side gate, and in the reverse biased source-drain configuration, current is limited by the nickel/n-side Schottky contact.

Dual-gate operation and carrier transport in SiGe p–n junction nanowires

DOE Office of Scientific and Technical Information (OSTI.GOV)

Delker, Collin James; Yoo, Jink Young; Bussmann, Ezra

Here, we investigate carrier transport in silicon–germanium nanowires with an axial p–n junction doping profile by fabricating these wires into transistors that feature separate top gates over each doping segment. By independently biasing each gate, carrier concentrations in the n- and p-side of the wire can be modulated. For these devices, which were fabricated with nickel source–drain electrical contacts, holes are the dominant charge carrier, with more favorable hole injection occurring on the p-side contact. Channel current exhibits greater sensitivity to the n-side gate, and in the reverse biased source–drain configuration, current is limited by the nickel/n-side Schottky contact.

A unified frame of predicting side effects of drugs by using linear neighborhood similarity.

PubMed

Zhang, Wen; Yue, Xiang; Liu, Feng; Chen, Yanlin; Tu, Shikui; Zhang, Xining

2017-12-14

Drug side effects are one of main concerns in the drug discovery, which gains wide attentions. Investigating drug side effects is of great importance, and the computational prediction can help to guide wet experiments. As far as we known, a great number of computational methods have been proposed for the side effect predictions. The assumption that similar drugs may induce same side effects is usually employed for modeling, and how to calculate the drug-drug similarity is critical in the side effect predictions. In this paper, we present a novel measure of drug-drug similarity named "linear neighborhood similarity", which is calculated in a drug feature space by exploring linear neighborhood relationship. Then, we transfer the similarity from the feature space into the side effect space, and predict drug side effects by propagating known side effect information through a similarity-based graph. Under a unified frame based on the linear neighborhood similarity, we propose method "LNSM" and its extension "LNSM-SMI" to predict side effects of new drugs, and propose the method "LNSM-MSE" to predict unobserved side effect of approved drugs. We evaluate the performances of LNSM and LNSM-SMI in predicting side effects of new drugs, and evaluate the performances of LNSM-MSE in predicting missing side effects of approved drugs. The results demonstrate that the linear neighborhood similarity can improve the performances of side effect prediction, and the linear neighborhood similarity-based methods can outperform existing side effect prediction methods. More importantly, the proposed methods can predict side effects of new drugs as well as unobserved side effects of approved drugs under a unified frame.

Drug side effect extraction from clinical narratives of psychiatry and psychology patients

PubMed Central

Kocher, Jean-Pierre A; Chute, Christopher G; Savova, Guergana K

2011-01-01

Objective To extract physician-asserted drug side effects from electronic medical record clinical narratives. Materials and methods Pattern matching rules were manually developed through examining keywords and expression patterns of side effects to discover an individual side effect and causative drug relationship. A combination of machine learning (C4.5) using side effect keyword features and pattern matching rules was used to extract sentences that contain side effect and causative drug pairs, enabling the system to discover most side effect occurrences. Our system was implemented as a module within the clinical Text Analysis and Knowledge Extraction System. Results The system was tested in the domain of psychiatry and psychology. The rule-based system extracting side effects and causative drugs produced an F score of 0.80 (0.55 excluding allergy section). The hybrid system identifying side effect sentences had an F score of 0.75 (0.56 excluding allergy section) but covered more side effect and causative drug pairs than individual side effect extraction. Discussion The rule-based system was able to identify most side effects expressed by clear indication words. More sophisticated semantic processing is required to handle complex side effect descriptions in the narrative. We demonstrated that our system can be trained to identify sentences with complex side effect descriptions that can be submitted to a human expert for further abstraction. Conclusion Our system was able to extract most physician-asserted drug side effects. It can be used in either an automated mode for side effect extraction or semi-automated mode to identify side effect sentences that can significantly simplify abstraction by a human expert. PMID:21946242

What matters when judging intentionality-moral content or normative status? Testing the rational scientist model of the side-effect.

PubMed

Papadopoulos, C; Hayes, B K

2018-06-01

Previous work has demonstrated a "side-effect effect," such that intentionality is more likely to be attributed to agents who bring about negatively valenced as opposed to positively valenced side effects. The rational-scientist model explains this by suggesting that norm-violating side effects are more informative for inferring intentionality than norm-conforming side effects. In the present study we reexamined this account, addressing limitations of previous empirical tests (e.g., Uttich & Lombrozo, Cognition 116: 87-100, 2010). Side-effect valence and norm status were manipulated factorially, enabling an examination of the impact of norm status on intentionality judgments in both positively and negatively valenced side effects. Additionally, the impact of side-effect norm status on the perceived valences of side effects and agents was examined. Effects of norm status were found for both positive and negative side effects. Violation of an ostensibly neutral norm led to negative perceptions of the side effect. However, a norm status effect on intentionality judgments persisted when these effects were controlled. These results support the view that the side-effect effect is the result of the rational use of social-cognitive evidence.

A theoretical study of topographic effects on coastal upwelling and cross-shore exchange

NASA Astrophysics Data System (ADS)

Song, Y. Tony; Chao, Yi

The effects of topographic variations on coastal upwelling and cross-shore exchange are examined with a theoretical, continuously stratified, three-dimensional coastal ocean model. The model takes into account topographic variations in both alongshore and cross-shore directions and allows analytical solutions with an Ekman surface layer that faithfully represents the physical nature of the coastal upwelling system. Theoretical solutions with any analytical form of alongshore-varying topography can be solved based on the perturbation method of Killworth [J. Phys. Oceanogr. 8 (1978) 188]. Analyses of the model solutions lead to the following conclusions: The variation of upwelling fronts and currents is shown to be caused by the combined effect of topography and stratification. Topographic variation causes uneven upwelling distribution and leads to density variation, which results in a varying horizontal pressure gradient field that causes the meandering currents. The variation index is dependent upon a bilinear function of their physical parameters--the ratio of the topographic variation depth to the total depth and Burger's number of stratification. Cross-shore slope is found to play a role in maintaining the meandering structure of the alongshore currents. The anticyclonic circulations can further induce downwelling on the offshore side of the current, while the cyclonic circulations enhance upwelling and form upwelling centers on the inshore side of the current. Alongshore topography does not change the total upwelled water, i.e., the total Ekman pumping is conserved. However, it increases cross-exchange of water masses by transporting inshore (offshore) water near topographic features far offshore (inshore) from the mean position of the front. The applicability and limitations of the theory are also discussed.

Generation of large scale GHZ states with the interactions of photons and quantum-dot spins

NASA Astrophysics Data System (ADS)

Miao, Chun; Fang, Shu-Dong; Dong, Ping; Yang, Ming; Cao, Zhuo-Liang

2018-03-01

We present a deterministic scheme for generating large scale GHZ states in a cavity-quantum dot system. A singly charged quantum dot is embedded in a double-sided optical microcavity with partially reflective top and bottom mirrors. The GHZ-type Bell spin state can be created and two n-spin GHZ states can be perfectly fused to a 2n-spin GHZ state with the help of n ancilla single-photon pulses. The implementation of the current scheme only depends on the photon detection and its need not to operate multi-qubit gates and multi-qubit measurements. Discussions about the effect of the cavity loss, side leakage and exciton cavity coupling strength for the fidelity of generated states show that the fidelity can remain high enough by controlling system parameters. So the current scheme is simple and feasible in experiment.

Arc fault detection system

DOEpatents

Jha, Kamal N.

1999-01-01

An arc fault detection system for use on ungrounded or high-resistance-grounded power distribution systems is provided which can be retrofitted outside electrical switchboard circuits having limited space constraints. The system includes a differential current relay that senses a current differential between current flowing from secondary windings located in a current transformer coupled to a power supply side of a switchboard, and a total current induced in secondary windings coupled to a load side of the switchboard. When such a current differential is experienced, a current travels through a operating coil of the differential current relay, which in turn opens an upstream circuit breaker located between the switchboard and a power supply to remove the supply of power to the switchboard.

Blockade of HERG human K+ channels and IKr of guinea-pig cardiomyocytes by the antipsychotic drug clozapine.

PubMed

Lee, So-Young; Kim, Young-Jin; Kim, Kyong-Tai; Choe, Han; Jo, Su-Hyun

2006-06-01

Clozapine, a commonly used antipsychotic drug, can induce QT prolongation, which may lead to torsades de pointes and sudden death. To investigate the arrhythmogenic side effects of clozapine, we studied the impact of clozapine on human ether-a-go-go-related gene (HERG) channels expressed in Xenopus oocytes and HEK293 cells, and on the delayed rectifier K(+) currents of guinea-pig cardiomyocytes. Clozapine dose-dependently decreased the amplitudes of the currents at the end of voltage steps, and the tail currents of HERG. The IC(50) for the clozapine blockade of HERG currents in Xenopus oocytes progressively decreased relative to depolarization (39.9 microM at -40 mV, 28.3 microM at 0 mV and 22.9 microM at +40 mV), whereas the IC(50) for the clozapine-induced blockade of HERG currents in HEK293 cells at 36 degrees C was 2.5 microM at +20 mV. The clozapine-induced blockade of HERG currents was time dependent: the fractional current was 0.903 of the control at the beginning of the pulse, but declined to 0.412 after 4 s at a test potential of 0 mV. The clozapine-induced blockade of HERG currents was use-dependent, exhibiting more rapid onset and greater steady state blockade at higher frequencies of activation, with a partial relief of blockade observed when the frequency of activation was decreased. In guinea-pig ventricular myocytes held at 36 degrees C, treatment with 1 and 5 microM clozapine blocked the rapidly activating delayed rectifier K(+) current (I(Kr)) by 24.7 and 79.6%, respectively, but did not significantly block the slowly activating delayed rectifier K(+) current (I(Ks)). Our findings collectively suggest that blockade of HERG currents and I(Kr), but not I(Ks), may contribute to the arrhythmogenic side effects of clozapine.

Blockade of HERG human K+ channels and IKr of guinea-pig cardiomyocytes by the antipsychotic drug clozapine

PubMed Central

Lee, So-Young; Kim, Young-Jin; Kim, Kyong-Tai; Choe, Han; Jo, Su-Hyun

2006-01-01

Clozapine, a commonly used antipsychotic drug, can induce QT prolongation, which may lead to torsades de pointes and sudden death. To investigate the arrhythmogenic side effects of clozapine, we studied the impact of clozapine on human ether-a-go-go-related gene (HERG) channels expressed in Xenopus oocytes and HEK293 cells, and on the delayed rectifier K+ currents of guinea-pig cardiomyocytes. Clozapine dose-dependently decreased the amplitudes of the currents at the end of voltage steps, and the tail currents of HERG. The IC50 for the clozapine blockade of HERG currents in Xenopus oocytes progressively decreased relative to depolarization (39.9 μM at −40 mV, 28.3 μM at 0 mV and 22.9 μM at +40 mV), whereas the IC50 for the clozapine-induced blockade of HERG currents in HEK293 cells at 36°C was 2.5 μM at +20 mV. The clozapine-induced blockade of HERG currents was time dependent: the fractional current was 0.903 of the control at the beginning of the pulse, but declined to 0.412 after 4 s at a test potential of 0 mV. The clozapine-induced blockade of HERG currents was use-dependent, exhibiting more rapid onset and greater steady state blockade at higher frequencies of activation, with a partial relief of blockade observed when the frequency of activation was decreased. In guinea-pig ventricular myocytes held at 36°C, treatment with 1 and 5 μM clozapine blocked the rapidly activating delayed rectifier K+ current (IKr) by 24.7 and 79.6%, respectively, but did not significantly block the slowly activating delayed rectifier K+ current (IKs). Our findings collectively suggest that blockade of HERG currents and IKr, but not IKs, may contribute to the arrhythmogenic side effects of clozapine. PMID:16633353

Incidence and severity of self-reported chemotherapy side effects in routine care: A prospective cohort study

PubMed Central

Haas, Marion; Viney, Rosalie; Pearson, Sallie-Anne; Haywood, Philip; Brown, Chris; Ward, Robyn

2017-01-01

Aim Chemotherapy side effects are often reported in clinical trials; however, there is little evidence about their incidence in routine clinical care. The objective of this study was to describe the frequency and severity of patient-reported chemotherapy side effects in routine care across treatment centres in Australia. Methods We conducted a prospective cohort study of individuals with breast, lung or colorectal cancer undergoing chemotherapy. Side effects were identified by patient self-report. The frequency, prevalence and incidence rates of side effects were calculated by cancer type and grade, and cumulative incidence curves for each side effect computed. Frequencies of side effects were compared between demographic subgroups using chi-squared statistics. Results Side effect data were available for 449 eligible individuals, who had a median follow-up of 5.64 months. 86% of participants reported at least one side effect during the study period and 27% reported a grade IV side effect, most commonly fatigue or dyspnoea. Fatigue was the most common side effect overall (85%), followed by diarrhoea (74%) and constipation (74%). Prevalence and incidence rates were similar across side effects and cancer types. Age was the only demographic factor associated with the incidence of side effects, with older people less likely to report side effects. Conclusion This research has produced the first Australian estimates of self-reported incidence of chemotherapy side effects in routine clinical care. Chemotherapy side effects in routine care are common, continue throughout chemotherapy and can be serious. This work confirms the importance of observational data in providing clinical practice-relevant information to decision-makers. PMID:29016607

Incidence and severity of self-reported chemotherapy side effects in routine care: A prospective cohort study.

PubMed

Pearce, Alison; Haas, Marion; Viney, Rosalie; Pearson, Sallie-Anne; Haywood, Philip; Brown, Chris; Ward, Robyn

2017-01-01

Chemotherapy side effects are often reported in clinical trials; however, there is little evidence about their incidence in routine clinical care. The objective of this study was to describe the frequency and severity of patient-reported chemotherapy side effects in routine care across treatment centres in Australia. We conducted a prospective cohort study of individuals with breast, lung or colorectal cancer undergoing chemotherapy. Side effects were identified by patient self-report. The frequency, prevalence and incidence rates of side effects were calculated by cancer type and grade, and cumulative incidence curves for each side effect computed. Frequencies of side effects were compared between demographic subgroups using chi-squared statistics. Side effect data were available for 449 eligible individuals, who had a median follow-up of 5.64 months. 86% of participants reported at least one side effect during the study period and 27% reported a grade IV side effect, most commonly fatigue or dyspnoea. Fatigue was the most common side effect overall (85%), followed by diarrhoea (74%) and constipation (74%). Prevalence and incidence rates were similar across side effects and cancer types. Age was the only demographic factor associated with the incidence of side effects, with older people less likely to report side effects. This research has produced the first Australian estimates of self-reported incidence of chemotherapy side effects in routine clinical care. Chemotherapy side effects in routine care are common, continue throughout chemotherapy and can be serious. This work confirms the importance of observational data in providing clinical practice-relevant information to decision-makers.

Intrusiveness of Behavioral Treatments for Children with Autism and Developmental Disabilities: An Initial Investigation

ERIC Educational Resources Information Center

Mayton, Michael R.; Carter, Stacy L.; Zhang, Jie; Wheeler, John J.

2014-01-01

The behaviors frequently displayed by students with autism can place them at risk for overly reactive behavior interventions with unwanted side effects. The current study examined the level of intrusiveness of behavioral treatments developed for 198 students with disabilities from 13 different states. Results demonstrated that students diagnosed…

[Use of methylphenidate in palliative patients with asthenia: a review].

PubMed

Saralegui, A; Palacio, P; Royo, P

2013-09-06

Asthenia (or fatigue) is one of the most common symptoms in palliative patients. Methylphenidate is currently being assessed for treating this condition. A review of related literature published to date was performed, revealing methylphenidate to be a safe drug which could decrease fatigue in palliative patients with a tolerable side-effects profile.

Novel angiogenesis inhibitory activity in cinnamon extract blocks VEGFR2 kinase and downstream signaling

USDA-ARS?s Scientific Manuscript database

VEGF is one of the most critical factors that induce angiogenesis, and has thus become an attractive target for anti-angiogenesis treatment. However, most of the current anti-VEGF agents that often cause side effects cannot be recommended for long term use. Identification of natural VEGF inhibitors...

[Current guidelines for prevention and management of chemotherapy extravasation].

PubMed

Bahyrycz, Jan; Pityński, Kazimierz; Ludwin, Artur; Ludwin, Inga; Gawlik, Małgorzata

2012-01-01

Cytostatic drugs extravasation is the serious side effect of chemotherapy. It may lead to health-threatening complications as well as to impairment of cancer patients quality of life. Prevention, early diagnosis and appropriate treatment significantly reduce the consequences of extravasation. Training of medical staff and patients education have enormous importance on this point.

Effect of potassium fertilizer application on the yield and quality of current sugarcane varieties in Louisiana

USDA-ARS?s Scientific Manuscript database

For many sugarcane producers in Louisiana the only fertilizer that is routinely applied to their crop is nitrogen that is side-dressed in the spring. This is due, primarily to the high cost of potassium and phosphorus fertilizers. Recent cooperative research conducted between the USDA/ARS Sugarcane ...

Psychotropic Drug Use among College Students: Patterns of Use, Misuse, and Medical Monitoring

ERIC Educational Resources Information Center

Oberleitner, Lindsay M. S.; Tzilos, Golfo K.; Zumberg, Kathryn M.; Grekin, Emily R.

2011-01-01

Objective: To assess whether college students who use psychotropic drugs are (1) aware of potential side effects, (2) appropriately monitored by prescribing physicians, and (3) taking medications as prescribed. Participants: Fifty-five college students, currently taking psychotropic medications, were recruited between Summer 2008 and Fall 2009.…

The Influence of Staff Training on Challenging Behaviour in Individuals with Intellectual Disability: A Review

ERIC Educational Resources Information Center

Cox, Alison D.; Dube, Charmayne; Temple, Beverley

2015-01-01

Many individuals with intellectual disability engage in challenging behaviour. This can significantly limit quality of life and also negatively impact caregivers (e.g., direct care staff, family caregivers and teachers). Fortunately, efficacious staff training may alleviate some negative side effects of client challenging behaviour. Currently, a…

Medical Systemic Therapies for Hepatocellular Carcinoma: Clinical Perspectives and Safety Profile.

PubMed

Facciorusso, Antonio; Antonino, Matteo; Del Prete, Valentina; Amoruso, Annabianca; Neve, Viviana; Barone, Michele

2015-01-01

A multidisciplinary approach based on clinical expertise and knowledge of molecular processes involved in hepatocarcinogenesis is needed for the proper management of hepatocellular carcinoma (HCC) patients. Such information must be considered in the context of pathobiology of the underlying liver disease. New drugs targeting specific molecular steps in pathways involved in HCC growth and development bear the promise to radically modify the pharmacological therapies currently in use in hepatooncology. Sorafenib was the first drug approved in the setting of advanced HCC, but although it produces some improvement in survival, the responses are not durable. In addition, there are significant side effects. Other angiogenesis inhibitors are in development to treat HCC both in the first-line setting and after progression following sorafenib failure; among them, tivantinib, an inhibitor of cMET receptor, showed interesting results in a recent phase-II study. Additional agents currently studied for the treatment of HCC patients are briefly examined in this review. Aim of this paper is to discuss the state of the art in the management of advanced HCC patients, with a particular interest for the description of their side effects.

Arcjet nozzle area ratio effects

NASA Technical Reports Server (NTRS)

Curran, Francis M.; Sarmiento, Charles J.; Birkner, Bjorn W.; Kwasny, James

1990-01-01

An experimental investigation was conducted to determine the effect of nozzle area ratio on the operating characteristics and performance of a low power dc arcjet thruster. Conical thoriated tungsten nozzle inserts were tested in a modular laboratory arcjet thruster run on hydrogen/nitrogen mixtures simulating the decomposition products of hydrazine. The converging and diverging sides of the inserts had half angles of 30 and 20 degrees, respectively, similar to a flight type unit currently under development. The length of the diverging side was varied to change the area ratio. The nozzle inserts were run over a wide range of specific power. Current, voltage, mass flow rate, and thrust were monitored to provide accurate comparisons between tests. While small differences in performance were observed between the two nozzle inserts, it was determined that for each nozzle insert, arcjet performance improved with increasing nozzle area ratio to the highest area ratio tested and that the losses become very pronounced for area ratios below 50. These trends are somewhat different than those obtained in previous experimental and analytical studies of low Re number nozzles. It appears that arcjet performance can be enhanced via area ratio optimization.

Arcjet Nozzle Area Ratio Effects

NASA Technical Reports Server (NTRS)

Curran, Francis M.; Sarmiento, Charles J.; Birkner, Bjorn W.; Kwasny, James

1990-01-01

An experimental investigation was conducted to determine the effect of nozzle area ratio on the operating characteristics and performance of a low power dc arcjet thruster. Conical thoriated tungsten nozzle inserts were tested in a modular laboratory arcjet thruster run on hydrogen/nitrogen mixtures simulating the decomposition products of hydrazine. The converging and diverging sides of the inserts had half angles of 30 and 20 degrees, respectively, similar to a flight type unit currently under development. The length of the diverging side was varied to change the area ratio. The nozzle inserts were run over a wide range of specific power. Current, voltage, mass flow rate, and thrust were monitored to provide accurate comparisons between tests. While small differences in performance were observed between the two nozzle inserts, it was determined that for each nozzle insert, arcjet performance improved with increasing nozzle area ratio to the highest area ratio tested and that the losses become very pronounced for area ratios below 50. These trends are somewhat different than those obtained in previous experimental and analytical studies of low Re number nozzles. It appears that arcjet performance can be enhanced via area ratio optimization.

Validation of accelerated ageing of Thales rotary Stirling cryocoolers for the estimation of MTTF

NASA Astrophysics Data System (ADS)

Seguineau, C.,; Cauquil, J.-M.; Martin, J.-Y.; Benschop, T.

2016-05-01

The cooled IR detectors are used in a wide range of applications. Most of the time, the cryocoolers are one of the components dimensioning the lifetime of the system. The current market needs tend to reliability figures higher than 15,000hrs in "standard conditions". Field returns are hardly useable mostly because of the uncertain environmental conditions of use, or the differences in user profiles. A previous paper explains how Thales Cryogenics has developed an approach based on accelerated ageing and statistical analysis [1]. The aim of the current paper is to compare results obtained on accelerated ageing on one side, and on the other side, specific field returns where the conditions of use are well known. The comparison between prediction and effective failure rate is discussed. Moreover, a specific focus is done on how some new applications of cryocoolers (continuous operation at a specific temperature) can increase the MTTF. Some assumptions are also exposed on how the failure modes, effects and criticality analysis evolves for continuous operation at a specific temperature and compared to experimental data.

The Effects of Self-Discharge on the Performance of Symmetric Electric Double-Layer Capacitors and Active Electrolyte-Enhanced Supercapacitors: Insights from Modeling and Simulation

NASA Astrophysics Data System (ADS)

Ike, Innocent S.; Sigalas, Iakovos; Iyuke, Sunny E.

2017-02-01

The effects of self-discharge on the performance of symmetric electric double-layer capacitors (EDLCs) and active electrolyte-enhanced supercapacitors were examined by incorporating self-discharge into electrochemical capacitor models during charging and discharging. The sources of self-discharge in capacitors were side reactions or redox reactions and several impurities and electric double-layer (EDL) instability. The effects of self-discharge during capacitor storage was negligible since it took a fully charged capacitor a minimum of 14.0 days to be entirely discharged by self-discharge in all conditions studied, hence self-discharge in storage condition can be ignored. The first and second charge-discharge cycle energy efficiencies η_{{{{E}}1}} and η_{{{{E}}2}} of a capacitor of electrode effective conductivity α1 = 0.05 S/cm with only EDL instability self-discharge with current density J_{{VR}} = 1.25 × 10-3 A/cm2 were 72.33% and 72.34%, respectively. Also, energy efficiencies η_{{{{E}}1}} and η_{{{{E}}2}} of a similar capacitor with both side reactions and redox reactions and EDL instability self-discharges with current densities J_{{VR}} = 0.00125 A/cm2 and J_{{{{VR}}1}} = 0.0032 A/cm2 were 38.13% and 38.14% respectively, compared with 84.24% and 84.25% in a similar capacitor without self-discharge. A capacitor with only EDL instability self-discharge and that with both side reactions and redox reactions and EDL instability self-discharge lost 9.73 Wh and 28.38 Wh of energy, respectively, through self-discharge during charging and discharging. Hence, EDLCs charging and discharging time is significantly dependent on the self-discharge rate which are too large to be ignored.

Oxcarbazepine in the treatment of bipolar and schizoaffective disorders.

PubMed

Popova, Ekaterine; Leighton, Caroline; Bernabarre, Antoni; Bernardo, Miquel; Vieta, Eduard

2007-06-01

Oxcarbazepine is an antiepileptic drug that has been approved by the US FDA and is indicated for use as monotherapy or adjunctive therapy in the treatment of partial seizures in adults and children aged over 4 years. The aim of this report is to investigate the results of clinical trials in order to ascertain the efficacy and safety of oxcarbazepine for use in bipolar disorder and schizoaffective disorder. Oxcarbazepine is a keto-congener of carbamazepine with fewer side effects and drug interactions. Orally administrated oxcarbazepine is rapidly and completely absorbed and has a half-life of 9 h. Currently, there is a lack of controlled clinical trials studying the use of oxcarbazepine. In light of controlled and open-label prospective studies, it may be useful for manic symptoms in the treatment of bipolar and schizoaffective patients. Case reports, retrospective and prospective studies suggest that oxcarbazepine might have prophylactic efficacy and long-term benefit for these patients. In addition, owing to its lower propensity for drug interactions and side effects, it may be useful in the treatment of refractory patients with bipolar and schizoaffective disorder. However, most of the trials have relevant methodological shortcomings. The side-effect profile of oxcarbazepine is similar to carbamazepine, but the severity of these effects appears to be slightly less. The symptoms that are most frequently associated with the use of oxcarbazepine are asthenia, headache, dizziness, somnolence, nausea, diplopia and skin rash. Isolated cases of hyponatremic coma have been reported, thus electrolyte abnormalities should be closely monitored. Oxcarbazepine is now a generic drug, but the metabolite licarbazepine and other related compounds, such as eslicarbazepine, are currently being studied under controlled conditions and might become useful therapies for bipolar and schizoaffective disorder in the future.

mGluR antagonists and GABA agonists as novel pharmacological agents for the treatment of autism spectrum disorders.

PubMed

Oberman, Lindsay M

2012-12-01

The CDC currently estimates the prevalence of autism spectrum disorders (ASD) at 1 in 88 children. Though the exact etiology of ASD is unknown, recent studies implicate synaptic maturation and plasticity in the pathogenesis of ASD leading to an imbalance of excitation and inhibition, and specifically a disproportionately high level of excitation. Pharmacological agents that modulate excitation and inhibition are currently in clinical trials for treatment of ASD and show promising preliminary results. This paper reviews the literature implicating the role of glutamate and GABA pathways in the pathophysiology of ASD. It also provides a review of the current results from both animal models and human clinical trials of drugs aimed at normalizing the imbalance of excitation and inhibition through the use of metabotropic glutamate receptor (mGluR) antagonists and GABA agonists. Both mGluR antagonists and GABA agonists have promising preliminary data from animal model and small-scale Phase II human trials. They show significant efficacy in subpopulations and appear to have favorable side-effect profiles. Though preliminary data are extremely promising, results from ongoing larger, double-blind, placebo-controlled studies will give a more complete understanding of the efficacy and side-effect profile related to these drugs.

Cardiovascular side effects of cancer therapies: a position statement from the Heart Failure Association of the European Society of Cardiology.

PubMed

Eschenhagen, Thomas; Force, Thomas; Ewer, Michael S; de Keulenaer, Gilles W; Suter, Thomas M; Anker, Stefan D; Avkiran, Metin; de Azambuja, Evandro; Balligand, Jean-Luc; Brutsaert, Dirk L; Condorelli, Gianluigi; Hansen, Arne; Heymans, Stephane; Hill, Joseph A; Hirsch, Emilio; Hilfiker-Kleiner, Denise; Janssens, Stefan; de Jong, Steven; Neubauer, Gitte; Pieske, Burkert; Ponikowski, Piotr; Pirmohamed, Munir; Rauchhaus, Mathias; Sawyer, Douglas; Sugden, Peter H; Wojta, Johann; Zannad, Faiez; Shah, Ajay M

2011-01-01

The reductions in mortality and morbidity being achieved among cancer patients with current therapies represent a major achievement. However, given their mechanisms of action, many anti-cancer agents may have significant potential for cardiovascular side effects, including the induction of heart failure. The magnitude of this problem remains unclear and is not readily apparent from current clinical trials of emerging targeted agents, which generally under-represent older patients and those with significant co-morbidities. The risk of adverse events may also increase when novel agents, which frequently modulate survival pathways, are used in combination with each other or with other conventional cytotoxic chemotherapeutics. The extent to which survival and growth pathways in the tumour cell (which we seek to inhibit) coincide with those in cardiovascular cells (which we seek to preserve) is an open question but one that will become ever more important with the development of new cancer therapies that target intracellular signalling pathways. It remains unclear whether potential cardiovascular problems can be predicted from analyses of such basic signalling mechanisms and what pre-clinical evaluation should be undertaken. The screening of patients, optimization of therapeutic schemes, monitoring of cardiovascular function during treatment, and the management of cardiovascular side effects are likely to become increasingly important in cancer patients. This paper summarizes the deliberations of a cross-disciplinary workshop organized by the Heart Failure Association of the European Society of Cardiology (held in Brussels in May 2009), which brought together clinicians working in cardiology and oncology and those involved in basic, translational, and pharmaceutical science.

μPIV measurements of two-phase flows of an operated direct methanol fuel cell

NASA Astrophysics Data System (ADS)

Burgmann, Sebastian; Blank, Mirja; Panchenko, Olha; Wartmann, Jens

2013-05-01

In direct methanol fuel cells (DMFCs), two-phase flows appear in the channels of the anode side (CO2 bubbles in a liquid water-methanol environment) as well as of the cathode side (water droplets or films in an ambient air flow). CO2 bubbles or water droplets may almost completely fill the cross-section of a channel. The instantaneous effect of the formation of two-phase flows on the cell performance has not been investigated in detail, yet. In the current project, the micro particle image velocimetry (μPIV) technique is used to elucidate the corresponding flow phenomena on the anode as well as on the cathode side of a DMFC and to correlate those phenomena with the performance of the cell. A single-channel DMFC with optical access at the anode and the cathode side is constructed and assembled that allows for μPIV measurements at both sides as well as a detailed time-resolved cell voltage recording. The appearance and evolution of CO2 bubbles on the anode side is qualitatively and quantitatively investigated. The results clearly indicate that the cell power increases when the free cross-section area of the channel is decreased by huge bubbles. Methanol is forced into the porous gas diffusion layer (GDL) between the channels and the membrane is oxidized to CO2, and hence, the fuel consumption is increased and the cell performance rises. Eventually, a bubble forms a moving slug that effectively cleans the channel from CO2 bubbles on its way downstream. The blockage effect is eliminated; the methanol flow is not forced into the GDL anymore. The remaining amount of methanol in the GDL is oxidized. The cell power decreases until enough CO2 is produced to eventually form bubbles again and the process starts again. On the other hand under the investigated conditions, water on the cathode side only forms liquid films on the channels walls rather than channel-filling droplets. Instantaneous changes of the cell power due to liquid water formation could not be observed. The timescales of the two-phase flow on the cathode side are significantly larger than on the anode side. However, the μPIV measurements at the cathode side demonstrate the ability of feeding gas flows in microchannels with liquid tracer particles and the ability to measure in two-phase flows in such a configuration.

Electrical-assisted double side incremental forming and processes thereof

DOEpatents

Roth, John; Cao, Jian

2014-06-03

A process for forming a sheet metal component using an electric current passing through the component is provided. The process can include providing a double side incremental forming machine, the machine operable to perform a plurality of double side incremental deformations on the sheet metal component and also apply an electric direct current to the sheet metal component during at least part of the forming. The direct current can be applied before or after the forming has started and/or be terminated before or after the forming has stopped. The direct current can be applied to any portion of the sheet metal. The electrical assistance can reduce the magnitude of force required to produce a given amount of deformation, increase the amount of deformation exhibited before failure and/or reduce any springback typically exhibited by the sheet metal component.

Electromigration Failure Mechanism in Sn-Cu Solder Alloys with OSP Cu Surface Finish

NASA Astrophysics Data System (ADS)

Chu, Ming-Hui; Liang, S. W.; Chen, Chih; Huang, Annie T.

2012-09-01

Organic solderable preservative (OSP) has been adopted as the Cu substrate surface finish in flip-chip solder joints for many years. In this study, the electromigration behavior of lead-free Sn-Cu solder alloys with thin-film under bump metallization and OSP surface finish was investigated. The results showed that severe damage occurred on the substrate side (cathode side), whereas the damage on the chip side (cathode side) was not severe. The damage on the substrate side included void formation, copper dissolution, and formation of intermetallic compounds (IMCs). The OSP Cu interface on the substrate side became the weakest point in the solder joint even when thin-film metallization was used on the chip side. Three-dimensional simulations were employed to investigate the current density distribution in the area between the OSP Cu surface finish and the solder. The results indicated that the current density was higher along the periphery of the bonding area between the solder and the Cu pad, consistent with the area of IMC and void formation in our experimental results.

Toward a redefinition and contextualization of the abortion issue.

PubMed

Hartman, A

1991-11-01

The current condition of the abortion issue is that of an ideological stalemate. Each side has retreated to defend positions that will tolerate compromise of consideration of the other's viewpoint. The result is that both sides fail to see the implications of their views. 1 reason for this current state of affairs is the effect of Roe v Wade. The decision is based in privacy rights, rather than bodily integrity, which means that women are to be left alone when it comes to abortion. This can be seen with the Harris v McRae decision which ended federal funding for abortion services and the Rust v Sullivan decision which further limited doctors to counsel, inform, or refer women about abortion if they take federal money. Both sides of the issue defended absolute, immutable rights which do not leave room for personal, civic, and collective responsibility. Both sides have inconsistencies: the pro-choice side does not recognize that while abortion as a backup to birth control is okay, abortion as a primary means of birth control is not. Yet this is the case in many countries today. The pro-life side maintains that the fetus has the right to be born, yet the conservative administration and its supporters do not want to pay for social and health programs that will give these fetuses a descent quality of life. If they care so much for life, how can they stand by while 20% of children live in poverty? The pro-life side continues to ignore that fact that the majority of Americans support the right to chose. The pro-choice side continues to ignore the fact that 40% of those that favor choice, also feel that abortion is immoral. The final result of these arguments about right, is that they do not exist in the context of the real world. They are formed without looking at the social, economic, and personal contexts in which abortion occurs. The right to abortion should not stand alone, it should be a fail safe combined with family planning education and universal contraception.

Side effects associated with anti-HIV drugs.

PubMed

Highleyman, L

1998-04-01

Many side effects are associated with the use of anti-HIV drugs, impacting the development of drug resistance and the quality of life for HIV-patients. Concern about side effects is a primary factor in deterring people from beginning HIV therapy. Frequency and severity of side effects vary greatly, but they are frequently more common and severe in people who are taking a new drug or who have advanced HIV disease. Information on side effects comes largely from clinical trials; however, many side effects are not discovered until the drug has been approved and used by larger numbers of people. Side effects vary from serious toxicities that require stopping treatment to uncomfortable or annoying side effects that interfere with daily life. A table categorizes the four major side effects (nausea, fever, skin rash, and fatigue) and divides them into grades that describe their intensity. A chart lists the side effects associated with specific anti-HIV drugs. Suggestions for managing side effects are included.

Management of the infant with respiratory syncytial virus.

PubMed

Corey, M A; Clore, E R

1991-04-01

This article examines updated clinical information concerning respiratory syncytial virus (RSV) infection including epidemiology, pathology, clinical manifestations, diagnosis, treatment, nosocomial infection, and prognosis. Also presented is current information on ribavirin therapy, its side effects, and precautions. Research related to the most effective isolation methodology is discussed, as well as nursing diagnoses based on Gordon's Functional Health Patterns and interventions for the infant hospitalized with RSV bronchiolitis and/or pneumonia.

European Science Notes Information Bulletin Reports on Current European/ Middle Eastern Science

DTIC Science & Technology

1988-07-01

41 Recently concluded and planned experiments are described which arc based on static Kerr effect dis- persion- spectroscopy , optical Kerr effect...studies, and both electric and magnetic resonance 6 molecular beam spectroscopy . These advanced techniques are used to measure with great precision...simuhItio , using thrcc-dimcn- flight using temperature-sensitive films and infrared sional singularities in a panel ncthod. camecras placed on either side

Ageostrophic Frontal Processes Controlling Phytoplankton Production in the Catalano-Balearic Sea (Western Mediterranean)

PubMed Central

Oguz, Temel; Macias, Diego; Tintore, Joaquin

2015-01-01

Buoyancy-induced unstable boundary currents and the accompanying retrograde density fronts are often the sites of pronounced mesoscale activity, ageostrophic frontal processes, and associated high biological production in marginal seas. Biophysical model simulations of the Catalano-Balearic Sea (Western Mediterranean) illustrated that the unstable and nonlinear southward frontal boundary current along the Spanish coast resulted in a strain-driven frontogenesis mechanism. High upwelling velocities of up to 80 m d-1 injected nutrients into the photic layer and promoted enhanced production on the less dense, onshore side of the front characterized by negative relative vorticity. Additional down-front wind stress and heat flux (cooling) intensified boundary current instabilities and thus ageostrophic cross-frontal circulation and augmented production. Specifically, entrainment of nutrients by relatively strong buoyancy-induced vertical mixing gave rise to a more widespread phytoplankton biomass distribution within the onshore side of the front. Mesoscale cyclonic eddies contributed to production through an eddy pumping mechanism, but it was less effective and more limited regionally than the frontal processes. The model was configured for the Catalano-Balearic Sea, but the mechanisms and model findings apply to other marginal seas with similar unstable frontal boundary current systems. PMID:26065688

Effectiveness of Citrus Fruits on Helicobacter pylori

PubMed Central

2017-01-01

It is known that Helicobacter pylori infection is associated with chronic gastritis, peptic ulcer, and gastric carcinoma. Due to the increased side effects of the treatment regimens and the development of antimicrobial resistance, a number of natural compounds have been tested as potential alternatives. In this review, we will examine the current knowledge on the effect of Citrus fruits and their derivatives against H. pylori, highlighting the remaining outstanding questions on the development of novel therapeutic strategies. PMID:28408943

Demonstration of hetero-gate-dielectric tunneling field-effect transistors (HG TFETs).

PubMed

Choi, Woo Young; Lee, Hyun Kook

2016-01-01

The steady scaling-down of semiconductor device for improving performance has been the most important issue among researchers. Recently, as low-power consumption becomes one of the most important requirements, there have been many researches about novel devices for low-power consumption. Though scaling supply voltage is the most effective way for low-power consumption, performance degradation is occurred for metal-oxide-semiconductor field-effect transistors (MOSFETs) when supply voltage is reduced because subthreshold swing (SS) of MOSFETs cannot be lower than 60 mV/dec. Thus, in this thesis, hetero-gate-dielectric tunneling field-effect transistors (HG TFETs) are investigated as one of the most promising alternatives to MOSFETs. By replacing source-side gate insulator with a high- k material, HG TFETs show higher on-current, suppressed ambipolar current and lower SS than conventional TFETs. Device design optimization through simulation was performed and fabrication based on simulation demonstrated that performance of HG TFETs were better than that of conventional TFETs. Especially, enlargement of gate insulator thickness while etching gate insulator at the source side was improved by introducing HF vapor etch process. In addition, the proposed HG TFETs showed higher performance than our previous results by changing structure of sidewall spacer by high- k etching process.

Systematic analysis of diffuse rear reflectors for enhanced light trapping in silicon solar cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pfeffer, Florian; Eisenlohr, Johannes; Basch, Angelika

Simple diffuse rear reflectors can enhance the light path length of weakly absorbed near infrared light in silicon solar cells and set a benchmark for more complex and expensive light trapping structures like dielectric gratings or plasmonic particles. We analyzed such simple diffuse rear reflectors systematically by optical and electrical measurements. We applied white paint, TiO 2 nanoparticles, white backsheets and a silver mirror to bifacial silicon solar cells and measured the enhancement of the external quantum efficiency for three different solar cell geometries: planar front and rear side, textured front and planar rear side, and textured front and rearmore » side. We showed that an air-gap between the solar cell and the reflector decreases the absorption enhancement significantly, thus white paint and TiO 2 nanoparticles directly applied to the rear cell surface lead to the highest short circuit current density enhancements. Here, the short circuit current density gains for a 200 um thick planar solar cell reached up to 1.8 mA/cm 2, compared to a non-reflecting black rear side and up to 0.8 mA/cm 2 compared to a high-quality silver mirror rear side. For solar cells with textured front side the short circuit current density gains are in the range between 0.5 and 1.0 mA/cm 2 compared to a non-reflecting black rear side and do not significantly depend on the angular characteristic of the rear side reflector but mainly on its absolute reflectance.« less

Systematic analysis of diffuse rear reflectors for enhanced light trapping in silicon solar cells

DOE PAGES

Pfeffer, Florian; Eisenlohr, Johannes; Basch, Angelika; ...

2016-04-08

Simple diffuse rear reflectors can enhance the light path length of weakly absorbed near infrared light in silicon solar cells and set a benchmark for more complex and expensive light trapping structures like dielectric gratings or plasmonic particles. We analyzed such simple diffuse rear reflectors systematically by optical and electrical measurements. We applied white paint, TiO 2 nanoparticles, white backsheets and a silver mirror to bifacial silicon solar cells and measured the enhancement of the external quantum efficiency for three different solar cell geometries: planar front and rear side, textured front and planar rear side, and textured front and rearmore » side. We showed that an air-gap between the solar cell and the reflector decreases the absorption enhancement significantly, thus white paint and TiO 2 nanoparticles directly applied to the rear cell surface lead to the highest short circuit current density enhancements. Here, the short circuit current density gains for a 200 um thick planar solar cell reached up to 1.8 mA/cm 2, compared to a non-reflecting black rear side and up to 0.8 mA/cm 2 compared to a high-quality silver mirror rear side. For solar cells with textured front side the short circuit current density gains are in the range between 0.5 and 1.0 mA/cm 2 compared to a non-reflecting black rear side and do not significantly depend on the angular characteristic of the rear side reflector but mainly on its absolute reflectance.« less

Mouse repeated electroconvulsive seizure (ECS) does not reverse social stress effects but does induce behavioral and hippocampal changes relevant to electroconvulsive therapy (ECT) side-effects in the treatment of depression

PubMed Central

Sigrist, Hannes; Seifritz, Erich; Fikse, Lianne; Bosker, Fokko J.; Schoevers, Robert A.; Klein, Hans C.

2017-01-01

Electroconvulsive therapy (ECT) is an effective treatment for depression, but can have negative side effects including amnesia. The mechanisms of action underlying both the antidepressant and side effects of ECT are not well understood. An equivalent manipulation that is conducted in experimental animals is electroconvulsive seizure (ECS). Rodent studies have provided valuable insights into potential mechanisms underlying the antidepressant and side effects of ECT. However, relatively few studies have investigated the effects of ECS in animal models with a depression-relevant manipulation such as chronic stress. In the present study, mice were first exposed to chronic social stress (CSS) or a control procedure for 15 days followed by ECS or a sham procedure for 10 days. Behavioral effects were investigated using an auditory fear conditioning (learning) and expression (memory) test and a treadmill-running fatigue test. Thereafter, immunohistochemistry was conducted on brain material using the microglial marker Iba-1 and the cholinergic fibre marker ChAT. CSS did not increase fear learning and memory in the present experimental design; in both the control and CSS mice ECS reduced fear learning and fear memory expression. CSS induced the expected fatigue-like effect in the treadmill-running test; ECS induced increased fatigue in CSS and control mice. In CSS and control mice ECS induced inflammation in hippocampus in terms of increased expression of Iba-1 in radiatum of CA1 and CA3. CSS and ECS both reduced acetylcholine function in hippocampus as indicated by decreased expression of ChAT in several hippocampal sub-regions. Therefore, CSS increased fatigue and reduced hippocampal ChAT activity and, rather than reversing these effects, a repeated ECS regimen resulted in impaired fear learning-memory, increased fatigue, increased hippocampal Iba-1 expression, and decreased hippocampal ChAT expression. As such, the current model does not provide insights into the mechanism of ECT antidepressant function but does provide evidence for pathophysiological mechanisms that might contribute to important ECT side-effects. PMID:28910337

Mouse repeated electroconvulsive seizure (ECS) does not reverse social stress effects but does induce behavioral and hippocampal changes relevant to electroconvulsive therapy (ECT) side-effects in the treatment of depression.

PubMed

van Buel, Erin M; Sigrist, Hannes; Seifritz, Erich; Fikse, Lianne; Bosker, Fokko J; Schoevers, Robert A; Klein, Hans C; Pryce, Christopher R; Eisel, Ulrich Lm

2017-01-01

Electroconvulsive therapy (ECT) is an effective treatment for depression, but can have negative side effects including amnesia. The mechanisms of action underlying both the antidepressant and side effects of ECT are not well understood. An equivalent manipulation that is conducted in experimental animals is electroconvulsive seizure (ECS). Rodent studies have provided valuable insights into potential mechanisms underlying the antidepressant and side effects of ECT. However, relatively few studies have investigated the effects of ECS in animal models with a depression-relevant manipulation such as chronic stress. In the present study, mice were first exposed to chronic social stress (CSS) or a control procedure for 15 days followed by ECS or a sham procedure for 10 days. Behavioral effects were investigated using an auditory fear conditioning (learning) and expression (memory) test and a treadmill-running fatigue test. Thereafter, immunohistochemistry was conducted on brain material using the microglial marker Iba-1 and the cholinergic fibre marker ChAT. CSS did not increase fear learning and memory in the present experimental design; in both the control and CSS mice ECS reduced fear learning and fear memory expression. CSS induced the expected fatigue-like effect in the treadmill-running test; ECS induced increased fatigue in CSS and control mice. In CSS and control mice ECS induced inflammation in hippocampus in terms of increased expression of Iba-1 in radiatum of CA1 and CA3. CSS and ECS both reduced acetylcholine function in hippocampus as indicated by decreased expression of ChAT in several hippocampal sub-regions. Therefore, CSS increased fatigue and reduced hippocampal ChAT activity and, rather than reversing these effects, a repeated ECS regimen resulted in impaired fear learning-memory, increased fatigue, increased hippocampal Iba-1 expression, and decreased hippocampal ChAT expression. As such, the current model does not provide insights into the mechanism of ECT antidepressant function but does provide evidence for pathophysiological mechanisms that might contribute to important ECT side-effects.

Effect of tapered magnetic field on expanding laser-produced plasma for heavy-ion inertial fusion

DOE PAGES

Kanesue, Takeshi; Ikeda, Shunsuke

2016-12-20

A laser ion source is a promising candidate as an ion source for heavy ion inertial fusion (HIF), where a pulsed ultra-intense and low-charged heavy ion beam is required. It is a key development for a laser ion source to transport laser-produced plasma with a magnetic field to achieve a high current beam. The effect of a tapered magnetic field on laser produced plasma is demonstrated by comparing the results with a straight solenoid magnet. The magnetic field of interest is a wider aperture on a target side and narrower aperture on an extraction side. Furthermore, based on the experimentallymore » obtained results, the performance of a scaled laser ion source for HIF was estimated.« less

Maternal side effects & fetal neuroprotection according to body mass index after magnesium sulfate in a multicenter randomized controlled trial.

PubMed

Vilchez, Gustavo; Dai, Jing; Lagos, Moraima; Sokol, Robert J

2018-01-01

Evidence supports the need of dose-adjustment of several drugs according to body mass index (BMI) to prevent toxicity in the underweight, and ensure efficacy in obese women. However, for MgSO 4 neuroprotection, the effect of BMI on maternal toxicity and fetal neuroprotection is understudied. We analyze the effect of BMI on maternal/infant outcomes after MgSO 4 . Secondary analysis of a clinical trial that studied MgSO 4 neuroprotection. Maternal side effects, magnesium cord levels, and offspring cerebral palsy/death were analyzed along BMI strata using ANOVA and chi-square test. Logistic regression was used to calculate adjusted odds ratios according to the treatment and BMI, using nonobese that received placebo as reference. Interaction analyses were performed to validate differential efficacy of BMI. From 2241 women, more side effects and higher magnesium cord levels were seen in underweight women (p = 0.05). MgSO 4 neuroprotection was effective in the non-obese (p = 0.02), but not in obese women (p = 1.00). In multivariate analyses, MgSO 4 significantly reduced cerebral palsy only in nonobese women. Interaction analyses showed the moderator effect of BMI (p = 0.169). Increasing MgSO 4 dose in obese mothers may ensure neuroprotective efficacy without representing increased maternal risks. Considering costs of studying this association, current analysis may form the basis for reasonable practice.

Small-molecule inhibitors of the receptor tyrosine kinases: promising tools for targeted cancer therapies.

PubMed

Hojjat-Farsangi, Mohammad

2014-08-08

Chemotherapeutic and cytotoxic drugs are widely used in the treatment of cancer. In spite of the improvements in the life quality of patients, their effectiveness is compromised by several disadvantages. This represents a demand for developing new effective strategies with focusing on tumor cells and minimum side effects. Targeted cancer therapies and personalized medicine have been defined as a new type of emerging treatments. Small molecule inhibitors (SMIs) are among the most effective drugs for targeted cancer therapy. The growing number of approved SMIs of receptor tyrosine kinases (RTKs) i.e., tyrosine kinase inhibitors (TKIs) in the clinical oncology imply the increasing attention and application of these therapeutic tools. Most of the current approved RTK-TKIs in preclinical and clinical settings are multi-targeted inhibitors with several side effects. Only a few specific/selective RTK-TKIs have been developed for the treatment of cancer patients. Specific/selective RTK-TKIs have shown less deleterious effects compared to multi-targeted inhibitors. This review intends to highlight the importance of specific/selective TKIs for future development with less side effects and more manageable agents. This article provides an overview of: (1) the characteristics and function of RTKs and TKIs; (2) the recent advances in the improvement of specific/selective RTK-TKIs in preclinical or clinical settings; and (3) emerging RTKs for targeted cancer therapies by TKIs.

Current-voltage characteristics of C70 solid near Meyer-Neldel temperature

NASA Astrophysics Data System (ADS)

Onishi, Koichi; Sezaimaru, Kouki; Nakashima, Fumihiro; Sun, Yong; Kirimoto, Kenta; Sakaino, Masamichi; Kanemitsu, Shigeru

2017-06-01

The current-voltage characteristics of the C70 solid with hexagonal closed-packed structures were measured in the temperature range of 250-450 K. The current-voltage characteristics can be described as a temporary expedient by a cubic polynomial of the voltage, i = a v 3 + b v 2 + c v + d . Moreover, the Meyer-Neldel temperature of the C70 solid was confirmed to be 310 K, at which a linear relationship between the current and voltage was observed. Also, at temperatures below the Meyer-Neldel temperature, the current increases with increasing voltage. On the other hand, at temperatures above the Meyer-Neldel temperature a negative differential conductivity effect was observed at high voltage side. The negative differential conductivity was related to the electric field and temperature effects on the mobility of charge carrier, which involve two variations in the carrier concentration and the activation energy for carrier hopping transport.

Side Effect Perceptions and Their Impact on Treatment Decisions in Women.

PubMed

Waters, Erika A; Pachur, Thorsten; Colditz, Graham A

2017-04-01

Side effects prompt some patients to forego otherwise-beneficial therapies. This study explored which characteristics make side effects particularly aversive. We used a psychometric approach, originating from research on risk perception, to identify the factors (or components) underlying side effect perceptions. Women ( N = 149) aged 40 to 74 years were recruited from a patient registry to complete an online experiment. Participants were presented with hypothetical scenarios in which an effective and necessary medication conferred a small risk of a single side effect (e.g., nausea, dizziness). They rated a broad range of side effects on several characteristics (e.g., embarrassing, treatable). In addition, we collected 4 measures of aversiveness for each side effect: choosing to take the medication, willingness to pay to avoid the side effect (WTP), negative affective attitude associated with the side effect, and how each side effect ranks among others in terms of undesirability. A principal components analysis (PCA) was used to identify the components underlying side effect perceptions. Then, for each aversiveness measure separately, regression analyses were used to determine which components predicted differences in aversiveness among the side effects. The PCA revealed 4 components underlying side effect perceptions: affective challenge (e.g., frightening), social challenge (e.g., disfiguring), physical challenge (e.g., painful), and familiarity (e.g., common). Side effects perceived as affectively and physically challenging elicited the highest levels of aversiveness across all 4 measures. Understanding what side effect characteristics are most aversive may inform interventions to improve medical decisions and facilitate the translation of novel biomedical therapies into clinical practice.

Side Effect Perceptions and their Impact on Treatment Decisions in Women

PubMed Central

Waters, Erika A.; Pachur, Thorsten; Colditz, Graham A.

2016-01-01

Background Side effects prompt some patients to forego otherwise-beneficial therapies. This study explored which characteristics make side effects particularly aversive. Methods We used a psychometric approach, originating from research on risk perception, to identify the factors (or components) underlying side effect perceptions. Women (N=149) aged 40–74 were recruited from a patient registry to complete an online experiment. Participants were presented with hypothetical scenarios in which an effective and necessary medication conferred a small risk of a single side effect (e.g., nausea, dizziness). They rated a broad range of side effects on several characteristics (e.g., embarrassing, treatable). In addition, we collected four measures of aversiveness for each side effect: choosing to take the medication, willingness to pay to avoid the side effect (WTP), negative affective attitude associated with the side effect, and how each side effect ranks among others in terms of undesirability. A principle-components analysis (PCA) was used to identify the components underlying side effect perceptions. Then, for each aversiveness measure separately, regression analyses were used to determine which components predicted differences in aversiveness among the side effects. Results The PCA revealed four components underlying side effect perceptions: affective challenge (e.g., frightening), social challenge (e.g., disfiguring), physical challenge (e.g., painful), and familiarity (e.g., common). Side effects perceived as affectively and physically challenging elicited the highest levels of aversiveness across all four measures. Conclusions Understanding what side effect characteristics are most aversive may inform interventions to improve medical decisions and facilitate the translation of novel biomedical therapies into clinical practice. PMID:27216581

Effectiveness of one-year pharmacological treatment of adult attention-deficit/hyperactivity disorder (ADHD): an open-label prospective study of time in treatment, dose, side-effects and comorbidity.

PubMed

Fredriksen, Mats; Dahl, Alv A; Martinsen, Egil W; Klungsøyr, Ole; Haavik, Jan; Peleikis, Dawn E

2014-12-01

How to generalize from randomized placebo controlled trials of ADHD drug treatment in adults to 'real-world' clinical practice is intriguing. This open-labeled prospective observational study examined the effectiveness of long-term stimulant and non-stimulant medication in adult ADHD including dose, side-effects and comorbidity in a clinical setting. A specialized ADHD outpatient clinic gave previously non-medicated adults (n=250) with ADHD methylphenidate as first-line drug according to current guidelines. Patients who were non-tolerant or experiencing low efficacy were switched to amphetamine or atomoxetine. Primary outcomes were changes of ADHD-symptoms evaluated with the Adult ADHD Self-Report Scale (ASRS) and overall severity by the Global Assessment of Functioning (GAF). Secondary outcomes were measures of mental distress, and response on the Clinical-Global-Impressions-Improvement Scale. Data at baseline and follow-ups were compared in longitudinal mixed model analyses for time on-medication, dosage, comorbidity, and side-effects. As results, 232 patients (93%) completed examination at the 12 month endpoint, and 163 (70%) remained on medication. Compared with the patients who discontinued medication, those still on medication had greater percentage reduction in ASRS-scores (median 39%, versus 13%, P<0.001) and greater improvement of GAF (median 20% versus 4%, P<0.001) and secondary outcomes. Continued medication and higher cumulated doses showed significant associations to sustained improvement. Conversely, psychiatric comorbidity and side-effects were related to lower effectiveness and more frequent termination of medication. Taken together, one-year treatment with stimulants or atomoxetine was associated with a clinically significant reduction in ADHD symptoms and mental distress, and improvement of measured function. No serious adverse events were observed. Copyright © 2014 Elsevier B.V. and ECNP. All rights reserved.

The effects of bariatric surgery: will understanding its mechanism render the knife unnecessary?

PubMed

Browning, Kirsteen N; Hajnal, Andras

2014-01-01

The incidence of obesity is increasing worldwide at a dramatic rate, accompanied by an associated increase in comorbid conditions. Bariatric surgery is the most effective treatment for morbid obesity with Roux-en-Y gastric bypass being the most commonly performed procedure, yet the underlying mechanisms by which it induces a wide-array of beneficial effects remains obscure. From basic science as well as clinical standpoints, there are several areas of current interest that warrant continued investigation. Several major focus areas have also emerged in current research that may guide future efforts in this field, particularly with regards to using novel, non-surgical approaches to mimic the success of bariatric surgery while minimizing its adverse side effects.

Effect of Communication Style on Perceptions of Medication Side Effect Risk among Pharmacy Students.

PubMed

Sawant, Ruta V; Beatty, Collin R; Sansgiry, Sujit S

2016-10-25

Objective. To assess the effect of communication style, and frequency and severity of medication side-effects, on pharmacy students' perception of risk of experiencing side effects. Methods. One hundred responses from pharmacy students were obtained using an online survey. Participants were presented with a drug information box containing drug name, drug usage, and one side-effect associated with the drug. Information on side-effect for each drug was presented in one of eight experimental conditions, in a 2 (side-effect frequency: low, high), X2 (side-effect severity: mild, severe) X2 (communication style: verbal, verbal + natural frequency) factorial design. Risk perception of experiencing side effects was measured. Results. Communication style was found to have a significant impact on risk perception depending on the context of frequency and severity associated with the side effect. Conclusion. Communication style plays a significant role in formulating risk perceptions of medication side effects. Training in pharmaceutical counseling should include special emphasis on effective language use.

Three-Dimensional Finite-Element Simulation for a Thermoelectric Generator Module

NASA Astrophysics Data System (ADS)

Hu, Xiaokai; Takazawa, Hiroyuki; Nagase, Kazuo; Ohta, Michihiro; Yamamoto, Atsushi

2015-10-01

A three-dimensional closed-circuit numerical model of a thermoelectric generator (TEG) module has been constructed with COMSOL® Multiphysics to verify a module test system. The Seebeck, Peltier, and Thomson effects and Joule heating are included in the thermoelectric conversion model. The TEG model is employed to simulate the operation of a 16-leg TEG module based on bismuth telluride with temperature-dependent material properties. The module is mounted on a test platform, and simulated by combining the heat conduction process and thermoelectric conversion process. Simulation results are obtained for the terminal voltage, output power, heat flow, and efficiency as functions of the electric current; the results are compared with measurement data. The Joule and Thomson heats in all the thermoelectric legs, as functions of the electric current, are calculated by finite-element volume integration over the entire legs. The Peltier heat being pumped at the hot side and released at the cold side of the module are also presented in relation to the electric current. The energy balance relations between heat and electricity are verified to support the simulation.

Acquiring Domain Knowledge for Planning by Experimentation

DTIC Science & Technology

1992-01-01

visel partt holding grinderi visel p=r1 size-of pull LENGTH k size-of part! LENGTH k ufsee-finish pertl side! ROUGH surface-tinish pan] side...prof-not-cached <nodal> <node2>) (current-goal <nodal> ( goali )) (current-goal (node2> <goal2>) (d@.s-top-protection-violat ion <goal2>) (not-does-top

8. Detail, typical shedroofed entry on south side. The current ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

8. Detail, typical shed-roofed entry on south side. The current project will replace these with similar structures that will allow handicap access to the lean-to portion of the building containing offices, restrooms, and other employee spaces. - Interurban Electric Railway Bridge Yard Shop, Interstate 80 at Alameda County Postmile 2.0, Oakland, Alameda County, CA

Nanoformulated water-soluble paclitaxel to enhance drug efficacy and reduce hemolysis side effect.

PubMed

Gu, Weiting; Chen, Jie; Patra, Prabir; Yang, Xiaoyan; Gu, Quanrong; Wei, Lingxuan; Acker, Jason P; Kong, Beihua

2017-07-01

Surgery, chemotherapy, and radiotherapy are the three top cancer treatment modalities. Paclitaxel (PTX) is one of the most widely used chemotherapy drugs. However, its clinical applications have been significantly limited due to: (i) serious hemolysis effect of currently available commercial paclitaxel formulations and (ii) its water insolubility. An easy way to deliver paclitaxel by a new nanocarrier system using pluronic copolymers of P123/F68 and Sorbitan monopalmitate (Span 40) was reported in our previous research article. The characterization of the formulation and analysis of drug release and cellular uptake were also presented. In this article, we reported discoveries of our follow-up in vivo antitumor and in vitro hemolytic study discoveries. The experimental results showed that the nanoformulated PTX achieved much better tumor suppression performance while reducing hemolysis side effects. This newly formulated drug can significantly improve patient outcomes in cancer chemotherapy.

Risperidone induced angioedema with concurrent EPS symptoms: a case report and review of literature

PubMed Central

Samra, Gursharan Singh; Kant, Saumitra; Chow, Robert

2018-01-01

ABSTRACT Angioedema has recently been reported as a side effect associated with the antipsychotic risperidone. We report a case of dystonia with concurrent angioedema due to risperidone. A 40-year-old male with a history of schizophrenia was started on 3 mg of risperidone BID and developed perioral and periorbital edema along with increased muscle rigidity and hand tremor within 24 h of initial administration. His symptoms abated after cessation of risperidone and intravenous administration of corticosteroids and antihistamine. This case study adds to the current literature, which has already established angioedema as a dose-dependent side effect of risperidone. Moreover, this case study aims to increase awareness about the potential for the simultaneous occurrence of angioedema and extrapyramidal symptoms, and promotes vigilance among prescribers so that the life-threatening consequences of such effects can be avoided. PMID:29686794

Present and Future: Pharmacologic Treatment of Obesity

PubMed Central

Glandt, Mariela; Raz, Itamar

2011-01-01

Obesity now presents one of the biggest health problems of our times. Diet and exercise are best for both prevention and treatment; unfortunately, both require much discipline and are difficult to maintain. Medications offer a possible adjunct, but their effect is modest, they are limited by side effects, and the weight loss lasts only as long as the drug is being taken, since as soon as treatment is stopped, the weight is regained. Sibutramine, a sympathomimetic medication which was available for long-term treatment, is the most recent of the drugs to be withdrawn from the market due to side effects; in this case it was an increased risk of cardiovascular events. This paper reviews those medications which are available for treatment of obesity, including many of those recently taken off the market. It also discusses some of the newer treatments that are currently being investigated. PMID:21331293

A Randomized, Double-Blind, Placebo-Controlled Study to Investigate the Safety, Tolerability, and Pharmacokinetics of Single Enantiomer (+)-Mefloquine Compared with Racemic Mefloquine in Healthy Persons

PubMed Central

Tansley, Robert; Lotharius, Julie; Priestley, Anthony; Bull, Fiona; Duparc, Stephan; Möhrle, Jörg

2010-01-01

Racemic mefloquine is a highly effective antimalarial whose clinical utility has been compromised by its association with neuropsychiatric and gastrointestinal side effects. It is hypothesized that the cause of the side effects may reside in the (−) enantiomer. We sought to compare the safety, tolerability and pharmacokinetic profile of (+)-mefloquine with racemic mefloquine in a randomized, ascending-dose, double-blind, active and placebo-controlled, parallel cohort study in healthy male and female adult volunteers. Although differing in its manifestations, both study drugs displayed a substantially worse tolerability profile compared with placebo. The systemic clearance was slower for (−)-mefloquine than (+)-mefloquine. Thus, (+)-mefloquine has a different safety and tolerability profile compared with racemic mefloquine but its global safety profile is not superior and replacement of the currently used antimalarial drug with (+)-mefloquine is not warranted. PMID:21118921

A Multidimensional Strategy to Detect Polypharmacological Targets in the Absence of Structural and Sequence Homology

PubMed Central

Durrant, Jacob D.; Amaro, Rommie E.; Xie, Lei; Urbaniak, Michael D.; Ferguson, Michael A. J.; Haapalainen, Antti; Chen, Zhijun; Di Guilmi, Anne Marie; Wunder, Frank; Bourne, Philip E.; McCammon, J. Andrew

2010-01-01

Conventional drug design embraces the “one gene, one drug, one disease” philosophy. Polypharmacology, which focuses on multi-target drugs, has emerged as a new paradigm in drug discovery. The rational design of drugs that act via polypharmacological mechanisms can produce compounds that exhibit increased therapeutic potency and against which resistance is less likely to develop. Additionally, identifying multiple protein targets is also critical for side-effect prediction. One third of potential therapeutic compounds fail in clinical trials or are later removed from the market due to unacceptable side effects often caused by off-target binding. In the current work, we introduce a multidimensional strategy for the identification of secondary targets of known small-molecule inhibitors in the absence of global structural and sequence homology with the primary target protein. To demonstrate the utility of the strategy, we identify several targets of 4,5-dihydroxy-3-(1-naphthyldiazenyl)-2,7-naphthalenedisulfonic acid, a known micromolar inhibitor of Trypanosoma brucei RNA editing ligase 1. As it is capable of identifying potential secondary targets, the strategy described here may play a useful role in future efforts to reduce drug side effects and/or to increase polypharmacology. PMID:20098496

Optimal vaccination choice, vaccination games, and rational exemption: an appraisal.

PubMed

Manfredi, Piero; Posta, Pompeo Della; d'Onofrio, Alberto; Salinelli, Ernesto; Centrone, Francesca; Meo, Claudia; Poletti, Piero

2009-12-10

A threat for vaccination policies might be the onset of "rational" exemption, i.e. the family's decision not to vaccinate children after a seemingly rational comparison between the perceived risk of infection and the perceived risk of vaccine side effects. We study the implications of rational exemption by models of vaccination choice. By a simple model of individual choice we first prove the "elimination impossible" result in presence of informed families, i.e. aware of herd immunity, and suggest that limited information might explain patterns of universal vaccination. Next, we investigate vaccination choice in a game-theoretic framework for communities stratified into two groups, "pro" and "anti" vaccinators, having widely different perceived costs of infection and of vaccine side effects. We show that under informed families neither a Nash nor a Stackelberg behaviour (characterized, respectively, by players acting simultaneously and by an asymmetric situation with a "leader" and a "follower) allow elimination, unless "pro-vaccinators" assign no costs to vaccine side effects. Elimination turns out to be possible when cooperation is encouraged by a social planner, provided, however, he incorporates in the "social loss function" the preferences of anti-vaccinators only. This allows an interpretation of the current Italian vaccination policy.

Theranostic Nanoseeds for Efficacious Internal Radiation Therapy of Unresectable Solid Tumors

NASA Astrophysics Data System (ADS)

Moeendarbari, Sina; Tekade, Rakesh; Mulgaonkar, Aditi; Christensen, Preston; Ramezani, Saleh; Hassan, Gedaa; Jiang, Ruiqian; Öz, Orhan K.; Hao, Yaowu; Sun, Xiankai

2016-02-01

Malignant tumors are considered “unresectable” if they are adhere to vital structures or the surgery would cause irreversible damages to the patients. Though a variety of cytotoxic drugs and radiation therapies are currently available in clinical practice to treat such tumor masses, these therapeutic modalities are always associated with substantial side effects. Here, we report an injectable nanoparticle-based internal radiation source that potentially offers more efficacious treatment of unresectable solid tumors without significant adverse side effects. Using a highly efficient incorporation procedure, palladium-103, a brachytherapy radioisotope in clinical practice, was coated to monodispersed hollow gold nanoparticles with a diameter about 120 nm, to form 103Pd@Au nanoseeds. The therapeutic efficacy of 103Pd@Au nanoseeds were assessed when intratumorally injected into a prostate cancer xenograft model. Five weeks after a single-dose treatment, a significant tumor burden reduction (>80%) was observed without noticeable side effects on the liver, spleen and other organs. Impressively, >95% nanoseeds were retained inside the tumors as monitored by Single Photon Emission Computed Tomography (SPECT) with the gamma emissions of 103Pd. These findings show that this nanoseed-based brachytherapy has the potential to provide a theranostic solution to unresectable solid tumors.

[Towards an improvement of the quality of life after radiotherapy in children].

PubMed

Demoor-Goldschmidt, Charlotte; Bernier, Valérie

2015-01-01

Pediatric radiotherapy did not differ technically from adult radiotherapy but its characteristics, its difficulties and challenges are specific. Thanks in part to this treatment, overall survival of French children with cancer is around 80%. It is therefore important to integrate in the elaboration of the treatment planning potential side long-term effects. Indeed, whatever the technique is, even the most sophisticated, it is usually inevitable that healthy nearby organs receive a dose of radiation. Dose limits on organs at risk come from adult data and are adapted for children. After the treatment, it is important to graduate the potential risks of side effects to propose a personalized monitoring protocol avoiding excessive medicalization. This article presents the medical thinking concerning radiotherapy in different anatomical areas (brain, head and neck, chest, abdomen) including concepts of dose level corresponding to side effects usually described. In parallel, we present follow-up recommendations with the aim to preserve an optimal quality of life for the adults cured of a childhood cancer, currently called survivors. Copyright © 2015 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

A multidimensional strategy to detect polypharmacological targets in the absence of structural and sequence homology.

PubMed

Durrant, Jacob D; Amaro, Rommie E; Xie, Lei; Urbaniak, Michael D; Ferguson, Michael A J; Haapalainen, Antti; Chen, Zhijun; Di Guilmi, Anne Marie; Wunder, Frank; Bourne, Philip E; McCammon, J Andrew

2010-01-22

Conventional drug design embraces the "one gene, one drug, one disease" philosophy. Polypharmacology, which focuses on multi-target drugs, has emerged as a new paradigm in drug discovery. The rational design of drugs that act via polypharmacological mechanisms can produce compounds that exhibit increased therapeutic potency and against which resistance is less likely to develop. Additionally, identifying multiple protein targets is also critical for side-effect prediction. One third of potential therapeutic compounds fail in clinical trials or are later removed from the market due to unacceptable side effects often caused by off-target binding. In the current work, we introduce a multidimensional strategy for the identification of secondary targets of known small-molecule inhibitors in the absence of global structural and sequence homology with the primary target protein. To demonstrate the utility of the strategy, we identify several targets of 4,5-dihydroxy-3-(1-naphthyldiazenyl)-2,7-naphthalenedisulfonic acid, a known micromolar inhibitor of Trypanosoma brucei RNA editing ligase 1. As it is capable of identifying potential secondary targets, the strategy described here may play a useful role in future efforts to reduce drug side effects and/or to increase polypharmacology.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Aeloiza, Eddy C.; Burgos, Rolando P.

A step-down AC/AC converter for use in an electric distribution system includes at least one chopper circuit for each one of a plurality of phases of the AC power, each chopper circuit including a four-quadrant switch coupled in series between primary and secondary sides of the chopper circuit and a current-bidirectional two-quadrant switch coupled between the secondary side of the chopper circuit and a common node. Each current-bidirectional two-quadrant switch is oriented in the same direction, with respect to the secondary side of the corresponding chopper circuit and the common node. The converter further includes a control circuit configured tomore » pulse-width-modulate control inputs of the switches, to convert a first multiphase AC voltage at the primary sides of the chopper circuits to a second multiphase AC voltage at the secondary sides of the chopper circuits, the second multiphase AC voltage being lower in voltage than the first multiphase AC voltage.« less

Arc fault detection system

DOEpatents

Jha, K.N.

1999-05-18

An arc fault detection system for use on ungrounded or high-resistance-grounded power distribution systems is provided which can be retrofitted outside electrical switchboard circuits having limited space constraints. The system includes a differential current relay that senses a current differential between current flowing from secondary windings located in a current transformer coupled to a power supply side of a switchboard, and a total current induced in secondary windings coupled to a load side of the switchboard. When such a current differential is experienced, a current travels through a operating coil of the differential current relay, which in turn opens an upstream circuit breaker located between the switchboard and a power supply to remove the supply of power to the switchboard. 1 fig.

On Leakage Current Measured at High Cell Voltages in Lithium-Ion Batteries

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vadivel, Nicole R.; Ha, Seungbum; He, Meinan

2017-01-01

In this study, parasitic side reactions in lithium-ion batteries were examined experimentally using a potentiostatic hold at high cell voltage. The experimental leakage current measured during the potentiostatic hold was compared to the Tafel expression and showed poor agreement with the expected transfer coefficient values, indicating that a more complicated expression could be needed to accurately capture the physics of this side reaction. Here we show that cross-talk between the electrodes is the primary contribution to the observed leakage current after the relaxation of concentration gradients has ceased. This cross-talk was confirmed with experiments using a lithium-ion conducting glass ceramicmore » (LICGC) separator, which has high conductance only for lithium cations. The cells with LICGC separators showed significantly less leakage current during the potentiostatic hold test compared to cells with standard microporous separators where cross-talk is present. In addition, direct-current pulse power tests show an impedance rise for cells held at high potentials and for cells held at high temperatures, which could be attributed to film formation from the parasitic side reaction. Based on the experimental findings, a phenomenological mechanism is proposed for the parasitic side reaction which accounts for cross-talk and mass transport of the decomposition products across the separator.« less

Combination studies of platinum(II)-based metallointercalators with buthionine-S,R-sulfoximine, 3-bromopyruvate, cisplatin or carboplatin.

PubMed

Garbutcheon-Singh, K Benjamin; Harper, Benjamin W J; Myers, Simon; Aldrich-Wright, Janice R

2014-01-01

With current chemotherapeutic treatment regimes often limited by adverse side effects, the synergistic combination of complexes with anticancer activity appears to offer a promising strategy for effective cancer treatment. This work investigates the anti-proliferative activity using a combination therapy approach where metallointercalators of the type [Pt(IL)(AL)](2+) (where IL is the intercalating ligand and AL is the ancillary ligand) are used in combination with currently approved anticancer drugs cisplatin and carboplatin and organic molecules buthionine-S,R-sulfoximine and 3-bromopyruvate. Synergistic relationships were observed, indicating a potential to decrease dose-dependent toxicity and improve therapeutic efficacy.

Novel biotherapies are needed in youth mental health.

PubMed

Amminger, G Paul; Berger, Maximus; Rice, Simon M; Davey, Christopher G; Schäfer, Miriam R; McGorry, Patrick D

2017-04-01

Adverse effects and lack of efficacy in a significant number of patients limit pharmaceutical interventions in youth psychiatry. This is exemplified by the fact that no medication is currently approved for the treatment of non-OCD anxiety disorders or major depressive disorder in young people younger than 18 years of age in Australia. Here, emerging biological therapies for youth with mental health problems are discussed. There is an urgent need for more research into biological interventions with acceptable risk-benefit balances. Omega-3 fatty acids, cannabidiol and N-acetylcysteine are currently being evaluated. If initial findings are confirmed, they may offer alternatives with more benign side-effect profiles than existing treatments.

Rodent analgesia: Assessment and therapeutics.

PubMed

Flecknell, Paul

2018-02-01

Current use of analgesics to control procedure-related pain in laboratory rodents is unacceptably low. Almost all currently available analgesics were developed in small rodents, prior to use in man, so that safety and efficacy data in laboratory assays are available. Greater use of analgesics would be encouraged by critical evaluation of the potential interactions of these compounds with the outcomes of specific research studies. As in other species, effective post-procedural analgesia requires reliable 'cage-side' methods of assessing pain. Recent advances in pain assessment should lead to both more extensive and more effective use of analgesics in these species. Copyright © 2017 Elsevier Ltd. All rights reserved.

Efficiency and specificity of RAAS inhibitors in cardiovascular diseases: how to achieve better end-organ protection?

PubMed

Nehme, Ali; Zibara, Kazem

2017-11-01

RAAS, a major pharmacological target in cardiovascular medicine, is inhibited by pharmacological classes including angiotensin converting enzyme (ACE) inhibitors (ACEIs), angiotensin-II type 1 blockers (ARBs) and aldosterone receptors antagonists, in addition to the recently introduced direct renin inhibitors (DRIs). However, currently used RAAS inhibitors still cannot achieve their desired effects and are associated with certain drawbacks, such as adverse side effects, incomplete blockage of the system and poor end-organ protection. In this review, we discuss the efficiency and specificity of the current RAAS inhibitors and propose some recommendations for achieving better treatments with better end-organ protection.

Health Related Quality of Life in Patients with Side-Effects after Antimuscarinic Treatment for Overactive Bladder.

PubMed

Kim, Aram; Lee, Kyu-Sung; Jung, Rangrhee; Na, Selee; Kim, Joon-Chul; Kim, Hyeong Gon; Choo, Myung-Soo

2017-09-01

Drug therapy is the mainstay of treatment for overactive bladder (OAB), but antimuscarinic agents possess side-effects. These side-effects decrease the patients' quality of life. We therefore assessed the impact of side-effects on health-related quality of life (HR-QoL) through an analysis of EQ-5D questionnaire. This study was designed to investigate the patients' satisfaction by quality weight of health status as affected by the side-effects of OAB medications. Patients who had OAB symptoms lasting longer than 3 months and have experienced side-effects after any antimuscarinic treatments filled in the EQ-5D questionnaire. The enrolled patients had two EQ-5D questionnaires for two different health statuses, i.e., presence or absence of side-effects. Quality weight was calculated using the ED-5D health status score with Korean tariff. One hundred patients were enrolled and completed the HR-QoL questionnaire. The most prevalent side-effect was dry mouth (61%) and 28% patients had dry mouth and constipation concurrently. Most of the patients with side-effects tried to endure and overcome these side-effects (79%), but 10% desired a change in medication, and 6% stopped medication altogether. The quality weight of EQ-5D without side-effects was 0.863, while the quality weight with side-effects was 0.666 (P < 0.001). The VAS score was 79 in patient without side-effects and 57 in those with side-effects, supporting the results of quality weight assessment. Overactive bladder patients may enjoy a better quality of life if side-effects associated with antimuscarinic therapy are fewer. © 2016 John Wiley & Sons Australia, Ltd.

The analgesic effects of intrathecal xylazine and detomidine in sheep and their antagonism with systemic atipamezole.

PubMed

Christina Haerdi-Landerer, M; Schlegel, Urs; Neiger-Aeschbacher, Gina

2005-09-01

To evaluate the analgesic and adverse side effects of intrathecal (IT) xylazine (XYL) and detomidine (DET) and the subsequent effects of two doses of intravenous (IV) atipamezole (ATI). Prospective, randomized, cross-over. Five adult healthy female sheep with mean body mass of 55 +/- 2.3 kg. Material and methods Each sheep underwent four treatments: 1) 50 microg kg(-1) XYL IT and 5 microg kg(-1) ATI IV, 2) 50 microg kg(-1) XYL IT and 2.5 microg kg(-1) ATI IV, 3) 10 microg kg(-1) DET IT and 5 microg kg(-1) ATI IV, 4) 10 microg kg(-1) DET IT and 2.5 microg kg(-1) ATI IV. Pain threshold (TH) was tested by applying pulsed and stepwise incremental direct current to the skin overlying the pastern. The current at the point of foot lift was recorded as the TH. Heart rate (HR), mean arterial pressure, arterial oxygen (PO(2)) and carbon dioxide (PCO(2)) tensions were monitored. Outcomes were derived as differences between baseline assessment and measurements after treatment. Two-way anova was used to analyse drug effects, treatment differences between groups were examined with an F-test or Wilcoxon's rank sum test in case of non-parametric data distribution. p was set at 0.05. Both drugs increased the pain TH, caused small increases in PCO(2), and small decreases in HR, the latter was only significant for XYL recipients. Xylazine produced a significantly higher TH, more rapidly and for longer than DET. Atipamezole only significantly affected PaCO(2) in the XYL group 2. The pain TH was not affected in either group after IV ATI. At the doses used, IT XYL, and to a lesser extent DET, induced pastern analgesia. Atipamezole 5 microg kg(-1) IV antagonized some side effects without affecting analgesia. Intrathecal XYL may be useful as an analgesic in sheep. Its safety is increased because IV ATI antagonizes side effects, but not analgesia.

Percolation effect in thick film superconductors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sali, R.; Harsanyi, G.

1994-12-31

A thick film superconductor paste has been developed to study the properties of granulated superconductor materials, to observe the percolation effect and to confirm the theory of the conducting mechanism in the superconducting thick films. This paste was also applied to make a superconducting planar transformer. Due to high T{sub c} and advantageous current density properties the base of the paste was chosen to be of Bi(Pb)SrCaCuO system. For contacts a conventional Ag/Pt paste was used. The critical temperature of the samples were between 110 K and 115 K depending on the printed layer thickness. The critical current density atmore » the boiling temperature of the liquid He- was between 200-300 A/cm{sup 2}. The R(T) and V(I) functions were measured with different parameters. The results of the measurements have confirmed the theory of conducting mechanism in the material. The percolation structure model has been built and described. As an application, a superconducting planar thick film transformer was planned and produced. Ten windings of the transformer were printed on one side of the alumina substrate and one winding was printed on the other side. The coupling between the two sides was possible through the substrate. The samples did not need special drying and firing parameters. After the preparation, the properties of the transformer were measured. The efficiency and the losses were determined. Finally, some fundamental advantages and problems of the process were discussed.« less

Scattering of the field of a multi-element phased array by human ribs

NASA Astrophysics Data System (ADS)

Gélat, P.; ter Haar, G.; Saffari, N.

2012-03-01

The efficacy of high intensity focused ultrasound (HIFU) for the non-invasive treatment of cancer has been demonstrated for a range of different cancers including those of the liver, kidney, prostate and breast. As a non-invasive focused therapy, HIFU offers considerable advantages over other techniques such as chemotherapy and surgical resection, in terms of invasiveness and risk of harmful side effects. Despite its advantages, however, there are a number of significant challenges currently hindering its widespread clinical application. One of these challenges is the need to transmit sufficient energy through the ribcage to induce tissue necrosis at the required foci whilst minimising the formation of side lobes. Multielement random arrays are currently showing great promise in overcoming the limitations of single-element transducers. Nevertheless, successfully treating a patient for liver tumours requires a thorough understanding of the way in which the ultrasonic pressure field from a HIFU array is scattered by the ribcage. A mesh of quadratic pressure patches was generated using CT scan data for ribs nine to twelve on the right side. A boundary element approach based on a Generalised Minimal Residual (GMRES) implementation of the Burton-Miller formulation was used, in conjunction with phase conjugation techniques to focus the field of a 256-element random HIFU array past the ribs at both intercostal and transcostal treatment locations. This method has the advantage of accounting for full effects of scattering and diffraction in three dimensions under continuous wave excitation.

Percolation effect in thick film superconductors: Using a Bi(Pb)SrCaCuO based paste to prepare a superconducting planar transformer

NASA Technical Reports Server (NTRS)

Sali, Robert; Harsanyi, Gabor

1995-01-01

A thick film superconductor paste has been developed to study the properties of granulated superconductor materials, to observe the percolation effect and to confirm the theory of the conducting mechanism in the superconducting thick films. This paste was also applied to make a superconducting planar transformer. Due to the T(sub c) and advantageous current density properties the base of the past was chosen to be of Bi(Pb)SrCaCu) system. For contacts a conventional Ag/Pt paste was used. The critical temperature of the samples were between 110 K and 115 K depending on the printed layer thickness. The critical current density -at the boiling temperature of the liquid He- was between 200 - 300 A/sq cm. The R(T) and V(I) functions were measured with different parameters. The results of the measurements have confirmed the theory of conducting mechanism in the material. The percolation structure model has been built and described. As an application, a superconducting planar thick film transformer was planned and produced. Ten windings of the transformer were printed on one side of the alumina substrate and one winding was printed on the other side. The coupling between the two sides was possible through the substrate. The samples did not need special drying and firing parameters. After the preparation, the properties of the transformer were measured. The efficiency ans the losses were determined. Finally, some fundamental advantages and problems of the process were discussed.

[Current prevention and treatment strategies for osteoporosis. Fracture-oriented, effective, low side effects and inexpensive].

PubMed

Bartl, R; Bartl, C

2015-12-01

Osteoporosis is still an underdiagnosed and insufficiently therapied widespread disease in Germany. Of the estimated 7 million osteoporosis patients only 1.5 million receive a guideline conform diagnosis and even less receive appropriate treatment. Some 90 % of patients are provided with analgesics but only 10 % receive an effective therapy, although efficacious, well-tested and affordable medications are available. In addition, approximately one half of the patients terminate treatment after only 1 year although according to the results of recent studies the duration of therapy should be at least 3-5 years. In view of the increasing average life expectancy, a consistent management for prevention of fractures associated with osteoporosis is always most important for society, even if only for reasons of costs. Achievement of this target depends on four circumstances: clarification of the origin of osteoporosis and fractures (bone consciousness), prophylaxis of bone loss and fractures (primary prevention), consistent guideline conform diagnostics and therapy (secondary and tertiary prevention) and cooperation of all disciplines in medicine (bone is everybody's business). This article describes the current state of diagnostics (bone density measurement with dual X-ray absorptiometry, FRAX®), prophylaxis of fractures (screening program) and therapy (use of economic and effective medications with low side effects). Novel medications are already undergoing clinical testing and a "healing" of bone reduction with restoration of the normal bone structure is to be expected.

Effect of neutral endopeptidase inhibition on substance-P-induced increase in short-circuit current of canine cultured tracheal epithelium.

PubMed

Tamaoki, J; Sakai, N; Isono, K; Kanemura, T; Chiyotani, A; Yamauchi, F; Takizawa, T; Konno, K

1991-01-01

We studied the effect of substance P (SP) on the electric properties of cultured canine tracheal epithelium and its possible modulation by neutral endopeptidase (NEP) by Ussing's short-circuited technique in vitro. Addition of SP (5 x 10(-6) M) to the mucosal side increased short-circuit current (SCC) from 5.1 +/- 0.9 to 10.3 +/- 2.2 microA/cm2 (mean +/- SE; p less than 0.01), which was accompanied by increases in transepithelial potential difference and conductance. The effect of the mucosal SP on SCC was dose-dependent, with the maximal increase from the baseline value being 5.8 +/- 1.0 microA/cm2 observed at 5 x 10(-5) M. The NEP inhibitor phosphoramidon (10(-5) M) did not affect these responses. On the other hand, SCC was not altered by the addition of SP to the submucosal side. However, it was increased dose-dependently in the presence of phosphoramidon (10(-5) M) but not in the presence of captopril, bestatin or leupeptin. This stimulatory effect of submucosal SP was abolished by furosemide, diphenylamine-2-carboxylate and Cl-free medium, but not by amiloride. These results suggest that SP may selectively stimulate Cl secretion across the airway epithelium and that this effect may be modulated by submucosal NEP.

Design of demand side response model in energy internet demonstration park

NASA Astrophysics Data System (ADS)

Zhang, Q.; Liu, D. N.

2017-08-01

The implementation of demand side response can bring a lot of benefits to the power system, users and society, but there are still many problems in the actual operation. Firstly, this paper analyses the current situation and problems of demand side response. On this basis, this paper analyses the advantages of implementing demand side response in the energy Internet demonstration park. Finally, the paper designs three kinds of feasible demand side response modes in the energy Internet demonstration park.

Facilitatory effect of AC-iontophoresis of lidocaine hydrochloride on the permeability of human enamel and dentine in extracted teeth.

PubMed

Ikeda, Hideharu; Suda, Hideaki

2013-04-01

The objectives of the present study were to quantitatively evaluate chemical permeability through human enamel/dentine using conductometry and to clarify if alternating current (AC) iontophoresis facilitates such permeability. Electrical impedance of different concentrations of lidocaine hydrochloride was measured using a bipolar platinum impedance probe. A quadratic curve closely fitted to the response functions between conductance and lidocaine hydrochloride. For analysis of the passage of lidocaine hydrochloride through human enamel/dentine, eight premolars that were extracted for orthodontic treatment were sectioned at the cemento-enamel junction. The tooth crowns were held between two chambers with a double O-ring. The enamel-side chamber was filled with lidocaine hydrochloride, and the pulp-side chamber was filled with extrapure water. Two platinum plate electrodes were set at the end of each chamber to pass alternating current. A simulated interstitial pulp pressure was applied to the pulp-side chamber. The change in the concentration of lidocaine hydrochloride in the pulp-side chamber was measured every 2min using a platinum recording probe positioned at the centre of the pulp-side chamber. Passive entry without iontophoresis was used as a control. The level of lidocaine hydrochloride that passed through enamel/dentine against the dentinal fluid flow increased with time. Electrical conductance (G, mho) correlated closely to the concentration (x, mmol/L) of lidocaine hydrochloride (G=2.16x(2)+0.0289x+0.000376, r(2)=0.999). Lidocaine hydrochloride can pass through enamel/dentine. Conductometry showed that the level of lidocaine hydrochloride that passed through enamel/dentine was increased by AC iontophoresis. Copyright © 2012 Elsevier Ltd. All rights reserved.

Painful Ejaculation with Cyclobenzaprine: A Case Report and Literature Review

PubMed Central

Wie, Christopher S.; Gorlin, Andrew W.; Wisenbaugh, Eric S.; Rosenfeld, David M.

2015-01-01

Abstract Introduction Sexual dysfunction is a well‐known side effect of antidepressants. Painful ejaculation is a rare side effect that has been reported with the use of some psychiatric drugs such as triclyclic antidepressants. Cyclobenzaprine is a muscle relaxant that is structurally similar to tricyclic antidepressants. It is the most commonly prescribed muscle relaxant in the United States and accounts for 18% of all prescriptions written for chronic back pain. Methods A 55‐year‐old man was referred to our pain medicine clinic for evaluation and treatment of pain with ejaculation. Main outcome Measure The main outcome measure was to review the current published literature and case reports on painful ejaculation from medication use, in particular tricyclic antidepressants. Results After discontinuation of cyclobenzaprine, our patient's sexual dysfunction resolved. This result was consistent with the literature reviewed on the topic. Conclusion Painful ejaculation is likely an underreported side effect of tricyclic antidepressants and cyclobenzaprine use. Fortunately, these symptoms are reversible and discontinuation of these medications is typically an effective cure. K raus MB , W ie CS , G orlin AW , W isenbaugh ES , and R osenfeld DM . Painful ejaculation with cyclobenzaprine: A case report and literature review. S ex M ed 2015;3:343–345. PMID:26797071

Pharmacokinetic and pharmacodynamic profile of dronedarone , a new antiarrhythmic agent for the treatment of atrial fibrillation.

PubMed

Rosa, Gian Marco; Bianco, Daniele; Parodi, Antonello; Valbusa, Alberto; Zawaideh, Camilla; Bizzarri, Nicolò; Ferrero, Simone; Brunelli, Claudio

2014-12-01

Atrial fibrillation (AF) is the most common arrhythmia and is associated with increased morbidity and mortality. Dronedarone is a recent antiarrhythmic drug that has been developed for treatment of AF, with electrophysiological properties similar to amiodarone but with a lower incidence of side effects. This review evaluates the efficacy, safety, tolerability and side effects of dronedarone in the treatment of AF. In particular, the review includes studies comparing: dronedarone and placebo (ANDROMEDA, ATHENA, DAFNE, ERATO, EURIDIS/ADONIS, HESTIA, PALLAS trials), dronedarone and amiodarone (DIONYSOS trial), ranolazine and dronedarone given alone and in combination (HARMONY trial). Dronedarone is an interesting antiarrhythmic agent in well-selected groups of patients. It also has several other pleiotropic effects that may potentially be beneficial in clinical practice, such as the reduction of the risk of stroke and acute coronary syndromes. In addition, combination therapies such as those with dronedarone and ranolazine, currently being investigated in the HARMONY trial, may provide another interesting approach to increase the antiarrhythmic efficacy and further reduce the incidence of side effects. A better understanding of the mechanisms underlying dronedarone's pleiotropic actions is expected to facilitate the selection of patients benefiting from dronedarone, as well as the development of novel antiarrhythmic drugs for AF.

Recent development in antihyperalgesic effect of phytochemicals: anti-inflammatory and neuro-modulatory actions.

PubMed

Singh, Ajeet Kumar; Kumar, Sanjay; Vinayak, Manjula

2018-05-16

Pain is an unpleasant sensation triggered by noxious stimulation. It is one of the most prevalent conditions, limiting productivity and diminishing quality of life. Non steroidal anti inflammatory drugs (NSAIDs) are widely used as pain relievers in present day practice as pain is mostly initiated due to inflammation. However, due to potentially serious side effects, long term use of these antihyperalgesic drugs raises concern. Therefore there is a demand to search novel medicines with least side effects. Herbal products have been used for centuries to reduce pain and inflammation, and phytochemicals are known to cause fewer side effects. However, identification of active phytochemicals of herbal medicines and clear understanding of the molecular mechanism of their action is needed for clinical acceptance. In this review, we have briefly discussed the cellular and molecular changes during hyperalgesia via inflammatory mediators and neuro-modulatory action involved therein. The review includes 54 recently reported phytochemicals with antihyperalgesic action, as per the literature available with PubMed, Google Scholar and Scopus. Compounds of high interest as potential antihyperalgesic agents are: curcumin, resveratrol, capsaicin, quercetin, eugenol, naringenin and epigallocatechin gallate (EGCG). Current knowledge about molecular targets of pain and their regulation by these phytochemicals is elaborated and the scope of further research is discussed.

FoodWiki: a Mobile App Examines Side Effects of Food Additives Via Semantic Web.

PubMed

Çelik Ertuğrul, Duygu

2016-02-01

In this article, a research project on mobile safe food consumption system (FoodWiki) is discussed that performs its own inferencing rules in its own knowledge base. Currently, the developed rules examines the side effects that are causing some health risks: heart disease, diabetes, allergy, and asthma as initial. There are thousands compounds added to the processed food by food producers with numerous effects on the food: to add color, stabilize, texturize, preserve, sweeten, thicken, add flavor, soften, emulsify, and so forth. Those commonly used ingredients or compounds in manufactured foods may have many side effects that cause several health risks such as heart disease, hypertension, cholesterol, asthma, diabetes, allergies, alzheimer etc. according to World Health Organization. Safety in food consumption, especially by patients in these risk groups, has become crucial, given that such health problems are ranked in the top ten health risks around the world. It is needed personal e-health knowledge base systems to help patients take control of their safe food consumption. The systems with advanced semantic knowledge base can provide recommendations of appropriate foods before consumption by individuals. The proposed FoodWiki system is using a concept based search mechanism that performs on thousands food compounds to provide more relevant information.

[Drooling therapy in children with neurological disorders].

PubMed

Táboas-Pereira, M Andrea; Paredes-Mercado, Cecilia; Alonso-Curcó, Xènia; Badosa-Pagès, Joaquim; Muchart, Jordi; Póo, Pilar

2015-07-16

Drooling is the inability to retain saliva in the mouth and its progression to the digestive tract, being a common problem in pediatric patients with neurological disorders. Three different treatment options are available. To assess the effectiveness and safety of trihexyphenidyl, scopolamine and botulinum toxin infiltration in the treatment of drooling in children with neurological disorders. This is an open and prospective type study. We include patients treated in the Neurology Service that present excessive drooling, affecting their quality of life, between 2009 and 2013. We enrolled 46 patients in the study. The treatment with oral trihexyphenidyl was indicated in 46, obtaining good result in 15 (32.6%), three with temporary effect and the rest with lasting effect. Three patients presented side effects (6.5%). Four out of 11 (36.36%) patients treated with scopolamine patch had beneficial effects. One was withdrawn due to lack of efficacy and six due to side effects. Twenty-five patients were infiltrated with botulinum toxin, with a significant decrease of drooling in 16 patients (64%) after the first injection. We observed no significant changes in nine patients. Only one out of 25 showed side effects (mild dysphagia). Currently there is not a fully effective therapeutic option for drooling. We recommend starting treatment with trihexyphenidyl. A second option could be the scopolamine patch and botulinum toxin as a third option. Botulinum toxin infiltration in salivary glands is shown as an effective and safe alternative in our study.

Beta-blockers in the management of hypertension: focus on nebivolol.

PubMed

Wojciechowski, David; Papademetriou, Vasilios

2008-04-01

Hypertension is a major cardiovascular risk factor but most patients remain asymptomatic for many years. Successful therapy not only needs to be effective, it also needs to be well tolerated. beta-blockers are well established as effective antihypertensive agents. However, one major drawback to the currently available beta-blockers, particularly the noncardioselective beta-blockers, is their side-effect profile, including sexual dysfunction, fatigue, depression and metabolic abnormalities such as impaired glucose tolerance and lipid abnormalities. Nebivolol (Bystolic), a novel, highly cardioselective, third-generation beta-blocker that recently received approval by the US FDA for the treatment of hypertension in the USA, is effective in treating blood pressure and has a favorable side-effect profile. Studies conducted in Europe, where nebivolol has been available for some time for the treatment of hypertension, have shown that nebivolol achieves blood pressure reductions comparable to other beta-blockers but with fewer side effects. Additionally, nebivolol has demonstrated similar efficacy in blood pressure reduction when compared with calcium channel blockers and inhibitors of the renin-angiotensin system. When combined with hydrochlorothiazide there was an additive antihypertensive effect. Lastly, nebivolol exhibits a vasodilatory property that is related to its effect on nitric oxide, an intrinsic vasodilator produced in the vascular endothelium. Nebivolol enhances nitric oxide bioavailability. Studies have also demonstrated nebivolol's ability to function as an antioxidant and decrease markers of oxidative stress. These effects are believed to ultimately produce a modulation of the endothelial dysfunction typically seen in hypertension.

Weight Bias in Schools and How Physical Educators Can Assist in Its Demise

ERIC Educational Resources Information Center

Ehlert, Chris; Marston, Rip; Fontana, Fabio; Waldron, Jennifer

2015-01-01

One of the unfortunate side effects of the current global obesity pandemic is an increasing anti-fat bias toward overweight and obese individuals. The teaching profession is not immune from having its members included in the ranks of those possessing negative stereotypes associated with overweight or obese individuals. We provide the reader with a…

Your First Year: A Reverence for Life

ERIC Educational Resources Information Center

Cookson, Peter W., Jr.

2006-01-01

There is no higher calling than that of a teacher. The current emphasis on standards and testing has the unfortunate side-effect of reducing this calling to matters of technical expertise and what is called, by the pundits, accountability. The author contends that the call to teach is far deeper than becoming an expert technician. Because teachers…

Effects of mesoscale structures on the distribution of cephalopod paralarvae in the Gulf of California and adjacent Pacific

NASA Astrophysics Data System (ADS)

Ruvalcaba-Aroche, Erick D.; Sánchez-Velasco, Laura; Beier, Emilio; Godínez, Victor M.; Barton, Eric D.; Pacheco, Ma. Rocío

2018-01-01

Vertical distribution of the cephalopod paralarvae was investigated in relation to a system of two cyclonic and three anticyclonic eddies in the southern Gulf of California and a front in the adjacent Pacific Ocean. Results showed that the preferential habitat for the Sthenoteuthis oualaniensis - Dosidicus gigas "SD-complex" in both regions was the oxygenated surface mixed layer and the thermocline. The highest abundances occurred in of one of the anticyclonic eddies and a frontal zone, which are convergent structures. Enoploteuthid and Pyroteuthid paralarvae both displayed their highest abundances in the thermocline. Pyroteuthids dominated in the cyclonic eddy whereas Enoploteuthidae were less evident in the eddy system. Pyroteuthids were observed on the western (California Current) side of the frontal zone, and Enoploteuthids on its eastern (Gulf of California) side. The octopods and the complex of Ommastrephes-Eucleoteuthis-Hyaloteuthis paralarvae were present below the thermocline. Both groups had a scarce presence in the eddy system and high abundance near the frontal zone. The octopods abounded on the eastern side in association with the low dissolved oxygen concentrations (< 44 μmol kg-1) of Subtropical-Subsurface Water; the complex on the western front side was immersed in California Current Water. It may be concluded that the spawning and early stages of development of these cephalopod groups are associated with particular mesoscale structures of the water masses. For example, the "SD complex" inhabits the surface water masses, preferentially in convergence zones generated by mesoscale activity.

Explanations for side effect aversion in preventive medical treatment decisions

PubMed Central

Waters, Erika A.; Weinstein, Neil D.; Colditz, Graham A.; Emmons, Karen

2008-01-01

Objective Many laypeople demonstrate excessive sensitivity to negative side effects of medical treatments, which may lead them to refuse beneficial therapies. This Internet-based experiment investigated three possible explanations for such “side effect aversion.” One was derived from mental accounting, one examined the mere presence of a side effect, and one focused on computational difficulties. Design Participants (N = 5,379) were presented with a hypothetical cancer preventive treatment situation that was or was not accompanied by one or two small side effects. The side effects were either beneficial or harmful. In all conditions the net absolute risk reduction associated with the treatment was 15%. Main Outcome Measures Participants indicated their willingness to accept treatment and their perceptions of the treatment’s effects on their overall cancer risk. Results Data were consistent only with the “mere presence” explanation of side effect aversion, the idea that side effects act as a strong negative cue that directly affects treatment appraisal. The number of negative side effects did not influence treatment willingness. Conclusion Side effect aversion is a challenge to informed decision making. Specific mechanisms that produce side effect aversion should be identified. PMID:19290712

Lost in laterality: interpreting ''preferred side of the head during mobile phone use and risk of brain tumour'' associations.

PubMed

Schüz, Joachim

2009-08-01

Due to the highly localized exposure from mobile phones, the preferred side of the head during their use is important information when investigating a possible link with brain tumour risk, but at the same time, error and bias hamper the assessment of this information in case-control studies. Current studies provide evidence of reporting bias insofar as cases appear to over-report the side of the head where the tumour occurred as the one that they preferred in the past when using mobile phones. More refined methods of analysis among only cases or prospective studies with an assessment of the laterality of mobile phone use before the diagnosis of disease are needed to evaluate whether associations seen in some studies are entirely due to reporting bias or a mixture of reporting bias and a causal effect.

Cognitive science in the era of artificial intelligence: A roadmap for reverse-engineering the infant language-learner.

PubMed

Dupoux, Emmanuel

2018-04-01

Spectacular progress in the information processing sciences (machine learning, wearable sensors) promises to revolutionize the study of cognitive development. Here, we analyse the conditions under which 'reverse engineering' language development, i.e., building an effective system that mimics infant's achievements, can contribute to our scientific understanding of early language development. We argue that, on the computational side, it is important to move from toy problems to the full complexity of the learning situation, and take as input as faithful reconstructions of the sensory signals available to infants as possible. On the data side, accessible but privacy-preserving repositories of home data have to be setup. On the psycholinguistic side, specific tests have to be constructed to benchmark humans and machines at different linguistic levels. We discuss the feasibility of this approach and present an overview of current results. Copyright © 2017 Elsevier B.V. All rights reserved.

Voltage Based Detection Method for High Impedance Fault in a Distribution System

NASA Astrophysics Data System (ADS)

Thomas, Mini Shaji; Bhaskar, Namrata; Prakash, Anupama

2016-09-01

High-impedance faults (HIFs) on distribution feeders cannot be detected by conventional protection schemes, as HIFs are characterized by their low fault current level and waveform distortion due to the nonlinearity of the ground return path. This paper proposes a method to identify the HIFs in distribution system and isolate the faulty section, to reduce downtime. This method is based on voltage measurements along the distribution feeder and utilizes the sequence components of the voltages. Three models of high impedance faults have been considered and source side and load side breaking of the conductor have been studied in this work to capture a wide range of scenarios. The effect of neutral grounding of the source side transformer is also accounted in this study. The results show that the algorithm detects the HIFs accurately and rapidly. Thus, the faulty section can be isolated and service can be restored to the rest of the consumers.

Comparative Effects of Antihistamines on Aircrew Performance of Simple and Complex Tasks Under Sustained Operations

DTIC Science & Technology

1991-12-01

personnel by identifying the potential symptoms and side effects of each antihistamine and a lactose intolerance reaction. These "symptoms" were then...bachelors degree. All subjects were screened for current prescription medication use, history of antihistamine use, and known lactose sensitivity. Study...assigned drug condition (Seldane, Benadryl, or lactose placebo; see Table 1). Drug group assignment was double-blind. Neither the investigators nor the

Codeine and its alternates for pain and cough relief*

PubMed Central

Eddy, Nathan B.; Friebel, Hans; Hahn, Klaus-Jürgen; Halbach, Hans

1969-01-01

In this report—the fourth of a series on codeine and its alternates for pain and cough relief—an attempt is made to evaluate, on the basis of experimental and clinical data, and wherever possible in comparison with codeine, the effectiveness of a number of antitussive substances currently in clinical use. In the discussion of the undesired side-effects particular attention is paid to the risk of dependence and abuse. PMID:4390406

AMTEC cell testing, optimization of rhodium/tungsten electrodes, and tests of other components

NASA Technical Reports Server (NTRS)

Williams, Roger M.; Ryan, Margaret A.; Jeffries-Nakamura, Barbara; Underwood, Mark L.; O'Connor, Dennis; Kikkert, Stan

1991-01-01

Electrodes, current collectors, ceramic to metal braze seals, and metallic components exposed to the high 'hot side' temperatures and sodium liquid and vapor environment have been tested and evaluated in laboratory cells running for hundreds of hours at 1100-1200 K. Rhodium/tungsten electrodes have been selected as the optimum electrodes based on performance parameters and durability. Current collectors have been evaluated under simulated and actual operating conditions. The microscopic effects of metal migration between electrode and current collector alloys as well as their thermal and electrical properties determined the suitability of current collector and lead materials. Braze seals suitable for long term application to AMTEC devices are being developed.

Reconfigurable Drive Current System

NASA Technical Reports Server (NTRS)

Alhorn, Dean C. (Inventor); Dutton, Kenneth R. (Inventor); Howard, David E. (Inventor); Smith, Dennis A. (Inventor)

2017-01-01

A reconfigurable drive current system includes drive stages, each of which includes a high-side transistor and a low-side transistor in a totem pole configuration. A current monitor is coupled to an output of each drive stage. Input channels are provided to receive input signals. A processor is coupled to the input channels and to each current monitor for generating at least one drive signal using at least one of the input signals and current measured by at least one of the current monitors. A pulse width modulation generator is coupled to the processor and each drive stage for varying the drive signals as a function of time prior to being supplied to at least one of the drive stages.

Why are US women not using long-acting contraceptives?

PubMed

Tanfer, K; Wierzbicki, S; Payn, B

2000-01-01

Given the level of unintended pregnancy in the United States, it is somewhat surprising that hormonal implants and injectables-methods that are long-acting, reversible, highly effective and convenient--have not attained the popularity enjoyed by other medical methods. Knowing the reasons why women have so far spurned these methods might lead to the design and implementation of interventions and targeted social marketing to promote their use. Data from the 1993 and 1995 rounds of the National Survey of Women are used to examine the reasons women gave for not having used the implant or injectables, whether they intended to use these methods and how their attitudes toward them may influence their decision to use such methods in the future. Logistic regression models were used to identify the social and demographic characteristics that influence women's decisions not to use these methods. Fewer than 2% of women who were at risk of an unintended pregnancy in 1995 were using the implant, and under 3% were using the injectable. Women gave three major reasons for not using either of these methods: lack of knowledge; fear of side effects or health hazards; and satisfaction with the method they were currently using. Age, education, marital status, parity and current contraceptive method strongly predicted fear of side effects, lack of knowledge and satisfaction with the current method as reasons for not using the implant or the injectable. For example, women aged 30 or older and those with a college education were half as likely as younger women and those with no college education to mention fear of side effects as their main reason for not using the implant. Likewise, single women, women with one or more children and those using a barrier method were 2-3 times as likely as married women, childless women and those using a medical method to attribute nonuse to the implant's side effects. Few women said they intended to use these methods in the next 12 months: 5% for the implant and 10% for the injectable. Single women, women with no college education, women with children, women wanting to have a child (or another child) and women with positive attitudes toward the effect of using an injectable were significantly more likely to say they intended to use the injectable. Nevertheless, substantial proportions of women reported quite negative attitudes about these methods. The low prevalence of use and the low level of use intention for the implant and for injectables raise questions about the promise for the future of these methods. Each method seems to appeal to certain subgroups of women, however. Thus, if proper interventions and social marketing are targeted to such groups, they may be disabused of misperceptions regarding these methods and possibly become more willing to try them.

Women's perceptions and treatment patterns related to contraception: results of a survey of US women.

PubMed

Nelson, Anita L; Cohen, Stephen; Galitsky, Alex; Hathaway, Mark; Kappus, Dale; Kerolous, Majid; Patel, Kiren; Dominguez, Linda

2018-03-01

The aim of this survey was to understand US women's contraception journey from her first prescribed method to her current one including reasons for choosing and stopping/switching methods, healthcare provider relationships, and bleeding preferences. We administered a nationally-representative, web-based survey of US women aged 16 to 50 years currently using (N=1656) or had previously used (N=1448) prescription contraception, or who had never used it but would consider using it in the future (N=103). Statistical analyses were based on overlap formulae with sample weights adjusted to 2010 US census demographic benchmarks. The survey was sent to 11,906 women, and 5957 responded (50% response rate). Among qualified respondents, 3104 had experience with prescription contraception. Oral contraceptives (OC) remain the most frequently prescribed method as first or subsequent contraception. However, as women switch to their current prescription method, more chose IUD contraception. As reported by respondents, only 48% of current users received counseling on how to use specific methods, and 58% were counseled on bleeding patterns to expect, while 67% were offered counseling on potential side effects. Many of the side effects reported in this study for first and current prescription contraception were nonspecific and may be related to a nocebo effect, lack of understanding about normal bodily fluctuations, or poor compliance. Many women (34%) reported 'making their periods lighter' as a reason for using their current prescription method, and 53% would prefer to skip their monthly period altogether. Misperceptions about contraception are common, and prescription contraception choice can be quite complex. Clinicians can enhance patient satisfaction by providing adequate information and matching methods to women's lifestyles, reproductive choices, and pregnancy risk. This study provides insight into modern women's attitudes and views toward prescription contraception that may be important to clinicians and women themselves. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Lipid-Based Drug Delivery Systems in Cancer Therapy: What Is Available and What Is Yet to Come.

PubMed

Yingchoncharoen, Phatsapong; Kalinowski, Danuta S; Richardson, Des R

2016-07-01

Cancer is a leading cause of death in many countries around the world. However, the efficacy of current standard treatments for a variety of cancers is suboptimal. First, most cancer treatments lack specificity, meaning that these treatments affect both cancer cells and their normal counterparts. Second, many anticancer agents are highly toxic, and thus, limit their use in treatment. Third, a number of cytotoxic chemotherapeutics are highly hydrophobic, which limits their utility in cancer therapy. Finally, many chemotherapeutic agents exhibit short half-lives that curtail their efficacy. As a result of these deficiencies, many current treatments lead to side effects, noncompliance, and patient inconvenience due to difficulties in administration. However, the application of nanotechnology has led to the development of effective nanosized drug delivery systems known commonly as nanoparticles. Among these delivery systems, lipid-based nanoparticles, particularly liposomes, have shown to be quite effective at exhibiting the ability to: 1) improve the selectivity of cancer chemotherapeutic agents; 2) lower the cytotoxicity of anticancer drugs to normal tissues, and thus, reduce their toxic side effects; 3) increase the solubility of hydrophobic drugs; and 4) offer a prolonged and controlled release of agents. This review will discuss the current state of lipid-based nanoparticle research, including the development of liposomes for cancer therapy, different strategies for tumor targeting, liposomal formulation of various anticancer drugs that are commercially available, recent progress in liposome technology for the treatment of cancer, and the next generation of lipid-based nanoparticles. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

Power Balance Modeling of Local Helicity Injection for Non-Solenoidal ST Startup

NASA Astrophysics Data System (ADS)

Weberski, J. D.; Barr, J. L.; Bongard, M. W.; Fonck, R. J.; Perry, J. M.; Reusch, J. A.

2017-10-01

A zero-dimensional power balance model for predicting Ip(t) for Local Helicity Injection (LHI) discharges has been used to interpret experimental results from recent experimental campaigns using high-field-side (HFS) helicity injection. This model quantifies LHI's effective drive (Veff) through helicity balance while enforcing the Taylor relaxation current limit and tracking inductive effects to determine Ip(t) . Recent analysis of HFS LHI discharges indicate LHI is the dominant source of drive and provides Veff up to 1.3 V while geometric effects and inductive drive provide < 0.1 V throughout much of the discharge. In contrast to previous analysis of low-field-side (LFS) LHI discharges, which were driven by Veff = 0.3 V and 2.0 V from geometric effects and inductive drive. A significant remaining uncertainty in the model is the resistive dissipation of LHI discharges. This requires greater understanding of LHI confinement scaling and impurity content, which are currently under investigation. However, the model and experimental Ip(t) exhibit good agreement for parameters consistent with previous experimental findings. Extrapolation of plasma parameters and shaping from recent experiments allow for the model to project the performance of LHI systems. These projections indicate Ip 0.3 MA can be accessed on Pegasus via HFS LHI through changes to injector geometry to provide more Veff. This regime can be accessed via a LFS system by increasing the Taylor relaxation current limit early in the discharge. Work supported by US DOE Grants DE-FG02-96ER54375 and DE-SC0006928.

Subjective Report of Side Effects of Prescribed and Nonprescribed Psychostimulant Use in Young Adults.

PubMed

Smith, Tess E; Martel, Michelle M; DeSantis, Alan D

2017-03-21

Side effects of prescribed and nonprescribed psychostimulant use are understudied. The study examined side effects of prescribed and nonprescribed psychostimulant use in a college sample with attention to possible gender differences. 2716 undergraduates (1448 male) between the ages of 17 and 57 years (M = 19.43 years, SD = 1.7 years) completed an online survey that included questions about the subjective side effects of prescribed and nonprescribed psychostimulant use. Results suggested that prescribed users more frequently reported side effects, compared to nonprescribed users. For prescribed users, females more frequently reported appetite, somatic, and anxiety-related side effects compared to males. For nonprescribed users, while females reported more somatic and anxiety-related side effects, males more frequently reported loss of sex drive and sweating as side effects. Conclusions/Importance: These findings suggest prescribed users of psychostimulants more frequently report side effects with prominent gender differences in line with gender roles.

Photo-thermal nanosystems for diseased cell treatment

NASA Astrophysics Data System (ADS)

Raeesi, Vahid

The prevalence of cancer and infectious disease demands for development of more effective treatment technologies. Current standard chemo- and radiotherapy for cancer offer only relative therapeutic efficacy at the cost of significant side-effects. On the other hand, resistance of microbes to current antibiotics has raised serious concern in public health sectors such as hospitals. Thermal therapy is an alternative technique that employs high temperatures to treat diseased cells via direct and indirect heat effects. Owing to its nature, this technique can offer enhanced therapeutic efficacy in local diseased regions via either mono- or combinatorial platforms and very minimal side-effects. However, existing bulk heating systems are limited in providing selective and controlled temperature rise in the desired region at tissue/cellular scales. This compromises the therapeutic efficacy of the treatment and increases the risk of off-target heating in healthy tissues. In this thesis, we propose the use of heat-generating nanoparticles to precisely target heat into small regions and study how they can be applied in cancer and bacteria treatment. Our model nanoparticle system generates heat by light stimulation. Different nanosystems based on this particle are developed and their thermal effects on therapeutic distribution are explored at tumor tissue and cellular scales. In addition, the thermal effect of these nanoparticles is utilized to overcome microbial resistance. By mechanistic understanding of nanoparticle thermal effects at different length scales, this research helps to rationalize proper design and development of heat- generating nanomedicine for cancer and microbial treatments.

Transcranial direct current stimulation (tDCS) reveals a dissociation between SNARC and MARC effects: Implication for the polarity correspondence account.

PubMed

Di Rosa, Elisa; Bardi, Lara; Umiltà, Carlo; Masina, Fabio; Forgione, Margherita; Mapelli, Daniela

2017-08-01

The concept of stimulus response compatibility (SRC) refers to the existence of a privileged association between a specific stimulus feature and a specific response feature. Two examples of SRC are the Spatial Numerical Association of Response Codes (SNARC) and the Markedness Association of Response Codes (MARC) effects. According to the polarity correspondence principle, these two SRC effects occur because of a match between the most salient dimensions of stimulus and response. Specifically, the SNARC effect would be caused by a match between right-sided responses and large numbers, while a match between right-sided responses and even numbers would give rise to the MARC effect. The aim of the present study was to test the validity of the polarity correspondence principle in explaining these two SRC effects. To this end, we applied transcranial direct current stimulation (tDCS) over left and right posterior parietal cortex (PPC), which is thought to be the neural basis of salience processing, during a parity judgement task. Results showed that cathodal tDCS over the PPC significantly reduced the MARC effect but did not affect the SNARC effect, suggesting a dissociation between the two effects. That is, the MARC would rely on a salience processing mechanism, whereas the SNARC would not. Despite this interpretation is in need of further experimental confirmations (i.e., testing different tasks or using different tDCS montages), our results suggest that the polarity correspondence principle can be a plausible explanation only for the MARC effect but not for the SNARC effect. Copyright © 2017 Elsevier Ltd. All rights reserved.

Automicroneedle therapy system combined with topical tretinoin shows better regenerative effects compared with each individual treatment.

PubMed

Kim, J H; Park, H Y; Jung, M; Choi, E H

2013-01-01

Regenerative therapy is a relatively new dermatological field. However, the currently available topical agents are unsuitable for transdermal drug delivery because of their high molecular weight and low liposolubility. Therefore, a more effective transdermal drug delivery system is needed in order to achieve better therapeutic effects with these agents. A recently introduced microneedle therapy system (MTS), which is a mechanical method for making minute holes in the skin, improves transdermal delivery. A recently developed refinement of this technique, the automicroneedle therapy system (AMTS), has several advantages over the traditional MTS, as it can achieve consistent results because of its automatic punching method. To evaluate the cutaneous effects of an AMTS in combination with topical tretinoin. Twelve hairless mice were divided into two groups, and the dorsal skin of each mouse was marked down the centre. The first group was treated with the AMTS plus 0.025% tretinoin on one side of the back, and with 0.025% tretinoin only on the other side. The other group was treated with the AMTS and vehicle on one side, while the other side was left untreated. The effects on cutaneous regeneration and the treatment side-effects were evaluated by functional assessment including transepidermal water loss and skin hydration, and by histopathology including epidermal and dermal thickness, and density of collagen fibres. Western blotting and real-time reverse transcriptase PCR were also performed to determine protein and mRNA expression of procollagen type 1 and matrix metalloproteinase-13. Compared with the individual treatments (the AMTS alone or tretinoin alone) the combination of tretinoin plus the AMTS produced greater dermal regeneration as a result of increased proliferation of collagen fibres. This combination therapy did not result in treatment-related adverse effects. An AMTS combined with topical tretinoin is a safe and effective method for skin regeneration, which works by increasing collagen production, and might be a new therapeutic option for regenerative therapy. © The Author(s). CED © 2012 British Association of Dermatologists.

A side-by-side comparison of CPV module and system performance

DOE Office of Scientific and Technical Information (OSTI.GOV)

Muller, Matthew; Marion, Bill; Kurtz, Sarah

A side-by-side comparison is made between concentrator photovoltaic module and system direct current aperture efficiency data with a focus on quantifying system performance losses. The individual losses measured/calculated, when combined, are in good agreement with the total loss seen between the module and the system. Results indicate that for the given test period, the largest individual loss of 3.7% relative is due to the baseline performance difference between the individual module and the average for the 200 modules in the system. A basic empirical model is derived based on module spectral performance data and the tabulated losses between the modulemore » and the system. The model predicts instantaneous system direct current aperture efficiency with a root mean square error of 2.3% relative.« less

Quantum transport in graphene Hall bars: Effects of side gates

NASA Astrophysics Data System (ADS)

Petrović, M. D.; Peeters, F. M.

2017-05-01

Quantum electron transport in side-gated graphene Hall bars is investigated in the presence of quantizing external magnetic fields. The asymmetric potential of four side-gates distorts the otherwise flat bands of the relativistic Landau levels, and creates new propagating states in the Landau spectrum (i.e. snake states). The existence of these new states leads to an interesting modification of the bend and Hall resistances, with new quantizing plateaus appearing in close proximity of the Landau levels. The electron guiding in this system can be understood by studying the current density profiles of the incoming and outgoing modes. From the fact that guided electrons fully transmit without any backscattering (similarly to edge states), we are able to analytically predict the values of the quantized resistances, and they match the resistance data we obtain with our numerical (tight-binding) method. These insights in the electron guiding will be useful in predicting the resistances for other side-gate configurations, and possibly in other system geometries, as long as there is no backscattering of the guided states.

The Promise of Biological Markers for Treatment Response in First-Episode Psychosis: A Systematic Review

PubMed Central

Fond, Guillaume; d’Albis, Marc-Antoine; Jamain, Stéphane; Tamouza, Ryad; Arango, Celso; Fleischhacker, W. Wolfgang; Glenthøj, Birte; Leweke, Markus; Lewis, Shôn; McGuire, Phillip; Meyer-Lindenberg, Andreas; Sommer, Iris E.; Winter-van Rossum, Inge; Kapur, Shitij; Kahn, René S.; Rujescu, Dan; Leboyer, Marion

2015-01-01

Successful treatment of first-episode psychosis is one of the major factors that impacts long-term prognosis. Currently, there are no satisfactory biological markers (biomarkers) to predict which patients with a first-episode psychosis will respond to which treatment. In addition, a non-negligible rate of patients does not respond to any treatment or may develop side effects that affect adherence to the treatments as well as negatively impact physical health. Thus, there clearly is a pressing need for defining biomarkers that may be helpful to predict response to treatment and sensitivity to side effects in first-episode psychosis. The present systematic review provides (1) trials that assessed biological markers associated with antipsychotic response or side effects in first-episode psychosis and (2) potential biomarkers associated with biological disturbances that may guide the choice of conventional treatments or the prescription of innovative treatments. Trials including first-episode psychoses are few in number. Most of the available data focused on pharmacogenetics markers with so far only preliminary results. To date, these studies yielded—beside markers for metabolism of antipsychotics—no or only a few biomarkers for response or side effects, none of which have been implemented in daily clinical practice. Other biomarkers exploring immunoinflammatory, oxidative, and hormonal disturbances emerged as biomarkers of first-episode psychoses in the last decades, and some of them have been associated with treatment response. In addition to pharmacogenetics, further efforts should focus on the association of emergent biomarkers with conventional treatments or with innovative therapies efficacy, where some preliminary data suggest promising results. PMID:25759473

Asymmetric Volcano Trend in Oxygen Reduction Activity of Pt and Non-Pt Catalysts: In Situ Identification of the Site-Blocking Effect.

PubMed

Li, Jingkun; Alsudairi, Amell; Ma, Zi-Feng; Mukerjee, Sanjeev; Jia, Qingying

2017-02-01

Proper understanding of the major limitations of current catalysts for oxygen reduction reaction (ORR) is essential for further advancement. Herein by studying representative Pt and non-Pt ORR catalysts with a wide range of redox potential (E redox ) via combined electrochemical, theoretical, and in situ spectroscopic methods, we demonstrate that the role of the site-blocking effect in limiting the ORR varies drastically depending on the E redox of active sites; and the intrinsic activity of active sites with low E redox have been markedly underestimated owing to the overlook of this effect. Accordingly, we establish a general asymmetric volcano trend in the ORR activity: the ORR of the catalysts on the overly high E redox side of the volcano is limited by the intrinsic activity; whereas the ORR of the catalysts on the low E redox side is limited by either the site-blocking effect and/or intrinsic activity depending on the E redox .

Chemotherapy-induced peripheral neuropathy: an update on the current understanding.

PubMed

Addington, James; Freimer, Miriam

2016-01-01

Chemotherapy-induced peripheral neuropathy is a common side effect of selected chemotherapeutic agents. Previous work has suggested that patients often under report the symptoms of chemotherapy-induced peripheral neuropathy and physicians fail to recognize the presence of such symptoms in a timely fashion. The precise pathophysiology that underlies chemotherapy-induced peripheral neuropathy, in both the acute and the chronic phase, remains complex and appears to be medication specific. Recent work has begun to demonstrate and further clarify potential pathophysiological processes that predispose and, ultimately, lead to the development of chemotherapy-induced peripheral neuropathy. There is increasing evidence that the pathway to neuropathy varies with each agent. With a clearer understanding of how these agents affect the peripheral nervous system, more targeted treatments can be developed in order to optimize treatment and prevent long-term side effects.

Cooled radiofrequency ablation for bilateral greater occipital neuralgia.

PubMed

Vu, Tiffany; Chhatre, Akhil

2014-01-01

This report describes a case of bilateral greater occipital neuralgia treated with cooled radiofrequency ablation. The case is considered in relation to a review of greater occipital neuralgia, continuous thermal and pulsed radiofrequency ablation, and current medical literature on cooled radiofrequency ablation. In this case, a 35-year-old female with a 2.5-year history of chronic suboccipital bilateral headaches, described as constant, burning, and pulsating pain that started at the suboccipital region and radiated into her vertex. She was diagnosed with bilateral greater occipital neuralgia. She underwent cooled radiofrequency ablation of bilateral greater occipital nerves with minimal side effects and 75% pain reduction. Cooled radiofrequency ablation of the greater occipital nerve in challenging cases is an alternative to pulsed and continuous RFA to alleviate pain with less side effects and potential for long-term efficacy.

Cooled Radiofrequency Ablation for Bilateral Greater Occipital Neuralgia

PubMed Central

Chhatre, Akhil

2014-01-01

This report describes a case of bilateral greater occipital neuralgia treated with cooled radiofrequency ablation. The case is considered in relation to a review of greater occipital neuralgia, continuous thermal and pulsed radiofrequency ablation, and current medical literature on cooled radiofrequency ablation. In this case, a 35-year-old female with a 2.5-year history of chronic suboccipital bilateral headaches, described as constant, burning, and pulsating pain that started at the suboccipital region and radiated into her vertex. She was diagnosed with bilateral greater occipital neuralgia. She underwent cooled radiofrequency ablation of bilateral greater occipital nerves with minimal side effects and 75% pain reduction. Cooled radiofrequency ablation of the greater occipital nerve in challenging cases is an alternative to pulsed and continuous RFA to alleviate pain with less side effects and potential for long-term efficacy. PMID:24716017

Glutamate Receptors in the Central Nucleus of the Amygdala Mediate Cisplatin-Induced Malaise and Energy Balance Dysregulation through Direct Hindbrain Projections

PubMed Central

Alhadeff, Amber L.; Holland, Ruby A.; Nelson, Alexandra; Grill, Harvey J.

2015-01-01

Cisplatin chemotherapy is used commonly to treat a variety of cancers despite severe side effects such as nausea, vomiting, and anorexia that compromise quality of life and limit treatment adherence. The neural mechanisms mediating these side effects remain elusive despite decades of clinical use. Recent data highlight the dorsal vagal complex (DVC), lateral parabrachial nucleus (lPBN), and central nucleus of the amygdala (CeA) as potential sites of action in mediating the side effects of cisplatin. Here, results from immunohistochemical studies in rats identified a population of cisplatin-activated DVC neurons that project to the lPBN and a population of cisplatin-activated lPBN calcitonin gene-related peptide (CGRP, a marker for glutamatergic neurons in the lPBN) neurons that project to the CeA, outlining a neuroanatomical circuit that is activated by cisplatin. CeA gene expressions of AMPA and NMDA glutamate receptor subunits were markedly increased after cisplatin treatment, suggesting that CeA glutamate receptor signaling plays a role in mediating cisplatin side effects. Consistent with gene expression results, behavioral/pharmacological data showed that CeA AMPA/kainate receptor blockade attenuates cisplatin-induced pica (a proxy for nausea/behavioral malaise in nonvomiting laboratory rodents) and that CeA NMDA receptor blockade attenuates cisplatin-induced anorexia and body weight loss in addition to pica, demonstrating that glutamate receptor signaling in the CeA is critical for the energy balance dysregulation caused by cisplatin treatment. Together, these data highlight a novel circuit and CGRP/glutamatergic mechanism through which cisplatin-induced malaise and energy balance dysregulation are mediated. SIGNIFICANCE STATEMENT To treat cancer effectively, patients must follow prescribed chemotherapy treatments without interruption, yet most cancer treatments produce side effects that devastate quality of life (e.g., nausea, vomiting, anorexia, weight loss). Although hundreds of thousands of patients undergo chemotherapies each year, the neural mechanisms mediating their side effects are unknown. The current data outline a neural circuit activated by cisplatin chemotherapy and demonstrate that glutamate signaling in the amygdala, arising from hindbrain projections, is required for the full expression of cisplatin-induced malaise, anorexia, and body weight loss. Together, these data help to characterize the neural circuits and neurotransmitters mediating chemotherapy-induced energy balance dysregulation, which will ultimately provide an opportunity for the development of well tolerated cancer and anti-emetic treatments. PMID:26245970

77 FR 34870 - Airworthiness Directives; Bombardier, Inc. Airplanes

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-12

... Bombardier, Inc. Model CL-600-2B19 (Regional Jet Series 100 & 440) airplanes. The existing AD currently requires a one-time inspection of the shafts of the main landing gear (MLG) side-brace fittings to detect...-brace fitting and replacing the side-brace fitting shaft with the re-designed side-brace fitting shaft...

Comparative trial of 5% dexpanthenol in water-in-oil formulation with 1% hydrocortisone ointment in the treatment of childhood atopic dermatitis: a pilot study.

PubMed

Udompataikul, Montree; Limpa-o-vart, Dipenn

2012-03-01

Atopic dermatitis (AD) is a common chronic relapsing disease particularly affecting children. The emollient used for protection of skin barrier function is the standard treatment for patients with AD. Currently, there is a growing interest in the use of nonsteroidal anti-inflammatory agents such as dexpanthenol (vitamin B5) as an alternative treatment. To compare the effectiveness of 5% dexpanthenol (DT) ointment with 1% hydrocortisone (HC) ointment in childhood AD therapy. Patients were treated topically with 5% DT ointment on the right side of the body and 1% HC ointment on the other side twice daily for 4 weeks. The clinical responses were evaluated by SCORAD (Scoring Atopic Dermatitis index) with statistical analysis using paired t-test. Of the 30 children enrolled, 26 completed the protocol; mean age was 7.19 years. The average baseline SCORAD score of the DT-treated side and the HC-treated side was 30.95 and 30.54, respectively. There was no statistically significant difference in SCORAD score reduction between the 2 agents. The edematous score of the HC-treated side exhibited faster resolution than that of the DT-treated side, with a statistically significant difference at week 1 and without a statistically significant difference at weeks 2 to 4. The lichenification response rate of HC treatment was more rapid than that of DT treatment; however, there was no statistical group difference. No adverse events were observed with either agent. The effectiveness of 5% DT ointment is equal to that of 1% HC ointment. DT ointment may be used as alternative treatment in mild to moderate childhood AD therapy.

Depot naltrexone in lieu of incarceration: a behavioral analysis of coerced treatment for addicted offenders.

PubMed

Marlowe, Douglas B

2006-09-01

This article is part of a series of articles examining a proposal to offer depot naltrexone to certain nonviolent opiate-addicted criminal offenders in exchange for release from incarceration or diversion from prosecution. This "negative-reinforcement" behavioral paradigm could have a better chance of success than what has heretofore been attempted with drug-abusing offenders. Traditional correctional efforts have been largely unsuccessful due to the complexities of implementation and the side effects of punishment. Although positive reinforcement can be more efficacious, it has often been strenuously resisted on the ground that it is inequitable to reward antisocial individuals for doing what is minimally expected of most citizens. Negative reinforcement steers between these hurdles by avoiding the iatrogenic effects of punishment, while also being palatable to stakeholders. More research is needed to identify the effects, costs, and side effects of negative-reinforcement arrangements for drug offenders. The current proposal provides an excellent platform for conducting this research because the target intervention (depot naltrexone) is demonstrably efficacious, nonpsychoactive, and has few, if any, side effects. Therefore, use of this medication would be unlikely to invoke the same types of legal and ethical objections that have traditionally been levied against the use of psychoactive medications with vulnerable populations of institutionalized offenders. Specific recommendations are offered for questions that must be addressed in future research studies.

Similarity-based prediction for Anatomical Therapeutic Chemical classification of drugs by integrating multiple data sources.

PubMed

Liu, Zhongyang; Guo, Feifei; Gu, Jiangyong; Wang, Yong; Li, Yang; Wang, Dan; Lu, Liang; Li, Dong; He, Fuchu

2015-06-01

Anatomical Therapeutic Chemical (ATC) classification system, widely applied in almost all drug utilization studies, is currently the most widely recognized classification system for drugs. Currently, new drug entries are added into the system only on users' requests, which leads to seriously incomplete drug coverage of the system, and bioinformatics prediction is helpful during this process. Here we propose a novel prediction model of drug-ATC code associations, using logistic regression to integrate multiple heterogeneous data sources including chemical structures, target proteins, gene expression, side-effects and chemical-chemical associations. The model obtains good performance for the prediction not only on ATC codes of unclassified drugs but also on new ATC codes of classified drugs assessed by cross-validation and independent test sets, and its efficacy exceeds previous methods. Further to facilitate the use, the model is developed into a user-friendly web service SPACE ( S: imilarity-based P: redictor of A: TC C: od E: ), which for each submitted compound, will give candidate ATC codes (ranked according to the decreasing probability_score predicted by the model) together with corresponding supporting evidence. This work not only contributes to knowing drugs' therapeutic, pharmacological and chemical properties, but also provides clues for drug repositioning and side-effect discovery. In addition, the construction of the prediction model also provides a general framework for similarity-based data integration which is suitable for other drug-related studies such as target, side-effect prediction etc. The web service SPACE is available at http://www.bprc.ac.cn/space. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Radiotherapy and "new" drugs-new side effects?

PubMed Central

2011-01-01

Background and purpose Targeted drugs have augmented the cancer treatment armamentarium. Based on the molecular specificity, it was initially believed that these drugs had significantly less side effects. However, currently it is accepted that all of these agents have their specific side effects. Based on the given multimodal approach, special emphasis has to be placed on putative interactions of conventional cytostatic drugs, targeted agents and other modalities. The interaction of targeted drugs with radiation harbours special risks, since the awareness for interactions and even synergistic toxicities is lacking. At present, only limited is data available regarding combinations of targeted drugs and radiotherapy. This review gives an overview on the current knowledge on such combined treatments. Materials and methods Using the following MESH headings and combinations of these terms pubmed database was searched: Radiotherapy AND cetuximab/trastuzumab/panitumumab/nimotuzumab, bevacizumab, sunitinib/sorafenib/lapatinib/gefitinib/erlotinib/sirolimus, thalidomide/lenalidomide as well as erythropoietin. For citation crosscheck the ISI web of science database was used employing the same search terms. Results Several classes of targeted substances may be distinguished: Small molecules including kinase inhibitors and specific inhibitors, antibodies, and anti-angiogenic agents. Combination of these agents with radiotherapy may lead to specific toxicities or negatively influence the efficacy of RT. Though there is only little information on the interaction of molecular targeted radiation and radiotherapy in clinical settings, several critical incidents are reported. Conclusions The addition of molecular targeted drugs to conventional radiotherapy outside of approved regimens or clinical trials warrants a careful consideration especially when used in conjunction in hypo-fractionated regimens. Clinical trials are urgently needed in order to address the open question in regard to efficacy, early and late toxicity. PMID:22188921

Patient preferences for outcomes of depression treatment in Germany: a choice-based conjoint analysis study.

PubMed

Zimmermann, Thomas M; Clouth, Johannes; Elosge, Michael; Heurich, Matthias; Schneider, Edith; Wilhelm, Stefan; Wolfrath, Anette

2013-06-01

In general, treatment efficacy in depressed patients is evaluated mainly based on the core symptoms of depression. However, patients might consider different outcomes. This study used choice-based conjoint analysis (CBC) to evaluate patient preferences for depression treatment outcomes. Adult subjects from Germany, currently or previously on antidepressant treatment, were presented with 18 pairs of hypothetical treatment outcome scenarios, differing in eight attributes (2-3 factor levels each): depressed mood, loss of interest and enjoyment, loss of energy/fatigue, sleep disturbance, feelings of guilt, depression-related pain, treatment duration, side effects after 2 weeks. Attributes and factor levels were defined by literature review, expert consultations, and in-depth subject interviews. Data were analyzed using multinomial logit modeling; individual part-worth utilities were estimated using hierarchical Bayes routines. Two hundred twenty-seven subjects (89.4% currently treated with antidepressants, 30.0% with depression-related pain) completed the survey. They valued the relative importance of outcomes as follows: loss of energy/fatigue 18.5%, side effects after 2 weeks 14.2%, loss of interest and enjoyment 13.5%, depression-related pain 12.0%, sleep disturbance 12.0%, feelings of guilt 11.5%, treatment duration 9.9%, depressed mood 8.5%. Participants were not required to meet ICD-10 or DSM-IV criteria for depression and had heterogeneous disease severity. CBC analysis was able to reveal patient preferences for outcomes of depression treatment. Subjects valued the ability to cope with activities of everyday living highest. They considered being free of depression-related pain and side effects more important than being free of depressed mood. These findings should be considered when making treatment decisions. Copyright © 2012 Elsevier B.V. All rights reserved.

Cadmium inhibits acid secretion in stimulated frog gastric mucosa

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gerbino, Andrea, E-mail: gerbino@biologia.uniba.i; Debellis, Lucantonio; Caroppo, Rosa

2010-06-01

Cadmium, a toxic environmental pollutant, affects the function of different organs such as lungs, liver and kidney. Less is known about its toxic effects on the gastric mucosa. The aim of this study was to investigate the mechanisms by which cadmium impacts on the physiology of gastric mucosa. To this end, intact amphibian mucosae were mounted in Ussing chambers and the rate of acid secretion, short circuit current (I{sub sc}), transepithelial potential (V{sub t}) and resistance (R{sub t}) were recorded in the continuous presence of cadmium. Addition of cadmium (20 {mu}M to 1 mM) on the serosal but not luminalmore » side of the mucosae resulted in inhibition of acid secretion and increase in NPPB-sensitive, chloride-dependent short circuit current. Remarkably, cadmium exerted its effects only on histamine-stimulated tissues. Experiments with TPEN, a cell-permeant chelator for heavy metals, showed that cadmium acts from the intracellular side of the acid secreting cells. Furthermore, cadmium-induced inhibition of acid secretion and increase in I{sub sc} cannot be explained by an action on: 1) H{sub 2} histamine receptor, 2) Ca{sup 2+} signalling 3) adenylyl cyclase or 4) carbonic anhydrase. Conversely, cadmium was ineffective in the presence of the H{sup +}/K{sup +}-ATPase blocker omeprazole suggesting that the two compounds likely act on the same target. Our findings suggest that cadmium affects the functionality of histamine-stimulated gastric mucosa by inhibiting the H{sup +}/K{sup +}-ATPase from the intracellular side. These data shed new light on the toxic effect of this dangerous environmental pollutant and may result in new avenues for therapeutic intervention in acute and chronic intoxication.« less

Modelling of the acoustic field of a multi-element HIFU array scattered by human ribs

NASA Astrophysics Data System (ADS)

Gélat, Pierre; ter Haar, Gail; Saffari, Nader

2011-09-01

The efficacy of high-intensity focused ultrasound (HIFU) for the treatment of a range of different cancers, including those of the liver, prostate and breast, has been demonstrated. As a non-invasive focused therapy, HIFU offers considerable advantages over techniques such as chemotherapy and surgical resection in terms of reduced risk of harmful side effects. Despite this, there are a number of significant challenges which currently hinder its widespread clinical application. One of these challenges is the need to transmit sufficient energy through the rib cage to induce tissue necrosis in the required volume whilst minimizing the formation of side lobes. Multi-element random-phased arrays are currently showing great promise in overcoming the limitations of single-element transducers. Nevertheless, successful treatment of a patient with liver tumours requires a thorough understanding of the way in which the ultrasonic pressure field from a HIFU array is scattered by the rib cage. In order to address this, a boundary element approach based on a generalized minimal residual (GMRES) implementation of the Burton-Miller formulation was used in conjunction with phase conjugation techniques to focus the field of a 256-element random HIFU array behind human ribs at locations requiring intercostal and transcostal treatment. Simulations were carried out on a 3D mesh of quadratic pressure patches generated using CT scan anatomical data for adult ribs 9-12 on the right side. The methodology was validated on spherical and cylindrical scatterers. Field calculations were also carried out for idealized ribs, consisting of arrays of strip-like scatterers, demonstrating effects of splitting at the focus. This method has the advantage of fully accounting for the effect of scattering and diffraction in 3D under continuous wave excitation.

Side effects of cytokines approved for therapy.

PubMed

Baldo, Brian A

2014-11-01

Cytokines, currently known to be more than 130 in number, are small MW (<30 kDa) key signaling proteins that modulate cellular activities in immunity, infection, inflammation and malignancy. Key to understanding their function is recognition of their pleiotropism and often overlapping and functional redundancies. Classified here into 9 main families, most of the 20 approved cytokine preparations (18 different cytokines; 3 pegylated), all in recombinant human (rh) form, are grouped in the hematopoietic growth factor, interferon, platelet-derived growth factor (PDGF) and transforming growth factor β (TGFβ) families. In the hematopoietin family, approved cytokines are aldesleukin (rhIL-2), oprelvekin (rhIL-11), filgrastim and tbo-filgrastim (rhG-CSF), sargramostim (rhGM-CSF), metreleptin (rh-leptin) and the rh-erythropoietins, epoetin and darbepoietin alfa. Anakinra, a recombinant receptor antagonist for IL-1, is in the IL-1 family; recombinant interferons alfa-1, alfa-2, beta-1 and gamma-1 make up the interferon family; palifermin (rhKGF) and becaplermin (rhPDGF) are in the PDGF family; and rhBMP-2 and rhBMP-7 represent the TGFβ family. The main physicochemical features, FDA-approved indications, modes of action and side effects of these approved cytokines are presented. Underlying each adverse events profile is their pleiotropism, potency and capacity to release other cytokines producing cytokine 'cocktails'. Side effects, some serious, occur despite cytokines being endogenous proteins, and this therefore demands caution in attempts to introduce individual members into the clinic. This caution is reflected in the relatively small number of cytokines currently approved by regulatory agencies and by the fact that 14 of the FDA-approved preparations carry warnings, with 10 being black box warnings.

Surgical Outcome in Patients Taking Concomitant or Recent Intake of Oral Isotretinoin: A Multicentric Study-ISO-AIMS Study.

PubMed

Mahadevappa, Omprakash Heggadahalli; Mysore, Venkataram; Viswanath, Vishalakshi; Thurakkal, Salim; Majid, Imran; Talwar, Suresh; Aurangabadkar, Sanjeev J; Chatterjee, Manas; Bhat, M Ramesh; Barua, Shyamanta; Ganjoo, Anil

2016-01-01

The current standard recommendation is to avoid surgical interventions in patients taking oral isotretinoin. However, this recommendation has been questioned in several recent publications. To document the safety of cosmetic and surgical interventions, among patients receiving or recently received oral isotretinoin. Association of Cutaneous Surgeons, India, in May 2012, initiated this study, at 11 centers in different parts of India. The data of 183 cases were collected monthly, from June 2012 to May 2013. Of these 61 patients had stopped oral isotretinoin before surgery and 122 were concomitantly taking oral isotretinoin during the study period. In these 183 patients, a total of 504 interventions were performed. These included[1] 246 sessions of chemical peels such as glycolic acid, salicylic acid, trichloroacetic acid, and combination peels;[2] 158 sessions of lasers such as ablative fractional laser resurfacing with erbium-doped yttrium aluminum garnet and CO2, conventional full face CO2 laser resurfacing, laser-assisted hair reduction with long-pulsed neodymium-doped yttrium aluminum garnet, diode laser, and LASIK surgery;[3] 27 sessions of cold steel surgeries such as microneedling, skin biopsy, subcision, punch elevation of scars, excision of skin lesion, and wisdom tooth extraction;[4] 1 session of electrosurgery. No significant side effects were noted in most patients. 2 cases of keloid were documented which amounted to 0.4% of side effects in 504 interventions, with a significant P value of 0.000. Reversible transient side effects were erythema in 10 interventions and hyperpigmentation in 15. The study showed that performing dermatosurgical and laser procedures in patients receiving or recently received isotretinoin is safe, and the current guidelines of avoiding dermatosurgical and laser interventions in such patients taking isotretinoin need to be revised.

Avoiding Braess' Paradox Through Collective Intelligence

NASA Technical Reports Server (NTRS)

Wolpert , David H.; Tumer, Kagan

1999-01-01

In an Ideal Shortest Path Algorithm (ISPA), at each moment each router in a network sends all of its traffic down the path that will incur the lowest cost to that traffic. In the limit of an infinitesimally small amount of traffic for a particular router, its routing that traffic via an ISPA is optimal, as far as cost incurred by that traffic is concerned. We demonstrate though that in many cases, due to the side-effects of one router's actions on another routers performance, having routers use ISPA's is suboptimal as far as global aggregate cost is concerned, even when only used to route infinitesimally small amounts of traffic. As a particular example of this we present an instance of Braess' paradox for ISPA'S, in which adding new links to a network decreases overall throughput. We also demonstrate that load-balancing, in which the routing decisions are made to optimize the global cost incurred by all traffic currently being routed, is suboptimal as far as global cost averaged across time is concerned. This is also due to "side-effects", in this case of current routing decision on future traffic. The theory of COllective INtelligence (COIN) is concerned precisely with the issue of avoiding such deleterious side-effects. We present key concepts from that theory and use them to derive an idealized algorithm whose performance is better than that of the ISPA, even in the infinitesimal limit. We present experiments verifying this, and also showing that a machine-learning-based version of this COIN algorithm in which costs are only imprecisely estimated (a version potentially applicable in the real world) also outperforms the ISPA, despite having access to less information than does the ISPA. In particular, this COIN algorithm avoids Braess' paradox.

Novel delivery approaches for cancer therapeutics.

PubMed

Mitra, Ashim K; Agrahari, Vibhuti; Mandal, Abhirup; Cholkar, Kishore; Natarajan, Chandramouli; Shah, Sujay; Joseph, Mary; Trinh, Hoang M; Vaishya, Ravi; Yang, Xiaoyan; Hao, Yi; Khurana, Varun; Pal, Dhananjay

2015-12-10

Currently, a majority of cancer treatment strategies are based on the removal of tumor mass mainly by surgery. Chemical and physical treatments such as chemo- and radiotherapies have also made a major contribution in inhibiting rapid growth of malignant cells. Furthermore, these approaches are often combined to enhance therapeutic indices. It is widely known that surgery, chemo- and radiotherapy also inhibit normal cells growth. In addition, these treatment modalities are associated with severe side effects and high toxicity which in turn lead to low quality of life. This review encompasses novel strategies for more effective chemotherapeutic delivery aiming to generate better prognosis. Currently, cancer treatment is a highly dynamic field and significant advances are being made in the development of novel cancer treatment strategies. In contrast to conventional cancer therapeutics, novel approaches such as ligand or receptor based targeting, triggered release, intracellular drug targeting, gene delivery, cancer stem cell therapy, magnetic drug targeting and ultrasound-mediated drug delivery, have added new modalities for cancer treatment. These approaches have led to selective detection of malignant cells leading to their eradication with minimal side effects. Lowering multi-drug resistance and involving influx transportation in targeted drug delivery to cancer cells can also contribute significantly in the therapeutic interventions in cancer. Copyright © 2015 Elsevier B.V. All rights reserved.

N-acetylcysteine prevents stress-induced anxiety behavior in zebrafish.

PubMed

Mocelin, Ricieri; Herrmann, Ana P; Marcon, Matheus; Rambo, Cassiano L; Rohden, Aline; Bevilaqua, Fernanda; de Abreu, Murilo Sander; Zanatta, Leila; Elisabetsky, Elaine; Barcellos, Leonardo J G; Lara, Diogo R; Piato, Angelo L

2015-12-01

Despite the recent advances in understanding the pathophysiology of anxiety disorders, the pharmacological treatments currently available are limited in efficacy and induce serious side effects. A possible strategy to achieve clinical benefits is drug repurposing, i.e., discovery of novel applications for old drugs, bringing new treatment options to the market and to the patients who need them. N-acetylcysteine (NAC), a commonly used mucolytic and paracetamol antidote, has emerged as a promising molecule for the treatment of several neuropsychiatric disorders. The mechanism of action of this drug is complex, and involves modulation of antioxidant, inflammatory, neurotrophic and glutamate pathways. Here we evaluated the effects of NAC on behavioral parameters relevant to anxiety in zebrafish. NAC did not alter behavioral parameters in the novel tank test, prevented the anxiety-like behaviors induced by an acute stressor (net chasing), and increased the time zebrafish spent in the lit side in the light/dark test. These data may indicate that NAC presents an anti-stress effect, with the potential to prevent stress-induced psychiatric disorders such as anxiety and depression. The considerable homology between mammalian and zebrafish genomes invests the current data with translational validity for the further clinical trials needed to substantiate the use of NAC in anxiety disorders. Copyright © 2015 Elsevier Inc. All rights reserved.

Currently used and investigational drugs for Cushing´s disease.

PubMed

Ciato, Denis; Mumbach, Aizhar G; Paez-Pereda, Marcelo; Stalla, Günter K

2017-01-01

Cushing's disease (CD) is caused by a corticotroph adenoma of the pituitary gland that secretes excess adrenocorticotropic hormone (ACTH) causing increased morbidity and mortality. Surgery is the treatment of choice, but is not always successful. Alternatives include radiotherapy, adrenal surgery, and pharmaceutical therapy. The latter is increasingly gaining momentum due to the recent development of compounds that reduce hypercortisolaemia or its symptoms, acting through different mechanisms. Areas covered: In this article, the authors provide a complete overview of the treatment options for Cushing´s disease, including adrenal-directed, tumor-targeted, and peripheral therapies that are currently used or in development, and discuss their potential advantages and limitations. Expert opinion: Considering the lack of long-term remission in up to half of the patients after surgery, and the delayed response to radiotherapy along with potential side effects, there is a strong need for an effective pharmaceutical treatment. Pasireotide, mifepristone, ketoconazole and metyrapone have been approved by regulatory authorities but their use remains limited due to considerable costs and side effects. Research in this field has focused recently on the improvement of pre-existing drugs and the development of safe new ones. However, few approaches aim at targeting the source of the disease, the ACTH-secreting adenoma.

The efficacy of prazosin for the treatment of posttraumatic stress disorder nightmares in U.S. military veterans.

PubMed

Breen, Annamarie; Blankley, Kory; Fine, Julie

2017-02-01

Nightmares associated with posttraumatic stress disorder (PTSD) are a hallmark symptom among U.S. military veterans who have seen combat. Management of combat-related nightmares can be difficult and current pharmacologic options are limited and tend to have adverse side effects. The aim of this review is to explore recent literature regarding the efficacy of prazosin for the treatment of nightmare disorder in the veteran population. Recent literature consisting of three systematic reviews was reviewed, as well as current clinical guidelines published by The Department of Veterans Affairs (VA) and The Department of Defense (DoD) and the American Academy of Sleep Medicine (AASM). Prazosin has been shown to be effective in the treatment of PTSD trauma-related nightmares. As a result of its low side effect profile and abilities to improve both sleep and reduce trauma nightmares, prazosin has been recommended as an adjunct therapy. Prazosin should be initiated as an adjunctive treatment to promote sleep in those suffering from PTSD nightmares. It should be initiated at 1 mg and then titrated upward until absence or desired reduction of nightmares is achieved, with a maximum dosage recommendation of 20 mg at bedtime and 5 mg midmorning. ©2016 American Association of Nurse Practitioners.

Combinatorial nanomedicines for colon cancer therapy.

PubMed

Anitha, A; Maya, S; Sivaram, Amal J; Mony, U; Jayakumar, R

2016-01-01

Colon cancer is one of the major causes of cancer deaths worldwide. Even after surgical resection and aggressive chemotherapy, 50% of colorectal carcinoma patients develop recurrent disease. Thus, the rationale of developing new therapeutic approaches to improve the current chemotherapeutic regimen would be highly recommended. There are reports on the effectiveness of combination chemotherapy in colon cancer and it has been practiced in clinics for long time. These approaches are associated with toxic side effects. Later, the drug delivery research had shown the potential of nanoencapsulation techniques and active targeting as an effective method to improve the effectiveness of chemotherapy with less toxicity. This current focus article provides a brief analysis of the ongoing research in the colon cancer area using the combinatorial nanomedicines and its outcome. © 2015 Wiley Periodicals, Inc.

Effect of Sn Grain Orientation on the Cu6Sn5 Formation in a Sn-Based Solder Under Current Stressing

NASA Astrophysics Data System (ADS)

Lin, Chih-Fan; Lee, Shang-Hua; Chen, Chih-Ming

2012-08-01

A SnAgCu-based solder stripe between two Cu electrodes is current stressed with a density of 5 × 104 A/cm2 at 393 K (120 °C). After current stressing for 24 hours, electromigration induces the Cu dissolution from the cathode-side Cu electrode, leading to the Cu6Sn5 formation in the solder stripe. Very interestingly, the Cu6Sn5 phase is selectively formed within a specific Sn grain. Electron backscattering diffraction analysis indicates the crystallographic orientations of Sn grains play an important role in the selective Cu6Sn5 formation.

Protein Supplement Usage Among Male University Students: Comparisons Between Current and Previous Users.

PubMed

Sung, Youngmo; Choi, Jinkyung

2018-02-01

Interest in specialized dietary supplements is leading market growth, and protein supplements are popular for increasing muscle mass among young males. Therefore, this study investigated the attitudes toward and satisfaction with protein supplements to identify detailed consumer behaviors related to the consumption of protein supplements. The study sample includes male university students in their 20s in South Korea. In total, 223 responses were entered for analysis. Questions related to attitudes, satisfaction, and future behavioral intentions were asked using 5-point Likert scales. The responses were divided into two groups, current and previous users, to identify significant differences in terms of attitudes, satisfaction, and future behavioral intentions. A descriptive analysis, analysis of variance (ANOVA), and multiple regression were run. The majority of respondents prefer the powdered form of supplements in bulk with a price range between 30,000 won and 60,000 won. Online shopping was preferred, while word of mouth and friends/family were considered credible information sources. The most common side effects experienced were problems with digestion and hives, although more than 78% did not experience side effects. In comparison between current and previous users in terms of attitudes and satisfaction, the following areas showed significances. Regarding attitudes, the importance of brand, preference for products from overseas, the search for nutritional facts, and reading carefully all product information were significant, while regarding satisfaction, price, effectiveness, and ease of consumption were significant. All significances showed that current users had more positive attitudes and greater satisfaction. Overall, consumers' satisfaction regarding ease of consumption influenced future behavioral intentions. The market for protein supplements has been growing, so measuring consumers' attitudes and satisfaction would help attract potential consumers. In addition, analyzing previous users' opinions on products could guide product development and encourage customers to return for repurchase.

Transport performance of a HTS current lead prepared by the TFA-MOD processed YBCO tapes

NASA Astrophysics Data System (ADS)

Shiohara, K.; Sakai, S.; Ohki, S.; Yamada, Y.; Tachikawa, K.; Koizumi, T.; Aoki, Y.; Hikichi, Y.; Nishioka, J.; Hasegawa, T.

2009-10-01

A superconducting current lead has been prepared using 12 tapes of the trifluoroacetates - metal organic deposition (TFA-MOD) processed Y 1Ba 2Cu 3O 7-δ (YBCO) coated conductors with critical current ( I c) of about 100 A at 77 K in self-field. The tapes are 4.5 mm in width, 220 mm in length and about 120 μm in overall thickness. The 1 μm thick superconducting YBCO layer was formed through the TFA-MOD process on Hastelloy TM substrate tapes with two buffer oxide layers of Gd 2Zr 2O 7 (GZO) and CeO 2. The 12 YBCO tapes were arrayed on the both sides (six tapes on each side) of a stainless steel board with 3 mm in thickness for a board type shape. They were similarly soldered to copper caps at the both ends. The transport current of 1000 A was stably applied for 10 min in the liquid nitrogen temperature without any voltage generation in all tapes. Although some voltage in some YBCO tapes generated at the applied currents of about 1100 A, the transport current of 1200 A was successfully applied without quenching. The voltage between both copper caps linearly increased with increasing the transport current, and it was about 300 μV at an applied current of 1000 A. A low joint resistance between the YBCO tapes and the copper caps resulted in small amounts of the Joule heating at the joints when 1000 A was applied. The overall (effective) thermal conductivity of the current leads composed of YBCO tapes and the stainless steel board was much lower than that of Non-superconducting current leads. Therefore, the present current leads with small heat leakage seemed to be practically promising for superconducting magnets.

LETTER: Investigation of the effect of Alfven resonance mode conversion on fast wave current drive in ITER

NASA Astrophysics Data System (ADS)

Alava, M. J.; Heikkinen, J. A.; Hellsten, T.

1995-07-01

In order to reduce or to avoid ion cyclotron damping, the use of frequencies below the ion cyclotron frequency of minority ion species or the second harmonic of majority ion species has been proposed for fast wave current drive based on direct electron absorption. For these scenarios, the Alfven or ion-ion hybrid resonance can appear on the high field side of a tokamak. The presence of these resonances causes parasitic absorption, competing with the electron Landau damping and transit time magnetic pumping responsible for the fast wave current drive. In the present study, neglecting effects from toroidicity, the mode conversion at the Alfven resonance is shown to be of the order of 5 to 10% in the current drive scenarios for the planned ITER experiment. If the single pass absorption in the centre can be made sufficiently high, the conversion at the Alfven resonance becomes negligible

A current perspective on cancer immune therapy: step-by-step approach to constructing the magic bullet.

PubMed

D'Errico, Gabriele; Machado, Heather L; Sainz, Bruno

2017-12-01

Immunotherapy is the new trend in cancer treatment due to the selectivity, long lasting effects, and demonstrated improved overall survival and tolerance, when compared to patients treated with conventional chemotherapy. Despite these positive results, immunotherapy is still far from becoming the perfect magic bullet to fight cancer, largely due to the facts that immunotherapy is not effective in all patients nor in all cancer types. How and when will immunotherapy overcome these hurdles? In this review we take a step back to walk side by side with the pioneers of immunotherapy in order to understand what steps need to be taken today to make immunotherapy effective across all cancers. While early scientists, such as Coley, elicited an unselective but effective response against cancer, the search for selectivity pushed immunotherapy to the side in favor of drugs focused on targeting cancer cells. Fortunately, the modern era would revive the importance of the immune system in battling cancer by releasing the brakes or checkpoints (anti-CTLA-4 and anti-PD-1/PD-L1) that have been holding the immune system at bay. However, there are still many hurdles to overcome before immunotherapy becomes a universal cancer therapy. For example, we discuss how the redundant and complex nature of the immune system can impede tumor elimination by teeter tottering between different polarization states: one eliciting anti-cancer effects while the other promoting cancer growth and invasion. In addition, we highlight the incapacity of the immune system to choose between a fight or repair action with respect to tumor growth. Finally we combine these concepts to present a new way to think about the immune system and immune tolerance, by introducing two new metaphors, the "push the accelerator" and "repair the car" metaphors, to explain the current limitations associated with cancer immunotherapy.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kanesue, Takeshi; Ikeda, Shunsuke

A laser ion source is a promising candidate as an ion source for heavy ion inertial fusion (HIF), where a pulsed ultra-intense and low-charged heavy ion beam is required. It is a key development for a laser ion source to transport laser-produced plasma with a magnetic field to achieve a high current beam. The effect of a tapered magnetic field on laser produced plasma is demonstrated by comparing the results with a straight solenoid magnet. The magnetic field of interest is a wider aperture on a target side and narrower aperture on an extraction side. Furthermore, based on the experimentallymore » obtained results, the performance of a scaled laser ion source for HIF was estimated.« less

Critical evaluation of biodegradable polymers used in nanodrugs

PubMed Central

Marin, Edgar; Briceño, Maria Isabel; Caballero-George, Catherina

2013-01-01

Use of biodegradable polymers for biomedical applications has increased in recent decades due to their biocompatibility, biodegradability, flexibility, and minimal side effects. Applications of these materials include creation of skin, blood vessels, cartilage scaffolds, and nanosystems for drug delivery. These biodegradable polymeric nanoparticles enhance properties such as bioavailability and stability, and provide controlled release of bioactive compounds. This review evaluates the classification, synthesis, degradation mechanisms, and biological applications of the biodegradable polymers currently being studied as drug delivery carriers. In addition, the use of nanosystems to solve current drug delivery problems are reviewed. PMID:23990720

Emerging role of amiodarone and dronedarone, as antiarrhythmic drugs, in treatment of leishmaniasis.

PubMed

Oryan, A; Bemani, E; Bahrami, S

2018-04-22

Leishmaniasis is a group of human and animal diseases causing 20,000-40,000 annual deaths and its etiological agents belong to the Leishmania genus. The most current treatment against leishmaniasis is chemotherapy. Pentavalent antimonials such as glucantime and pentostam have been administrated as the first-line drugs in treatment of various forms of leishmaniasis. The second-line drugs such as amphotericin B, liposomal amphotericin B, miltefosine, pentamidine, azole drugs and paromomycin are used in resistant cases to pentavalent antimonials. Because of drawbacks of the first-line and second-line drugs including adverse side effects on different organs, increasing resistance, high cost, need to hospitalization and long-term treatment, it is necessary to find an alternative drug for leishmaniasis treatment. Several investigations have reported the effectiveness of amiodarone, the most commonly used antiarrhythmic drug, against fungi, Trypanosomes and Leishmania spp. in vitro, in vivo and clinical conditions. Moreover, the beneficial effects of dronedarone, amiodarone analogues, against Trypanosoma cruzi and Leishmania mexicana have recently been demonstrated and such treatment regimens resulted in lower side effects. The anti- leishmanial and anti- trypanosomal effectiveness of amiodarone and dronedarone has been attributed to destabilization of intracellular Ca 2+ homeostasis, inhibition of sterol biosynthesis and collapse of mitochondrial membrane potential. Because of relative low cost, excellent pharmacokinetic properties, easy accessibility and beneficial effects of amiodarone and dronedarone on leishmaniasis, they are proper candidates to replace the current drugs used in leishmaniasis treatment. Copyright © 2018 Elsevier B.V. All rights reserved.

“So far it’s been choosing which side effects I want or I can deal with”: A grounded theory of HIV treatment side effects among people living with HIV

PubMed Central

Holmes, Dave

2016-01-01

Despite the availability of new antiretroviral drugs and the simplification of treatment options, side effects continue to affect people living with HIV. In this paper, we present the findings of a grounded theory study designed to gain a critical understanding of the experience of side effects. Three main categories emerged from the data: the side effects, the experience, and the connections. The first category suggests that we need to change how we think about side effects in order to take into account the context in which they are experienced as well as the types and nature of side effects. The second category puts forward the idea that the experience of side effects is composed of three interrelated processes: becoming with, living with, and dealing with. Finally, the third category points to new connections that are formed with people, things and systems in the presence of side effects. PMID:27867446

Relation between therapeutic response and side effects induced by methylphenidate as observed by parents and teachers of children with ADHD.

PubMed

Lee, James; Grizenko, Natalie; Bhat, Venkataramana; Sengupta, Sarojini; Polotskaia, Anna; Joober, Ridha

2011-04-21

The desired (therapeutic) and undesired (side) effects of methylphenidate might have underlying correlations. The aim of this study was to explore the strength and the possible sources of these correlations. One hundred and fifty-seven children with ADHD (6-12 years) were administered placebo and methylphenidate (0.5 mg/kg in a divided b.i.d. dose), each for a one-week period, in a double-blind, crossover trial. Therapeutic response was assessed using the Conners' Global Index for parents (CGI-Parents) and teachers (CGI-Teachers), while side effects were assessed using the Barkley Side Effects Rating Scale (SERS). The side effect profile as assessed by the SERS was similar to that of previous studies with insomnia, decreased appetite, and headaches showing significant treatment effects (p < 0.005). These "somatic/physical" side effects did not correlate with CGI-Parents or CGI-Teachers. However, the side effects of "irritability", "proneness to crying", and "anxiousness" showed significant relationships with CGI-Parents. These "mood/anxiety" side effects showed no significant correlations with the CGI-Teachers. The greater "mood/anxiety" side effects on methylphenidate and placebo, the less the parents observe improvement of their children while treated with methylphenidate. This suggests that the correlations between "mood/anxiety" side effects and poor response to treatment may be driven by observer effects rather than biological commonalities between therapeutic and side effects of methylphenidate.

Kelvin probe microscopic visualization of charge storage at polystyrene interfaces with pentacene and gold

NASA Astrophysics Data System (ADS)

Dawidczyk, T. J.; Johns, G. L.; Ozgun, R.; Alley, O.; Andreou, A. G.; Markovic, N.; Katz, H. E.

2012-02-01

Charge carriers trapped in polystyrene (PS) were investigated with Kelvin probe microscopy (KPM) and thermally stimulated discharge current (TSDC). Lateral heterojunctions of pentacene/PS were scanned using KPM, effectively observing polarization along a side view of a lateral nonvolatile organic field-effect transistor dielectric interface. TSDC was used to observe charge migration out of PS films and to estimate the trap energy level inside the PS, using the initial rise method.

Side Effects

Cancer.gov

Side effects are problems that occur when cancer treatment affects healthy tissues or organs. Learn about side effects caused by cancer treatment. Know what signs and symptoms to call your doctor about. Learn about treatments for side effects.

Water exchange between Algeciras Bay and the Strait of Gibraltar: A study based on HF coastal radar

NASA Astrophysics Data System (ADS)

Chioua, J.; Dastis, C.; González, C. J.; Reyes, E.; Mañanes, R.; Ruiz, M. I.; Álvarez, E.; Yanguas, F.; Romero, J.; Álvarez, O.; Bruno, M.

2017-09-01

This study analyses the water mass exchanges at subinertial scale between Algeciras Bay and the adjacent Strait of Gibraltar. The mechanisms triggering this exchange process is investigated with the aid of recently-acquired data on surface currents obtained using a system of HF coastal radars deployed on the eastern side of the Strait, and remotely-sensed images of sea surface temperature (SST) and chlorophyll from the MODIS sensor of the Aqua satellite. HF radar data on surface currents are analyzed by the application of real empirical orthogonal function (EOF) decomposition, which produces three EOF modes explaining more than 70% of the variance of the surface currents at the mouth of the Bay (modes 2, 3, and 6). Mode 2 is related to the fluctuations of the Atlantic Jet in the central zone of the Strait, mainly due to a combined effect of the atmospheric pressure fluctuations in the Western Mediterranean Sea and local wind in the eastern side of the Strait; mode 3 is related to the coastal currents induced by zonal wind forcing on the north-western coast of the Strait and Alboran Sea; and mode 6 seems to be related to water transport induced by winds blowing with a significant north component into and out of the Bay.

The Processing of the Right-Sided Accent Mark in Left Neglect Dyslexia

ERIC Educational Resources Information Center

Cubelli, Roberto; Beschin, Nicoletta

2005-01-01

Italian polysyllabic words with stress falling on the last syllable are written with a diacritic sign on the last vowel. It allows discrimination between two words with the same orthographic segments (e.g., papa [pope], papa [dad]). The effect of the accent mark in left neglect dyslexia has never been investigated. In the current study, six…

78 FR 76884 - Self-Regulatory Organizations; Topaz Exchange, LLC; Notice of Filing and Immediate Effectiveness...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-19

..., based on current fee levels, the Exchange will charge a fee of $0.48 per contract in Penny Symbols and... Member are assessed fees and rebates at the same level as Market Maker orders. See footnote 2, Schedule... rotation in order to avoid the negative economics associated with paying a rebate on both sides of each...

Methylprednisolone for acute spinal cord injury: an increasingly philosophical debate.

PubMed

Bowers, Christian A; Kundu, Bornali; Hawryluk, Gregory W J

2016-06-01

Following publication of NASCIS II, methylprednisolone sodium succinate (MPSS) was hailed as a breakthrough for patients with acute spinal cord injury (SCI). MPSS use for SCI has since become very controversial and it is our opinion that additional evidence is unlikely to break the stalemate amongst clinicians. Patient opinion has the potential to break this stalemate and we review our recent findings which reported that spinal cord injured patients informed of the risks and benefits of MPSS reported a preference for MPSS administration. We discuss the implications of the current MPSS debate on translational research and seek to address some misconceptions which have evolved. As science has failed to resolve the MPSS debate we argue that the debate is an increasingly philosophical one. We question whether SCI might be viewed as a serious condition like cancer where serious side effects of therapeutics are tolerated even when benefits may be small. We also draw attention to the similarity between the side effects of MPSS and isotretinoin which is prescribed for the cosmetic disorder acne vulgaris. Ultimately we question how patient autonomy should be weighed in the context of current SCI guidelines and MPSS's status as a historical standard of care.

Preferences for a potential longer-acting injectable contraceptive: perspectives from women, providers, and policy makers in Kenya and Rwanda.

PubMed

Tolley, Elizabeth E; McKenna, Kevin; Mackenzie, Caroline; Ngabo, Fidele; Munyambanza, Emmanuel; Arcara, Jennet; Rademacher, Kate H; Lendvay, Anja

2014-05-01

Between 1995 and 2005, injectable use doubled worldwide. However, discontinuation rates remain high, partly because of side effects but also because of missed appointments for reinjection. A longer-acting injectable (LAI) may improve compliance by reducing the required number of reinjection visits, thereby reducing unintentional discontinuation. This study examined acceptability of LAI characteristics comprising the target product profile (TPP). In 2012, we conducted qualitative case studies in Kenya and Rwanda, consisting of 19 focus group discussions (FGDs) with 177 current, previous, or never users of injectables and 46 in-depth interviews (IDIs) with providers, program implementers, and policy makers. FGDs and IDIs assessed current injectable experiences; attitudes toward potential LAI products; and perceptions of TPP attributes, including ranking preferences for the most and least important characteristics. In addition, we obtained completed electronic surveys from 28 international family planning opinion leaders about the perceived need for an LAI, important product characteristics, and challenges to LAI development or introduction. Many FGD participants and interviewees spontaneously expressed strong interest in an LAI, but there was some variation in TPP preferences. The majority of participants ranked effectiveness as the most important TPP attribute. Providers were generally more concerned about side effects than potential users; some potential users suggested that side effects were related less to the product than to their own body chemistry and that side effects were acceptable as long as they did not last a long time or disrupt daily activities. Women and providers, especially in Kenya, preferred a method with a predictable return to fertility. Some participants associated amenorrhea with delayed or reduced fertility. Most women and providers preferred delivery of the LAI in a single, prepackaged, disposable injection system to facilitate injections by providers and to reduce the risk of pain or discomfort for women. While providers and policy makers ranked cost as one of the most important issues, it was among the least important issues for most potential users. Many Kenyan, but few Rwandan, participants appeared willing to pay for an LAI, with some presuming cost savings from reduced menstruation and fewer clinic visits. Some TPP preferences for an LAI have implications for product development decisions about formulation, delivery mechanism, or presentation, while others point to the need for tailored communication and counseling approaches to ensure acceptability and adherence within clinical trials and beyond.

Side Effects of HIV Medicines: HIV and Lactic Acidosis

MedlinePlus

... Drugs Clinical Trials Apps skip to content Side Effects of HIV Medicines Home Understanding HIV/AIDS Fact ... and Immunizations What is a Drug Interaction? Side Effects of HIV Medicines HIV Medicines and Side Effects ...

Monitoring Wind Turbine Loading Using Power Converter Signals

NASA Astrophysics Data System (ADS)

Rieg, C. A.; Smith, C. J.; Crabtree, C. J.

2016-09-01

The ability to detect faults and predict loads on a wind turbine drivetrain's mechanical components cost-effectively is critical to making the cost of wind energy competitive. In order to investigate whether this is possible using the readily available power converter current signals, an existing permanent magnet synchronous generator based wind energy conversion system computer model was modified to include a grid-side converter (GSC) for an improved converter model and a gearbox. The GSC maintains a constant DC link voltage via vector control. The gearbox was modelled as a 3-mass model to allow faults to be included. Gusts and gearbox faults were introduced to investigate the ability of the machine side converter (MSC) current (I q) to detect and quantify loads on the mechanical components. In this model, gearbox faults were not detectable in the I q signal due to shaft stiffness and damping interaction. However, a model that predicts the load change on mechanical wind turbine components using I q was developed and verified using synthetic and real wind data.

77 FR 457 - Implementation of Statute of Limitations Provisions for Office Disciplinary Proceedings

Federal Register 2010, 2011, 2012, 2013, 2014

2012-01-05

... OED Director seeks the practitioner's side of the story, if at all, only after the OED Director... possible grounds for discipline, the OED Director seeks the practitioner's side of the story--the second... practitioner has had the opportunity to present his or her side of the story. Based on current caseload and...

Framing effects on expectations, decisions, and side effects experienced: the case of influenza immunization.

PubMed

O'Connor, A M; Pennie, R A; Dales, R E

1996-11-01

To examine the effects of using positive or negative frames to describe influenza vaccine benefits and side effects on patients' expectations, decisions, decisional conflict, and reported side effects. 292 previously unimmunized patients with chronic respiratory or cardiac disease were randomly assigned to receive benefit/risk information that was framed: (1) positively as the percentage who remain free of influenza and have no vaccine side effects, or (2) negatively as the percentage who acquire influenza and have vaccine side effects. Questionnaires elicited expectations, decisions, and decisional conflict. Vaccines were telephoned 3 days later for a self-report of local and systemic side effects and work absenteeism. Both groups had similar immunization rates and decisional conflict scores. The positive frame group had lower and more realistic expectations of vaccine side effects, fewer systemic side effects, and less work absenteeism (p < 0.05). In contrast to previous studies of health care workers, framing did not influence patients' decisions, possibly due to the patients' awareness of their higher risk of influenza complications and greater desire to follow recommendations. The common practice of using negative frames when describing probabilities of side effects may need to be reexamined, considering its deleterious influence on self-reported side effects and work absenteeism.

Observation of a stationary, current-free double layer in a plasma

NASA Technical Reports Server (NTRS)

Hairapetian, G.; Stenzel, R. L.

1990-01-01

A stationary, current-free, potential double layer is formed in a two-electron-population plasma due to self-consistent separation of the two electron species. The position and amplitude of the double layer are controlled by the relative densities of the two electron populations. The steady-state double layer traps the colder electrons on the high potential side, and generates a neutralized, monoenergetic ion beam on the low potential side. The field-aligned double layer is annihilated when an electron current is drawn through the plasma.

Emerging nanotechnology approaches for HIV/AIDS treatment and prevention

PubMed Central

Mamo, Tewodros; Moseman, E Ashley; Kolishetti, Nagesh; Salvador-Morales, Carolina; Shi, Jinjun; Kuritzkes, Daniel R; Langer, Robert; von Andrian, Ulrich

2010-01-01

Currently, there is no cure and no preventive vaccine for HIV/AIDS. Combination antiretroviral therapy has dramatically improved treatment, but it has to be taken for a lifetime, has major side effects and is ineffective in patients in whom the virus develops resistance. Nanotechnology is an emerging multidisciplinary field that is revolutionizing medicine in the 21st century. It has a vast potential to radically advance the treatment and prevention of HIV/AIDS. In this review, we discuss the challenges with the current treatment of the disease and shed light on the remarkable potential of nanotechnology to provide more effective treatment and prevention for HIV/AIDS by advancing antiretroviral therapy, gene therapy, immunotherapy, vaccinology and microbicides. PMID:20148638

Wigner Transport Simulation of Resonant Tunneling Diodes with Auxiliary Quantum Wells

NASA Astrophysics Data System (ADS)

Lee, Joon-Ho; Shin, Mincheol; Byun, Seok-Joo; Kim, Wangki

2018-03-01

Resonant-tunneling diodes (RTDs) with auxiliary quantum wells ( e.g., emitter prewell, subwell, and collector postwell) are studied using a Wigner transport equation (WTE) discretized by a thirdorder upwind differential scheme. A flat-band potential profile is used for the WTE simulation. Our calculations revealed functions of the auxiliary wells as follows: The prewell increases the current density ( J) and the peak voltage ( V p ) while decreasing the peak-to-valley current ratio (PVCR), and the postwell decreases J while increasing the PVCR. The subwell affects J and PVCR, but its main effect is to decrease V p . When multiple auxiliary wells are used, each auxiliary well contributes independently to the transport without producing side effects.

Mesenchymal Stem/Stromal Cells: A New "Cells as Drugs" Paradigm. Efficacy and Critical Aspects in Cell Therapy

PubMed Central

de Girolamo, Laura; Lucarelli, Enrico; Alessandri, Giulio; Avanzini, Maria Antonietta; Bernardo, Maria Ester; Biagi, Ettore; Brini, Anna Teresa; D’Amico, Giovanna; Fagioli, Franca; Ferrero, Ivana; Locatelli, Franco; Maccario, Rita; Marazzi, Mario; Parolini, Ornella; Pessina, Augusto; Torre, Maria Luisa

2013-01-01

Mesenchymal stem cells (MSCs) were first isolated more than 50 years ago from the bone marrow. Currently MSCs may also be isolated from several alternative sources and they have been used in more than a hundred clinical trials worldwide to treat a wide variety of diseases. The MSCs mechanism of action is undefined and currently under investigation. For in vivo purposes MSCs must be produced in compliance with good manufacturing practices and this has stimulated research on MSCs characterization and safety. The objective of this review is to describe recent developments regarding MSCs properties, physiological effects, delivery, clinical applications and possible side effects. PMID:23278600

The use of stem cells in aesthetic dermatology and plastic surgery procedures. A compact review of experimental and clinical applications

PubMed Central

Nowacki, Maciej; Kloskowski, Tomasz; Pietkun, Katarzyna; Zegarski, Maciej; Pokrywczyńska, Marta; Habib, Samy L.; Drewa, Tomasz

2017-01-01

The aim of this paper was to collect currently available data related to the use of stem cells in aesthetic dermatology and plastic surgery based on a systemic review of experimental and clinical applications. We found that the use of stem cells is very promising but the current state of art is still not effective. This situation is connected with not fully known mechanisms of cell interactions, possible risks and side effects. We think that there is a big need to create and conduct different studies which could resolve problems of stem cells use for implementation into aesthetic dermatology and plastic surgery. PMID:29422816

The use of stem cells in aesthetic dermatology and plastic surgery procedures. A compact review of experimental and clinical applications.

PubMed

Nowacki, Maciej; Kloskowski, Tomasz; Pietkun, Katarzyna; Zegarski, Maciej; Pokrywczyńska, Marta; Habib, Samy L; Drewa, Tomasz; Zegarska, Barbara

2017-12-01

The aim of this paper was to collect currently available data related to the use of stem cells in aesthetic dermatology and plastic surgery based on a systemic review of experimental and clinical applications. We found that the use of stem cells is very promising but the current state of art is still not effective. This situation is connected with not fully known mechanisms of cell interactions, possible risks and side effects. We think that there is a big need to create and conduct different studies which could resolve problems of stem cells use for implementation into aesthetic dermatology and plastic surgery.

Side Effects of Leukotriene Receptor Antagonists in Asthmatic Children.

PubMed

Erdem, Semiha Bahceci; Nacaroglu, Hikmet Tekin; Unsal Karkiner, Canan Sule; Gunay, Ilker; Can, Demet

2015-10-01

Leukotriene receptor antagonists (LTRAs) are drugs which have been widely used more than ten years. As the use of LTRAs increases, our knowledge with respect to their side effects increases as well. The objective of our study was to evaluat the observed side effects of LTRAs used in patients with astma. 1024 patients treated only with LTRAs owing to asthma or early wheezing were included in the study for a five-year period. The observed side effects of LTRAs in these patients were retrospectively investigated. The side effects were divided into two parts as psychiatric and non-psychiatric. Among the 1024 cases included in the study, 67.5% of the patients out of 41 with side effects were male, 32.5% were female and the average age was 6.5 years. The rate of patients with asthma was 63.41% and 36.58% of the patients had early wheezing. It was determined that sex, age and diagnosis (early wheezing or asthma) of the patients were ineffective in the emergence of side effects. The average period for the emergence of side effects was the first month. It was observed that hyperactivity was the most frequently observed psychiatric side effect and that abdominal pain was the non-psychiatric side effect. The side effects of LTRAs were common in children. Therefore, patients must be informed at the beginning of the treatment and they must be evaluated at certain intervals.

Classification of ictal and seizure-free HRV signals with focus on lateralization of epilepsy.

PubMed

Behbahani, Soroor; Dabanloo, Nader Jafarnia; Nasrabadi, Ali Motie; Dourado, Antonio

2016-01-01

Epileptic onsets often affect the autonomic function of the body during a seizure, whether it is in ictal, interictal or post-ictal periods. The different effects of localization and lateralization of seizures on heart rate variability (HRV) emphasize the importance of autonomic function changes in epileptic patients. On the other hand, the detection of seizures is of primary interests in evaluating the epileptic patients. In the current paper, we analyzed the HRV signal to develop a reliable offline seizure-detection algorithm to focus on the effects of lateralization on HRV. We assessed the HRV during 5-min segments of continuous electrocardiogram (ECG) recording with a total number of 170 seizures occurred in 16 patients, composed of 86 left-sided and 84 right-sided focus seizures. Relatively high and low-frequency components of the HRV were computed using spectral analysis. Poincaré parameters of each heart rate time series considered as non-linear features. We fed these features to the Support Vector Machines (SVMs) to find a robust classification method to classify epileptic and non-epileptic signals. Leave One Out Cross-Validation (LOOCV) approach was used to demonstrate the consistency of the classification results. Our obtained classification accuracy confirms that the proposed scheme has a potential in classifying HRV signals to epileptic and non-epileptic classes. The accuracy rates for right-sided and left-sided focus seizures were obtained as 86.74% and 79.41%, respectively. The main finding of our study is that the patients with right-sided focus epilepsy showed more reduction in parasympathetic activity and more increase in sympathetic activity. It can be a marker of impaired vagal activity associated with increased cardiovascular risk and arrhythmias. Our results suggest that lateralization of the seizure onset zone could exert different influences on heart rate changes. A right-sided seizure would cause an ictal tachycardia whereas a left-sided seizure would result in an ictal bradycardia.

Updates on the role of adrenal steroidogenesis inhibitors in Cushing's syndrome: a focus on novel therapies.

PubMed

Fleseriu, Maria; Castinetti, Frederic

2016-12-01

Endogenous Cushing's syndrome (CS) is a rare disease that results from exposure to high levels of cortisol; Cushing's disease (CD) is the most frequent form of CS. Patients with CS suffer from a variety of comorbidities that increase the risk of mortality. Surgical resection of the disease-causing lesion is generally the first-line treatment of CS. However, some patients may not be eligible for surgery due to comorbidities, and approximately 25 % of patients, especially those with CD, have recurrent disease. For these patients, adrenal steroidogenesis inhibitors may control cortisol elevation and subsequent symptomatology. CS is rare overall, and clinical studies of adrenal steroidogenesis inhibitors are often small and, in many cases, data are limited regarding the efficacy and safety of these treatments. Our aim was to better characterize the profiles of efficacy and safety of currently available adrenal steroidogenesis inhibitors, including drugs currently in development. We performed a systematic review of the literature regarding adrenal steroidogenesis inhibitors, focusing on novel drugs. Currently available adrenal steroidogenesis inhibitors, including ketoconazole, metyrapone, etomidate, and mitotane, have variable efficacy and significant side effects, and none are approved by the US Food and Drug Administration for CS. Therefore, there is a clear need for novel, prospectively studied agents that have greater efficacy and a low rate of adverse side effects. Efficacy and safety data of current and emerging adrenal steroidogenesis inhibitors, including osilodrostat (LCI699) and levoketoconazole (COR-003), show promising results that will have to be confirmed in larger-scale phase 3 studies (currently ongoing). The management of CS, and particularly CD, remains challenging. Adrenal steroidogenesis inhibitors can be of major interest to control the hypercortisolism at any time point, either before or after surgery, as discussed in this review.

High performance ripple feedback for the buck unity-power-factor rectifier

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lo, Y.W.; King, R.J.

1995-03-01

The buck unity-power-factor rectifier has harmonic-free input current with complete load regulation down to zero output voltage. A new ``nonlinear ripple feedback`` is proposed which exactly cancels the spoiling effect of dc-side current ripple on the low-distortion ac line current waveforms, even for large amounts of ripple. This cancellation is independent of operating point and readily implemented with analog hardware, thereby permitting economies in the design of the dc filter while maintaining harmonic-free operation. Both large-signal and incremental analyses of the rectifier are given. Confirming experimental results from a 1-kW 48-V isolated battery charger operating with current-ripple levels ranging frommore » 50% to discontinuous-conduction-mode operation are given.« less

St. John's wort: a new alternative for depression?

PubMed

Josey, E S; Tackett, R L

1999-03-01

The primary purpose of this article is to review the existing literature concerning the therapeutic uses, adverse effects, and possible drug interactions of St. John's wort (Hypericum perforatum) as compared to other antidepressant medications. Reference material was obtained through database searches with time restrictions of 1985 to the present. Studies selected were those written in the English language which compared the role of St. John's wort, tricyclic antidepressants, monoamine oxidase inhibitors, and serotonin-selective reuptake inhibitors in the treatment of depression. Other studies were selected based on their evaluation of the safety and efficacy of St. John's wort as an antidepressant for a minimum of four weeks. A review of existing literature recognized nine clinical trials that reported the efficacy of St. John's wort as compared to placebo and to other antidepressant medications. Of these nine, four controlled studies were chosen based upon their large patient populations and their consistency in brand and dosage of St. John's wort used. These four studies demonstrated that St. John's wort was as effective as other antidepressant medications and more effective than placebo, as the clinical symptoms of depression greatly decreased upon administration of H. perforatum. The side-effect profile of H. perforatum at this time appears to be superior to any current U.S.-approved antidepressant medication. From the existing literature, St. John's wort appears to be a safe and effective alternative in the treatment of depression. Tricylic antidepressants and monoamine oxidase inhibitors can produce serious cardiac side-effects, such as tachycardia and postural hypotension, and many unwanted anticholinergic side-effects, including dry mouth and constipation. St. John's wort has proven to be free of any cardiac, as well as anticholinergic, side-effects normally seen with antidepressant medications. Based upon limited studies, St. John's wort appears to be an acceptable alternative to traditional antidepressant therapy, although trials on a larger scale are warranted in this area. Hypericum is available to the lay public as an over-the-counter preparation and may be misused if not fully understood.

A Comparison of Sexual Side Effects of Antidepressants With and Without Naltrexone.

PubMed

Thapa, Mona; Petrakis, Ismene; Ralevski, Elizabeth

2017-01-01

The aim of the study was to compare the rate of sexual side effects of the selective serotonin reuptake inhibitor paroxetine versus the tricyclic antidepressant desipramine and to examine the effect of co-prescription of naltrexone on sexual side effects among participants in a randomized clinical trial. This was a secondary analysis (N = 88) of veterans who participated in a 12-week trial. All veterans were randomized into one of four treatment groups: (a) desipramine/naltrexone, (b) desipramine/placebo, (c) paroxetine/naltrexone, and (d) paroxetine/placebo. The main outcome measure was the frequency of sexual side effects consisting of "decreased sex drive" and/or "impotence" reported by veterans at each weekly visit. Approximately 61% of the veterans reported sexual side effects at least once during the trial, and 26.4% reported sexual side effects throughout the study. There were no significant differences in the frequency of sexual side effects among the four treatment groups. The results were similar when the comparison was made between the two antidepressant groups. There were no significant differences in the reporting of sexual side effects between those receiving desipramine and paroxetine. Also, the comparison between naltrexone and placebo did not alter the results. This is the first study to compare frequency of sexual side effect reporting between paroxetine and desipramine. We found no statistically significant differences in sexual side effect reporting between the two antidepressants. Also, the addition of naltrexone did not show any beneficial effect on the sexual side effect profile.

Core-shell homojunction silicon vertical nanowire tunneling field-effect transistors.

PubMed

Yoon, Jun-Sik; Kim, Kihyun; Baek, Chang-Ki

2017-01-23

We propose three-terminal core-shell (CS) silicon vertical nanowire tunneling field-effect transistors (TFETs), which can be fabricated by conventional CMOS technology. CS TFETs show lower subthreshold swing (SS) and higher on-state current than conventional TFETs through their high surface-to-volume ratio, which increases carrier-tunneling region with no additional device area. The on-state current can be enhanced by increasing the nanowire height, decreasing equivalent oxide thickness (EOT) or creating a nanowire array. The off-state current is also manageable for power saving through selective epitaxial growth at the top-side nanowire region. CS TFETs with an EOT of 0.8 nm and an aspect ratio of 20 for the core nanowire region provide the largest drain current ranges with point SS values below 60 mV/dec and superior on/off current ratio under all operation voltages of 0.5, 0.7, and 1.0 V. These devices are promising for low-power applications at low fabrication cost and high device density.

Forback DC-to-DC converter

NASA Technical Reports Server (NTRS)

Lukemire, Alan T. (Inventor)

1995-01-01

A pulse-width modulated DC-to-DC power converter including a first inductor, i.e. a transformer or an equivalent fixed inductor equal to the inductance of the secondary winding of the transformer, coupled across a source of DC input voltage via a transistor switch which is rendered alternately conductive (ON) and nonconductive (OFF) in accordance with a signal from a feedback control circuit is described. A first capacitor capacitively couples one side of the first inductor to a second inductor which is connected to a second capacitor which is coupled to the other side of the first inductor. A circuit load shunts the second capacitor. A semiconductor diode is additionally coupled from a common circuit connection between the first capacitor and the second inductor to the other side of the first inductor. A current sense transformer generating a current feedback signal for the switch control circuit is directly coupled in series with the other side of the first inductor so that the first capacitor, the second inductor and the current sense transformer are connected in series through the first inductor. The inductance values of the first and second inductors, moreover, are made identical. Such a converter topology results in a simultaneous voltsecond balance in the first inductance and ampere-second balance in the current sense transformer.

Thoracic Injury Risk as a Function of Crash Severity – Car-to-car Side Impact Tests with WorldSID Compared to Real-life Crashes

PubMed Central

Sunnevång, Cecilia; Rosén, Erik; Boström, Ola; Lechelt, Ulf

2010-01-01

Side airbags reduce the risk of fatal injury by approximately 30%. Due to limited real-life data the risk reducing effect for serious injury has not yet been established. Since side airbags are mainly designed and validated for crash severities used in available test procedures little is known regarding the protective effect when severity increases. The objective of this study was to understand for which crash severities AIS3+ thorax occupant protection in car-to-car nearside collisions need to and can be improved. The aim was fulfilled by means of real life data, for older cars without side airbag, and a series of car-to-car tests performed with the WorldSID 50%-ile in modern and older cars at different impact speeds. The real life data showed that the risk of AIS3+ injury was highest for the thorax followed by the pelvis and head. For both non-senior and senior occupants, most thorax injuries were sustained at lateral delta-v from 20 km/h to 40 km/h. In this severity range, senior occupants were found to have approximately four times higher risk of thoracic injury than non-senior occupants. The crash tests at lateral impact speed 55 km/h (delta-v 32 km/h) confirmed the improved performance at severities represented in current legal and rating tests. The structural integrity of the modern car impacted at 70 km/h showed a potential for improved side impact protection by interior countermeasures. PMID:21050600

Thoracic Injury Risk as a Function of Crash Severity - Car-to-car Side Impact Tests with WorldSID Compared to Real-life Crashes.

PubMed

Sunnevång, Cecilia; Rosén, Erik; Boström, Ola; Lechelt, Ulf

2010-01-01

Side airbags reduce the risk of fatal injury by approximately 30%. Due to limited real-life data the risk reducing effect for serious injury has not yet been established. Since side airbags are mainly designed and validated for crash severities used in available test procedures little is known regarding the protective effect when severity increases.The objective of this study was to understand for which crash severities AIS3+ thorax occupant protection in car-to-car nearside collisions need to and can be improved. The aim was fulfilled by means of real life data, for older cars without side airbag, and a series of car-to-car tests performed with the WorldSID 50%-ile in modern and older cars at different impact speeds.The real life data showed that the risk of AIS3+ injury was highest for the thorax followed by the pelvis and head. For both non-senior and senior occupants, most thorax injuries were sustained at lateral delta-v from 20 km/h to 40 km/h. In this severity range, senior occupants were found to have approximately four times higher risk of thoracic injury than non-senior occupants. The crash tests at lateral impact speed 55 km/h (delta-v 32 km/h) confirmed the improved performance at severities represented in current legal and rating tests. The structural integrity of the modern car impacted at 70 km/h showed a potential for improved side impact protection by interior countermeasures.

Molecular dynamics simulation of amino acid ionic liquids near a graphene electrode: effects of alkyl side-chain length.

PubMed

Sadeghi Moghadam, Behnoosh; Razmkhah, Mohammad; Hamed Mosavian, Mohammad Taghi; Moosavi, Fatemeh

2016-12-07

Electric double layer (EDL) supercapacitors, using ionic liquid electrolytes, have been receiving a great deal of attention in response to the growing demand for energy storage systems. In the present study, the nanoscopic structure of amino acid ionic liquids (AAILs) as biodegradable electrolytes near a neutral graphene surface was studied by molecular dynamics (MD) simulation. In order to explore the influence of the anion type and structure, the effect of the alkyl side-chain length of amino acids on the EDL was investigated. The results for the AAILs, composed of 1-ethyl-3-methylimidazolium ([EMIM]) cations near alanine ([ALA]) and isoleucine ([ILE]) anions, were compared to a conventional electrolyte, [EMIM][PF 6 ]. A lower mobility of AAIL compared to [EMIM][PF 6 ], with diffusions as low as 10 -11 m 2 s -1 , was observed. The structural results demonstrated a layered structure near the surface and most of the adsorbed imidazolium cation rings lay flat on the graphene surface. Both MD and quantum computations were performed to shed light on the charge behavior of AAIL electrolytes. As the current results demonstrate, an increase in the anion side-chain length leads to a decrease in both the number of adsorbed ions on the surface and the thickness of the first adsorbed layer. More impressively, it was observed that a low charge concentration in the EDL of AAILs is due to more side-side interactions. This remarkable feature could introduce AAILs as more efficient electrolyte materials than conventional [EMIM][PF 6 ].

Analysis of the electron-beam-induced current of a polycrystalline p-n junction when the diffusion lengths of the material on either side of a grain boundary differ

NASA Technical Reports Server (NTRS)

Von Roos, O.; Luke, K. L.

1984-01-01

The short circuit current generated by the electron beam of a scanning electron microscope in p-n junctions is reduced by enhanced recombination at grain boundaries in polycrystalline material. Frequently, grain boundaries separate the semiconductor into regions possessing different minority carrier life times. This markedly affects the short circuit current I(sc) as a function of scanning distance from the grain boundary. It will be shown theoretically that (1) the minimum of the I(sc) in crossing the grain boundary with the scanning electron beam is shifted away from the grain boundary toward the region with smaller life time (shorter diffusion length), (2) the magnitude of the minimum differs markedly from those calculated under the assumption of equal diffusion lengths on either side of the grain boundary, and (3) the minimum disappears altogether for small surface recombination velocities (s less than 10,000 cm/s). These effects become negligible, however, for large recombination velocities s at grain boundaries. For p-type silicon this happens for s not less than 100,000 cm/s.

The in situ side-to-side bypass technique: a comprehensive review of the technical characteristics, current anastomosis approaches and surgical experience.

PubMed

Wang, Long; Cai, Li; Qian, Hai; Lawton, Michael T; Shi, Xiang'en

2018-05-02

In situ side-to-side (STS) revascularization is an intracranial-intracranial (IC-IC) bypass technique that is increasingly used to treat complex aneurysms and cerebral ischemia. This sophisticated technique involves connecting two proximal parallel vessels to create an artificial conduit for blood flow. This study aims to provide a detailed description of the configuration of the STS bypass technique and extensive information regarding its technical characteristics, current anastomosis approaches and surgical significance. A literature search was performed using the PubMed, Medline, ScienceDirect, Embase, Wiley Online Library, Cambridge Journals, SAGE Journals, Oxford Journals, Research Gate, and Google Scholar databases. The terms "intracranial-intracranial bypass", "in situ bypass", "communicating bypass" and "STS anastomosis" were searched to identify pertinent articles. Articles involving in situ STS anastomosis combined with other bypass methods were excluded. Computer tablet-drawn illustrations of this technique are provided to enhance comprehension. In total, seventy articles that met our search and inclusion criteria were identified. Overall, the radiographical and clinical outcomes of one-hundred and thirty-two (125 aneurysm and 7 cerebral ischemia) patients who underwent in situ STS revascularization were analyzed. IC-IC bypass in the STS fashion can be a safe and effective strategy for the management of complex intracranial aneurysms and cerebral ischemia and is particularly attractive in rescue, anticipated and troubleshooting cases. Despite its extreme rarity, a de novo aneurysm may be observed following STS anastomosis; thus, long-term follow-up is mandatory. Vascular neurosurgeons should consider including this procedure in their treatment armamentarium. Copyright © 2018. Published by Elsevier Inc.

Electromagnetically Clean Solar Arrays

NASA Technical Reports Server (NTRS)

Stem, Theodore G.; Kenniston, Anthony E.

2008-01-01

The term 'electromagnetically clean solar array' ('EMCSA') refers to a panel that contains a planar array of solar photovoltaic cells and that, in comparison with a functionally equivalent solar-array panel of a type heretofore used on spacecraft, (1) exhibits less electromagnetic interferences to and from other nearby electrical and electronic equipment and (2) can be manufactured at lower cost. The reduction of electromagnetic interferences is effected through a combination of (1) electrically conductive, electrically grounded shielding and (2) reduction of areas of current loops (in order to reduce magnetic moments). The reduction of cost is effected by designing the array to be fabricated as a more nearly unitary structure, using fewer components and fewer process steps. Although EMCSAs were conceived primarily for use on spacecraft they are also potentially advantageous for terrestrial applications in which there are requirements to limit electromagnetic interference. In a conventional solar panel of the type meant to be supplanted by an EMCSA panel, the wiring is normally located on the back side, separated from the cells, thereby giving rise to current loops having significant areas and, consequently, significant magnetic moments. Current-loop geometries are chosen in an effort to balance opposing magnetic moments to limit far-0field magnetic interactions, but the relatively large distances separating current loops makes full cancellation of magnetic fields problematic. The panel is assembled from bare photovoltaic cells by means of multiple sensitive process steps that contribute significantly to cost, especially if electomagnetic cleanliness is desired. The steps include applying a cover glass and electrical-interconnect-cell (CIC) sub-assemble, connecting the CIC subassemblies into strings of series-connected cells, laying down and adhesively bonding the strings onto a panel structure that has been made in a separate multi-step process, and mounting the wiring on the back of the panel. Each step increases the potential for occurrence of latent defects, loss of process control, and attrition of components. An EMCSA panel includes an integral cover made from a transparent material. The silicone cover supplants the individual cover glasses on the cells and serves as an additional unitary structural support that offers the advantage, relative to glass, of the robust, forgiving nature of the silcone material. The cover contains pockets that hold the solar cells in place during the lamination process. The cover is coated with indium tin oxide to make its surface electrically conductive, so that it serves as a contiguous, electrically grounded shield over the entire panel surface. The cells are mounted in proximity to metallic printed wiring. The painted-wiring layer comprises metal-film traces on a sheet of Kapton (or equivalent) polyimide. The traces include contact pads on one side of the sheet for interconnecting the cells. Return leads are on the opposite side of the sheet, positioned to form the return currents substantially as mirror images of, and in proximity to, the cell sheet currents, thereby minimizing magnetic moments. The printed-wiring arrangement mimics the back-wiring arrangement of conventional solar arrays, but the current-loop areas and the resulting magnetic moments are much smaller because the return-current paths are much closer to the solar-cell sheet currents. The contact pads are prepared with solder fo electrical and mechanical bonding to the cells. The pocketed cover/shield, the solar cells, the printed-wiring layer, an electrical bonding agent, a mechanical-bonding agent, a composite structural front-side face sheet, an aluminum honeycomb core, and a composite back-side face sheet are all assembled, then contact pads are soldered to the cells and the agents are cured in a single lamination process.

Effect of cyclic aromatics on sodium active transport in frog skin

DOE Office of Scientific and Technical Information (OSTI.GOV)

Blankemeyer, J.T.; Bowerman, M.C.

1993-01-01

A modified glass Ussing-chamber was used to mount the skin. The electrical potential difference (PD) was measured by two 3% agar-frog Ringer's bridges. Current (i.e. short-circuit current, or ISC) was passed by Ag-AgCl electrodes placed so that current density was uniform across the skin. Ringer's solution, bathing each side of the frog skin, was stirred and aerated by gas-lift pumps. The effect of toxicants on the ISC was determined by using the 15 min prior to toxicant administration as a control period, then calculating the change in ISC during the toxicant period as a percent of the control ISC. Phenolmore » and benzene are components of crude oil and crude oil waste. These hydrocarbons and phenanthrene were tested for their effect on frog skin. The results show that the effect of organics on sodium active transport of an epithelium is to alter the active transport of sodium ions. 5 refs., 3 figs., 1 tab.« less

Effect of atomic layer deposition temperature on current conduction in Al2O3 films formed using H2O oxidant

NASA Astrophysics Data System (ADS)

Hiraiwa, Atsushi; Matsumura, Daisuke; Kawarada, Hiroshi

2016-08-01

To develop high-performance, high-reliability gate insulation and surface passivation technologies for wide-bandgap semiconductor devices, the effect of atomic layer deposition (ALD) temperature on current conduction in Al2O3 films is investigated based on the recently proposed space-charge-controlled field emission model. Leakage current measurement shows that Al2O3 metal-insulator-semiconductor capacitors formed on the Si substrates underperform thermally grown SiO2 capacitors at the same average field. However, using equivalent oxide field as a more practical measure, the Al2O3 capacitors are found to outperform the SiO2 capacitors in the cases where the capacitors are negatively biased and the gate material is adequately selected to reduce virtual dipoles at the gate/Al2O3 interface. The Al2O3 electron affinity increases with the increasing ALD temperature, but the gate-side virtual dipoles are not affected. Therefore, the leakage current of negatively biased Al2O3 capacitors is approximately independent of the ALD temperature because of the compensation of the opposite effects of increased electron affinity and permittivity in Al2O3. By contrast, the substrate-side sheet of charge increases with increasing ALD temperature above 210 °C and hence enhances the current of positively biased Al2O3 capacitors more significantly at high temperatures. Additionally, an anomalous oscillatory shift of the current-voltage characteristics with ALD temperature was observed in positively biased capacitors formed by low-temperature (≤210 °C) ALD. This shift is caused by dipoles at the Al2O3/underlying SiO2 interface. Although they have a minimal positive-bias leakage current, the low-temperature-grown Al2O3 films cause the so-called blisters problem when heated above 400 °C. Therefore, because of the absence of blistering, a 450 °C ALD process is presently the most promising technology for growing high-reliability Al2O3 films.

Side Effects to Antidepressant Treatment in Patients With Depression and Comorbid Panic Disorder.

PubMed

Shankman, Stewart A; Gorka, Stephanie M; Katz, Andrea C; Klein, Daniel N; Markowitz, John C; Arnow, Bruce A; Manber, Rachel; Rothbaum, Barbara O; Thase, Michael E; Schatzberg, Alan F; Keller, Martin B; Trivedi, Madhukar H; Kocsis, James H

2017-04-01

Side effects to antidepressant medication can affect the efficacy of treatment, but few predictors foretell who experiences side effects and which side effects they experience. This secondary data analysis examined whether depressed patients with comorbid panic disorder were more likely to experience side effects than those without panic disorder. The study also examined whether greater burden of side effects predicted a poorer treatment course for patients with panic disorder than those without panic disorder. To examine the specificity of these effects, analyses also examined 2 other anxiety disorders-social phobia and generalized anxiety disorder (GAD). Between 2002 and 2006, a large sample (N = 808) of chronically depressed individuals (assessed using the Structured Clinical Interview for DSM-IV-TR Axis I Disorders [SCID-IV]) received antidepressants according to a predetermined algorithm for 12 weeks. Every 2 weeks, depressive symptoms (per the Hamilton Depression Rating Scale) and side effects (specific side effects as well as several indicators of side effect burden) were assessed. Lifetime diagnosis of panic disorder (assessed using the SCID-IV) at baseline was associated with higher likelihood of gastrointestinal (OR = 1.6 [95% CI, 1.0-2.6]), cardiac (OR = 1.8 [95% CI, 1.1-3.1]), neurologic (OR = 2.6 [95% CI, 1.6-4.2]), and genitourinary side effects (OR = 3.0 [95% CI, 1.7-5.3]) during treatment. Increases in side effect frequency, intensity, and impairment over time were more strongly associated with increases in depressive symptoms for patients with panic disorder compared to those without panic disorder. Neither social phobia nor GAD was associated with these effects. Potentially due to heighte​ned interoceptive awareness of changes in their body, chronically depressed individuals with panic disorder may be at greater risk than those without panic disorder for antidepressant side effects and to experience a worsening of depressive symptoms as a result of these side effects over time. ClinicalTrials.gov identifier: NCT00057551​. © Copyright 2017 Physicians Postgraduate Press, Inc.

Evaluation of nicotine and cotinine analogs as potential neuroprotective agents for Alzheimer's disease.

PubMed

Gao, Jie; Adam, Bao-Ling; Terry, Alvin V

2014-03-15

The currently available therapies for Alzheimer's disease (AD) and related forms of dementia are limited by modest efficacy, adverse side effects, and the fact that they do not prevent the relentless progression of the illness. The purpose of the studies described here was to investigate the neuroprotective effects of the nicotine metabolite cotinine as well as a small series of cotinine and nicotine analogs (including stereoisomers) and to compare their effects to the four clinically prescribed AD therapies. Copyright © 2014 Elsevier Ltd. All rights reserved.

Medications and Side Effects

MedlinePlus

... to fully work. You might feel some side effects of your medication before your feel the benefits – ... as sleepiness, anxiety or headache) is a side effect or a symptom of your illness. Many side ...

Neuromodulation of chronic headaches: position statement from the European Headache Federation

PubMed Central

2013-01-01

The medical treatment of patients with chronic primary headache syndromes (chronic migraine, chronic tension-type headache, chronic cluster headache, hemicrania continua) is challenging as serious side effects frequently complicate the course of medical treatment and some patients may be even medically intractable. When a definitive lack of responsiveness to conservative treatments is ascertained and medication overuse headache is excluded, neuromodulation options can be considered in selected cases. Here, the various invasive and non-invasive approaches, such as hypothalamic deep brain stimulation, occipital nerve stimulation, stimulation of sphenopalatine ganglion, cervical spinal cord stimulation, vagus nerve stimulation, transcranial direct current stimulation, repetitive transcranial magnetic stimulation, and transcutaneous electrical nerve stimulation are extensively published although proper RCT-based evidence is limited. The European Headache Federation herewith provides a consensus statement on the clinical use of neuromodulation in headache, based on theoretical background, clinical data, and side effect of each method. This international consensus further gives recommendations for future studies on these new approaches. In spite of a growing field of stimulation devices in headaches treatment, further controlled studies to validate, strengthen and disseminate the use of neurostimulation are clearly warranted. Consequently, until these data are available any neurostimulation device should only be used in patients with medically intractable syndromes from tertiary headache centers either as part of a valid study or have shown to be effective in such controlled studies with an acceptable side effect profile. PMID:24144382

Frequency of sexual dysfunction and other reproductive side-effects in patients with schizophrenia treated with risperidone, olanzapine, quetiapine, or haloperidol: the results of the EIRE study.

PubMed

Bobes, J; Garc A-Portilla, M P; Rejas, J; Hern Ndez, G; Garcia-Garcia, M; Rico-Villademoros, F; Porras, A

2003-01-01

Atypical antipsychotics seem to differ mainly in their tolerability profile. The aim of this cross-sectional study, the Estudio de Investigaci n de Resultados en Esquizofrenia (Outcomes Research Study in Schizophrenia; EIRE study), was to assess in a clinical setting the frequency of several side-effects related to haloperidol, risperidone, olanzapine, and quetiapine. This article addresses sexual dysfunction and other reproductive side-effects (gynecomastia, menorrhage, amenorrhea, and galactorrhea). We recruited outpatients diagnosed with schizophrenia according to Diagnostic and Statistical Manual of Mental Disorders (DSM-IV; American Psychiatric Association, 1994) criteria and who had received a single antipsychotic (risperidone, olanzapine, quetiapine, or haloperidol) for at least 4 weeks. During a single visit, we collected data, including demographic and clinical characteristics, current antipsychotic and concomitant treatment, and adverse effects listed in a modified version of the UKU Scale. We used a Chi-squared test to determine pairs comparisons of the frequency of adverse reactions between treatments. To estimate risk of a given adverse reaction with a given treatment, we used a logistic regression method. We assessed 636 evaluable patients out of 669 recruited. Frequency of sexual dysfunction was high with haloperidol (38.1%) and also with olanzapine (35.3%), quetiapine (18.2%), and risperidone (43.2%). We found the frequency of other reproductive side-effects to be relatively low with all four drugs: haloperidol (6.9%), olanzapine (6.4%), quetiapine (2.7%), and risperidone (11.7%). Sexual dysfunction appeared to be dose-related with haloperidol, risperidone, and olanzapine. Risperidone and olanzapine showed a higher risk of sexual dysfunction and other reproductive sideeffects than haloperidol. Quetiapine showed a lower risk of sexual dysfunction during short-term treatment (< 12 weeks). However, data on longer-term treatment (> 12 weeks) are lacking. Our results suggest that none of the atypical antipsychotics that we studied significantly improved sexual dysfunction and other reproductive side-effects of the conventional antipsychotic, haloperidol, in stabilized patients during long-term treatment. Quetiapine appears to improve this profile during short-term treatment; however, longterm data, with larger samples, are required with this latter drug.

Cancer Treatment for Women: Possible Sexual Side Effects

MedlinePlus

... the clitoris. These play a major part in sexual arousal in women. Removing the vulva and the clitoris ... www.cancer.org/treatment/treatments-and-side-effects/physical-side-effects/fertility-and-sexual-side-effects/sexuality-for-women-with-cancer.html. ...

"There is a chain of connections": using syndemics theory to understand HIV treatment side effects.

PubMed

Gagnon, Marilou

2018-03-12

Side effects are central to the experience of living longer with HIV but rarely have they been studied alone. Unlike other aspects of that experience, like quality of life, treatment adherence, chronicity, episodic disability, aging, health, and viral load suppression, side effects have not benefited from the same level of empirical and theoretical engagement from qualitative researchers. In this paper, we draw on syndemics theory and 50 qualitative interviews to better understand the experience of HIV treatment side effects. Two main categories were identified in the data: side effects as a product and side effects as a risk factor. The first category suggests that side effects are not just the product of taking antiretroviral drugs. They are also the product of particular conditions and tend to cluster with other health problems. The second category puts forward the idea that side effects can act as a syndemic risk factor by exposing PLWH to a greater risk of developing health problems and creating conditions in which psychosocial issues are more likely to emerge. The paper concludes by calling for more research on the complex nature of side effects and for the development of comprehensive approaches for the assessment and management of side effects.

Patient-provider communication and hormonal therapy side effects in breast cancer survivors.

PubMed

Lin, Jenny J; Chao, Jennifer; Bickell, Nina A; Wisnivesky, Juan P

2017-09-01

Side effects from hormonal therapy (HT) for breast cancer treatment occur frequently and are associated with worse quality of life and HT non-adherence. Whether improved patient-physician communication is associated with patients' reporting of side effects is unknown. We undertook this study to assess factors associated with women's reports of HT side effects. Between December 2012 and April 2013, we conducted a cross-sectional survey of breast cancer patients undergoing HT in an urban medical center. Descriptive statistics, univariate analyses, and multivariate analyses were used to evaluate associations. Of the 100 participants, 67% reported having HT side effects. However, when prompted, an additional 9% reported experiencing specific HT-related symptoms. Despite very high communication scores, one-third of participants reported they had not discussed side effects with providers. Multivariate analysis showed that after controlling for age, education, race, and medication beliefs, women who had difficulty asking providers for more information were more likely to report side effects (odds ratio 8.27, 95% confidence interval 1.01-69.88). Although HT side effects often occur and are bothersome, patient-provider discussions about side effects remain suboptimal. Providers should actively ask patients about medication side effects so that they can be addressed to improve quality of life and potentially, medication adherence.

Acupuncture for Cancer-Induced Bone Pain?

PubMed Central

Paley, Carole A.; Bennett, Michael I.; Johnson, Mark I.

2011-01-01

Bone pain is the most common type of pain in cancer. Bony metastases are common in advanced cancers, particularly in multiple myeloma, breast, prostate or lung cancer. Current pain-relieving strategies include the use of opioid-based analgesia, bisphosphonates and radiotherapy. Although patients experience some pain relief, these interventions may produce unacceptable side-effects which inevitably affect the quality of life. Acupuncture may represent a potentially valuable adjunct to existing strategies for pain relief and it is known to be relatively free of harmful side-effects. Although acupuncture is used in palliative care settings for all types of cancer pain the evidence-base is sparse and inconclusive and there is very little evidence to show its effectiveness in relieving cancer-induced bone pain (CIBP). The aim of this critical review is to consider the known physiological effects of acupuncture and discuss these in the context of the pathophysiology of malignant bone pain. The aim of future research should be to produce an effective protocol for treating CIBP with acupuncture based on a sound, evidence-based rationale. The physiological mechanisms presented in this review suggest that this is a realistic objective. PMID:21799687

Knowledge, attitude and practice of pharmacists and health-care workers regarding oral contraceptives correct usage, side-effects and contraindications.

PubMed

Sattari, M; Mokhtari, Z; Jabari, H; Mashayekhi, S O

2013-06-01

Despite the success of the Iranian family planning programme, the number of unwanted pregnancies remains high. To investigate whether health workers in Tabriz are providing correct information and counselling about OCP use, the current study was planned to examine the level of knowledge, attitude and practice of OCP providers. A sample of 150 health-care workers in health houses and 150 community/hospital pharmacists answered a questionnaire about knowledge of correct use of OCP, side-effects, contraindications, danger signs/symptoms and non-contraceptive benefits, and whether they counselled patients about these subjects. Knowledge of pharmacists and health workers was not as high as expected and in many topics they were counselling patients even when they had incorrect knowledge and in other areas they were not providing information to patients despite having the correct knowledge. Better continuing education for OCP providers and especially for pharmacists seems necessary.

Phytochemical and pharmacological properties of essential oils from Cedrus species.

PubMed

Saab, Antoine M; Gambari, Roberto; Sacchetti, Gianni; Guerrini, Alessandra; Lampronti, Ilaria; Tacchini, Massimo; El Samrani, Antoine; Medawar, Samir; Makhlouf, Hassane; Tannoury, Mona; Abboud, Jihad; Diab-Assaf, Mona; Kijjoa, Anake; Tundis, Rosa; Aoun, Jawad; Efferth, Thomas

2018-06-01

Natural products frequently exert pharmacological activities. The present review gives an overview of the ethnobotany, phytochemistry and pharmacology of the Cedrus genus, e.g. cytotoxic, spasmolytic immunomodulatory, antiallergic, anti-inflammatory and analgesic activities. Cancer patients frequently seek remedies from traditional medicinal plants that are believed to exert less side effects than conventional therapy with synthetic drugs. A long-lasting goal of anti-cancer and anti-microbial therapy research is to find compounds with reduced side effects compared to currently approved drugs. In this respect, Cedrus species might be of interest. The essential oil isolated from Cedrus libani leaves may bear potential for drug development due to its high concentrations of germacrene D and β-caryophyllene. The essential oils from Cedrus species also show bioactivity against bacteria and viruses. More preclinical analyses (e.g. in vivo experiments) as well as clinical trials are required to evaluate the potential of essential oils from Cedrus species for drug development.

Sweet proteins – Potential replacement for artificial low calorie sweeteners

PubMed Central

Kant, Ravi

2005-01-01

Exponential growth in the number of patients suffering from diseases caused by the consumption of sugar has become a threat to mankind's health. Artificial low calorie sweeteners available in the market may have severe side effects. It takes time to figure out the long term side effects and by the time these are established, they are replaced by a new low calorie sweetener. Saccharine has been used for centuries to sweeten foods and beverages without calories or carbohydrate. It was also used on a large scale during the sugar shortage of the two world wars but was abandoned as soon as it was linked with development of bladder cancer. Naturally occurring sweet and taste modifying proteins are being seen as potential replacements for the currently available artificial low calorie sweeteners. Interaction aspects of sweet proteins and the human sweet taste receptor are being investigated. PMID:15703077

Evidence for motivational effects elicited by activation of GABA-A or dopamine receptors in the nucleus accumbens shell.

PubMed

Wirtshafter, David; Stratford, Thomas R

2010-09-01

Microinjections of the inhibitory GABA-A receptor agonist muscimol into the shell region of the nucleus accumbens (AcbSh) have been reported to induce large increases in food intake, but the effect of these injections on motivational processes is less clear. In the current study, bilateral injections of saline, muscimol (50ng/side) or d-amphetamine (10mug/side) were made into the AcbSh of rats trained to lever press on a progressive ratio schedule for food reward. Injections of both muscimol and amphetamine were found to produce a large increase in the breaking point relative to saline injections. This result suggests that inactivation of the AcbSh does not simply drive ingestive behavior, but also affects motivational processes assessed by the progressive ratio schedule. Breaking points were also increased by injections of amphetamine into the AcbSh. Copyright 2010 Elsevier Inc. All rights reserved.

Evidence for motivational effects elicited by activation of GABA-A or dopamine receptors in the nucleus accumbens shell

PubMed Central

Wirtshafter, David; Stratford, Thomas R.

2011-01-01

Microinjections of the inhibitory GABA-A receptor agonist muscimol into the shell region of the nucleus accumbens (AcbSh) have been reported to induce large increases in food intake, but the effect of these injections on motivational processes is less clear. In the current study, bilateral injections of saline, muscimol (50 ng/side) or D-amphetamine (10 μg/side) were made into the AcbSh of rats trained to lever press on a progressive ratio schedule for food reward. Injections of both muscimol and amphetamine were found to produce a large increase in the breaking point relative to saline injections. This result suggests that inactivation of the AcbSh does not simply drive ingestive behavior, but also affects motivational processes assessed by the progressive ratio schedule. Breaking points were also increased by injections of amphetamine into the AcbSh. PMID:20598739

Power flow controller with a fractionally rated back-to-back converter

DOEpatents

Divan, Deepakraj M.; Kandula, Rajendra Prasad; Prasai, Anish

2016-03-08

A power flow controller with a fractionally rated back-to-back (BTB) converter is provided. The power flow controller provide dynamic control of both active and reactive power of a power system. The power flow controller inserts a voltage with controllable magnitude and phase between two AC sources at the same frequency; thereby effecting control of active and reactive power flows between the two AC sources. A transformer may be augmented with a fractionally rated bi-directional Back to Back (BTB) converter. The fractionally rated BTB converter comprises a transformer side converter (TSC), a direct-current (DC) link, and a line side converter (LSC). By controlling the switches of the BTB converter, the effective phase angle between the two AC source voltages may be regulated, and the amplitude of the voltage inserted by the power flow controller may be adjusted with respect to the AC source voltages.

Identification and characterization of carprofen as a multitarget fatty acid amide hydrolase/cyclooxygenase inhibitor.

PubMed

Favia, Angelo D; Habrant, Damien; Scarpelli, Rita; Migliore, Marco; Albani, Clara; Bertozzi, Sine Mandrup; Dionisi, Mauro; Tarozzo, Glauco; Piomelli, Daniele; Cavalli, Andrea; De Vivo, Marco

2012-10-25

Pain and inflammation are major therapeutic areas for drug discovery. Current drugs for these pathologies have limited efficacy, however, and often cause a number of unwanted side effects. In the present study, we identify the nonsteroidal anti-inflammatory drug carprofen as a multitarget-directed ligand that simultaneously inhibits cyclooxygenase-1 (COX-1), COX-2, and fatty acid amide hydrolase (FAAH). Additionally, we synthesized and tested several derivatives of carprofen, sharing this multitarget activity. This may result in improved analgesic efficacy and reduced side effects (Naidu et al. J. Pharmacol. Exp. Ther.2009, 329, 48-56; Fowler, C. J.; et al. J. Enzyme Inhib. Med. Chem.2012, in press; Sasso et al. Pharmacol. Res.2012, 65, 553). The new compounds are among the most potent multitarget FAAH/COX inhibitors reported so far in the literature and thus may represent promising starting points for the discovery of new analgesic and anti-inflammatory drugs.

The effect of side motion in the dynamics of interacting molecular motors

NASA Astrophysics Data System (ADS)

Midha, Tripti; Gupta, Arvind Kumar; Kolomeisky, Anatoly B.

2017-07-01

To mimic the collective motion of interacting molecular motors, we propose and discuss an open two-lane symmetrically coupled interactive TASEP model that incorporates interaction in the thermodynamically consistent fashion. We study the effect of both repulsive and attractive interaction on the system’s dynamical properties using various cluster mean field analysis and extensive Monte Carlo simulations. The interactions bring correlations into the system, which were found to be reduced due to the side motion of particles. We produce the steady-state phase diagrams for symmetrically split interaction strength. The behavior of the maximal particle current with respect to the interaction energy E is analyzed for different coupling rates and interaction splittings. The results suggest that for strong coupling and large splittings, the maximal flow of the motors occurs at a weak attractive interaction strength which matches with the known experimental results on kinesin motor protein.

Reduction of chronic abdominal pain in patients with inflammatory bowel disease through transcranial direct current stimulation: a randomized controlled trial.

PubMed

Volz, Magdalena S; Farmer, Annabelle; Siegmund, Britta

2016-02-01

Inflammatory bowel disease (IBD) is frequently associated with chronic abdominal pain (CAP). Transcranial direct current stimulation (tDCS) has been proven to reduce chronic pain. This study aimed to investigate the effects of tDCS in patients with CAP due to IBD. This randomized, sham-controlled, double blind, parallel-designed study included 20 patients with either Crohn disease or ulcerative colitis with CAP (≥3/10 on the visual analog scale (VAS) in 3/6 months). Anodal or sham tDCS was applied over the primary motor cortex for 5 consecutive days (2 mA, 20 minutes). Assessments included VAS, pressure pain threshold, inflammatory markers, and questionnaires on quality of life, functional and disease specific symptoms (Irritable Bowel Syndrome-Severity Scoring System [IBS-SSS]), disease activity, and pain catastrophizing. Follow-up data were collected 1 week after the end of the stimulation. Statistical analyses were performed using analysis of variance and t tests. There was a significant reduction of abdominal pain in the anodal tDCS group compared with sham tDCS. This effect was evident in changes in VAS and pressure pain threshold on the left and right sides of the abdomen. In addition, 1 week after stimulation, pain reduction remained significantly decreased in the right side of the abdomen. There was also a significant reduction in scores on pain catastrophizing and on IBS-SSS when comparing both groups. Inflammatory markers and disease activity did not differ significantly between groups throughout the experiment. Transcranial direct current stimulation proved to be an effective and clinically relevant therapeutic strategy for CAP in IBD. The analgesic effects observed are unrelated to inflammation and disease activity, which emphasizes central pain mechanisms in CAP.

A Review of Nanoparticle Photosensitizer Drug Delivery Uptake Systems for Photodynamic Treatment of Lung Cancer.

PubMed

Gift, Mokwena Mpho; Ann, Kruger Cherie; Ivan, Mfouo-Tynga; Heidi, Abrahamse

2018-03-24

Lung cancer is a leading cause of cancer related deaths worldwide and so current research is focused on trying to improve treatment modalities, such as photodynamic therapy (PDT). PDT has 3 fundamental factors, namely a photosensitizer (PS) drug, light and oxygen. When a PS drug is administered to a patient, it can either passively or actively accumulate within a tumour site and once exposed to a specific wavelength of light, it is stimulated to produce reactive oxygen species (ROS), resulting in tumour destruction. However, the efficacy of ROS generation for tumour destruction is highly dependent on the accumulation of the PS in tumour cells. Thus PS selective / targeted uptake and delivery in tumour cells is a crucial factor in PDT cancer drug absorption studies. Generally, within non-targeted drug delivery mechanisms, only small amounts of PS is able to passively accumulates in tumour sites due to the enhanced permeability and retention (EPR) effect and the remainder distributes into healthy tissues, causing side effects. Thus to improve the efficacy of PDT, research is currently focused on the development of specific receptor based photosynthetic nanocarrier drugs, which promotes the active uptake and absorption of PS drugs in tumour sites only, avoiding unwanted side effects. The aim of this review is to focus on current non-targeted passive versus specifically active targeted PS nanoparticle drug delivery systems, that have been investigated for the PDT treatment of lung cancer and so to deduce its efficacy and recent advancements. Copyright © 2018. Published by Elsevier B.V.

Side effect burden of antipsychotic drugs in real life - Impact of gender and polypharmacy.

PubMed

Iversen, Trude Seselie Jahr; Steen, Nils Eiel; Dieset, Ingrid; Hope, Sigrun; Mørch, Ragni; Gardsjord, Erlend Strand; Jørgensen, Kjetil Nordbø; Melle, Ingrid; Andreassen, Ole A; Molden, Espen; Jönsson, Erik G

2018-03-02

Antipsychotic-associated side effects are well known and represent a significant treatment challenge. Still, few large studies have investigated the overall side effect burden of antipsychotics in real-life settings. To describe the occurrence of side effects and perceived burden of antipsychotics in a large naturalistic sample, taking polypharmacy and patient characteristics into account. Patients (n=1087) with psychotic disorders were assessed for side effects using the Udvalg for Kliniske Undersøgelser (UKU) side effect rating scale in addition to assessment of clinical and pharmacological data. Statistical analyses were performed controlling for possible confounding factors. Use of antipsychotics showed significant associations to neurologic and sexual symptoms, sedation and weight gain, and >75% of antipsychotics-users reported side effects. More side effects were observed in patients using several antipsychotics (p=0.002), with increasing total dose (p=0.021) and with antipsychotics in combinations with other psychotropic drugs. Patients and investigators evaluated the side effect burden differently, particularly related to severity, gender and antipsychotics dose. Twice as many females described side effect burden as severe (p=0.004). Patients with psychotic disorders have a high occurrence of symptoms associated with use of antipsychotics, and polypharmacy and female gender are seemingly risk factors for reporting a severe side effect burden. Due to the cross-sectional design evaluation of causality is tentative, and these findings should be further investigated in prospective studies. Copyright © 2017 Elsevier Inc. All rights reserved.

The Glasgow antipsychotic side-effects scale for clozapine in inpatients and outpatients with schizophrenia or schizoaffective disorder.

PubMed

Ignjatović Ristić, Dragana; Cohen, Dan; Obradović, Andrea; Nikić-Đuričić, Katarina; Drašković, Marija; Hinić, Darko

2018-02-01

The inconsistency in clinician and patient ratings of clozapine-induced side effects underscore the need to supplement clinician-based estimates of side effects with patient-reported ones. The main aims of the study are validation of the Glasgow antipsychotic side-effects scale for clozapine (GASS-C) in Serbian inpatients/outpatients with schizophrenia or schizo-affective disorder and recommendations for its future use, based on common and rare clozapine-associated side-effects. The GASS-C was administered to 95 outpatients/inpatients diagnosed with schizophrenia, schizoaffective, or chronic psychotic disorder. The scale showed good overall reliability, with an internal consistency coefficient of α = 0.84, an average retest coefficient of rho = 0.76, and a Spearman-Brown coefficient of validity of 0.81. Side effects were absent or mild in 64.2% of the patients, moderate in 31.6%, severe in 4.2%; 14% of the subjects considered their symptoms distressing. The most commonly reported side-effects were drowsiness, thirst, frequent urination, and dry mouth. Women reported more side effects than men, and patients not in a relationship reported significantly fewer side effects than patients in a relationship. Results indicate a weak positive correlation (rho = 0.231; p = .025) between severity of side effects and clozapine dose. The GASS-C showed good psychometric characteristics in clinical population of patients on clozapine. In future studies, clozapine serum concentrations should be measured when using the GASS-C to monitor side effects.

Learning to experience side effects after antidepressant intake - Results from a randomized, controlled, double-blind study.

PubMed

Rheker, Julia; Winkler, Alexander; Doering, Bettina K; Rief, Winfried

2017-02-01

Side effects play a key role in patients' failure to take antidepressants. There is evidence that verbal suggestions and informed consent elicit expectations that can in turn trigger the occurrence of side effects. Prior experience or learning mechanisms are also assumed to contribute to the development of side effects, although their role has not been thoroughly investigated. In this study, we examined whether an antidepressant's side effects can be learned via Pavlovian conditioning. Participants (n = 39) were randomly allocated to one of two groups and were exposed to a classical conditioning procedure. During acquisition, 19 participants received amitriptyline and 20 participants received a placebo pill. Pills were taken for four nights together with a novel-tasting drink. After a washout phase, both groups received a placebo pill together with the novel-tasting drink (evocation). Side effects were assessed via the Generic Assessment of Side Effects Scale prior to acquisition (baseline), after acquisition, and after evocation. A score of antidepressant-specific side effects was calculated. Participants taking amitriptyline reported significantly more antidepressant-specific side effects after acquisition compared to both baseline and the placebo group. After evocation, participants who underwent the conditioning procedure with amitriptyline reported significantly more antidepressant-specific side effects than those who never received amitriptyline, even though both groups received a placebo. Our results indicate that antidepressant side effects can be learned using a conditioning paradigm and evoked via a placebo pill when applied with the same contextual factors as the verum.

A versatile genetic tool for post-translational control of gene expression in Drosophila melanogaster

PubMed Central

Sethi, Sachin

2017-01-01

Several techniques have been developed to manipulate gene expression temporally in intact neural circuits. However, the applicability of current tools developed for in vivo studies in Drosophila is limited by their incompatibility with existing GAL4 lines and side effects on physiology and behavior. To circumvent these limitations, we adopted a strategy to reversibly regulate protein degradation with a small molecule by using a destabilizing domain (DD). We show that this system is effective across different tissues and developmental stages. We further show that this system can be used to control in vivo gene expression levels with low background, large dynamic range, and in a reversible manner without detectable side effects on the lifespan or behavior of the animal. Additionally, we engineered tools for chemically controlling gene expression (GAL80-DD) and recombination (FLP-DD). We demonstrate the applicability of this technology in manipulating neuronal activity and for high-efficiency sparse labeling of neuronal populations. PMID:29140243

Fear appeals and treatment side-effects: an effective combination for HIV prevention?

PubMed

Slavin, S; Batrouney, C; Murphy, D

2007-01-01

Recent rises in the incidence of HIV infections among gay men in Australia have produced widespread discussion about appropriate health promotion responses. This has sometimes included calls for a return to fear-based campaigns, exemplified by the Grim Reaper advertisements in HIV. This paper discusses results from four focus groups that tested mock campaign material based on an appeal to fear. Five different poster images were tested among groups distinguished by age and HIV serostatus. Three posters used side-effects from treatments as the fear trigger and two used death from AIDS. A number of themes arose in response to the material including 'othering', shame and scepticism about HIV treatments. The meanings of these themes are explored in the light of current health-promotion theory. This data demonstrates that fear is an ineffective tool for HIV health promotion. It further demonstrates that feelings of shame and stigma are likely to be exacerbated in gay men, leading to poorer health outcomes in various ways.

Muscle wasting and sarcopenia in heart failure and beyond: update 2017

PubMed Central

Springer, Joshua‐I.; Anker, Stefan D.

2017-01-01

Abstract Sarcopenia (loss of muscle mass and muscle function) is a strong predictor of frailty, disability and mortality in older persons and may also occur in obese subjects. The prevalence of sarcopenia is increased in patients suffering from chronic heart failure. However, there are currently few therapy options. The main intervention is resistance exercise, either alone or in combination with nutritional support, which seems to enhance the beneficial effects of training. Also, testosterone has been shown to increased muscle power and function; however, a possible limitation is the side effects of testosterone. Other investigational drugs include selective androgen receptor modulators, growth hormone, IGF‐1, compounds targeting myostatin signaling, which have their own set of side effects. There are abundant prospective targets for improving muscle function in the elderly with or without chronic heart failure, and the continuing development of new treatment strategies and compounds for sarcopenia and cardiac cachexia makes this field an exciting one. PMID:29154428

DEVELOPING A VACCINE AGAINST MULTIPLE PSYCHOACTIVE TARGETS: A CASE STUDY OF HEROIN

PubMed Central

Stowe, G. Neil; Schlosburg, Joel E.; Vendruscolo, Leandro F.; Edwards, Scott; Misra, Kaushik K.; Schulteis, Gery; Zakhari, Joseph S.; Koob, George F.; Janda, Kim D.

2012-01-01

Heroin addiction is a wide-reaching problem with a spectrum of damaging social consequences. Currently approved heroin addiction medications include drugs that bind at the same receptors (e.g. opioid receptors) occupied by heroin and/or its metabolites in the brain, but undesired side effects of these treatments, maintenance dependence and relapse to drug taking remains problematic. A vaccine capable of blocking heroin’s effects could provide an economical, long-lasting and sustainable adjunct to heroin addiction therapy without the side effects associated with available treatment options. Heroin, however, presents a particularly challenging vaccine target as it is metabolized to multiple psychoactive molecules of differing lipophilicity, with differing abilities to cross the blood brain barrier. In this review, we discuss the opiate scaffolding and hapten design considerations to confer immunogenicity as well as the specificity of the immune response towards structurally similar opiates. In addition, we detail different strategies employed in the design of immunoconjugates for a vaccine-based therapy for heroin addiction treatment. PMID:22229311

Triptorelin embonate: a 6-month formulation for prostate cancer.

PubMed

Whelan, Peter

2010-12-01

Luteinizing hormone releasing hormone (LH RH) agonists are the major agent for androgen deprivation therapy in advanced and metastatic prostate cancer. They also have a role in endometriosis, uterine fibroids and central precocious puberty. Triptorelin embonate 22.5 mg is a new, sustained-release, 6-month formulation of an LH RH agonist. It possesses longer duration of action than the current standard 3-month preparation and appears to have similar efficacy and side effects. The use of LH RH agonists for androgen deprivation in prostate cancer has increased considerably in the last 20 years. Recent work has shown that some of this usage has constituted overtreatment and it is within these newer paradigms of therapy that the new 6-month preparation is situated. The new 6-month LH RH preparation - triptorelin embonate - will be of help in several key areas of therapy for prostate cancer, notably as an adjunct to radiation therapy and chemotherapy. It possesses a similar effect, but with fewer side effects, than those that are now commonly available.

Concurrent Group Treatment for Hepatitis C: Implementation and Outcomes in a Methadone Maintenance Treatment Program

PubMed Central

Stein, Melissa R.; Soloway, Irene J.; Jefferson, Karen S.; Roose, Robert J.; Arnsten, Julia H.; Litwin, Alain H.

2012-01-01

Chronic hepatitis C virus (HCV) infection is highly prevalent among current and former drug users. However, the minority of patients enrolled in drug treatment programs have initiated HCV treatment. New models are needed to overcome barriers to care. In this retrospective study, we describe the implementation and outcomes of 42 patients treated in a Concurrent Group Treatment (CGT) program. Patients participated in weekly provider-led group treatment sessions which included review of side effects; discussion of adherence and side effect management; administration of interferon injections; brief physical exam; and ended with brief meditation. Of the first 27 patients who initiated CGT, 42% achieved a sustained viral response. Additionally, 87% (13/15) of genotype-1 infected patients treated with direct acting antiviral agent achieved an undetectable viral load at 24 weeks. The CGT model may be effective in overcoming barriers to treatment and improving adherence and outcomes among patients enrolled in drug treatment programs. PMID:23036920

Overview of clinical use and side effect profile of valsartan in Chinese hypertensive patients

PubMed Central

Huang, Qi-Fang; Li, Yan; Wang, Ji-Guang

2014-01-01

We reviewed the Chinese and English literature for the efficacy and safety data of valsartan monotherapy or combination therapy in Chinese hypertensive patients. According to the data of ten randomized controlled trials, valsartan monotherapy was as efficacious as another angiotensin receptor blocker or other classes of antihypertensive drugs, excepting the slightly inferior diastolic blood pressure-lowering effect in comparison with calcium channel blockers. According to the data of six randomized controlled trials, valsartan combination, with hydrochlorothiazide, amlodipine, or nifedipine gastrointestinal therapeutic system, was more efficacious than monotherapy of valsartan, amlodipine, or nifedipine gastrointestinal therapeutic system. According to these trials, valsartan had an acceptable tolerability, regardless of whether it was used as monotherapy or in combination therapy. Nonetheless, several rare side effects have been reported, indicating that it should still be used with caution. This is of particular importance given that there are millions of hypertensive patients, worldwide, currently exposed to the drug. PMID:24403822

Co-treatment with a C1B5 peptide of protein kinase Cγ and a low dose of gemcitabine strongly attenuated pancreatic cancer growth in mice through T cell activation.

PubMed

Ishiguro, Susumu; Kawabata, Atsushi; Zulbaran-Rojas, Alejandro; Monson, Kelsey; Uppalapati, Deepthi; Ohta, Naomi; Inui, Makoto; Pappas, Charalampos G; Tzakos, Andreas G; Tamura, Masaaki

2018-01-01

Although gemcitabine is an effective chemotherapeutic for pancreatic cancer, severe side effects often accompany its use. Since we have discovered that locally administered C1B domain peptides effectively control tumor growth without any side effects, the efficacy of co-treatment with this peptide and a low dose of gemcitabine on the growth of pancreatic cancer was examined. Two- and three-dimensional cell culture studies clarified that a co-treatment with C1B5 peptide and gemcitabine significantly attenuated growth of PAN02 mouse and PANC-1 human pancreatic cancer cells in 2D and 3D cultures. Although treatment with the low dose of gemcitabine alone (76%) or the C1B5 peptide alone (39%) inhibited tumor growth moderately, a co-treatment with C1B5 peptide and a low dose of gemcitabine markedly inhibited the growth of PAN02 autografts in the mouse peritoneal cavity (94% inhibition) without any noticeable adverse effect. The number of peritoneal cavity-infiltrating neutrophils and granzyme B + lymphocytes was significantly higher in the co-treatment group than in the control group. A significant increase of granzyme B mRNA expression was also detected in human T cells by the co-treatment. Taken together, the current study suggests that C1B5 peptide offers a remarkably effective combination treatment strategy to reduce side effects associated with gemcitabine, without losing its tumoricidal effect. Copyright © 2017 Elsevier Inc. All rights reserved.

Effect of cAMP on short-circuit current in isolated human ciliary body.

PubMed

Wu, Ren-yi; Ma, Ning; Hu, Qian-qian

2013-07-01

Cyclic adenosine monophosphate (cAMP) could activate chloride channels in bovine ciliary body and trigger an increase in the ionic current (short-circuit current, Isc) across the ciliary processes in pigs. The purpose of this study was to investigate how cAMP modulates Isc in isolated human ciliary processes and the possible involvement of chloride transport across the tissue in cAMP-induced Isc change. In an Ussing-type chamber system, the Isc changes induced by the cAMP analogue 8-bromo-cAMP and an adenylyl cyclase activator forskolin in isolated human ciliary processes were assessed. The involvement of Cl(-) component in the bath solution was investigated. The effect of Cl(-) channel (10 µmol/L niflumic acid and 1 mmol/L 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS)), K(+) channel (10 mmol/L tetraethylammonium chloride (TEA)), or Na(+) channel blockers (1 mmol/L amiloride) on 8-bromo-cAMP-induced Isc change was also studied. Dose-dependently, 8-bromo-cAMP (10 nmol/L-30 µmol/L) or forskolin (10 nmol/L-3 µmol/L) increased Isc across the ciliary processes with an increase in negative potential difference on the non-pigmented epithelium (NPE) side of the tissue. Isc increase induced by 8-bromo-cAMP was more pronounced when the drug was applied on the NPE side than on the pigmented epithelium side. When the tissue was bathed in low Cl(-) solutions, the Isc increase was significantly inhibited. Finally, niflumic acid and DIDS, but not TEA or amiloride, significantly prevented the Isc increase induced by 8-bromo-cAMP. cAMP stimulates stroma-to-aqueous anionic transport in isolated human ciliary processes. Chloride is likely to be among the ions, the transportation of which across the tissue is triggered by cAMP, suggesting the potential role of cAMP in the process of aqueous humor formation in human eyes.

Occurrence of serious injury in real-world side impacts of vehicles with good side-impact protection ratings.

PubMed

Brumbelow, Matthew L; Mueller, Becky C; Arbelaez, Raul A

2015-01-01

The Insurance Institute for Highway Safety (IIHS) introduced its side impact consumer information test program in 2003. Since that time, side airbags and structural improvements have been implemented across the fleet and the proportion of good ratings has increased to 93% of 2012-2014 model year vehicles. Research has shown that drivers of good-rated vehicles are 70% less likely to die in a left-side crash than drivers of poor-rated vehicles. Despite these improvements, side impact fatalities accounted for about one quarter of passenger vehicle occupant fatalities in 2012. This study is a detailed analysis of real-world cases with serious injury resulting from side crashes of vehicles with good ratings in the IIHS side impact test. NASS-CDS and Crash Injury Research and Engineering Network (CIREN) were queried for occupants of good-rated vehicles who sustained an Abbreviated Injury Scale (AIS) ≥ 3 injury in a side-impact crash. The resulting 110 cases were categorized by impact configuration and other factors that contributed to injury. Patterns of impact configuration, restraint performance, and occupant injury were identified and discussed in the context of potential upgrades to the current IIHS side impact test. Three quarters of the injured occupants were involved in near-side impacts. For these occupants, the most common factors contributing to injury were crash severities greater than the IIHS test, inadequate side-airbag performance, and lack of side-airbag coverage for the injured body region. In the cases where an airbag was present but did not prevent the injury, occupants were often exposed to loading centered farther forward on the vehicle than in the IIHS test. Around 40% of the far-side occupants were injured from contact with the struck-side interior structure, and almost all of these cases were more severe than the IIHS test. The remaining far-side occupants were mostly elderly and sustained injury from the center console, instrument panel, or seat belt. In addition, many far-side occupants were likely out of position due to events preceding the side impact and/or being unbelted. Individual changes to the IIHS side impact test have the potential to reduce the number of serious injuries in real-world crashes. These include impacting the vehicle farther forward (relevant to 28% of all cases studied), greater test severity (17%), the inclusion of far-side occupants (9%), and more restrictive injury criteria (9%). Combinations of these changes could be more effective.

Analysis and elimination method of the effects of cables on LVRT testing for offshore wind turbines

NASA Astrophysics Data System (ADS)

Jiang, Zimin; Liu, Xiaohao; Li, Changgang; Liu, Yutian

2018-02-01

The current state, characteristics and necessity of the low voltage ride through (LVRT) on-site testing for grid-connected offshore wind turbines are introduced firstly. Then the effects of submarine cables on the LVRT testing are analysed based on the equivalent circuit of the testing system. A scheme for eliminating the effects of cables on the proposed LVRT testing method is presented. The specified voltage dips are guaranteed to be in compliance with the testing standards by adjusting the ratio between the current limiting impedance and short circuit impedance according to the steady voltage relationship derived from the equivalent circuit. Finally, simulation results demonstrate that the voltage dips at the high voltage side of wind turbine transformer satisfy the requirements of testing standards.

Adverse reactions and interactions with beta-adrenoceptor blocking drugs.

PubMed

Lewis, R V; McDevitt, D G

1986-01-01

beta-Blocking drugs are widely used throughout the world and serious adverse reactions are relatively uncommon. Most of those which do occur are pharmacologically predictable and may be avoided by ensuring that patients who are to be given beta-blockers do not have a predisposition to the development of bronchospasm, cardiac failure or peripheral ischaemia. In some situations, the use of a beta 1-selective blocking drug may reduce the risk of a severe adverse reaction, but there is little evidence that other ancillary properties such as partial agonist activity are of relevance in this context. Long term experience with many of the beta-blockers in current use suggests that unpredictable major adverse reactions such as the practolol oculomucocutaneous syndrome are unlikely to be repeated, although some of these drugs may be associated with immunological disturbances and some have been implicated in the development of retroperitoneal fibrosis. beta-Blocking drugs appear to be associated with a number of subjective side effects including muscle fatigue, peripheral coldness and some neurological symptoms. These side effects are highly subjective and are therefore difficult to quantify and it is not known whether they are of major importance in terms of their effect upon patients' overall well-being. It cannot be assumed that simply because such side effects can be elicited that they do, in fact, matter. However, because beta-blockers are often prescribed for patients who have no symptoms and for whom the benefits of therapy are generally small, such side effects would be of considerable importance if they had an overall effect upon quality of life. There are theoretical reasons to suppose that the incidence and severity of such side effects may be related to the ancillary properties of the individual drugs, but there is little evidence that parameters such as beta 1-selectivity, or partial agonist activity are clinically important determinants of the severity of these side effects. Lipophilicity, however, may be associated with an increased incidence of neurological symptoms. beta-Blocking drugs may cause a variety of metabolic disturbances including an increase in serum VLDL-cholesterol concentrations. However, long term studies have not shown that such disturbances are associated with an increased risk of cardiovascular disease, indicating that such metabolic changes may not be of major importance in practice. beta-Blocking drugs may be involved in a number of interactions with other drugs, but few of these have been shown to be of clinical significance.(ABSTRACT TRUNCATED AT 400 WORDS)

Decreasing the Burden of Side Effects Through Positive Message Framing: an Experimental Proof-of-Concept Study.

PubMed

Wilhelm, Marcel; Rief, Winfried; Doering, Bettina K

2018-05-21

Informing patients about treatment side effects increases the occurrence and intensity of side effects. Since the obligatory informed consent procedure in drug treatments requires transparency and nocebo research suggests that the informed consent of a drug leads to an increased occurrence of the mentioned side effects, the aim of this proof of concept study was to determine the effect of two different framings of informed consent on the occurrence, intensity, and perceived threat of side effects. Healthy male participants (n = 80) were randomized to one of two framing groups. The positive framing group was informed that the common side effect dizziness was a sign that the drug had started to work, while the neutral framing group was told that dizziness is an unpleasant but well-known side effect. Side effects were measured after the administration of metoprolol, an antihypertensive agent. Post hoc moderator analyses investigated the effect of pre-existing negative beliefs about the general harm of medication on the framing manipulation. Metoprolol-specific drug-attributed side effects were rated significantly less threatening in the positive framing group. The between-group effect size (Cohen's d) was small (d = 0.38, p = 0.049). Exploratory post hoc moderator analyses suggest that participants who believed that medication is a source of harmful effects benefited from positive framing, compared to neutral framing of drug-attributed side effects. Positive framing was partially effective in decreasing specific side effect measures, particularly among participants with a tendency to believe that medicine is harmful. Informed consent procedures should therefore be personalized, focusing on patients with negative treatment beliefs.

Side effects of radiotherapy in breast cancer patients : The Internet as an information source.

PubMed

Janssen, S; Käsmann, L; Fahlbusch, F B; Rades, D; Vordermark, D

2018-02-01

Breast cancer is the most common cancer type among women necessitating adjuvant radiotherapy. As the Internet has become a major source of information for cancer patients, this study aimed to evaluate the quality of websites giving information on side effects of radiotherapy for breast cancer patients. A patients' search for the English terms "breast cancer - radiotherapy - side effects" and the corresponding German terms "Brustkrebs - Strahlentherapie - Nebenwirkungen" was carried out twice (5 months apart) using the search engine Google. The first 30 search results each were evaluated using the validated 16-question DISCERN Plus instrument, the Health on the Net Code of Conduct (HONcode) certification and the Journal of the American Medical Association (JAMA) benchmark criteria. The overall quality (DISCERN score) of the retrieved websites was further compared to queries via Bing and Yahoo search engines. The DISCERN score showed a great range, with the majority of websites ranking fair to poor. Significantly superior results were found for English websites, particularly for webpages run by hospitals/universities and nongovernmental organizations (NGO), when compared to the respective German categories. In general, only a minority of websites met all JAMA benchmarks and was HONcode certified (both languages). We did not determine a relevant temporal change in website ranking among the top ten search hits, while significant variation occurred thereafter. Mean overall DISCERN score was similar between the various search engines. The Internet can give breast cancer patients seeking information on side effects of radiotherapy an overview. However, based on the currently low overall quality of websites and the lack of transparency for the average layperson, we emphasize the value of personal contact with the treating radio-oncologist in order to integrate and interpret the information found online.

Combined use of alcohol and energy drinks: Dose relationship with self-reported physiological stimulation and sedation side effects.

PubMed

Droste, Nicolas; Peacock, Amy; Bruno, Raimondo; Pennay, Amy; Zinkiewicz, Lucy; Lubman, Dan I; Miller, Peter

2017-08-01

Negative physiological stimulation and sedation side effects are experienced by a significant proportion of consumers who consume alcohol mixed with energy drinks (AmED). Few studies have compared the frequency of side effects between sessions of AmED and sessions of alcohol only within-subject, and none have explored a dose relationship. Explore the occurrence of self-reported physiological stimulant and sedative side effects between sessions of AmED and alcohol only, and at varying ED dosage levels within AmED sessions. A convenience sample of 2953 residents of New South Wales, Australia completed an online survey. N=731 AmED users reported daily caffeine intake, typical alcohol and AmED consumption, and past 12-month experience of physiological stimulation and sedation side effects during AmED and alcohol only sessions. Within-subject analyses compared occurrence of side effects between session types. Hierarchical binary logistic regression analyses explored the association of ED dose during AmED sessions with the experience of physiological side effects. There were greater odds of most stimulant side effects, and lower odds of sedation side effects, during AmED sessions compared to alcohol only sessions. Compared to one ED, consumption of three or more EDs was significantly associated with the majority of both stimulant and alcohol intoxication side effects after controlling for demographics and consumption covariates. AmED is associated with perceived changes in physiological stimulant and sedation side effects of alcohol. Experience of side effects is positively associated with ED dosage. Future research should account for varying ED dosage, and reflect real world consumption levels. Copyright © 2017 Elsevier Ltd. All rights reserved.

Genome-wide association studies in pharmacogenetics research debate

PubMed Central

Bailey, Kent R; Cheng, Cheng

2016-01-01

Will genome-wide association studies (GWAS) ‘work’ for pharmacogenetics research? This question was the topic of a staged debate, with pro and con sides, aimed to bring out the strengths and weaknesses of GWAS for pharmacogenetics studies. After a full day of seminars at the Fifth Statistical Analysis Workshop of the Pharmacogenetics Research Network, the lively debate was held – appropriately – at Goonies Comedy Club in Rochester (MN, USA). The pro side emphasized that the many GWAS successes for identifying genetic variants associated with disease risk show that it works; that the current genotyping platforms are efficient, with good imputation methods to fill in missing data; that its global assessment is always a success even if no significant associations are detected; and that genetic effects are likely to be large because humans have not evolved in a drug-therapy environment. By contrast, the con side emphasized that we have limited knowledge of the complexity of the genome; limited clinical phenotypes compromise studies; the likely multifactorial nature of drug response clouding the small genetic effects; and limitations of sample size and replication studies in pharmacogenetic studies. Lively and insightful discussions emphasized further research efforts that might benefit GWAS in pharmacogenetics. PMID:20235786

Experimental study of humidity changes on the performance of an elliptical single four-channel PEM fuel cell

NASA Astrophysics Data System (ADS)

Gholizadeh, Mohammad; Ghazikhani, Mohsen; Khazaee, Iman

2017-01-01

Humidity and humidification in a proton exchange membrane fuel cells (PEM) can significantly affect the performance of these energy generating devices. Since protons (H+) needs to be accompanied by water molecules to pass from the anode side to the cathode side, the PEM fuel cell membrane should be sufficiently wet. Low or high amount of water in the membrane can interrupt the flow of protons and thus reduce the efficiency of the fuel cell. In this context, several experimental studies and modeling have been carried out on PEM fuel cell and interesting results have been achieved. In this paper, the humidity and flow rate of gas in the anode and cathode are modified to examine its effect on fuel cell performance. The results show that the effect of humidity changing in the anode side is greater than that of the cathode so that at zero humidity of anode and 70 % humidity of the cathode, a maximum current flow of 0.512 A/cm2 for 0.12 V was obtained. However, at 70 % anode humidity and zero cathode humidity, a maximum flow of 0.86 A/cm2 for 0.13 V was obtained.

Do Teachers Need Structure or Freedom to Effectively Teach Urban Students? A Review of the Educational Debate

ERIC Educational Resources Information Center

Margolis, Jason; Meese, Alison A.; Doring, Anne

2016-01-01

This article presents both sides of the debate as to whether urban teachers need structure or freedom, and then takes a stand on urban teaching in the current high-stakes assessment climate. First, we trace the 30-year development of American educational policy in the area of structuring teaching. Then, we present research from proponents of…

Effects of Direct Systematic Instruction on Google Glass Orientation with Individuals with Intellectual Disability

ERIC Educational Resources Information Center

Kelley, Kelly R.; Rivera, Christopher J.; Kellems, Ryan O.

2016-01-01

Glass, designed by Google, is a fairly new wearable and mobile technology that projects an image into a glass prism above the eye and is currently in beta testing. A touch pad on the side of Glass allows users to engage with the device through swiping gestures and voice control to perform several functions similar to mobile devices. This initial…

Drug-induced Sweet's syndrome secondary to hepatitis C antiviral therapy.

PubMed

Gheorghe, Liana; Cotruta, Bogdan; Trifu, Viorel; Cotruta, Cristina; Becheanu, Gabriel; Gheorghe, Cristian

2008-09-01

Pegylated interferon-alpha in combination with ribavirin currently represents the therapeutic standard for the hepatitis C virus infection. Interferon based therapy may be responsible for many cutaneous side effects. We report a case of drug-induced Sweet's syndrome secondary to hepatitis C antiviral therapy. To our knowledge, this is the first reported case of Sweet's syndrome in association with pegylated interferon-alpha therapy.

Status and perspective of the DarkSide experiment at LNGS

DOE PAGES

Agnes, P.

2018-09-01

The DarkSide experiment aims to perform a background-free direct search for dark matter with a dual-phase argon TPC. The current phase of the experiment, DarkSide-50, is acquiring data at Laboratori Nazionali del Gran Sasso and produced the most sensitive limit on the WIMP-nucleon cross section ever obtained with a liquid argon target (2.0 × 10 -44 cm2 for a WIMP mass of 100 GeV/c 2). The future phase of the experiment will be a 20 t fiducial mass detector, designed to reach a sensitivity of ~1 × 10 -47 cm2 (at 1 TeV/c 2 WIMP mass) with a background-free exposuremore » of 100 ty. Here, this work contains a discussion of the current status of the DarkSide-50 WIMP search and of the results which are more relevant for the construction of the future detector.« less

Status and perspective of the DarkSide experiment at LNGS

DOE Office of Scientific and Technical Information (OSTI.GOV)

Agnes, P.

The DarkSide experiment aims to perform a background-free direct search for dark matter with a dual-phase argon TPC. The current phase of the experiment, DarkSide-50, is acquiring data at Laboratori Nazionali del Gran Sasso and produced the most sensitive limit on the WIMP-nucleon cross section ever obtained with a liquid argon target (2.0 × 10 -44 cm2 for a WIMP mass of 100 GeV/c 2). The future phase of the experiment will be a 20 t fiducial mass detector, designed to reach a sensitivity of ~1 × 10 -47 cm2 (at 1 TeV/c 2 WIMP mass) with a background-free exposuremore » of 100 ty. Here, this work contains a discussion of the current status of the DarkSide-50 WIMP search and of the results which are more relevant for the construction of the future detector.« less

Treatment factors affecting longitudinal quality of life in new onset pediatric epilepsy.

PubMed

Modi, Avani C; Ingerski, Lisa M; Rausch, Joseph R; Glauser, Tracy A

2011-05-01

Recognizing the importance of patient-reported outcomes, this longitudinal, prospective study examined: Changes in health-related quality of life (HRQOL) over seven months following antiepileptic drug (AED) initiation and the relationship of seizures, AED side-effects, and AED type to HRQOL. Parents of 124 children with newly diagnosed epilepsy completed measures of HRQOL and side-effects at each clinic visit. Treatment information was also collected. HRQOL remained stable over time; however, seizures and AED side-effects significantly affected multiple HRQOL domains. Higher seizure activity was associated with decreased Physical HRQOL. Side-effects were negatively associated with all HRQOL domains. Children taking carbamazepine who experienced higher side-effects early in therapy demonstrated declining emotional functioning compared to children experiencing no/some side-effects. AED side-effects, AED type, and seizure frequency were associated with longitudinal HRQOL in children with newly-diagnosed epilepsy. Routine assessment of AED side-effects and HRQOL may be useful for clinical decision making.

Investigation of environmental change pattern in Japan. Investigation of variations in the prominent oceanic current, Kuroshio

NASA Technical Reports Server (NTRS)

Maruyasu, T.; Shoji, D. (Principal Investigator)

1976-01-01

The author has identified the following significant results. From ocean current analysis, it is concluded that the vortex was formed when the stream axis of the Kuroshio was gradually approaching Shiono Misaki. The sea surface temperatures in the area were found to be nearly homogenious having the values of 27.3 to 27.8C. Transparency of the water was better on the east side of Shiono Misaki than on the west side, the values being 20 to 27 m against 13m. Surface salinity distribution had a considerably high value of 33.7% on the east side, decreasing toward the west to become 32%.

Test Report - Fault Current Through Graphite Filament Reinforced Plastic

NASA Technical Reports Server (NTRS)

Evans, R. W.

1997-01-01

Tests were performed to determine the damage to samples of composite material when a current carrying wire is shorted to the surface of the composite material, and to determine whether enough current can flow through the material to blow a fuse before damage can occur. Fault current tests were performed on samples of graphite epoxy materials. Samples consisted of six layers of IM7 graphite fiber mat in Hercules 8552 epoxy resin. A variable power supply provided up to 35 amps of current. The high voltage side of the power supply was attached to a wire at the end of a hinged arm, and the low side was attached to the edge of the sample. To test joints, the return was connected to the edge of one sample, and the high side was shorted to the top of the other sample. Tests show that when current exceeds approximately 5 amps, the graphite glows, and the epoxy melts out at the shorted contact. At higher current levels the epoxy burns. At voltages above 15 volts the epoxy outer coat is easily broken, and fire, flame, and a rise in current occur suddenly. When joints are introduced, resistance is increased, and the maximum current resulting from a short circuit to the graphite epoxy is reduced. This condition can easily result in fault current lower than the circuit breaker limit and higher than the 5 amp ignition level. The shorting contact and the joint become hot spots with melting epoxy, smoke, and fire.

A Comprehensive Review of Non-Steroidal Anti-Inflammatory Drug Use in The Elderly

PubMed Central

Wongrakpanich, Supakanya; Wongrakpanich, Amaraporn; Melhado, Katie; Rangaswami, Janani

2018-01-01

NSAIDs, non-steroidal anti-inflammatory drugs, are one of the most commonly prescribed pain medications. It is a highly effective drug class for pain and inflammation; however, NSAIDs are known for multiple adverse effects, including gastrointestinal bleeding, cardiovascular side effects, and NSAID induced nephrotoxicity. As our society ages, it is crucial to have comprehensive knowledge of this class of medication in the elderly population. Therefore, we reviewed the pharmacodynamics and pharmacokinetics, current guidelines for NSAIDs use, adverse effect profile, and drug interaction of NSAIDs and commonly used medications in the elderly. PMID:29392089

[Treatment side effects and compliance in patients with depression].

PubMed

Petrova, N N; Kucher, E O

2012-01-01

The impact of treatment side-effects on the compliance was studied in 85 depressive patients with different mental disorders - recurrent depressive disorder, postschizophrenic depression and organic affective disorder. The comparison of objective and subjective evaluations of compliance and a comparative analysis of the level of compliance, with its dependence on the treatment specifics, in different diseases were done. A significant role of efficacy and treatment side-effects was identified. The levels of "mental" and "autonomous" side-effects were highest in the treatment of depression: patients with postschizophrenic depression had the highest risk in respect of maintenance treatment; patients with recurrent depressive disorder and organic (affective) disorder were more tolerant to the treatment side-effects and their treatment, including the maintenance therapy, was rather effective. The compliance of all patients with depression was negatively correlated with the severity of side-effects of pharmacotherapy. The greatest side-effects and the lowest level of compliance were observed in the complex treatment with antidepressants and atypical neuroleptics. The effect of side-effects on the compliance was dependent on their severity and subjective tolerability and, to a lesser extent, on the amount of drugs.

Ion Fluxes in Giant Excised Cardiac Membrane Patches Detected and Quantified with Ion-selective Microelectrodes

PubMed Central

Kang, Tong Mook; Markin, Vladislav S.; Hilgemann, Donald W.

2003-01-01

We have used ion-selective electrodes (ISEs) to quantify ion fluxes across giant membrane patches by measuring and simulating ion gradients on both membrane sides. Experimental conditions are selected with low concentrations of the ions detected on the membrane side being monitored. For detection from the cytoplasmic (bath) side, the patch pipette is oscillated laterally in front of an ISE. For detection on the extracellular (pipette) side, ISEs are fabricated from flexible quartz capillary tubing (tip diameters, 2–3 microns), and an ISE is positioned carefully within the patch pipette with the tip at a controlled distance from the mouth of the patch pipette. Transport activity is then manipulated by solution changes on the cytoplasmic side. Ion fluxes can be quantified by simulating the ion gradients with appropriate diffusion models. For extracellular (intrapatch pipette) recordings, ion diffusion coefficients can be determined from the time courses of concentration changes. The sensitivity and utility of the methods are demonstrated with cardiac membrane patches by measuring (a) potassium fluxes via ion channels, valinomycin, and Na/K pumps; (b) calcium fluxes mediated by Na/Ca exchangers; (c) sodium fluxes mediated by gramicidin and Na/K pumps; and (d) proton fluxes mediated by an unknown electrogenic mechanism. The potassium flux-to-current ratio for the Na/K pump is approximately twice that determined for potassium channels and valinomycin, as expected for a 3Na/2K pump stoichiometery (i.e., 2K/charge moved). For valinomycin-mediated potassium currents and gramicidin-mediated sodium currents, the ion fluxes calculated from diffusion models are typically 10–15% smaller than expected from the membrane currents. As presently implemented, the ISE methods allow reliable detection of calcium and proton fluxes equivalent to monovalent cation currents <1 pA in magnitude, and they allow detection of sodium and potassium fluxes equivalent to <5 pA currents. The capability to monitor ion fluxes, independent of membrane currents, should facilitate studies of both electrogenic and electroneutral ion–coupled transporters in giant patches. PMID:12668735

Industrial demand side management: A status report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hopkins, M.F.; Conger, R.L.; Foley, T.J.

This report provides an overview of and rationale for industrial demand side management (DSM) programs. Benefits and barriers are described, and data from the Manufacturing Energy Consumption Survey are used to estimate potential energy savings in kilowatt hours. The report presents types and examples of programs and explores elements of successful programs. Two in-depth case studies (from Boise Cascade and Eli Lilly and Company) illustrate two types of effective DSM programs. Interviews with staff from state public utility commissions indicate the current thinking about the status and future of industrial DSM programs. A comprehensive bibliography is included, technical assistance programsmore » are listed and described, and a methodology for evaluating potential or actual savings from projects is delineated.« less

Sodium channel slow inactivation as a therapeutic target for myotonia congenita

PubMed Central

Novak, Kevin R; Norman, Jennifer; Mitchell, Jacob R; Pinter, Martin J; Rich, Mark M

2014-01-01

Objective Patients with myotonia congenita have muscle hyperexcitability due to loss-of-function mutations in the chloride channel in skeletal muscle, which causes spontaneous firing of muscle action potentials (myotonia), producing muscle stiffness. In patients, muscle stiffness lessens with exercise, a change known as the warm-up phenomenon. Our goal was to identify the mechanism underlying warm up and to use this information to guide development of novel therapy. Methods To determine the mechanism underlying warm-up, we used a recently discovered drug to eliminate muscle contraction, thus allowing prolonged intracellular recording from individual muscle fibers during induction of warm-up in a mouse model of myotonia congenita. Results Changes in action potentials suggested slow inactivation of sodium channels as an important contributor to warm-up. These data suggested enhancing slow inactivation of sodium channels might offer effective therapy for myotonia. Lacosamide and ranolazine enhance slow inactivation of sodium channels and are FDA-approved for other uses in patients. We compared the efficacy of both drugs to mexiletine, a sodium channel blocker currently used to treat myotonia. In vitro studies suggested both lacosamide and ranolazine were superior to mexiletine. However, in vivo studies in a mouse model of myotonia congenita suggested side effects could limit the efficacy of lacosamide. Ranolazine produced fewer side effects and was as effective as mexiletine at a dose that produced none of mexiletine’s hypoexcitability side effects. Interpretation We conclude ranolazine has excellent therapeutic potential for treatment of patients with myotonia congenita. PMID:25515836

Reconstruction of paleoenvironmental changes based on the planktonic foraminiferal assemblages off Shimokita (Japan) in the northwestern North Pacific

NASA Astrophysics Data System (ADS)

Kuroyanagi, Azumi; Kawahata, Hodaka; Narita, Hisashi; Ohkushi, Ken'ichi; Aramaki, Takafumi

2006-08-01

Planktonic foraminifera live in the upper ocean, and their assemblages can record the surrounding environment. To reconstruct changes in water masses and the timing of flow of the Oyashio and Tsugaru currents through the Tsugaru Strait after the Last Glacial Maximum, when the Japan Sea had been almost isolated from the surrounding seas, we investigated at high resolution the planktonic foraminiferal fauna in seafloor sediments off the Shimokita (core MD01-2409: 41°33.9'N, 141°52.1'E), in the northwestern North Pacific, over the last 26,900 years. Factor analysis of the foraminiferal assemblage suggests that the water mass changed significantly as a result of the deglacial sea-level rise and opening of the straits into the Japan Sea. Mass accumulation rates of some selected foraminiferal species that inhabit characteristic environments (e.g., warm stratified water, Oyashio Current, Tsushima Current) corroborate these changes in water mass and water column structure. We also used the ratio of the dextral form to total Neogloboquadrina pachyderma as an indicator of subsurface (below the pycnocline) water temperature. We recognized five distinct periods of oceanographic change at the study site, which is just east of the Tsugaru Strait: (1) Oyashio Current affecting both surface and subsurface waters (26.9-15.7 thousand calendar years before present (cal. kyr BP)); (2) vertical mixing and subsurface warming as the Oyashio Current began to flow into the Japan Sea through the Tsugaru Strait (15.7-10.6 cal. kyr BP); (3) outflow of the Tsugaru Current from the Japan Sea into the Pacific, leading to baroclinic conditions, with the surface layer under the influence of the Tsugaru and the subsurface layers of the Oyashio Current (10.6-9.0 cal. kyr BP); (4) stratification of the water column developed as the flow of the Tsugaru Current increased (9.0-6.2 cal. kyr BP); and (5) warming of the subsurface layer, disruption of the stratification, and dominance of the Tsugaru Current in both surface and subsurface layers, similar to the present situation (6.2-1.5 cal. kyr BP). The timing of flow of the Oyashio and Tsugaru currents through the strait at the study site off Shimokita is generally compatible with the results of studies in the Japan Sea. The flow of the Tsugaru Current led to progressive warming of the waters, from the surface to the subsurface layers and from the Japan Sea side to the Pacific side of the Tsugaru Strait, beginning in 8.3-6.8 cal. kyr BP on the western side, and in 6.2 cal. kyr BP on the eastern side of the strait. By 4.8 cal. kyr BP on the western side, and by ˜ 3.4 cal. kyr BP on the eastern side of the strait, warm water prevailed in both surface and subsurface layers.

Exploring the associations between drug side-effects and therapeutic indications.

PubMed

Wang, Fei; Zhang, Ping; Cao, Nan; Hu, Jianying; Sorrentino, Robert

2014-10-01

Drug therapeutic indications and side-effects are both measurable patient phenotype changes in response to the treatment. Inferring potential drug therapeutic indications and identifying clinically interesting drug side-effects are both important and challenging tasks. Previous studies have utilized either chemical structures or protein targets to predict indications and side-effects. In this study, we compared drug therapeutic indication prediction using various information including chemical structures, protein targets and side-effects. We also compared drug side-effect prediction with various information sources including chemical structures, protein targets and therapeutic indication. Prediction performance based on 10-fold cross-validation demonstrates that drug side-effects and therapeutic indications are the most predictive information source for each other. In addition, we extracted 6706 statistically significant indication-side-effect associations from all known drug-disease and drug-side-effect relationships. We further developed a novel user interface that allows the user to interactively explore these associations in the form of a dynamic bipartitie graph. Many relationship pairs provide explicit repositioning hypotheses (e.g., drugs causing postural hypotension are potential candidates for hypertension) and clear adverse-reaction watch lists (e.g., drugs for heart failure possibly cause impotence). All data sets and highly correlated disease-side-effect relationships are available at http://astro.temple.edu/∼tua87106/druganalysis.html. Copyright © 2014 Elsevier Inc. All rights reserved.

Parental Expectation of Side Effects Following Vaccination Is Self-fulfilling: A Prospective Cohort Study.

PubMed

Smith, Louise E; Weinman, John; Amlôt, Richard; Yiend, Jenny; Rubin, G James

2018-06-02

One of the major factors contributing to parental refusal of vaccinations is the perception that vaccines cause side effects. Although symptoms are commonly reported following vaccinations, their causes are not always straightforward. Although some may be directly attributable to the vaccine itself, others may reflect pre-existing or coincidental symptoms that are misattributed to the vaccine. To investigate psychological factors associated with parental report of side effects following vaccination with the child influenza vaccine, and parental intention to re-vaccinate one's child the following year. A prospective cohort study was run in primary care practices in London in the 2016-2017 influenza season (ClinicalTrials.gov number NCT02909855). Two hundred seventy parents from 14 practices completed a questionnaire before their child's vaccination. Follow-up questionnaires were completed 3 days after vaccination and one month after vaccination. Parental report of side effects and vaccination intention for the subsequent year were measured. Parental report of side effects was strongly associated with pre-vaccination expectation of side effects. Suggestions received from the media, National Health Service (NHS) vaccination leaflet, and health care workers, as well as uncertainty-related beliefs, perceived sensitivity of the child to medicines, pessimism, and anxiety were also associated with reporting side effects. Side effect report was associated with lower vaccination intention for the following influenza season. Side effect perception following vaccination is influenced by psychological factors, in particular expectations. Perceiving side effects reduces future vaccination intention. Future public health communications should aim to decrease unrealistic expectations of side effects to increase vaccine uptake.

Pharmacogenomic and clinical data link non-pharmacokinetic metabolic dysregulation to drug side effect pathogenesis

PubMed Central

Zielinski, Daniel C.; Filipp, Fabian V.; Bordbar, Aarash; Jensen, Kasper; Smith, Jeffrey W.; Herrgard, Markus J.; Mo, Monica L.; Palsson, Bernhard O.

2015-01-01

Drug side effects cause a significant clinical and economic burden. However, mechanisms of drug action underlying side effect pathogenesis remain largely unknown. Here, we integrate pharmacogenomic and clinical data with a human metabolic network and find that non-pharmacokinetic metabolic pathways dysregulated by drugs are linked to the development of side effects. We show such dysregulated metabolic pathways contain genes with sequence variants affecting side effect incidence, play established roles in pathophysiology, have significantly altered activity in corresponding diseases, are susceptible to metabolic inhibitors and are effective targets for therapeutic nutrient supplementation. Our results indicate that metabolic dysregulation represents a common mechanism underlying side effect pathogenesis that is distinct from the role of metabolism in drug clearance. We suggest that elucidating the relationships between the cellular response to drugs, genetic variation of patients and cell metabolism may help managing side effects by personalizing drug prescriptions and nutritional intervention strategies. PMID:26055627

Effects of Double-Leakage Tip Clearance Flow on the Performance of a Compressor Stage with a Large Rotor Tip Gap

NASA Technical Reports Server (NTRS)

Hah, Chunill

2016-01-01

Effects of a large rotor tip gap on the performance of a one and half stage axial compressor are investigated in detail with a numerical simulation based on LES and available PIV data. The current paper studies the main flow physics, including why and how the loss generation is increased with the large rotor tip gap. The present study reveals that when the tip gap becomes large, tip clearance fluid goes over the tip clearance core vortex and enters into the next blade's tip gap, which is called double-leakage tip clearance flow. As the tip clearance flow enters into the adjacent blade's tip gap, a vortex rope with a lower pressure core is generated. This vortex rope breaks up the tip clearance core vortex of the adjacent blade, resulting in a large additional mixing. This double-leakage tip clearance flow occurs at all operating conditions, from design flow to near stall condition, with the large tip gap for the current compressor stage. The double-leakage tip clearance flow, its interaction with the tip clearance core vortex of the adjacent blade, and the resulting large mixing loss are the main flow mechanism of the large rotor tip gap in the compressor. When the tip clearance is smaller, flow near the end wall follows more closely with the main passage flow and this double-leakage tip clearance flow does not happen near the design flow condition for the current compressor stage. When the compressor with a large tip gap operates at near stall operation, a strong vortex rope is generated near the leading edge due to the double-leakage flow. Part of this vortex separates from the path of the tip clearance core vortex and travels from the suction side of the blade toward the pressure side of the blade. This vortex is generated periodically at near stall operation with a large tip gap. As the vortex travels from the suction side to the pressure side of the blade, a large fluctuation of local pressure forces blade vibration. Nonsynchronous blade vibration occurs due to this vortex as the frequency of this vortex generation is not the same as the rotor. The present investigation confirms that this vortex is a part of separated tip clearance vortex, which is caused by the double-leakage tip clearance flow.

Radiation Therapy Side Effects

Cancer.gov

Radiation therapy has side effects because it not only kills or slows the growth of cancer cells, it can also affect nearby healthy cells. Many people who get radiation therapy experience fatigue. Other side effects depend on the part of the body that is being treated. Learn more about possible side effects.

Influence of opioid-related side effects on disability, mood, and opioid misuse risk among patients with chronic pain in primary care.

PubMed

Jamison, Robert N; Dorado, Kathleen; Mei, Anna; Edwards, Robert R; Martel, Marc O

2017-03-01

There is increasing concern among primary care practitioners about the use of opioids for chronic pain, including their adverse effects, but little attention has been given to how reports of side effects from prescription medication can contribute to outcomes among patients with chronic pain. The aim of this study was to investigate the impact of frequently reported side effects on mood, disability, and opioid misuse in patients with chronic pain prescribed opioids within primary care. Two hundred (N = 200) patients with chronic pain taking opioids for pain were recruited into the study. All patients completed baseline measures and a monthly side effects checklist once a month for 6 months. Patients were divided evenly based on a median split of the number of endorsed side effects over 6 months. The subjects repeated the baseline measures at the end of the study period. Over time, reports of medication side effects tended to decrease, but differences in frequency of reported side effects from baseline to follow-up (6-month time) were not significant, and the order of the frequency of the reported side effects remained similar. Patients who reported significant medication-related adverse effects reported significantly greater activity interference, negative affect, and catastrophizing compared with those with fewer side effects ( P < 0.01). In addition, those patients with pain who reported more side effects showed significantly higher scores on opioid misuse risk ( P < 0.001). This study demonstrates the important role of monitoring medication-related side effects among patients with chronic pain who are prescribed opioid medication for pain within primary care.