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Sample records for lsd post hoc

  1. Post hoc subgroups in clinical trials: Anathema or analytics?

    Science.gov (United States)

    Weisberg, Herbert I; Pontes, Victor P

    2015-08-01

    There is currently much interest in generating more individualized estimates of treatment effects. However, traditional statistical methods are not well suited to this task. Post hoc subgroup analyses of clinical trials are fraught with methodological problems. We suggest that the alternative research paradigm of predictive analytics, widely used in many business contexts, can be adapted to help. We compare the statistical and analytics perspectives and suggest that predictive modeling should often replace subgroup analysis. We then introduce a new approach, cadit modeling, that can be useful to identify and test individualized causal effects. The cadit technique is particularly useful in the context of selecting from among a large number of potential predictors. We describe a new variable-selection algorithm that has been applied in conjunction with cadit. The cadit approach is illustrated through a reanalysis of data from the Randomized Aldactone Evaluation Study trial, which studied the efficacy of spironolactone in heart-failure patients. The trial was successful, but a serious adverse effect (hyperkalemia) was subsequently discovered. Our reanalysis suggests that it may be possible to predict the degree of hyperkalemia based on a logistic model and to identify a subgroup in which the effect is negligible. Cadit modeling is a promising alternative to subgroup analyses. Cadit regression is relatively straightforward to implement, generates results that are easy to present and explain, and can mesh straightforwardly with many variable-selection algorithms. © The Author(s) 2015.

  2. simulate_CAT: A Computer Program for Post-Hoc Simulation for Computerized Adaptive Testing

    Directory of Open Access Journals (Sweden)

    İlker Kalender

    2015-06-01

    Full Text Available This paper presents a computer software developed by the author. The software conducts post-hoc simulations for computerized adaptive testing based on real responses of examinees to paper and pencil tests under different parameters that can be defined by user. In this paper, short information is given about post-hoc simulations. After that, the working principle of the software is provided and a sample simulation with required input files is shown. And last, output files are described

  3. A-priori and post-hoc segmentation in the design of healthy eating campaigns

    DEFF Research Database (Denmark)

    Kazbare, Laura; van Trijp, Hans C. M.; Eskildsen, Jacob Kjær

    2010-01-01

    . Although such practice may be justifiable from the practical point of view, it is unclear how effective these implicit segmentations are. In this study the authors argue that  it is important to transcend demographic boundaries and to further segment demographic groups. A study with 13-15-year-old...... and a post-hoc segmentation. The results of the study show that it is useful and also ethical to differentiate people using segmentation methods, since it facilitates reaching more vulnerable segments of society that in general resist change. It also demonstrates that post-hoc segmentation is more helpful...

  4. Correctness-by-construction and post-hoc verification : a marriage of convenience?

    NARCIS (Netherlands)

    Watson, B.W.; Kourie, D.G.; Schaefer, I.; Cleophas, L.G.W.A.; Margaria, T.; Steffen, B.

    2016-01-01

    Correctness-by-construction (CbC), traditionally based on weakest precondition semantics, and post-hoc verification (PhV) aspire to ensure functional correctness. We argue for a lightweight approach to CbC where lack of formal rigour increases productivity. In order to mitigate the risk of

  5. Regressive research: The pitfalls of post hoc data selection in the study of unconscious mental processes.

    Science.gov (United States)

    Shanks, David R

    2017-06-01

    Many studies of unconscious processing involve comparing a performance measure (e.g., some assessment of perception or memory) with an awareness measure (such as a verbal report or a forced-choice response) taken either concurrently or separately. Unconscious processing is inferred when above-chance performance is combined with null awareness. Often, however, aggregate awareness is better than chance, and data analysis therefore employs a form of extreme group analysis focusing post hoc on participants, trials, or items where awareness is absent or at chance. The pitfalls of this analytic approach are described with particular reference to recent research on implicit learning and subliminal perception. Because of regression to the mean, the approach can mislead researchers into erroneous conclusions concerning unconscious influences on behavior. Recommendations are made about future use of post hoc selection in research on unconscious cognition.

  6. Level of literacy and dementia: A secondary post-hoc analysis from North-West India

    Directory of Open Access Journals (Sweden)

    Sunil Kumar Raina

    2014-01-01

    Full Text Available Introduction: A relation between literacy and dementia has been studied in past and an association has been documented. This is in spite of some studies pointing to the contrary. The current study was aimed at investigating the influence of level of literacy on dementia in a sample stratified by geography (Migrant, Urban, Rural and Tribal areas of sub-Himalayan state of Himachal Pradesh, India. Materials and Methods: The study was based on post-hoc analysis of data obtained from a study conducted on elderly population (60 years and above from selected geographical areas (Migrant, Urban, Rural and Tribal of Himachal Pradesh state in North-west India. Results: Analysis of variance revealed an effect of education on cognitive scores [F = 2.823, P =0.01], however, post-hoc Tukey′s HSD test did not reveal any significant pairwise comparisons. Discussion: The possibility that education effects dementia needs further evaluation, more so in Indian context.

  7. The post hoc use of randomised controlled trials to explore drug associated cancer outcomes

    DEFF Research Database (Denmark)

    Stefansdottir, Gudrun; Zoungas, Sophia; Chalmers, John

    2013-01-01

    on public health before proper regulatory action can be taken. This paper aims to discuss challenges of exploring drug-associated cancer outcomes by post-hoc analyses of Randomised controlled trials (RCTs) designed for other purposes. METHODOLOGICAL CHALLENGES TO CONSIDER: We set out to perform a post......-hoc nested case-control analysis in the ADVANCE trial in order to examine the association between insulin use and cancer. We encountered several methodological challenges that made the results difficult to interpret, including short duration of exposure of interest, lack of power, and correlation between...... exposure and potential confounders. Considering these challenges, we concluded that using the data would not enlighten the discussion about insulin use and cancer risk and only serve to further complicate any understanding. Therefore, we decided to use our experience to illustrate methodological challenges...

  8. LSD in pubic hair in a fatality.

    Science.gov (United States)

    Gaulier, Jean-michel; Maublanc, Julie; Lamballais, Florence; Bargel, Sophie; Lachâtre, Gérard

    2012-05-10

    Lysergic acid diethylamide (LSD) is a potent hallucinogen, active at very low dosage and its determination in body fluids in a forensic context may present some difficulties, even more so in hair. A dedicated liquid chromatography-electrospray-tandem mass spectrometry (LC-ES-MS/MS) assay in hair was used to document the case of a 24-year-old man found dead after a party. Briefly, after a decontamination step, a 50mg sample of the victim's pubic hair was cut into small pieces (LSD. A LSD concentration of 0.66pg/mg of pubic hair was observed. However, this result remains difficult to interpret owing to the concomitant LSD presence in the victim's post mortem blood and urine, the lack of previously reported LSD concentrations in hair, and the absence of data about LSD incorporation and stability in pubic hair. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  9. LSD and Genetic Damage

    Science.gov (United States)

    Dishotsky, Norman I.; And Others

    1971-01-01

    Reviews studies of the effects of lysergic acid diethylamide (LSD) on man and other organisms. Concludes that pure LSD injected in moderate doses does not cause chromosome or detectable genetic damage and is not a teratogen or carcinogen. (JM)

  10. LSD. Specialized Information Service.

    Science.gov (United States)

    Do It Now Foundation, Phoenix, AZ.

    The document presents a collection of articles about LSD. The first article discusses the increasingly popular use of blotter acid (tiny squares of absorbent paper soaked in liquid LSD). Article 2 furthers this look at the newer LSD formats and describes rumors of lick-'n-stick stamps and color-transfer tattoos as examples of techniques aimed at…

  11. Sigsearch: a new term for post hoc unplanned search for statistically significant relationships with the intent to create publishable findings.

    Science.gov (United States)

    Hashim, Muhammad Jawad

    2010-09-01

    Post-hoc secondary data analysis with no prespecified hypotheses has been discouraged by textbook authors and journal editors alike. Unfortunately no single term describes this phenomenon succinctly. I would like to coin the term "sigsearch" to define this practice and bring it within the teaching lexicon of statistics courses. Sigsearch would include any unplanned, post-hoc search for statistical significance using multiple comparisons of subgroups. It would also include data analysis with outcomes other than the prespecified primary outcome measure of a study as well as secondary data analyses of earlier research.

  12. Preventive Ceftriaxone in Patients with Stroke Treated with Intravenous Thrombolysis: Post Hoc Analysis of the Preventive Antibiotics in Stroke Study

    NARCIS (Netherlands)

    Vermeij, Jan-Dirk; Westendorp, Willeke F.; Roos, Yvo B.; Brouwer, Matthijs C.; van de Beek, Diederik; Nederkoorn, Paul J.

    2016-01-01

    The Preventive Antibiotics in Stroke Study (PASS), a randomized open-label masked endpoint trial, showed that preventive ceftriaxone did not improve functional outcome at 3 months in patients with acute stroke (adjusted common OR 0.95; 95% CI 0.82-1.09). Post-hoc analyses showed that among patients

  13. LSD enhances suggestibility in healthy volunteers.

    Science.gov (United States)

    Carhart-Harris, R L; Kaelen, M; Whalley, M G; Bolstridge, M; Feilding, A; Nutt, D J

    2015-02-01

    Lysergic acid diethylamide (LSD) has a history of use as a psychotherapeutic aid in the treatment of mood disorders and addiction, and it was also explored as an enhancer of mind control. The present study sought to test the effect of LSD on suggestibility in a modern research study. Ten healthy volunteers were administered with intravenous (i.v.) LSD (40-80 μg) in a within-subject placebo-controlled design. Suggestibility and cued mental imagery were assessed using the Creative Imagination Scale (CIS) and a mental imagery test (MIT). CIS and MIT items were split into two versions (A and B), balanced for 'efficacy' (i.e. A ≈ B) and counterbalanced across conditions (i.e. 50 % completed version 'A' under LSD). The MIT and CIS were issued 110 and 140 min, respectively, post-infusion, corresponding with the peak drug effects. Volunteers gave significantly higher ratings for the CIS (p = 0.018), but not the MIT (p = 0.11), after LSD than placebo. The magnitude of suggestibility enhancement under LSD was positively correlated with trait conscientiousness measured at baseline (p = 0.0005). These results imply that the influence of suggestion is enhanced by LSD. Enhanced suggestibility under LSD may have implications for its use as an adjunct to psychotherapy, where suggestibility plays a major role. That cued imagery was unaffected by LSD implies that suggestions must be of a sufficient duration and level of detail to be enhanced by the drug. The results also imply that individuals with high trait conscientiousness are especially sensitive to the suggestibility-enhancing effects of LSD.

  14. Post hoc support vector machine learning for impedimetric biosensors based on weak protein-ligand interactions.

    Science.gov (United States)

    Rong, Y; Padron, A V; Hagerty, K J; Nelson, N; Chi, S; Keyhani, N O; Katz, J; Datta, S P A; Gomes, C; McLamore, E S

    2018-04-30

    Impedimetric biosensors for measuring small molecules based on weak/transient interactions between bioreceptors and target analytes are a challenge for detection electronics, particularly in field studies or in the analysis of complex matrices. Protein-ligand binding sensors have enormous potential for biosensing, but achieving accuracy in complex solutions is a major challenge. There is a need for simple post hoc analytical tools that are not computationally expensive, yet provide near real time feedback on data derived from impedance spectra. Here, we show the use of a simple, open source support vector machine learning algorithm for analyzing impedimetric data in lieu of using equivalent circuit analysis. We demonstrate two different protein-based biosensors to show that the tool can be used for various applications. We conclude with a mobile phone-based demonstration focused on the measurement of acetone, an important biomarker related to the onset of diabetic ketoacidosis. In all conditions tested, the open source classifier was capable of performing as well as, or better, than the equivalent circuit analysis for characterizing weak/transient interactions between a model ligand (acetone) and a small chemosensory protein derived from the tsetse fly. In addition, the tool has a low computational requirement, facilitating use for mobile acquisition systems such as mobile phones. The protocol is deployed through Jupyter notebook (an open source computing environment available for mobile phone, tablet or computer use) and the code was written in Python. For each of the applications, we provide step-by-step instructions in English, Spanish, Mandarin and Portuguese to facilitate widespread use. All codes were based on scikit-learn, an open source software machine learning library in the Python language, and were processed in Jupyter notebook, an open-source web application for Python. The tool can easily be integrated with the mobile biosensor equipment for rapid

  15. Impulse control disorder related behaviours during long-term rotigotine treatment: a post hoc analysis.

    Science.gov (United States)

    Antonini, A; Chaudhuri, K R; Boroojerdi, B; Asgharnejad, M; Bauer, L; Grieger, F; Weintraub, D

    2016-10-01

    Dopamine agonists in Parkinson's disease (PD) are associated with impulse control disorders (ICDs) and other compulsive behaviours (together called ICD behaviours). The frequency of ICD behaviours reported as adverse events (AEs) in long-term studies of rotigotine transdermal patch in PD was evaluated. This was a post hoc analysis of six open-label extension studies up to 6 years in duration. Analyses included patients treated with rotigotine for at least 6 months and administered the modified Minnesota Impulse Disorders Interview. ICD behaviours reported as AEs were identified and categorized. For 786 patients, the mean (±SD) exposure to rotigotine was 49.4 ± 17.6 months. 71 (9.0%) patients reported 106 ICD AEs cumulatively. Occurrence was similar across categories: 2.5% patients reported 'compulsive sexual behaviour', 2.3% 'buying disorder', 2.0% 'compulsive gambling', 1.7% 'compulsive eating' and 1.7% 'punding behaviour'. Examining at 6-month intervals, the incidence was relatively low during the first 30 months; it was higher over the next 30 months, peaking in the 54-60-month period. No ICD AEs were serious, and 97% were mild or moderate in intensity. Study discontinuation occurred in seven (9.9%) patients with ICD AEs; these then resolved in five patients. Dose reduction occurred for 23 AEs, with the majority (73.9%) resolving. In this analysis of >750 patients with PD treated with rotigotine, the frequency of ICD behaviour AEs was 9.0%, with a specific incidence timeline observed. Active surveillance as duration of treatment increases may help early identification and management; once ICD behaviours are present rotigotine dose reduction may be considered. © 2016 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.

  16. Deconstructing tolerance with clobazam: Post hoc analyses from an open-label extension study.

    Science.gov (United States)

    Gidal, Barry E; Wechsler, Robert T; Sankar, Raman; Montouris, Georgia D; White, H Steve; Cloyd, James C; Kane, Mary Clare; Peng, Guangbin; Tworek, David M; Shen, Vivienne; Isojarvi, Jouko

    2016-10-25

    To evaluate potential development of tolerance to adjunctive clobazam in patients with Lennox-Gastaut syndrome. Eligible patients enrolled in open-label extension study OV-1004, which continued until clobazam was commercially available in the United States or for a maximum of 2 years outside the United States. Enrolled patients started at 0.5 mg·kg -1 ·d -1 clobazam, not to exceed 40 mg/d. After 48 hours, dosages could be adjusted up to 2.0 mg·kg -1 ·d -1 (maximum 80 mg/d) on the basis of efficacy and tolerability. Post hoc analyses evaluated mean dosages and drop-seizure rates for the first 2 years of the open-label extension based on responder categories and baseline seizure quartiles in OV-1012. Individual patient listings were reviewed for dosage increases ≥40% and increasing seizure rates. Data from 200 patients were included. For patients free of drop seizures, there was no notable change in dosage over 24 months. For responder groups still exhibiting drop seizures, dosages were increased. Weekly drop-seizure rates for 100% and ≥75% responders demonstrated a consistent response over time. Few patients had a dosage increase ≥40% associated with an increase in seizure rates. Two-year findings suggest that the majority of patients do not develop tolerance to the antiseizure actions of clobazam. Observed dosage increases may reflect best efforts to achieve seizure freedom. It is possible that the clinical development of tolerance to clobazam has been overstated. NCT00518713 and NCT01160770. This study provides Class III evidence that the majority of patients do not develop tolerance to clobazam over 2 years of treatment. © 2016 American Academy of Neurology.

  17. Clinical Factors Associated with Dose of Loop Diuretics After Pediatric Cardiac Surgery: Post Hoc Analysis.

    Science.gov (United States)

    Haiberger, Roberta; Favia, Isabella; Romagnoli, Stefano; Cogo, Paola; Ricci, Zaccaria

    2016-06-01

    A post hoc analysis of a randomized controlled trial comparing the clinical effects of furosemide and ethacrynic acid was conducted. Infants undergoing cardiac surgery with cardiopulmonary bypass were included in order to explore which clinical factors are associated with diuretic dose in infants with congenital heart disease. Overall, 67 patients with median (interquartile range) age of 48 (13-139) days were enrolled. Median diuretic dose was 0.34 (0.25-0.4) mg/kg/h at the end of postoperative day (POD) 0 and it significantly decreased (p = 0.04) over the following PODs; during this period, the ratio between urine output and diuretic dose increased significantly (p = 0.04). Age (r -0.26, p = 0.02), weight (r -0.28, p = 0.01), cross-clamp time (r 0.27, p = 0.03), administration of ethacrynic acid (OR 0.01, p = 0.03), and, at the end of POD0, creatinine levels (r 0.3, p = 0.009), renal near-infrared spectroscopy saturation (-0.44, p = 0.008), whole-blood neutrophil gelatinase-associated lipocalin levels (r 0.30, p = 0.01), pH (r -0.26, p = 0.02), urinary volume (r -0.2755, p = 0.03), and fluid balance (r 0.2577, p = 0.0266) showed a significant association with diuretic dose. At multivariable logistic regression cross-clamp time (OR 1.007, p = 0.04), use of ethacrynic acid (OR 0.2, p = 0.01) and blood pH at the end of POD0 (OR 0.0001, p = 0.03) was independently associated with diuretic dose. Early resistance to loop diuretics continuous infusion is evident in post-cardiac surgery infants: Higher doses are administered to patients with lower urinary output. Independently associated variables with diuretic dose in our population appeared to be cross-clamping time, the administration of ethacrynic acid, and blood pH.

  18. Protective effect of yerba mate intake on the cardiovascular system: a post hoc analysis study in postmenopausal women

    OpenAIRE

    da Veiga, D.T.A.; Bringhenti, R.; Copes, R.; Tatsch, E.; Moresco, R.N.; Comim, F.V.; Premaor, M.O.

    2018-01-01

    The prevalence of cardiovascular and metabolic diseases is increased in postmenopausal women, which contributes to the burden of illnesses in this period of life. Yerba mate (Ilex paraguariensis) is a native bush from Southern South America. Its leaves are rich in phenolic components, which may have antioxidant, vasodilating, hypocholesterolemic, and hypoglycemic proprieties. This post hoc analysis of the case-control study nested in the Obesity and Bone Fracture Cohort evaluated the consumpt...

  19. Is LSD toxic?

    Science.gov (United States)

    Nichols, David E; Grob, Charles S

    2018-03-01

    LSD (lysergic acid diethylamide) was discovered almost 75 years ago, and has been the object of episodic controversy since then. While initially explored as an adjunctive psychiatric treatment, its recreational use by the general public has persisted and on occasion has been associated with adverse outcomes, particularly when the drug is taken under suboptimal conditions. LSD's potential to cause psychological disturbance (bad trips) has been long understood, and has rarely been associated with accidental deaths and suicide. From a physiological perspective, however, LSD is known to be non-toxic and medically safe when taken at standard dosages (50-200μg). The scientific literature, along with recent media reports, have unfortunately implicated "LSD toxicity" in five cases of sudden death. On close examination, however, two of these fatalities were associated with ingestion of massive overdoses, two were evidently in individuals with psychological agitation after taking standard doses of LSD who were then placed in maximal physical restraint positions (hogtied) by police, following which they suffered fatal cardiovascular collapse, and one case of extreme hyperthermia leading to death that was likely caused by a drug substituted for LSD with strong effects on central nervous system temperature regulation (e.g. 25i-NBOMe). Given the renewed interest in the therapeutic potential of LSD and other psychedelic drugs, it is important that an accurate understanding be established of the true causes of such fatalities that had been erroneously attributed to LSD toxicity, including massive overdoses, excessive physical restraints, and psychoactive drugs other than LSD. Copyright © 2018 Elsevier B.V. All rights reserved.

  20. Modern Clinical Research on LSD.

    Science.gov (United States)

    Liechti, Matthias E

    2017-10-01

    All modern clinical studies using the classic hallucinogen lysergic acid diethylamide (LSD) in healthy subjects or patients in the last 25 years are reviewed herein. There were five recent studies in healthy participants and one in patients. In a controlled setting, LSD acutely induced bliss, audiovisual synesthesia, altered meaning of perceptions, derealization, depersonalization, and mystical experiences. These subjective effects of LSD were mediated by the 5-HT 2A receptor. LSD increased feelings of closeness to others, openness, trust, and suggestibility. LSD impaired the recognition of sad and fearful faces, reduced left amygdala reactivity to fearful faces, and enhanced emotional empathy. LSD increased the emotional response to music and the meaning of music. LSD acutely produced deficits in sensorimotor gating, similar to observations in schizophrenia. LSD had weak autonomic stimulant effects and elevated plasma cortisol, prolactin, and oxytocin levels. Resting-state functional magnetic resonance studies showed that LSD acutely reduced the integrity of functional brain networks and increased connectivity between networks that normally are more dissociated. LSD increased functional thalamocortical connectivity and functional connectivity of the primary visual cortex with other brain areas. The latter effect was correlated with subjective hallucinations. LSD acutely induced global increases in brain entropy that were associated with greater trait openness 14 days later. In patients with anxiety associated with life-threatening disease, anxiety was reduced for 2 months after two doses of LSD. In medical settings, no complications of LSD administration were observed. These data should contribute to further investigations of the therapeutic potential of LSD in psychiatry.

  1. Perioperative hyperoxia - Long-term impact on cardiovascular complications after abdominal surgery, a post hoc analysis of the PROXI trial

    DEFF Research Database (Denmark)

    Fonnes, Siv; Gogenur, Ismail; Sondergaard, Edith Smed

    2016-01-01

    BACKGROUND: Increased long-term mortality was found in patients exposed to perioperative hyperoxia in the PROXI trial, where patients undergoing laparotomy were randomised to 80% versus 30% oxygen during and after surgery. This post hoc follow-up study assessed the impact of perioperative hyperoxia...... included myocardial infarction, other heart disease, and acute coronary syndrome or death. Data were analysed in the Cox proportional hazards model. RESULTS: The primary outcome, acute coronary syndrome, occurred in 2.5% versus 1.3% in the 80% versus 30% oxygen group; HR 2.15 (95% CI 0.96-4.84). Patients...

  2. Neutrino astronomy at Mont Blanc: from LSD to LSD-2

    International Nuclear Information System (INIS)

    Saavedra, O.; Aglietta, M.; Badino, G.

    1988-01-01

    In this paper we present the upgrading of the LSD experiment, presently running in the Mont Blanc Laboratory. The data recorded during the period when supernova 1987A exploded are analysed in detail. The research program of LSD-2, the same experiment as LSD but with an higher sensitivity to search for neutrino burst from collapsing stars, is also discussed

  3. Modern Clinical Research on LSD

    OpenAIRE

    Liechti, Matthias E.

    2017-01-01

    All modern clinical studies using the classic hallucinogen lysergic acid diethylamide (LSD) in healthy subjects or patients in the last 25 years are reviewed herein. There were five recent studies in healthy participants and one in patients. In a controlled setting, LSD acutely induced bliss, audiovisual synesthesia, altered meaning of perceptions, derealization, depersonalization, and mystical experiences. These subjective effects of LSD were mediated by the 5-HT2A receptor. LSD increased fe...

  4. LSD Now: 1973

    Science.gov (United States)

    Chunko, John A.

    1973-01-01

    LSD NOW is a nationwide, statistical survey and analysis of hallucinogenic drug use by individuals presently in formal educational surroundings. Analysis, concentrating on the extent and rationale related to the use of such drugs, now offers a deeper and more meaningful understanding of a particular facet of the drug culture. This understanding…

  5. A SAS(®) macro implementation of a multiple comparison post hoc test for a Kruskal-Wallis analysis.

    Science.gov (United States)

    Elliott, Alan C; Hynan, Linda S

    2011-04-01

    The Kruskal-Wallis (KW) nonparametric analysis of variance is often used instead of a standard one-way ANOVA when data are from a suspected non-normal population. The KW omnibus procedure tests for some differences between groups, but provides no specific post hoc pair wise comparisons. This paper provides a SAS(®) macro implementation of a multiple comparison test based on significant Kruskal-Wallis results from the SAS NPAR1WAY procedure. The implementation is designed for up to 20 groups at a user-specified alpha significance level. A Monte-Carlo simulation compared this nonparametric procedure to commonly used parametric multiple comparison tests. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  6. Illustrating, Quantifying, and Correcting for Bias in Post-hoc Analysis of Gene-Based Rare Variant Tests of Association

    Directory of Open Access Journals (Sweden)

    Kelsey E. Grinde

    2017-09-01

    Full Text Available To date, gene-based rare variant testing approaches have focused on aggregating information across sets of variants to maximize statistical power in identifying genes showing significant association with diseases. Beyond identifying genes that are associated with diseases, the identification of causal variant(s in those genes and estimation of their effect is crucial for planning replication studies and characterizing the genetic architecture of the locus. However, we illustrate that straightforward single-marker association statistics can suffer from substantial bias introduced by conditioning on gene-based test significance, due to the phenomenon often referred to as “winner's curse.” We illustrate the ramifications of this bias on variant effect size estimation and variant prioritization/ranking approaches, outline parameters of genetic architecture that affect this bias, and propose a bootstrap resampling method to correct for this bias. We find that our correction method significantly reduces the bias due to winner's curse (average two-fold decrease in bias, p < 2.2 × 10−6 and, consequently, substantially improves mean squared error and variant prioritization/ranking. The method is particularly helpful in adjustment for winner's curse effects when the initial gene-based test has low power and for relatively more common, non-causal variants. Adjustment for winner's curse is recommended for all post-hoc estimation and ranking of variants after a gene-based test. Further work is necessary to continue seeking ways to reduce bias and improve inference in post-hoc analysis of gene-based tests under a wide variety of genetic architectures.

  7. Outcome when adrenaline (epinephrine) was actually given vs. not given - post hoc analysis of a randomized clinical trial.

    Science.gov (United States)

    Olasveengen, Theresa M; Wik, Lars; Sunde, Kjetil; Steen, Petter A

    2012-03-01

    IV line insertion and drugs did not affect long-term survival in an out-of-hospital cardiac arrest (OHCA) randomized clinical trial (RCT). In a previous large registry study adrenaline was negatively associated with survival from OHCA. The present post hoc analysis on the RCT data compares outcomes for patients actually receiving adrenaline to those not receiving adrenaline. Patients from a RCT performed May 2003 to April 2008 were included. Three patients from the original intention-to-treat analysis were excluded due to insufficient documentation of adrenaline administration. Quality of cardiopulmonary resuscitation (CPR) and clinical outcomes were compared. Clinical characteristics were similar and CPR quality comparable and within guideline recommendations for 367 patients receiving adrenaline and 481 patients not receiving adrenaline. Odds ratio (OR) for being admitted to hospital, being discharged from hospital and surviving with favourable neurological outcome for the adrenaline vs. no-adrenaline group was 2.5 (CI 1.9, 3.4), 0.5 (CI 0.3, 0.8) and 0.4 (CI 0.2, 0.7), respectively. Ventricular fibrillation, response interval, witnessed arrest, gender, age and endotracheal intubation were confounders in multivariate logistic regression analysis. OR for survival for adrenaline vs. no-adrenaline adjusted for confounders was 0.52 (95% CI: 0.29, 0.92). Receiving adrenaline was associated with improved short-term survival, but decreased survival to hospital discharge and survival with favourable neurological outcome after OHCA. This post hoc survival analysis is in contrast to the previous intention-to-treat analysis of the same data, but agrees with previous non-randomized registry data. This shows limitations of non-randomized or non-intention-to-treat analyses. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  8. Switching to olanzapine long-acting injection from either oral olanzapine or any other antipsychotic: comparative post hoc analyses

    Directory of Open Access Journals (Sweden)

    Ciudad A

    2013-11-01

    Full Text Available Antonio Ciudad,1 Ernie Anand,2 Lovisa Berggren,3 Marta Casillas,4 Alexander Schacht,3 Elena Perrin5 1Department of Clinical Research and Development, Eli Lilly & Co, Madrid, Spain; 2Neuroscience Medical Affairs – EU, Lilly Research Centre, Windlesham, Surrey, UK; 3Global Statistical Sciences, Eli Lilly & Co, Bad Homburg, Germany; 4European Scientific Communications, Eli Lilly & Co, Madrid, Spain; 5Medical Department, Eli Lilly & Co, Suresnes, Paris, France Background: A considerable proportion of patients suffering from schizophrenia show suboptimal responses to oral antipsychotics due to inadequate adherence. Hence, they are likely to benefit from switching to a long-acting injectable formulation. These post hoc analyses assessed the clinical effects of switching to olanzapine long-acting injection (OLAI from either oral olanzapine (OLZ or other antipsychotics (non-OLZ. Methods: Post hoc analyses were done based on two randomized studies (one short-term, one long-term conducted in patients suffering from schizophrenia and treated with OLAI. The short-term study was an 8-week placebo-controlled, double-blind trial in acute patients, and the long-term study was a 2-year, oral olanzapine-controlled, open-label, follow-up of stabilized outpatients. Results: These analyses used data from 62 OLAI-treated patients (12 switched from OLZ, 50 from non-OLZ from the short-term study and 190 OLAI-treated patients (56 switched from OLZ, 134 from non-OLZ from the long-term study. Kaplan–Meier survival analyses of time to all-cause discontinuation of OLAI treatment did not differ significantly between OLZ and non-OLZ patients in the short-term study (P=0.209 or long-term study (P=0.448. Similarly, the proportions of OLZ and non-OLZ patients that discontinued OLAI were not statistically different in the short-term (16.7% versus 36.0%, respectively; P=0.198 or long-term (57.1% versus 47.8% respectively; P=0.238 studies. In the short-term study, no

  9. Lenient vs. strict rate control in patients with atrial fibrillation and heart failure: a post-hoc analysis of the RACE II study

    NARCIS (Netherlands)

    Mulder, Bart A.; van Veldhuisen, Dirk J.; Crijns, Harry J. G. M.; Tijssen, Jan G. P.; Hillege, Hans L.; Alings, Marco; Rienstra, Michiel; Groenveld, Hessel F.; van den Berg, Maarten P.; van Gelder, Isabelle C.

    2013-01-01

    It is unknown whether lenient rate control is an acceptable strategy in patients with AF and heart failure. We evaluated differences in outcome in patients with AF and heart failure treated with lenient or strict rate control. This post-hoc analysis of the RACE II trial included patients with an

  10. Influencing Anesthesia Provider Behavior Using Anesthesia Information Management System Data for Near Real-Time Alerts and Post Hoc Reports.

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    Epstein, Richard H; Dexter, Franklin; Patel, Neil

    2015-09-01

    In this review article, we address issues related to using data from anesthesia information management systems (AIMS) to deliver near real-time alerts via AIMS workstation popups and/or alphanumeric pagers and post hoc reports via e-mail. We focus on reports and alerts for influencing the behavior of anesthesia providers (i.e., anesthesiologists, anesthesia residents, and nurse anesthetists). Multiple studies have shown that anesthesia clinical decision support (CDS) improves adherence to protocols and increases financial performance through facilitation of billing, regulatory, and compliance documentation; however, improved clinical outcomes have not been demonstrated. We inform developers and users of feedback systems about the multitude of concerns to consider during development and implementation of CDS to increase its effectiveness and to mitigate its potentially disruptive aspects. We discuss the timing and modalities used to deliver messages, implications of outlier-only versus individualized feedback, the need to consider possible unintended consequences of such feedback, regulations, sustainability, and portability among systems. We discuss statistical issues related to the appropriate evaluation of CDS efficacy. We provide a systematic review of the published literature (indexed in PubMed) of anesthesia CDS and offer 2 case studies of CDS interventions using AIMS data from our own institution illustrating the salient points. Because of the considerable expense and complexity of maintaining near real-time CDS systems, as compared with providing individual reports via e-mail after the fact, we suggest that if the same goal can be accomplished via delayed reporting versus immediate feedback, the former approach is preferable. Nevertheless, some processes require near real-time alerts to produce the desired improvement. Post hoc e-mail reporting from enterprise-wide electronic health record systems is straightforward and can be accomplished using system

  11. Illustrating, Quantifying, and Correcting for Bias in Post-hoc Analysis of Gene-Based Rare Variant Tests of Association

    Science.gov (United States)

    Grinde, Kelsey E.; Arbet, Jaron; Green, Alden; O'Connell, Michael; Valcarcel, Alessandra; Westra, Jason; Tintle, Nathan

    2017-01-01

    To date, gene-based rare variant testing approaches have focused on aggregating information across sets of variants to maximize statistical power in identifying genes showing significant association with diseases. Beyond identifying genes that are associated with diseases, the identification of causal variant(s) in those genes and estimation of their effect is crucial for planning replication studies and characterizing the genetic architecture of the locus. However, we illustrate that straightforward single-marker association statistics can suffer from substantial bias introduced by conditioning on gene-based test significance, due to the phenomenon often referred to as “winner's curse.” We illustrate the ramifications of this bias on variant effect size estimation and variant prioritization/ranking approaches, outline parameters of genetic architecture that affect this bias, and propose a bootstrap resampling method to correct for this bias. We find that our correction method significantly reduces the bias due to winner's curse (average two-fold decrease in bias, p bias and improve inference in post-hoc analysis of gene-based tests under a wide variety of genetic architectures. PMID:28959274

  12. Symptomatic efficacy of rasagiline monotherapy in early Parkinson's disease: post-hoc analyses from the ADAGIO trial.

    Science.gov (United States)

    Jankovic, Joseph; Berkovich, Elijahu; Eyal, Eli; Tolosa, Eduardo

    2014-06-01

    The ADAGIO study included a large cohort of patients with early PD (baseline total-UPDRS = 20) who were initially randomized to rasagiline and placebo, thereby allowing analyses of symptomatic efficacy. Post-hoc analyses comparing the efficacy of rasagiline 1 mg/day (n = 288) versus placebo (n = 588) on key symptoms at 36 weeks, and on total-UPDRS scores over 72 weeks (completer population: rasagiline 1 mg/day n = 221, placebo n = 392) were performed. Treatment with rasagiline resulted in significantly better tremor, bradykinesia, rigidity and postural-instability-gait-difficulty scores at week 36 versus placebo. Whereas the placebo group experienced progressive deterioration from baseline (2.6 UPDRS points at week 36), patients in the rasagiline group were maintained at baseline values at week 60 (UPDRS-change of 0.3 points). At week 72, patients who had received continuous monotherapy with rasagiline experienced a worsening of only 1.6 points. Treatment with rasagiline maintained motor function to baseline values for at least a year with significant benefits observed in all key PD motor symptoms. Copyright © 2014 Elsevier Ltd. All rights reserved.

  13. Fluoxetine-clonazepam cotherapy for anxious depression: an exploratory, post-hoc analysis of a randomized, double blind study.

    Science.gov (United States)

    Papakostas, George I; Clain, Alisabet; Ameral, Victoria E; Baer, Lee; Brintz, Carrie; Smith, Ward T; Londborg, Peter D; Glaudin, Vincent; Painter, John R; Fava, Maurizio

    2010-01-01

    Anxious depression, defined as major depressive disorder (MDD) accompanied by high levels of anxiety, seems to be both common and difficult to treat, with antidepressant monotherapy often yielding modest results. We sought to examine the relative benefits of antidepressant-anxiolytic cotherapy versus antidepressant monotherapy for patients with anxious depression versus without anxious depression. We conducted a post-hoc analysis of an existing dataset (N=80), from a 3-week, randomized, double-blind trial which demonstrated cotherapy with fluoxetine and clonazepam to result in superior efficacy than fluoxetine monotherapy in MDD. The present analysis involved examining whether anxious depression status served as a predictor and moderator of symptom improvement. Anxious depression status was not found to predict symptom improvement, or serve as a moderator of clinical improvement to cotherapy versus monotherapy. However, the advantage in remission rates in favor of cotherapy versus monotherapy was, numerically, much larger for patients with anxious depression (32.2%) than it was for patients without anxious MDD (9.7%). The respective number needed to treat statistic for these two differences in response rates were, approximately, one in three for patients with anxious depression versus one in 10 for patients without anxious depression. The efficacy of fluoxetine-clonazepam cotherapy compared with fluoxetine monotherapy was numerically but not statistically enhanced for patients with anxious depression than those without anxious depression.

  14. Post-hoc simulation study to adopt a computerized adaptive testing (CAT) for a Korean Medical License Examination.

    Science.gov (United States)

    Seo, Dong Gi; Choi, Jeongwook

    2018-05-17

    Computerized adaptive testing (CAT) has been adopted in license examinations due to a test efficiency and accuracy. Many research about CAT have been published to prove the efficiency and accuracy of measurement. This simulation study investigated scoring method and item selection methods to implement CAT in Korean medical license examination (KMLE). This study used post-hoc (real data) simulation design. The item bank used in this study was designed with all items in a 2017 KMLE. All CAT algorithms for this study were implemented by a 'catR' package in R program. In terms of accuracy, Rasch and 2parametric logistic (PL) model performed better than 3PL model. Modal a Posteriori (MAP) or Expected a Posterior (EAP) provided more accurate estimates than MLE and WLE. Furthermore Maximum posterior weighted information (MPWI) or Minimum expected posterior variance (MEPV) performed better than other item selection methods. In terms of efficiency, Rasch model was recommended to reduce test length. Simulation study should be performed under varied test conditions before adopting a live CAT. Based on a simulation study, specific scoring and item selection methods should be predetermined before implementing a live CAT.

  15. Risk reductions for cardiovascular disease with pravastatin treatment by dyslipidemia phenotype: a post hoc analysis of the MEGA Study.

    Science.gov (United States)

    Nishiwaki, Masato; Ikewaki, Katsunori; Ayaori, Makoto; Mizuno, Kyoichi; Ohashi, Yasuo; Ohsuzu, Fumitaka; Ishikawa, Toshitsugu; Nakamura, Haruo

    2013-03-01

    The beneficial effect of statins for cardiovascular disease (CVD) prevention has been well established. However, the effectiveness among different phenotypes of dyslipidemia has not been confirmed. We evaluated the effect of pravastatin on the incidence of CVD in relation to the phenotype of dyslipidemia. The MEGA Study evaluated the effect of low-dose pravastatin on primary prevention of CVD in 7832 Japanese patients, who were randomized to diet alone or diet plus pravastatin and followed for more than 5 years. These patients were classified into phenotype IIa (n=5589) and IIb (n=2041) based on the electrophoretic pattern for this post hoc analysis. In the diet group there was no significant difference in the incidence of coronary heart disease (CHD), stroke, CVD, and total mortality between the two phenotypes. Phenotype IIb patients, compared to phenotype IIa, had lower levels of high-density lipoprotein cholesterol (HDL-C) and a significantly higher incidence of CVD in relation to a low HDL-C level (dyslipidemia. Significant risk reductions were observed for CHD by 38% (p=0.04) and CVD by 31% (p=0.02) in type IIa dyslipidemia but not in phenotype IIb. Pravastatin therapy provided significant risk reductions for CHD and CVD in patients with phenotype IIa dyslipidemia, but not in those with phenotype IIb dyslipidemia. Copyright © 2012 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

  16. TRIBUNALES PENALES INTERNACIONALES AD HOC DEL POST-GUERRA FRÍA: CAMBIANDO PARADIGMAS EN EL TRATAMIENTO DE CUESTIONES DE GÉNERO

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    Camila Soares Lippi

    2011-12-01

    Full Text Available Analizaremos como la jurisprudencia de los Tribunales Penales Internacionales ad hoc del post-Guerra Fría representa un cambio de paradigmas en cuestiones de género en el Derecho Penal Internacional y en el Derecho Internacional Humanitario. Para eso, partimos del concepto de género, o sea, las construcciones sociales cuanto a los roles masculino y femenino, como categoría central de análisis. Analizamos, primeramente, el post-Segunda Guerra Mundial. Ese momento histórico, ejemplificado por los Tribunales de Núremberg y de Tokio y por los Convenios de Ginebra de 1949. Después analizase los Tribunales Penales Internacionales ad hoc del post-Guerra Fría. Finalmente, analizamos la definición de género en el Estatuto de Roma, que instituye el Tribunal Penal Internacional.

  17. Post-hoc pattern-oriented testing and tuning of an existing large model: lessons from the field vole.

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    Christopher J Topping

    Full Text Available Pattern-oriented modeling (POM is a general strategy for modeling complex systems. In POM, multiple patterns observed at different scales and hierarchical levels are used to optimize model structure, to test and select sub-models of key processes, and for calibration. So far, POM has been used for developing new models and for models of low to moderate complexity. It remains unclear, though, whether the basic idea of POM to utilize multiple patterns, could also be used to test and possibly develop existing and established models of high complexity. Here, we use POM to test, calibrate, and further develop an existing agent-based model of the field vole (Microtus agrestis, which was developed and tested within the ALMaSS framework. This framework is complex because it includes a high-resolution representation of the landscape and its dynamics, of the individual's behavior, and of the interaction between landscape and individual behavior. Results of fitting to the range of patterns chosen were generally very good, but the procedure required to achieve this was long and complicated. To obtain good correspondence between model and the real world it was often necessary to model the real world environment closely. We therefore conclude that post-hoc POM is a useful and viable way to test a highly complex simulation model, but also warn against the dangers of over-fitting to real world patterns that lack details in their explanatory driving factors. To overcome some of these obstacles we suggest the adoption of open-science and open-source approaches to ecological simulation modeling.

  18. Tiotropium and Salmeterol in COPD Patients at Risk of Exacerbations: A Post Hoc Analysis from POET-COPD(®).

    Science.gov (United States)

    Vogelmeier, Claus F; Asijee, Guus M; Kupas, Katrin; Beeh, Kai M

    2015-06-01

    Among patients with chronic obstructive pulmonary disease (COPD), the frequency and severity of past exacerbations potentiates future events. The impact of current therapies on exacerbation frequency and severity in patients with different exacerbation risks is not well known. A post hoc analysis of patients at low (≤1 exacerbation [oral steroids/antibiotics requirement] and no COPD-related hospitalization in the year preceding trial entry) or high (≥2 exacerbations [oral steroids/antibiotics requirement] or ≥1 COPD-related hospitalization[s] in the year preceding trial entry) exacerbation risk, from the Prevention of Exacerbations with Tiotropium in Chronic Obstructive Pulmonary Disease (POET-COPD(®)) database. Compared with salmeterol, tiotropium significantly increased time to first COPD exacerbation (hazard ratio 0.84; 95% confidence interval [CI] 0.76-0.92; p = 0.0002) and reduced the number of COPD exacerbations (rate ratio 0.90; 95% CI 0.81-0.99; p = 0.0383) in patients at high exacerbation risk. With treatment, the risk of remaining in the high-risk exacerbator subgroup was statistically lower with tiotropium versus salmeterol (risk ratio [RR] 0.89; 95% CI 0.80-1.00; p = 0.0478). For low-risk patients, time to first COPD exacerbation and number of COPD exacerbations were numerically lower with tiotropium versus salmeterol. With treatment, the risk of transitioning from a low to a high exacerbation risk was lower with tiotropium versus salmeterol (RR 0.87; 95% CI 0.71-1.07; p = 0.1968). This analysis confirms the higher efficacy of tiotropium versus salmeterol in prolonging time to first COPD exacerbation and reducing number of exacerbations in patients both at low and high exacerbation risk. Boehringer Ingelheim and Pfizer. ClinicalTrials.gov NCT00563381.

  19. Protective effect of yerba mate intake on the cardiovascular system: a post hoc analysis study in postmenopausal women.

    Science.gov (United States)

    da Veiga, D T A; Bringhenti, R; Copes, R; Tatsch, E; Moresco, R N; Comim, F V; Premaor, M O

    2018-01-01

    The prevalence of cardiovascular and metabolic diseases is increased in postmenopausal women, which contributes to the burden of illnesses in this period of life. Yerba mate (Ilex paraguariensis) is a native bush from Southern South America. Its leaves are rich in phenolic components, which may have antioxidant, vasodilating, hypocholesterolemic, and hypoglycemic proprieties. This post hoc analysis of the case-control study nested in the Obesity and Bone Fracture Cohort evaluated the consumption of yerba mate and the prevalence of hypertension, dyslipidemia, and coronary diseases in postmenopausal women. Ninety-five postmenopausal women were included in this analysis. A questionnaire was applied to evaluate the risk factors and diagnosis of cardiovascular diseases and consumption of yerba mate infusion. Student's t-test and chi-square test were used to assess significant differences between groups. The group that consumed more than 1 L/day of mate infusion had significantly fewer diagnoses of coronary disease, dyslipidemia, and hypertension (P<0.049, P<0.048, and P<0.016, respectively). Furthermore, the serum levels of glucose were lower in the group with a higher consumption of yerba mate infusion (P<0.013). The serum levels of total cholesterol, LDL-cholesterol, HDL-cholesterol, and triglycerides were similar between the groups. This pragmatic study points out the benefits of yerba mate consumption for the cardiovascular and metabolic systems. The ingestion of more than 1 L/day of mate infusion was associated with fewer self-reported cardiovascular diseases and lower serum levels of glucose. Longitudinal studies are needed to evaluate the association between yerba mate infusion and reduction of cardiovascular diseases in postmenopausal women.

  20. Radiographic progression with nonrising PSA in metastatic castration-resistant prostate cancer: post hoc analysis of PREVAIL.

    Science.gov (United States)

    Bryce, A H; Alumkal, J J; Armstrong, A; Higano, C S; Iversen, P; Sternberg, C N; Rathkopf, D; Loriot, Y; de Bono, J; Tombal, B; Abhyankar, S; Lin, P; Krivoshik, A; Phung, D; Beer, T M

    2017-06-01

    Advanced prostate cancer is a phenotypically diverse disease that evolves through multiple clinical courses. PSA level is the most widely used parameter for disease monitoring, but it has well-recognized limitations. Unlike in clinical trials, in practice, clinicians may rely on PSA monitoring alone to determine disease status on therapy. This approach has not been adequately tested. Chemotherapy-naive asymptomatic or mildly symptomatic men (n=872) with metastatic castration-resistant prostate cancer (mCRPC) who were treated with the androgen receptor inhibitor enzalutamide in the PREVAIL study were analyzed post hoc for rising versus nonrising PSA (empirically defined as >1.05 vs ⩽1.05 times the PSA level from 3 months earlier) at the time of radiographic progression. Clinical characteristics and disease outcomes were compared between the rising and nonrising PSA groups. Of 265 PREVAIL patients with radiographic progression and evaluable PSA levels on the enzalutamide arm, nearly one-quarter had a nonrising PSA. Median progression-free survival in this cohort was 8.3 months versus 11.1 months in the rising PSA cohort (hazard ratio 1.68; 95% confidence interval 1.26-2.23); overall survival was similar between the two groups, although less than half of patients in either group were still at risk at 24 months. Baseline clinical characteristics of the two groups were similar. Non-rising PSA at radiographic progression is a common phenomenon in mCRPC patients treated with enzalutamide. As restaging in advanced prostate cancer patients is often guided by increases in PSA levels, our results demonstrate that disease progression on enzalutamide can occur without rising PSA levels. Therefore, a disease monitoring strategy that includes imaging not entirely reliant on serial serum PSA measurement may more accurately identify disease progression.

  1. Perampanel with concomitant levetiracetam and topiramate: Post hoc analysis of adverse events related to hostility and aggression.

    Science.gov (United States)

    Chung, Steve; Williams, Betsy; Dobrinsky, Cindy; Patten, Anna; Yang, Haichen; Laurenza, Antonio

    2017-10-01

    In 4 Phase III registration trials (3 in patients with partial seizures, N=1480; 1 in patients with PGTCS, N=163), perampanel administered to patients already receiving 1-3 concomitant antiepileptic drugs (AEDs) demonstrated statistically superior efficacy compared to placebo in reducing seizure frequency. However, use of perampanel in these studies was associated with a risk of psychiatric and behavioral adverse reactions, including aggression, hostility, irritability, anger, and homicidal ideation and threats. The present study is a post hoc analysis of pooled data from these 4 trials to determine if concomitant treatment with levetiracetam and/or topiramate increased the risk of hostility- and aggression-related AEs. Treatment-emergent AEs (TEAEs) were determined using a "Narrow & Broad" search based on the Medical Dictionary for Regulatory Activities (MedDRA) standard MedDRA query (SMQ) for hostility- and aggression-related events. The rate of hostility- and aggression-related TEAEs was observed to be similar among perampanel-treated patients: a) receiving levetiracetam (N=340) compared to those not receiving levetiracetam (N=779); b) receiving topiramate (N=223) compared to those not receiving topiramate (N=896); and c) receiving both levetiracetam and topiramate (N=47) compared to those not receiving levetiracetam and topiramate (N=1072). Severe and serious TEAEs related to hostility and aggression were rare and occurred at a similar rate regardless of concomitant levetiracetam and/or topiramate therapy. Taken together, these results suggest that concomitant treatment with levetiracetam and/or topiramate has no appreciable effect on the occurrence of hostility- or aggression-related TEAEs in patients receiving perampanel. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  2. Post hoc interlaboratory comparison of single particle ICP-MS size measurements of NIST gold nanoparticle reference materials.

    Science.gov (United States)

    Montoro Bustos, Antonio R; Petersen, Elijah J; Possolo, Antonio; Winchester, Michael R

    2015-09-01

    Single particle inductively coupled plasma-mass spectrometry (spICP-MS) is an emerging technique that enables simultaneous measurement of nanoparticle size and number quantification of metal-containing nanoparticles at realistic environmental exposure concentrations. Such measurements are needed to understand the potential environmental and human health risks of nanoparticles. Before spICP-MS can be considered a mature methodology, additional work is needed to standardize this technique including an assessment of the reliability and variability of size distribution measurements and the transferability of the technique among laboratories. This paper presents the first post hoc interlaboratory comparison study of the spICP-MS technique. Measurement results provided by six expert laboratories for two National Institute of Standards and Technology (NIST) gold nanoparticle reference materials (RM 8012 and RM 8013) were employed. The general agreement in particle size between spICP-MS measurements and measurements by six reference techniques demonstrates the reliability of spICP-MS and validates its sizing capability. However, the precision of the spICP-MS measurement was better for the larger 60 nm gold nanoparticles and evaluation of spICP-MS precision indicates substantial variability among laboratories, with lower variability between operators within laboratories. Global particle number concentration and Au mass concentration recovery were quantitative for RM 8013 but significantly lower and with a greater variability for RM 8012. Statistical analysis did not suggest an optimal dwell time, because this parameter did not significantly affect either the measured mean particle size or the ability to count nanoparticles. Finally, the spICP-MS data were often best fit with several single non-Gaussian distributions or mixtures of Gaussian distributions, rather than the more frequently used normal or log-normal distributions.

  3. Residual symptoms and functioning in depression, does the type of residual symptom matter? A post-hoc analysis

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    Romera Irene

    2013-02-01

    Full Text Available Abstract Background The degrees to which residual symptoms in major depressive disorder (MDD adversely affect patient functioning is not known. This post-hoc analysis explored the association between different residual symptoms and patient functioning. Methods Patients with MDD who responded (≥50% on the 17-item Hamilton Rating Scale for Depression; HAMD-17 after 3 months of treatment (624/930 were included. Residual core mood-symptoms (HAMD-17 core symptom subscale ≥1, residual insomnia-symptoms (HAMD-17 sleep subscale ≥1, residual anxiety-symptoms (HAMD-17-anxiety subscale ≥1, residual somatic-symptoms (HAMD-17 Item 13 ≥1, pain (Visual Analogue Scale ≥30, and functioning were assessed after 3 months treatment. A stepwise logistic regression model with normal functioning (Social and Occupational Functioning Assessment Scale ≥80 as the dependent variable was used. Results After 3 months, 59.5% of patients (371/624 achieved normal functioning and 66.0% (412/624 were in remission. Residual symptom prevalence was: core mood symptoms 72%; insomnia 63%; anxiety 78%; and somatic symptoms 41%. Pain reported in 18%. Factors associated with normal functioning were absence of core mood symptoms (odds ratio [OR] 8.7; 95% confidence interval [CI], 4.6–16.7, absence of insomnia symptoms (OR 1.8; 95% CI, 1.2–2.7, episode length (4–24 weeks vs. ≥24 weeks [OR 2.0; 95% CI, 1.1–3.6] and better baseline functioning (OR 1.0; 95% CI, 1.0–1.1. A significant interaction between residual anxiety symptoms and pain was found (p = 0.0080. Conclusions Different residual symptoms are associated to different degrees with patient functioning. To achieve normal functioning, specific residual symptoms domains might be targeted for treatment.

  4. Response to duloxetine in chronic low back pain: exploratory post hoc analysis of a Japanese Phase III randomized study

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    Tsuji T

    2017-09-01

    Full Text Available Toshinaga Tsuji,1 Naohiro Itoh,1 Mitsuhiro Ishida,2 Toshimitsu Ochiai,3 Shinichi Konno4 1Medical Affairs Department, 2Clinical Research Development, 3Biostatistics Department, Shionogi & Co. Ltd, Osaka, 4Department of Orthopedic Surgery, Fukushima Medical University, Fukushima, Japan Purpose: Duloxetine is efficacious for chronic low back pain (CLBP. This post hoc analysis of a Japanese randomized, placebo-controlled trial (ClinicalTrials.gov, NCT01855919 assessed whether patients with CLBP with early pain reduction or treatment-related adverse events of special interest (TR-AESIs; nausea, somnolence, constipation have enhanced responses to duloxetine. Patients and methods: Patients (N = 456 with CLBP for ≥6 months and Brief Pain Inventory (BPI average pain severity score of ≥4 were randomized (1:1 to duloxetine 60 mg/day or placebo for 14 weeks. Primary outcome was change from baseline in BPI average pain severity score (pain reduction. Subgroup analyses included early pain reduction (≥30%, 10%–30%, or <10% at Week 4 and early TR-AESIs (with or without TR-AESIs by Week 2. Measures included changes from baseline in BPI average pain severity score and BPI Interference scores (quality of life; QOL, and response rate (≥30% or ≥50% pain reduction at Week 14. Results: Patients with ≥30% early pain reduction (n = 108 or early TR-AESIs (n = 50 had significantly greater improvements in pain and QOL than placebo-treated patients (n = 226, whereas patients with 10%–30% (n = 63 or <10% (n = 48 pain reduction did not; patients without early TR-AESIs (n = 180 had significant improvements in pain at Week 14. Response rates (≥30%/≥50% pain reduction were 94.4%/82.4%, 66.7%/49.2%, and 25.0%/18.8% for patients with ≥30%, 10%–30%, and <10% early pain reduction, respectively, 74.0%/64.0% for patients with early TR-AESIs, 67.2%/54.4% for patients without early TR-AESIs, and 52.2%/39.4% for placebo.Conclusion: Early pain reduction or TR

  5. Relationship between intraoperative regional cerebral oxygen saturation trends and cognitive decline after total knee replacement: a post-hoc analysis.

    Science.gov (United States)

    Salazar, Fátima; Doñate, Marta; Boget, Teresa; Bogdanovich, Ana; Basora, Misericordia; Torres, Ferran; Gracia, Isabel; Fàbregas, Neus

    2014-01-01

    Bilateral regional brain oxygen saturation (rSO2) trends, reflecting intraoperative brain oxygen imbalance, could warn of brain dysfunction. Various types of cognitive impairment, such as memory decline, alterations in executive function or subjective complaints, have been described three months after surgery. Our aim was to explore the potential utility of rSO2 values as a warning sign for the development of different types of decline in postoperative psychological function. Observational post-hoc analysis of data for the patient sample (n = 125) of a previously conducted clinical trial in patients over the age of 65 years undergoing total knee replacement under spinal anesthesia. Demographic, hemodynamic and bilateral rSO2 intraoperative values were recorded. An absolute rSO2 value of 20% or >25% below baseline were chosen as relevant cutoffs. Composite function test scores were created from baseline to three months for each patient and adjusted for the mean (SD) score changes for a control group (n = 55). Tests were used to assess visual-motor coordination and executive function (VM-EF) (Wechsler Digit Symbol-Coding and Visual Reproduction, Trail Making Test) and memory (Auditory Verbal Learning, Wechsler Memory Scale); scales were used to assess psychological symptoms. We observed no differences in baseline rSO2 values; rSO2 decreased significantly in all patients during surgery (P Left and right rSO2 values were asymmetric in patients who had memory decline (mean [SD] left-right ratio of 95.03 [8.51] vs 101.29 [6.7] for patients with no changes, P = 0.0012). The mean right-left difference in rSO2 was also significant in these patients (-2.87% [4.73%], lower on the right, P = 0.0034). Detection of a trend to asymmetry in rSO2 values can warn of possible postoperative onset of memory decline. Psychological symptoms and memory decline were common three months after knee replacement in our patients over the age of 65 years.

  6. Efficacy of lisdexamfetamine dimesylate in children with attention-deficit/hyperactivity disorder previously treated with methylphenidate: a post hoc analysis

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    Jain Rakesh

    2011-11-01

    Full Text Available Abstract Background Attention-deficit/hyperactivity disorder (ADHD is a common neurobehavioral psychiatric disorder that afflicts children, with a reported prevalence of 2.4% to 19.8% worldwide. Stimulants (methylphenidate [MPH] and amphetamine are considered first-line ADHD pharmacotherapy. MPH is a catecholamine reuptake inhibitor, whereas amphetamines have additional presynaptic activity. Although MPH and amphetamine can effectively manage ADHD symptoms in most pediatric patients, many still fail to respond optimally to either. After administration, the prodrug stimulant lisdexamfetamine dimesylate (LDX is converted to l-lysine and therapeutically active d-amphetamine in the blood. The objective of this study was to evaluate the clinical efficacy of LDX in children with ADHD who remained symptomatic (ie, nonremitters; ADHD Rating Scale IV [ADHD-RS-IV] total score > 18 on MPH therapy prior to enrollment in a 4-week placebo-controlled LDX trial, compared with the overall population. Methods In this post hoc analysis of data from a multicenter, randomized, double-blind, forced-dose titration study, we evaluated the clinical efficacy of LDX in children aged 6-12 years with and without prior MPH treatment at screening. ADHD symptoms were assessed using the ADHD-RS-IV scale, Conners' Parent Rating Scale-Revised short form (CPRS-R, and Clinical Global Impressions-Improvement scale, at screening, baseline, and endpoint. ADHD-RS-IV total and CPRS-R ADHD Index scores were summarized as mean (SD. Clinical response for the subgroup analysis was defined as a ≥ 30% reduction from baseline in ADHD-RS-IV score and a CGI-I score of 1 or 2. Dunnett test was used to compare change from baseline in all groups. Number needed to treat to achieve one clinical responder or one symptomatic remitter was calculated as the reciprocal of the difference in their proportions on active treatment and placebo at endpoint. Results Of 290 randomized participants enrolled, 28

  7. Nausea and Vomiting following Balanced Xenon Anesthesia Compared to Sevoflurane: A Post-Hoc Explorative Analysis of a Randomized Controlled Trial.

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    Astrid V Fahlenkamp

    Full Text Available Like other inhalational anesthetics xenon seems to be associated with post-operative nausea and vomiting (PONV. We assessed nausea incidence following balanced xenon anesthesia compared to sevoflurane, and dexamethasone for its prophylaxis in a randomized controlled trial with post-hoc explorative analysis.220 subjects with elevated PONV risk (Apfel score ≥2 undergoing elective abdominal surgery were randomized to receive xenon or sevoflurane anesthesia and dexamethasone or placebo after written informed consent. 93 subjects in the xenon group and 94 subjects in the sevoflurane group completed the trial. General anesthesia was maintained with 60% xenon or 2.0% sevoflurane. Dexamethasone 4mg or placebo was administered in the first hour. Subjects were analyzed for nausea and vomiting in predefined intervals during a 24h post-anesthesia follow-up.Logistic regression, controlled for dexamethasone and anesthesia/dexamethasone interaction, showed a significant risk to develop nausea following xenon anesthesia (OR 2.30, 95% CI 1.02-5.19, p = 0.044. Early-onset nausea incidence was 46% after xenon and 35% after sevoflurane anesthesia (p = 0.138. After xenon, nausea occurred significantly earlier (p = 0.014, was more frequent and rated worse in the beginning. Dexamethasone did not markedly reduce nausea occurrence in both groups. Late-onset nausea showed no considerable difference between the groups.In our study setting, xenon anesthesia was associated with an elevated risk to develop nausea in sensitive subjects. Dexamethasone 4mg was not effective preventing nausea in our study. Group size or dosage might have been too small, and change of statistical analysis parameters in the post-hoc evaluation might have further contributed to a limitation of our results. Further trials will be needed to address prophylaxis of xenon-induced nausea.EU Clinical Trials EudraCT-2008-004132-20 ClinicalTrials.gov NCT00793663.

  8. Genie in a blotter: A comparative study of LSD and LSD analogues' effects and user profile.

    Science.gov (United States)

    Coney, Leigh D; Maier, Larissa J; Ferris, Jason A; Winstock, Adam R; Barratt, Monica J

    2017-05-01

    This study aimed to describe self-reported patterns of use and effects of lysergic acid diethylamide (LSD) analogues (AL-LAD, 1P-LSD, and ETH-LAD) and the characteristics of those who use them. An anonymous self-selected online survey of people who use drugs (Global Drug Survey 2016; N = 96,894), which measured perceived drug effects of LSD and its analogues. Most LSD analogue users (91%) had also tried LSD. The proportion of U.K. and U.S. respondents reporting LSD analogue use in the last 12 months was higher than for LSD only. LSD analogue users described the effects as psychedelic (93%), over half (55%) obtained it online, and almost all (99%) reported an oral route of administration. The modal duration (8 hr) and time to peak (2 hr) of LSD analogues were not significantly different from LSD. Ratings for pleasurable high, strength of effect, comedown, urge to use more drugs, value for money, and risk of harm following use were significantly lower for LSD analogues compared with LSD. LSD analogues were reported as similar in time to peak and duration as LSD but weaker in strength, pleasurable high, and comedown. Future studies should seek to replicate these findings with chemical confirmation and dose measurement. Copyright © 2017 John Wiley & Sons, Ltd.

  9. Improvement in 24-hour bronchodilation and symptom control with aclidinium bromide versus tiotropium and placebo in symptomatic patients with COPD: post hoc analysis of a Phase IIIb study

    Directory of Open Access Journals (Sweden)

    Beier J

    2017-06-01

    Full Text Available Jutta Beier,1 Robert Mroz,2,3 Anne-Marie Kirsten,4 Ferran Chuecos,5 Esther Garcia Gil5 1insaf Respiratory Research Institute, Wiesbaden, Germany; 2Centrum Medycyny Oddechowej, 3Medical University of Białystok, Białystok, Poland; 4Pulmonary Research Institute at LungenClinic Grosshansdorf, Airway Research Center North, German Center for Lung Research, Grosshansdorf, Germany; 5AstraZeneca PLC, Barcelona, Spain Background: A previous Phase IIIb study (NCT01462929 in patients with moderate to severe COPD demonstrated that 6 weeks of treatment with aclidinium led to improvements in 24-hour bronchodilation comparable to those with tiotropium, and improvement of symptoms versus placebo. This post hoc analysis was performed to assess the effect of treatment in the symptomatic patient group participating in the study. Methods: Symptomatic patients (defined as those with Evaluating Respiratory Symptoms [E-RS™] in COPD baseline score ≥10 units received aclidinium bromide 400 µg twice daily (BID, tiotropium 18 µg once daily (QD, or placebo, for 6 weeks. Lung function, COPD respiratory symptoms, and incidence of adverse events (AEs were assessed. Results: In all, 277 symptomatic patients were included in this post hoc analysis. Aclidinium and tiotropium treatment improved forced expiratory volume in 1 second (FEV1 from baseline to week 6 at all time points over 24 hours versus placebo. In addition, improvements in FEV1 from baseline during the nighttime period were observed for aclidinium versus tiotropium on day 1 (aclidinium 157 mL, tiotropium 67 mL; P<0.001 and week 6 (aclidinium 153 mL, tiotropium 90 mL; P<0.05. Aclidinium improved trough FEV1 from baseline versus placebo and tiotropium at day 1 (aclidinium 136 mL, tiotropium 68 mL; P<0.05 and week 6 (aclidinium 137 mL, tiotropium 71 mL; P<0.05. Aclidinium also improved early-morning and nighttime symptom severity, limitation of early-morning activities, and E-RS Total and domain scores versus

  10. Assessment of direct analgesic effect of duloxetine for chronic low back pain: post hoc path analysis of double-blind, placebo-controlled studies

    Directory of Open Access Journals (Sweden)

    Enomoto H

    2017-06-01

    Full Text Available Hiroyuki Enomoto,1 Shinji Fujikoshi,2 Jumpei Funai,3 Nao Sasaki,4 Michael H Ossipov,5 Toshinaga Tsuji,6 Levent Alev,7 Takahiro Ushida8 1Medical Science, Eli Lilly Japan K.K., Tokyo, 2Statistical Science, 3Science Communications, 4Medical Science, Eli Lilly Japan K.K., Kobe, Japan; 5Clinical Division, inVentiv Health, LLC, Blue Bell, PA, USA; 6Medical Affairs Department, Shionogi & Co., Ltd., Osaka, Japan; 7Medical Department, Lilly Turkey, Istanbul, Turkey; 8Multidisciplinary Pain Center, Aichi Medical University, Nagakute, Aichi, Japan Background: Comorbid depression and depressive symptoms are common in patients with chronic low back pain (CLBP. Duloxetine is clinically effective in major depressive disorder and several chronic pain states, including CLBP. The objective of this post hoc meta-analysis was to assess direct and indirect analgesic efficacy of duloxetine for patients with CLBP in previous clinical trials. Methods: Post hoc path analyses were conducted of 3 randomized, double-blind, clinical studies of patients receiving duloxetine or placebo for CLBP. The primary outcome measure for pain was the Brief Pain Inventory, average pain score. A secondary outcome measure, the Beck Depression Inventory-II, was used for depressive symptoms. The changes in score from baseline to endpoint were determined for each index. Path analyses were employed to calculate the proportion of analgesia that may be attributed to a direct effect of duloxetine on pain.Results: A total of 851 patients (400 duloxetine and 451 placebo were included in this analysis. Duloxetine significantly improved pain scores compared with placebo (p<0.001. It also significantly improved depressive scores compared with placebo (p=0.015. Path analyses showed that 91.1% of the analgesic effect of duloxetine could be attributed to a direct analgesic effect, and 8.9% to its antidepressant effect. Similar results were obtained when data were evaluated at weeks 4 and 7, and when

  11. Anti-Vascular Endothelial Growth Factor Comparative Effectiveness Trial for Diabetic Macular Edema: Additional Efficacy Post Hoc Analyses of a Randomized Clinical Trial.

    Science.gov (United States)

    Jampol, Lee M; Glassman, Adam R; Bressler, Neil M; Wells, John A; Ayala, Allison R

    2016-12-01

    Post hoc analyses from the Diabetic Retinopathy Clinical Research Network randomized clinical trial comparing aflibercept, bevacizumab, and ranibizumab for diabetic macular edema (DME) might influence interpretation of study results. To provide additional outcomes comparing 3 anti-vascular endothelial growth factor (VEGF) agents for DME. Post hoc analyses performed from May 3, 2016, to June 21, 2016, of a randomized clinical trial performed from August 22, 2012, to September 23, 2015, of 660 participants comparing 3 anti-VEGF treatments in eyes with center-involved DME causing vision impairment. Randomization to intravitreous aflibercept (2.0 mg), bevacizumab (1.25 mg), or ranibizumab (0.3 mg) administered up to monthly based on a structured retreatment regimen. Focal/grid laser treatment was added after 6 months for the treatment of persistent DME. Change in visual acuity (VA) area under the curve and change in central subfield thickness (CST) within subgroups based on whether an eye received laser treatment for DME during the study. Post hoc analyses were performed for 660 participants (mean [SD] age, 61 [10] years; 47% female, 65% white, 16% black or African American, 16% Hispanic, and 3% other). For eyes with an initial VA of 20/50 or worse, VA improvement was greater with aflibercept than the other agents at 1 year but superior only to bevacizumab at 2 years. Mean (SD) letter change in VA over 2 years (area under curve) was greater with aflibercept (+17.1 [9.7]) than with bevacizumab (+12.1 [9.4]; 95% CI, +1.6 to +7.3; P grid laser treatment was performed for DME, the only participants to have a substantial reduction in mean CST between 1 and 2 years were those with a baseline VA of 20/50 or worse receiving bevacizumab and laser treatment (mean [SD], -55 [108] µm; 95% CI, -82 to -28 µm; P grid laser treatment, ceiling and floor effects, or both may account for mean thickness reductions noted only in bevacizumab-treated eyes between 1 and 2 years

  12. Atomoxetine treatment outcomes in adolescents and young adults with attention-deficit/hyperactivity disorder: results from a post hoc, pooled analysis.

    Science.gov (United States)

    Adler, Lenard A; Wilens, Timothy; Zhang, Shuyu; Dittmann, Ralf W; D'Souza, Deborah N; Schuh, Leslie; Durell, Todd M

    2012-02-01

    Many children with attention-deficit/hyperactivity disorder (ADHD) continue to experience this disorder as adults, which may, in part, be due to the discontinuity of health care that often occurs during the transition period between late adolescence and young adulthood. Although atomoxetine is reported to be efficacious in both adolescents and young adults, no longitudinal studies have been designed to assess directly the effects of atomoxetine treatment during this transition period. As a first step, we present the results of a post hoc, pooled analysis that compared the efficacy and safety profile of atomoxetine in these 2 patient populations. The aim of the present study was to assess the efficacy and safety profile of atomoxetine treatment in adolescents and young adults with ADHD. A post hoc, pooled analysis was conducted by combining data from 6 double-blind trials (6-9 weeks in duration) that studied adolescents (12-17 years of age; atomoxetine, n = 154; placebo, n = 88; mean final dose = 1.38 mg/kg) and 3 trials (10 weeks in duration) that studied young adults (18-30 years of age; atomoxetine, n = 117; placebo, n = 125; mean final dose = 1.21 mg/kg). Efficacy measures used in these analyses were ADHD Rating Scale (ADHDRS) for adolescents, Conners' Adult ADHD Rating Scale (CAARS) for young adults, and Clinical Global Impressions-ADHD-Severity (CGI-ADHD-S) for both age groups. Treatment response was defined as ≥30% reduction from baseline in total ADHD symptom score. In adolescents (mean age, 13.4 years), atomoxetine improved ADHD significantly compared with placebo (ADHDRS total score change, -12.9 vs -7.5; P young adults (mean age, 24.7 years), atomoxetine improved ADHD significantly (CAARS total score change, -13.6 vs -7.7; P young adults (13.7% vs 4.8%, respectively; P = 0.024); in adolescents no statistically significant differences were observed in frequency of nausea between atomoxetine and placebo treatment (4.5% vs 10.2%, respectively; P = 0

  13. Inherent Risk Factors for Nosocomial Infection in the Long Stay Critically Ill Child Without Known Baseline Immunocompromise: A Post Hoc Analysis of the CRISIS Trial.

    Science.gov (United States)

    Carcillo, Joseph A; Dean, J Michael; Holubkov, Richard; Berger, John; Meert, Kathleen L; Anand, Kanwaljeet J S; Zimmerman, Jerry; Newth, Christopher J; Harrison, Rick; Burr, Jeri; Willson, Douglas F; Nicholson, Carol; Bell, Michael J; Berg, Robert A; Shanley, Thomas P; Heidemann, Sabrina M; Dalton, Heidi; Jenkins, Tammara L; Doctor, Allan; Webster, Angie

    2016-11-01

    Nosocomial infection remains an important health problem in long stay (>3 days) pediatric intensive care unit (PICU) patients. Admission risk factors related to the development of nosocomial infection in long stay immune competent patients in particular are not known. Post-hoc analysis of the previously published Critical Illness Stress induced Immune Suppression (CRISIS) prevention trial database, to identify baseline risk factors for nosocomial infection. Because there was no difference between treatment arms of that study in nosocomial infection in the population without known baseline immunocompromise, both arms were combined and the cohort that developed nosocomial infection was compared with the cohort that did not. There were 254 long stay PICU patients without known baseline immunocompromise. Ninety (35%) developed nosocomial infection, and 164 (65%) did not. Admission characteristics associated with increased nosocomial infection risk were increased age, higher Pediatric Risk of Mortality version III score, the diagnoses of trauma or cardiac arrest and lymphopenia (P risk of developing nosocomial infection (P risk factors (P < 0.05); whereas trauma tended to be related to nosocomial infection development (P = 0.07). These data suggest that increasing age, cardiac arrest and lymphopenia predispose long stay PICU patients without known baseline immunocompromise to nosocomial infection. These findings may inform pre-hoc stratification randomization strategies for prospective studies designed to prevent nosocomial infection in this population.

  14. LSD: Large Survey Database framework

    Science.gov (United States)

    Juric, Mario

    2012-09-01

    The Large Survey Database (LSD) is a Python framework and DBMS for distributed storage, cross-matching and querying of large survey catalogs (>10^9 rows, >1 TB). The primary driver behind its development is the analysis of Pan-STARRS PS1 data. It is specifically optimized for fast queries and parallel sweeps of positionally and temporally indexed datasets. It transparently scales to more than >10^2 nodes, and can be made to function in "shared nothing" architectures.

  15. Detection of metabolites of lysergic acid diethylamide (LSD) in human urine specimens: 2-oxo-3-hydroxy-LSD, a prevalent metabolite of LSD.

    Science.gov (United States)

    Poch, G K; Klette, K L; Hallare, D A; Manglicmot, M G; Czarny, R J; McWhorter, L K; Anderson, C J

    1999-03-05

    Seventy-four urine specimens previously found to contain lysergic acid diethylamide (LSD) by gas chromatography-mass spectrometry (GC-MS) were analyzed by a new procedure for the LSD metabolite 2-oxo-3-hydroxy-LSD (O-H-LSD) using a Finnigan LC-MS-MS system. This procedure proved to be less complex, shorter to perform and provides cleaner chromatographic characteristics than the method currently utilized by the Navy Drug Screening Laboratories for the extraction of LSD from urine by GC-MS. All of the specimens used in the study screened positive for LSD by radioimmunoassay (Roche Abuscreen). Analysis by GC-MS revealed detectable amounts of LSD in all of the specimens. In addition, isolysergic diethylamide (iso-LSD), a byproduct of LSD synthesis, was quantitated in 64 of the specimens. Utilizing the new LC-MS-MS method, low levels of N-desmethyl-LSD (nor-LSD), another identified LSD metabolite, were detected in some of the specimens. However, all 74 specimens contained O-H-LSD at significantly higher concentrations than LSD, iso-LSD, or nor-LSD alone. The O-H-LSD concentration ranged from 732 to 112 831 pg/ml (mean, 16340 pg/ml) by quantification with an internal standard. The ratio of O-H-LSD to LSD ranged from 1.1 to 778.1 (mean, 42.9). The presence of O-H-LSD at substantially higher concentrations than LSD suggests that the analysis for O-H-LSD as the target analyte by employing LC-MS-MS will provide a much longer window of detection for the use of LSD than the analysis of the parent compound, LSD.

  16. Post-hoc principal component analysis on a largely illiterate elderly population from North-west India to identify important elements of mini-mental state examination

    Directory of Open Access Journals (Sweden)

    Sunil Kumar Raina

    2016-01-01

    Full Text Available Background: Mini-mental state examination (MMSE scale measures cognition using specific elements that can be isolated, defined, and subsequently measured. This study was conducted with the aim to analyze the factorial structure of MMSE in a largely, illiterate, elderly population in India and to reduce the number of variables to a few meaningful and interpretable combinations. Methodology: Principal component analysis (PCA was performed post-hoc on the data generated by a research project conducted to estimate the prevalence of dementia in four geographically defined habitations in Himachal Pradesh state of India. Results: Questions on orientation and registration account for high percentage of cumulative variance in comparison to other questions. Discussion: The PCA conducted on the data derived from a largely, illiterate population reveals that the most important components to consider for the estimation of cognitive impairment in illiterate Indian population are temporal orientation, spatial orientation, and immediate memory.

  17. Post-hoc principal component analysis on a largely illiterate elderly population from North-west India to identify important elements of mini-mental state examination.

    Science.gov (United States)

    Raina, Sunil Kumar; Chander, Vishav; Raina, Sujeet; Grover, Ashoo

    2016-01-01

    Mini-mental state examination (MMSE) scale measures cognition using specific elements that can be isolated, defined, and subsequently measured. This study was conducted with the aim to analyze the factorial structure of MMSE in a largely, illiterate, elderly population in India and to reduce the number of variables to a few meaningful and interpretable combinations. Principal component analysis (PCA) was performed post-hoc on the data generated by a research project conducted to estimate the prevalence of dementia in four geographically defined habitations in Himachal Pradesh state of India. Questions on orientation and registration account for high percentage of cumulative variance in comparison to other questions. The PCA conducted on the data derived from a largely, illiterate population reveals that the most important components to consider for the estimation of cognitive impairment in illiterate Indian population are temporal orientation, spatial orientation, and immediate memory.

  18. Investigating the Reliability and Factor Structure of Kalichman's "Survey 2: Research Misconduct" Questionnaire: A Post Hoc Analysis Among Biomedical Doctoral Students in Scandinavia.

    Science.gov (United States)

    Holm, Søren; Hofmann, Bjørn

    2017-10-01

    A precondition for reducing scientific misconduct is evidence about scientists' attitudes. We need reliable survey instruments, and this study investigates the reliability of Kalichman's "Survey 2: research misconduct" questionnaire. The study is a post hoc analysis of data from three surveys among biomedical doctoral students in Scandinavia (2010-2015). We perform reliability analysis, and exploratory and confirmatory factor analysis using a split-sample design as a partial validation. The results indicate that a reliable 13-item scale can be formed (Cronbach's α = .705), and factor analysis indicates that there are four reliable subscales each tapping a different construct: (a) general attitude to misconduct (α = .768), (b) attitude to personal misconduct (α = .784), (c) attitude to whistleblowing (α = .841), and (d) attitude to blameworthiness/punishment (α = .877). A full validation of the questionnaire requires further research. We, nevertheless, hope that the results will facilitate the increased use of the questionnaire in research.

  19. Post-hoc analysis of randomised, placebo-controlled, double-blind study (MCI186-19) of edaravone (MCI-186) in amyotrophic lateral sclerosis.

    Science.gov (United States)

    Takei, Koji; Takahashi, Fumihiro; Liu, Shawn; Tsuda, Kikumi; Palumbo, Joseph

    2017-10-01

    Post-hoc analyses of the ALS Functional Rating Scale-Revised (ALSFRS-R) score data, the primary endpoint in the 24-week double-blind placebo-controlled study of edaravone (MCI186-19, NCT01492686), were performed to confirm statistical robustness of the result. The previously reported original analysis had used a last observation carried forward (LOCF) method and also excluded patients with fewer than three completed treatment cycles. The post-hoc sensitivity analyses used different statistical methods as follows: 1) including all patients regardless of treatment cycles received (ALL LOCF); 2) a mixed model for repeated measurements (MMRM) analysis; and 3) the Combined Assessment of Function and Survival (CAFS) endpoint. Findings were consistent with the original primary analysis in showing superiority of edaravone over placebo. We also investigated the distribution of change in ALSFRS-R total score across all patients in the study as well as which ALSFRS-R items and domains may have contributed to the overall efficacy findings. The distribution of changes in ALSFRS-R total score from baseline to the end of cycle 6 (ALL LOCF) shifted in favour of edaravone compared to placebo. Edaravone was descriptively favoured for each ALSFRS-R item and each of the four ALSFRS-R domains at the end of cycle 6 (ALL LOCF), suggesting a generalised effect of edaravone in slowing functional decline across all anatomical regions. The effect of edaravone appeared to be similar in patients with bulbar onset and limb onset. Together, these observations would be consistent with its putative neuroprotective effects against the development of oxidative damage unspecific to anatomical regions.

  20. A post-hoc subgroup analysis of outcomes in the first phase III clinical study of edaravone (MCI-186) in amyotrophic lateral sclerosis.

    Science.gov (United States)

    2017-10-01

    Our first phase III study failed to demonstrate efficacy of edaravone for amyotrophic lateral sclerosis (ALS) compared to placebo. Here, we performed post-hoc subgroup analysis to identify a subgroup in which edaravone might be expected to show efficacy. We focussed on two newly defined subgroups, EESP and dpEESP2y. The EESP was defined as the efficacy-expected subpopulation with % forced vital capacity of ≥80%, and ≥2 points for all item scores in the revised ALS functional rating scale (ALSFRS-R) score before treatment. The dpEESP2y was defined as the greater-efficacy-expected subpopulation within EESP having a diagnosis of 'definite' or 'probable' ALS according to the El Escorial revised Airlie House diagnostic criteria and onset of disease within two years. The primary endpoint of the post-hoc analysis was the change in the ALSFRS-R score during the 24-week treatment period. The intergroup differences of the least-squares mean change in the ALSFRS-R score ± standard error during treatment were 0.65 ± 0.78 (p = 0.4108) in the full analysis set, 2.20 ± 1.03 (p = 0.0360) in the EESP, and 3.01 ± 1.33 (p = 0.0270) in the dpEESP2y. Edaravone exhibited efficacy in the dpEESP2y subgroup. A further clinical study in patients meeting dpEESP2y criteria is warranted.

  1. Insight and Treatment Outcomes in Schizophrenia: Post-hoc Analysis of a Long-term, Double-blind Study Comparing Lurasidone and Quetiapine XR.

    Science.gov (United States)

    Harvey, Philip D; Siu, Cynthia O; Loebel, Antony D

    2017-12-01

    Objective: The objective of this post-hoc analysis was to evaluate the effect of lurasidone and quetiapine extended-release (XR) on insight and judgment and assess the longitudinal relationships between improvement in insight and cognitive performance, functional capacity, quality of well-being, and depressive symptoms in patients with schizophrenia. Design: Clinically unstable patients with schizophrenia (N=488) were randomized to once-daily, fixed-dose treatment with lurasidone 80mg, lurasidone 160mg, quetiapine XR 600mg, or placebo, followed by a long-term, double-blind, flexible-dose continuation study involving these agents. Results: Significantly greater improvement in insight and judgment (assessed by the Positive and Negative Syndrome Scale G12 item) for the lurasidone and quetiapine XR groups, compared to the placebo group, was observed at Week 6. Over a subsequent six-month continuation period, the flexible dose lurasidone group showed significantly greater improvement in insight from acute phase baseline compared to the flexible-dose quetiapine XR group (QXR-QXR) (p=0.032). Improvement in insight was significantly correlated with improvement in cognition ( p =0.014), functional capacity (p=0.006, UPSA-B), quality of well-being ( p =0.033, QWB), and depressive symptoms ( p =0.05, Montgomery-Åsberg Depression Rating Scale [MADRS] score) across treatment groups and study periods. Conclusion: In this post-hoc analysis, flexibly dosed lurasidone 40 to 160mg/d was found to be associated with significantly greater improvement in insight compared to flexibly dosed quetiapine XR 200 to 800mg/d over long-term treatment in patients with schizophrenia. Across treatment groups, improvement in insight and judgment was significantly associated with improvement in cognition, functional capacity, quality of well-being, and depressive symptoms over time.

  2. Elevated central venous pressure is associated with impairment of microcirculatory blood flow in sepsis: a hypothesis generating post hoc analysis

    NARCIS (Netherlands)

    Vellinga, Namkje A. R.; Ince, C.; Boerma, E. C.

    2013-01-01

    Microcirculatory driving pressure is defined as the difference between post-arteriolar and venular pressure. In previous research, an absence of correlation between mean arterial blood pressure (MAP) and microcirculatory perfusion has been observed. However, the microcirculation may be considered as

  3. Subsequent Chemotherapy and Treatment Patterns After Abiraterone Acetate in Patients with Metastatic Castration-resistant Prostate Cancer: Post Hoc Analysis of COU-AA-302.

    Science.gov (United States)

    de Bono, Johann S; Smith, Matthew R; Saad, Fred; Rathkopf, Dana E; Mulders, Peter F A; Small, Eric J; Shore, Neal D; Fizazi, Karim; De Porre, Peter; Kheoh, Thian; Li, Jinhui; Todd, Mary B; Ryan, Charles J; Flaig, Thomas W

    2017-04-01

    Treatment patterns for metastatic castration-resistant prostate cancer (mCRPC) have changed substantially in the last few years. In trial COU-AA-302 (chemotherapy-naïve men with mCRPC), abiraterone acetate plus prednisone (AA) significantly improved radiographic progression-free survival and overall survival (OS) when compared to placebo plus prednisone (P). This post hoc analysis investigated clinical responses to docetaxel as first subsequent therapy (FST) among patients who progressed following protocol-specified treatment with AA, and characterized subsequent treatment patterns among older (≥75 yr) and younger (AA arm received subsequent treatment with one or more agents approved for mCRPC. Efficacy analysis was performed for patients for whom baseline and at least one post-baseline prostate-specific antigen (PSA) values were available. Baseline and at least one post-baseline PSA values were available for 100 AA patients who received docetaxel as FST. While acknowledging the limitations of post hoc analyses, 40% (40/100) of these patients had an unconfirmed ≥50% PSA decline with first subsequent docetaxel therapy, and 27% (27/100) had a confirmed ≥50% PSA decline. The median docetaxel treatment duration among these 100 patients was 4.2 mo. Docetaxel was the most common FST among older and younger patients from each treatment arm. However, 43% (79/185) of older patients who progressed on AA received no subsequent therapy for mCRPC, compared with 17% (60/361) of younger patients. Patients with mCRPC who progress with AA treatment may still derive benefit from subsequent docetaxel therapy. These data support further assessment of treatment patterns following AA treatment for mCRPC, particularly among older patients. ClinicalTrials.gov NCT00887198. Treatment patterns for advanced prostate cancer have changed substantially in the last few years. This additional analysis provides evidence of clinical benefit for subsequent chemotherapy in men with advanced

  4. LSD-induced entropic brain activity predicts subsequent personality change.

    Science.gov (United States)

    Lebedev, A V; Kaelen, M; Lövdén, M; Nilsson, J; Feilding, A; Nutt, D J; Carhart-Harris, R L

    2016-09-01

    Personality is known to be relatively stable throughout adulthood. Nevertheless, it has been shown that major life events with high personal significance, including experiences engendered by psychedelic drugs, can have an enduring impact on some core facets of personality. In the present, balanced-order, placebo-controlled study, we investigated biological predictors of post-lysergic acid diethylamide (LSD) changes in personality. Nineteen healthy adults underwent resting state functional MRI scans under LSD (75µg, I.V.) and placebo (saline I.V.). The Revised NEO Personality Inventory (NEO-PI-R) was completed at screening and 2 weeks after LSD/placebo. Scanning sessions consisted of three 7.5-min eyes-closed resting-state scans, one of which involved music listening. A standardized preprocessing pipeline was used to extract measures of sample entropy, which characterizes the predictability of an fMRI time-series. Mixed-effects models were used to evaluate drug-induced shifts in brain entropy and their relationship with the observed increases in the personality trait openness at the 2-week follow-up. Overall, LSD had a pronounced global effect on brain entropy, increasing it in both sensory and hierarchically higher networks across multiple time scales. These shifts predicted enduring increases in trait openness. Moreover, the predictive power of the entropy increases was greatest for the music-listening scans and when "ego-dissolution" was reported during the acute experience. These results shed new light on how LSD-induced shifts in brain dynamics and concomitant subjective experience can be predictive of lasting changes in personality. Hum Brain Mapp 37:3203-3213, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  5. Modern status of the LSD experiment

    International Nuclear Information System (INIS)

    Dadykin, V.L.; Zatsepin, G.T.; Korchagin, V.B.

    1989-01-01

    Possibility of experiment statement using LSD neutrino detector is considered in order to investigate probability of detection of solar neutrino flux within >or approx. 7 MeV energy range. Main sources of background, its characteristics, energy yield spectrum of γ quanta in LSD counter are presented

  6. CHARACTERIZING THE PSYCHOLOGICAL STATE PRODUCED BY LSD.

    Science.gov (United States)

    KATZ, MARTIN M.; AND OTHERS

    THE DEVELOPMENT AND COMPONENTS OF LYSERGIC ACID DIETHYLAMIDE (LSD) PRODUCED PSYCHOLOGICAL STATES ARE INVESTIGATED. THE SUBJECTS WERE PAID VOLUNTEERS FROM THE PATUXENT INSTITUTION, A TREATMENT CENTER FOR EMOTIONALLY UNSTABLE CRIMINAL OFFENDERS. IN ONE STUDY, GROUPS OF 23 SUBJECTS RECEIVED LSD, AN AMPHETAMINE, OR A PLACEBO. IN THE SECOND STUDY, 11…

  7. History of early abuse as a predictor of treatment response in patients with fibromyalgia : A post-hoc analysis of a 12-week, randomized, double-blind, placebo-controlled trial of paroxetine controlled release

    NARCIS (Netherlands)

    Pae, Chi-Un; Masand, Prakash S.; Marks, David M.; Krulewicz, Stan; Han, Changsu; Peindl, Kathleen; Mannelli, Paolo; Patkar, Ashwin A.

    2009-01-01

    Objectives. We conducted a post-hoc analysis to determine whether a history of physical or sexual abuse was associated with response to treatment in a double-blind, randomized, placebo-controlled trial of paroxetine controlled release (CR) in fibromyalgia. Methods. A randomized, double-blind,

  8. Sustained disease-activity-free status in patients with relapsing-remitting multiple sclerosis treated with cladribine tablets in the CLARITY study: a post-hoc and subgroup analysis

    DEFF Research Database (Denmark)

    Giovannoni, Gavin; Cook, Stuart; Rammohan, Kottil

    2011-01-01

    /kg over 96 weeks was more effective than placebo. Achieving sustained freedom from disease activity is becoming a viable treatment goal in RRMS; we therefore aimed to assess the effects of cladribine on this composite outcome measure by doing a post-hoc analysis of data from the CLARITY study....

  9. Neuromathematical Trichotomous Mixed Methods Analysis: Using the Neuroscientific Tri-Squared Test Statistical Metric as a Post Hoc Analytic to Determine North Carolina School of Science and Mathematics Leadership Efficacy

    Science.gov (United States)

    Osler, James Edward, II; Mason, Letita R.

    2016-01-01

    This study examines the leadership efficacy amongst graduates of The North Carolina School of Science and Mathematics (NCSSM) for the classes of 2000 through 2007 from a neuroscientific and neuromathematic perspective. NCSSM alumni (as the primary unit of analysis) were examined using a novel neuromathematic post hoc method of analysis. This study…

  10. Does the effect of one-day simulation team training in obstetric emergencies decline within one year? A post-hoc analysis of a multicentre cluster randomised controlled trial

    NARCIS (Netherlands)

    van de Ven, J.; Fransen, A F; Schuit, E.; van Runnard Heimel, P.J.; Mol, Ben W.; Oei, Swan G.

    2017-01-01

    Does the effect of one-day simulation team training in obstetric emergencies decline within one year? A post-hoc analysis of a multicentre cluster randomised controlled trial. J van de Ven, AF Fransen, E Schuit, PJ van Runnard Heimel, BW Mol, SG Oei Objective To investigate whether the effect of a

  11. Structural effects of sprifermin in knee osteoarthritis: a post-hoc analysis on cartilage and non-cartilaginous tissue alterations in a randomized controlled trial.

    Science.gov (United States)

    Roemer, Frank W; Aydemir, Aida; Lohmander, Stefan; Crema, Michel D; Marra, Monica Dias; Muurahainen, Norma; Felson, David T; Eckstein, Felix; Guermazi, Ali

    2016-07-09

    A recent publication on efficacy of Sprifermin for knee osteoarthritis (OA) using quantitatively MRI-defined central medial tibio-femoral compartment cartilage thickness as the structural primary endpoint reported no statistically significant dose response. However, Sprifermin was associated with statistically significant, dose-dependent reductions in loss of total and lateral tibio-femoral cartilage thickness. Based on these preliminary promising data a post-hoc analysis of secondary assessment and endpoints was performed to evaluate potential effects of Sprifermin on semi-quantitatively evaluated structural MRI parameters. Aim of the present analysis was to determine effects of sprifermin on several knee joint tissues over a 12 month period. 1.5 T or 3 T MRIs were acquired at baseline and 12 months follow-up using a standard protocol. MRIs were read according to the Whole-Organ Magnetic Resonance Imaging Score (WORMS) scoring system (in 14 articular subregions) by four muskuloskeletal radiologists independently. Analyses focused on semiquantitative changes in the 100 μg subgroup and matching placebo of multiple MRI-defined structural alterations. Analyses included a delta-subregional and delta-sum approach for the whole knee and the medial and lateral tibio-femoral (MTFJ, LTFJ), and patello-femoral (PFJ) compartments, taking into account number of subregions showing no change, improvement or worsening and changes in the sum of subregional scores. Mann-Whitney - Wilcoxon tests assessed differences between groups. Fifty-seven and 18 patients were included in the treatment and matched placebo subgroups. Less worsening of cartilage damage was observed from baseline to 12 months in the PFJ (0.02, 95 % confidence interval (CI) (-0.04, 0.08) vs. placebo 0.22, 95 % CI (-0.05, 0.49), p = 0.046). For bone marrow lesions (BMLs), more improvement was observed from 6 to 12 months for whole knee analyses (-0.14, 95 % CI (-0.48, 0.19) vs. placebo 0.44, 95

  12. Are we drawing the right conclusions from randomised placebo-controlled trials? A post-hoc analysis of data from a randomised controlled trial

    Directory of Open Access Journals (Sweden)

    Bone Kerry M

    2009-06-01

    Full Text Available Abstract Background Assumptions underlying placebo controlled trials include that the placebo effect impacts on all study arms equally, and that treatment effects are additional to the placebo effect. However, these assumptions have recently been challenged, and different mechanisms may potentially be operating in the placebo and treatment arms. The objective of the current study was to explore the nature of placebo versus pharmacological effects by comparing predictors of the placebo response with predictors of the treatment response in a randomised, placebo-controlled trial of a phytotherapeutic combination for the treatment of menopausal symptoms. A substantial placebo response was observed but no significant difference in efficacy between the two arms. Methods A post hoc analysis was conducted on data from 93 participants who completed this previously published study. Variables at baseline were investigated as potential predictors of the response on any of the endpoints of flushing, overall menopausal symptoms and depression. Focused tests were conducted using hierarchical linear regression analyses. Based on these findings, analyses were conducted for both groups separately. These findings are discussed in relation to existing literature on placebo effects. Results Distinct differences in predictors were observed between the placebo and active groups. A significant difference was found for study entry anxiety, and Greene Climacteric Scale (GCS scores, on all three endpoints. Attitude to menopause was found to differ significantly between the two groups for GCS scores. Examination of the individual arms found anxiety at study entry to predict placebo response on all three outcome measures individually. In contrast, low anxiety was significantly associated with improvement in the active treatment group. None of the variables found to predict the placebo response was relevant to the treatment arm. Conclusion This study was a post hoc analysis

  13. Validated ultra-performance liquid chromatography-tandem mass spectrometry method for analyzing LSD, iso-LSD, nor-LSD, and O-H-LSD in blood and urine.

    Science.gov (United States)

    Chung, Angela; Hudson, John; McKay, Gordon

    2009-06-01

    The Royal Canadian Mounted Police Forensic Science and Identification Services was looking for a confirmatory method for lysergic acid diethylamide (LSD). As a result, an ultra-performance liquid chromatography-tandem mass spectrometry method was validated for the confirmation and quantitation of LSD, iso-LSD, N-demethyl-LSD (nor-LSD), and 2-oxo-3-hydroxy-LSD (O-H-LSD). Relative retention time and ion ratios were used as identification parameters. Limits of detection (LOD) in blood were 5 pg/mL for LSD and iso-LSD and 10 pg/mL for nor-LSD and O-H-LSD. In urine, the LOD was 10 pg/mL for all analytes. Limits of quantitation (LOQ) in blood and urine were 20 pg/mL for LSD and iso-LSD and 50 pg/mL for nor-LSD and O-H-LSD. The method was linear, accurate, and precise from 10 to 2000 pg/mL in blood and 20 to 2000 pg/mL in urine for LSD and iso-LSD and from 20 to 2000 pg/mL in blood and 50 to 2000 pg/mL in urine for nor-LSD and O-H-LSD with a coefficient of determination (R(2)) > or = 0.99. The method was applied to blinded biological control samples and biological samples taken from a suspected LSD user. This is the first reported detection of O-H-LSD in blood from a suspected LSD user.

  14. Once-monthly injection of paliperidone palmitate in patients with recently diagnosed and chronic schizophrenia: a post-hoc comparison of efficacy and safety.

    Science.gov (United States)

    Si, Tianmei; Zhuo, Jianmin; Turkoz, Ibrahim; Mathews, Maju; Tan, Wilson; Feng, Yu

    2017-12-01

    The use of long-acting injectable antipsychotics in recently diagnosed schizophrenia remains less explored. We evaluated the efficacy and safety of paliperidone palmitate once-monthly (PP1M) treatment in adult patients with recently diagnosed vs. chronic schizophrenia. These post-hoc analyses included two multicenter studies. Study 1 (NCT01527305) enrolled recently diagnosed (≤5 years) and chronic (>5 years) patients; Study 2 (NCT01051531) enrolled recently diagnosed patients only. Recently diagnosed patients were further sub-grouped into ≤2 years or 2-5 years. The primary efficacy endpoint was the change from baseline in Positive and Negative Syndrome Scale (PANSS) total score. In Study 1, 41.5% patients had recent diagnosis (≤2 years: 56.8%; 2-5 years: 43.2%); 58.5% had chronic schizophrenia. In Study 2, 52.8% and 47.2% patients were grouped into ≤2 years and 2-5 years, respectively. PANSS total score showed significantly greater improvement in patients with recently diagnosed vs. chronic schizophrenia. Similar results were obtained for PANSS responder rate, improvements in PANSS, and CGI-S scores. PP1M was efficacious in both recently diagnosed and chronic schizophrenia, with the benefits being more pronounced in patients with recently diagnosed schizophrenia. This adds to growing evidence recommending long-acting antipsychotic interventions at early stages of schizophrenia.

  15. Comparison of Efficacy and Safety of Liraglutide 3.0 mg in Individuals with BMI above and below 35 kg/m²: A Post-hoc Analysis.

    Science.gov (United States)

    le Roux, Carel; Aroda, Vanita; Hemmingsson, Joanna; Cancino, Ana Paula; Christensen, Rune; Pi-Sunyer, Xavier

    2017-01-01

    To investigate whether the efficacy and safety of liraglutide 3.0 mg differed between two subgroups, BMI 27 to 3.0 mg were evaluated by testing the interaction between treatment group and baseline BMI subgroup. Significantly greater weight loss (0-56 weeks) was observed with liraglutide 3.0 mg versus placebo in all patient groups while on treatment. There was no evidence that the weight-lowering effect of liraglutide 3.0 mg differed between BMI subgroups (interaction p > 0.05). Similarly, for most secondary endpoints significantly greater improvements were observed with liraglutide 3.0 mg versus placebo, with no indication treatment effects differing between subgroups. The safety profile of liraglutide 3.0 mg was broadly similar across BMI subgroups. This post-hoc analysis did not indicate any differences in the treatment effects, or safety profile, of liraglutide 3.0 mg for individuals with BMI 27 to 3.0 mg can therefore be considered for individuals with a BMI of ≥35 as well as for those with a BMI of 27 to <35 kg/m². © 2017 The Author(s) Published by S. Karger GmbH, Freiburg.

  16. Comparison of Efficacy and Safety of Liraglutide 3.0 mg in Individuals with BMI above and below 35 kg/m²: A Post-hoc Analysis

    Science.gov (United States)

    le Roux, Carel; Aroda, Vanita; Hemmingsson, Joanna; Cancino, Ana Paula; Christensen, Rune; Pi-Sunyer, Xavier

    2018-01-01

    Objective To investigate whether the efficacy and safety of liraglutide 3.0 mg differed between two subgroups, BMI 27 to 3.0 mg were evaluated by testing the interaction between treatment group and baseline BMI subgroup. Results Significantly greater weight loss (0–56 weeks) was observed with liraglutide 3.0 mg versus placebo in all patient groups while on treatment. There was no evidence that the weight-lowering effect of liraglutide 3.0 mg differed between BMI subgroups (interaction p > 0.05). Similarly, for most secondary endpoints significantly greater improvements were observed with liraglutide 3.0 mg versus placebo, with no indication treatment effects differing between subgroups. The safety profile of liraglutide 3.0 mg was broadly similar across BMI subgroups. Conclusion This post-hoc analysis did not indicate any differences in the treatment effects, or safety profile, of liraglutide 3.0 mg for individuals with BMI 27 to 3.0 mg can therefore be considered for individuals with a BMI of ≥35 as well as for those with a BMI of 27 to <35 kg/m². PMID:29145215

  17. Records of pan (floodplain wetland) sedimentation as an approach for post-hoc investigation of the hydrological impacts of dam impoundment: The Pongolo river, KwaZulu-Natal.

    Science.gov (United States)

    Heath, S K; Plater, A J

    2010-07-01

    River impoundment by dams has far-reaching consequences for downstream floodplains in terms of hydrology, water quality, geomorphology, ecology and ecosystem services. With the imperative of economic development, there is the danger that potential environmental impacts are not assessed adequately or monitored appropriately. Here, an investigation of sediment composition of two pans (floodplain wetlands) in the Pongolo River floodplain, KwaZulu-Natal, downstream of the Pongolapoort dam constructed in 1974, is considered as a method for post-hoc assessment of the impacts on river hydrology, sediment supply and water quality. Bumbe and Sokhunti pans have contrasting hydrological regimes in terms of their connection to the main Pongolo channel - Bumbe is a shallow ephemeral pan and Sokhunti is a deep, perennial water body. The results of X-ray fluorescence (XRF) geochemical analysis of their sediment records over a depth of >1 m show that whilst the two pans exhibit similar sediment composition and variability in their lower part, Bumbe pan exhibits a shift toward increased fine-grained mineral supply and associated nutrient influx at a depth of c. 45 cm whilst Sokhunti pan is characterised by increased biogenic productivity at a depth of c. 26 cm due to enhanced nutrient status. The underlying cause is interpreted as a shift in hydrology to a 'post-dam' flow regime of reduced flood frequencies with more regular baseline flows which reduce the average flow velocity. In addition, Sokhunti shows a greater sensitivity to soil influx during flood events due to the nature of its 'background' of autochthonous biogenic sedimentation. The timing of the overall shift in sediment composition and the dates of the mineral inwash events are not well defined, but the potential for these wetlands as sensitive recorders of dam-induced changes in floodplain hydrology, especially those with a similar setting to Sokhunti pan, is clearly demonstrated. Copyright 2010 Elsevier Ltd. All

  18. Metabolism of lysergic acid diethylamide (LSD) to 2-oxo-3-hydroxy LSD (O-H-LSD) in human liver microsomes and cryopreserved human hepatocytes.

    Science.gov (United States)

    Klette, K L; Anderson, C J; Poch, G K; Nimrod, A C; ElSohly, M A

    2000-10-01

    The metabolism of lysergic acid diethylamide (LSD) to 2-oxo-3-hydroxy lysergic acid diethylamide (O-H-LSD) was investigated in liver microsomes and cyropreserved hepatocytes from humans. Previous studies have demonstrated that O-H-LSD is present in human urine at concentrations 16-43 times greater than LSD, the parent compound. Additionally, these studies have determined that O-H-LSD is not generated during the specimen extraction and analytical processes or due to parent compound degradation in aqueous urine samples. However, these studies have not been conclusive in demonstrating that O-H-LSD is uniquely produced during in vivo metabolism. Phase I drug metabolism was investigated by incubating human liver microsomes and cryopreserved human hepatocytes with LSD. The reaction was quenched at various time points, and the aliquots were extracted using liquid partitioning and analyzed by liquid chromatography-mass spectrometry. O-H-LSD was positively identified in all human liver microsomal and human hepatocyte fractions incubated with LSD. In addition, O-H-LSD was not detected in any microsomal or hepatocyte fraction not treated with LSD nor in LSD specimens devoid of microsomes or hepatocytes. This study provides definitive evidence that O-H-LSD is produced as a metabolic product following incubation of human liver microsomes and hepatocytes with LSD.

  19. The Role of Programmed Cell Death Regulator LSD1 in Nematode-Induced Syncytium Formation

    Science.gov (United States)

    Matuszkiewicz, Mateusz; Sobczak, Miroslaw; Cabrera, Javier; Escobar, Carolina; Karpiński, Stanislaw; Filipecki, Marcin

    2018-01-01

    Cyst-forming plant-parasitic nematodes are common pests of many crops. They inject secretions into host cells to induce the developmental and metabolic reprogramming that leads to the formation of a syncytium, which is the sole food source for growing nematodes. As in other host-parasite models, avirulence leads to rapid and local programmed cell death (PCD) known as the hypersensitive response (HR), whereas in the case of virulence, PCD is still observed but is limited to only some cells. Several regulators of PCD were analyzed to understand the role of PCD in compatible plant–nematode interactions. Thus, Arabidopsis plants carrying recessive mutations in LESION SIMULATING DISEASE1 (LSD1) family genes were subjected to nematode infection assays with juveniles of Heterodera schachtii. LSD1 is a negative and conditional regulator of PCD, and fewer and smaller syncytia were induced in the roots of lsd1 mutants than in wild-type Col-0 plants. Mutation in LSD ONE LIKE2 (LOL2) revealed a pattern of susceptibility to H. schachtii antagonistic to lsd1. Syncytia induced on lsd1 roots compared to Col0 showed significantly retarded growth, modified cell wall structure, increased vesiculation, and some myelin-like bodies present at 7 and 12 days post-infection. To place these data in a wider context, RNA-sequencing analysis of infected and uninfected roots was conducted. During nematode infection, the number of transcripts with changed expression in lsd1 was approximately three times smaller than in wild-type plants (1440 vs. 4206 differentially expressed genes, respectively). LSD1-dependent PCD in roots is thus a highly regulated process in compatible plant–nematode interactions. Two genes identified in this analysis, coding for AUTOPHAGY-RELATED PROTEIN 8F and 8H were down-regulated in syncytia in the presence of LSD1 and showed an increased susceptibility to nematode infection contrasting with lsd1 phenotype. Our data indicate that molecular regulators belonging to the

  20. The Role of Programmed Cell Death Regulator LSD1 in Nematode-Induced Syncytium Formation

    Directory of Open Access Journals (Sweden)

    Mateusz Matuszkiewicz

    2018-03-01

    Full Text Available Cyst-forming plant-parasitic nematodes are common pests of many crops. They inject secretions into host cells to induce the developmental and metabolic reprogramming that leads to the formation of a syncytium, which is the sole food source for growing nematodes. As in other host-parasite models, avirulence leads to rapid and local programmed cell death (PCD known as the hypersensitive response (HR, whereas in the case of virulence, PCD is still observed but is limited to only some cells. Several regulators of PCD were analyzed to understand the role of PCD in compatible plant–nematode interactions. Thus, Arabidopsis plants carrying recessive mutations in LESION SIMULATING DISEASE1 (LSD1 family genes were subjected to nematode infection assays with juveniles of Heterodera schachtii. LSD1 is a negative and conditional regulator of PCD, and fewer and smaller syncytia were induced in the roots of lsd1 mutants than in wild-type Col-0 plants. Mutation in LSD ONE LIKE2 (LOL2 revealed a pattern of susceptibility to H. schachtii antagonistic to lsd1. Syncytia induced on lsd1 roots compared to Col0 showed significantly retarded growth, modified cell wall structure, increased vesiculation, and some myelin-like bodies present at 7 and 12 days post-infection. To place these data in a wider context, RNA-sequencing analysis of infected and uninfected roots was conducted. During nematode infection, the number of transcripts with changed expression in lsd1 was approximately three times smaller than in wild-type plants (1440 vs. 4206 differentially expressed genes, respectively. LSD1-dependent PCD in roots is thus a highly regulated process in compatible plant–nematode interactions. Two genes identified in this analysis, coding for AUTOPHAGY-RELATED PROTEIN 8F and 8H were down-regulated in syncytia in the presence of LSD1 and showed an increased susceptibility to nematode infection contrasting with lsd1 phenotype. Our data indicate that molecular regulators

  1. Pregabalin versus SSRIs and SNRIs in benzodiazepine-refractory outpatients with generalized anxiety disorder: a post hoc cost-effectiveness analysis in usual medical practice in Spain

    Directory of Open Access Journals (Sweden)

    De Salas-Cansado M

    2012-06-01

    Full Text Available Marina De Salas-Cansado,1 José M Olivares,2 Enrique Álvarez,3 Jose L Carrasco,4 Andoni Barrueta,5 Javier Rejas,51Trial Form Support Spain, Madrid; 2Department of Psychiatry, Hospital Meixoeiro, Complejo Hospitalario Universitario, Vigo; 3Department of Psychiatry, Hospital de la Santa Creu i San Pau, Barcelona; 4Department of Psychiatry, Hospital Clínico San Carlos, Madrid; 5Health Outcomes Research Department, Medical Unit, Pfizer Spain, Alcobendas, Madrid, SpainBackground: Generalized anxiety disorder (GAD is a prevalent health condition which seriously affects both patient quality of life and the National Health System. The aim of this research was to carry out a post hoc cost-effectiveness analysis of the effect of pregabalin versus selective serotonin reuptake inhibitors (SSRIs/serotonin norepinephrine reuptake inhibitors (SNRIs in treated benzodiazepine-refractory outpatients with GAD.Methods: This post hoc cost-effectiveness analysis used secondary data extracted from the 6-month cohort, prospective, noninterventional ADAN study, which was conducted to ascertain the cost of illness in GAD subjects diagnosed according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria. Benzodiazepine-refractory subjects were those who claimed persistent symptoms of anxiety and showed a suboptimal response (Hamilton Anxiety Rating Scale ≥16 to benzodiazepines, alone or in combination, over 6 months. Patients could switch to pregabalin (as monotherapy or addon or to an SSRI or SNRI, alone or in combination. Effectiveness was expressed as quality-adjusted life years gained, and the perspective was that of the National Health System in the year 2008. A sensitivity analysis was performed using bootstrapping techniques (10,000 resamples were obtained in order to obtain a cost-effectiveness plane and a corresponding acceptability curve.Results: A total of 282 subjects (mean Hamilton Anxiety Rating Scale score 25.8 were

  2. Report of the evaluation by the Ad Hoc Review Committee on Materials Science Research. Ex-post evaluation in fiscal year 2003

    International Nuclear Information System (INIS)

    2004-06-01

    The Research Evaluation Committee, which consisted of 13 members from outside of the Japan Atomic Energy Research Institute (JAERI), set up an Ad Hoc Review Committee on Materials Science Research in accordance with the Fundamental Guideline for the Evaluation of Research and Development (R and D) at JAERI' and its subsidiary regulations in order to evaluate the adequacy of the R and D results achieved for five years until Fiscal Year 2002 at Department of Materials Science in Tokai Research Establishment of JAERI. The Ad Hoc Review Committee consisted of eight specialists from outside of JAERI. The Ad Hoc Review Committee conducted its activities from October 2003 to February 2004. The evaluation was performed on the basis of the materials submitted in advance and of the oral presentations made at the Ad Hoc Review Committee meeting which was held on November 14, 2003, in line with the items, viewpoints, and criteria for the evaluation specified by the Research Evaluation Committee. The result of the evaluation by the Ad Hoc Review Committee was submitted to the Research Evaluation Committee, and was judged to be appropriate at its meeting held on March 8, 2004. This report describes the result of the evaluation by the Ad Hoc Review Committee on Materials Science Research. (author)

  3. Effect of Concomitant Medications on the Safety and Efficacy of Extended-Release Carbidopa-Levodopa (IPX066) in Patients With Advanced Parkinson Disease: A Post Hoc Analysis.

    Science.gov (United States)

    LeWitt, Peter A; Verhagen Metman, Leo; Rubens, Robert; Khanna, Sarita; Kell, Sherron; Gupta, Suneel

    Extended-release (ER) carbidopa-levodopa (CD-LD) (IPX066/RYTARY/NUMIENT) produces improvements in "off" time, "on" time without troublesome dyskinesia, and Unified Parkinson Disease Rating Scale scores compared with immediate-release (IR) CD-LD or IR CD-LD plus entacapone (CLE). Post hoc analyses of 2 ER CD-LD phase 3 trials evaluated whether the efficacy and safety of ER CD-LD relative to the respective active comparators were altered by concomitant medications (dopaminergic agonists, monoamine oxidase B [MAO-B] inhibitors, or amantadine). ADVANCE-PD (n = 393) assessed safety and efficacy of ER CD-LD versus IR CD-LD. ASCEND-PD (n = 91) evaluated ER CD-LD versus CLE. In both studies, IR- and CLE-experienced patients underwent a 6-week, open-label dose-conversion period to ER CD-LD prior to randomization. For analysis, the randomized population was divided into 3 subgroups: dopaminergic agonists, rasagiline or selegiline, and amantadine. For each subgroup, changes from baseline in PD diary measures ("off" time and "on" time with and without troublesome dyskinesia), Unified Parkinson Disease Rating Scale Parts II + III scores, and adverse events were analyzed, comparing ER CD-LD with the active comparator. Concomitant dopaminergic agonist or MAO-B inhibitor use did not diminish the efficacy (improvement in "off" time and "on" time without troublesome dyskinesia) of ER CD-LD compared with IR CD-LD or CLE, whereas the improvement with concomitant amantadine failed to reach significance. Safety and tolerability were similar among the subgroups, and ER CD-LD did not increase troublesome dyskinesia. For patients on oral LD regimens and taking a dopaminergic agonist, and/or a MAO-B inhibitor, changing from an IR to an ER CD-LD formulation provides approximately an additional hour of "good" on time.

  4. The Impact of Conscious Sedation versus General Anesthesia for Stroke Thrombectomy on the Predictive Value of Collateral Status: A Post Hoc Analysis of the SIESTA Trial.

    Science.gov (United States)

    Schönenberger, S; Pfaff, J; Uhlmann, L; Klose, C; Nagel, S; Ringleb, P A; Hacke, W; Kieser, M; Bendszus, M; Möhlenbruch, M A; Bösel, J

    2017-08-01

    Radiologic selection criteria to identify patients likely to benefit from endovascular stroke treatment are still controversial. In this post hoc analysis of the recent randomized Sedation versus Intubation for Endovascular Stroke TreAtment (SIESTA) trial, we aimed to investigate the impact of sedation mode (conscious sedation versus general anesthesia) on the predictive value of collateral status. Using imaging data from SIESTA, we assessed collateral status with the collateral score of Tan et al and graded it from absent to good collaterals (0-3). We examined the association of collateral status with 24-hour improvement of the NIHSS score, infarct volume, and mRS at 3 months according to the sedation regimen. In a cohort of 104 patients, the NIHSS score improved significantly in patients with moderate or good collaterals (2-3) compared with patients with no or poor collaterals (0-1) ( P = .011; mean, -5.8 ± 7.6 versus -1.1 ± 10.7). Tan 2-3 was also associated with significantly higher ASPECTS before endovascular stroke treatment (median, 9 versus 7; P collateral status (0.1 versus 2.3), the sedation modes conscious sedation and general anesthesia were not associated with significant differences in the predictive value of collateral status regarding infarction size or functional outcome. The sedation mode, conscious sedation or general anesthesia, did not influence the predictive value of collaterals in patients with large-vessel occlusion anterior circulation stroke undergoing thrombectomy in the SIESTA trial. © 2017 by American Journal of Neuroradiology.

  5. Impact of time of initiation of once-monthly paliperidone palmitate in hospitalized Asian patients with acute exacerbation of schizophrenia: a post hoc analysis from the PREVAIL study.

    Science.gov (United States)

    Li, Huafang; Li, Yan; Feng, Yu; Zhuo, Jianmin; Turkoz, Ibrahim; Mathews, Maju; Tan, Wilson

    2018-01-01

    To evaluate the differences in efficacy and safety outcomes in acute exacerbating schizophrenia patients between 2 subgroups (≤1 week and >1 week), differing in time interval from hospitalization to time of initiation of once-monthly paliperidone palmitate. PREVAIL was a multicenter, single-arm, open-label, prospective Phase IV study in hospitalized Asian patients (either sex, aged 18-65 years) diagnosed with schizophrenia ( Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition). Change from baseline to week 13 in primary (Positive and Negative Syndrome Scale [PANSS] total score), secondary endpoints (PANSS responder rate, PANSS subscale, PANSS Marder factor, Clinical Global Impression-Severity, and Personal and Social Performance scale scores, readiness for hospital discharge questionnaire) and safety were assessed in this post hoc analysis. Significant mean reduction from baseline to week 13 in the PANSS total score, 30% PANSS responder rates ( P ≤0.01), PANSS subscales (positive and general psychopathology; all P ≤0.01), PANSS Marder factor (positive symptoms, uncontrolled hostility, and excitement and anxiety/depression; all P ≤0.01), Personal and Social Performance scale scores ( P ≤0.05) and Clinical Global Impression-Severity categorical summary ( P ≤0.05) were significantly greater in the ≤1 week subgroup versus >1 week subgroup ( P ≤0.05). The readiness for hospital discharge questionnaire improved over time for the overall study population, but remained similar between subgroups at all-time points. Treatment-emergent adverse events were similar between the subgroups. Early initiation of once-monthly paliperidone palmitate in hospitalized patients with acute exacerbation of schizophrenia led to greater improvements in psychotic symptoms with comparable safety than treatment initiation following 1 week of hospitalization.

  6. The PREVAIL trial of enzalutamide in men with chemotherapy-naïve, metastatic castration-resistant prostate cancer: Post hoc analysis of Korean patients.

    Science.gov (United States)

    Kim, Choung-Soo; Theeuwes, Ad; Kwon, Dong Deuk; Choi, Young Deuk; Chung, Byung Ha; Lee, Hyun Moo; Lee, Kang Hyun; Lee, Sang Eun

    2016-05-01

    This post hoc analysis evaluated treatment effects, safety, and pharmacokinetics of enzalutamide in Korean patients in the phase 3, double-blind, placebo-controlled PREVAIL trial. Asymptomatic or mildly symptomatic chemotherapy-naive men with metastatic castration-resistant prostate cancer that progressed on androgen deprivation therapy received 160 mg/d oral enzalutamide or placebo (1:1) until death or discontinuation due to radiographic progression or skeletal-related event and initiation of subsequent therapy. Coprimary end points were centrally assessed radiographic progression-free survival (rPFS) and overall survival (OS). Secondary end points included investigator-assessed rPFS, time to initiation of chemotherapy, time to prostate-specific antigen (PSA) progression, PSA response (≥50% decline), and time to skeletal-related event. Of 1,717 total patients, 78 patients were enrolled in Korea (enzalutamide, n=40; placebo, n=38). Hazard ratios (95% confidence interval) for enzalutamide versus placebo were 0.23 (0.02-2.24) for centrally assessed rPFS, 0.77 (0.28-2.15) for OS, 0.21 (0.08-0.51) for time to chemotherapy, and 0.31 (0.17-0.56) for time to PSA progression. A PSA response was observed in 70.0% of enzalutamide-treated and 10.5% of placebo-treated Korean patients. Adverse events of grade ≥3 occurred in 33% of enzalutamide-treated and 11% of placebo-treated Korean patients, with median treatment durations of 13.0 and 5.1 months, respectively. At 13 weeks, the plasma concentration of enzalutamide plus N-desmethyl enzalutamide was similar in Korean and non-Korean patients (geometric mean ratio, 1.04; 90% confidence interval, 0.97-1.10). In Korean patients, treatment effects and safety of enzalutamide were consistent with those observed in the overall PREVAIL study population (ClinicalTrials.gov Identifier: NCT01212991).

  7. Blood transfusion strategy and risk of postoperative delirium in nursing homes residents with hip fracture. A post hoc analysis based on the TRIFE randomized controlled trial.

    Science.gov (United States)

    Blandfort, Sif; Gregersen, Merete; Borris, Lars Carl; Damsgaard, Else Marie

    2017-06-01

    To investigate whether a liberal blood transfusion strategy [Hb levels ≥11.3 g/dL (7 mmol/L)] reduces the risk of postoperative delirium (POD) on day 10, among nursing home residents with hip fracture, compared to a restrictive transfusion strategy [Hb levels ≥9.7 g/dL (6 mmol/L)]. Furthermore, to investigate whether POD influences mortality within 90 days after hip surgery. This is a post hoc analysis based on The TRIFE - a randomized controlled trial. Frail anemic patients from the Orthopedic Surgical Ward at Aarhus University Hospital were enrolled consecutively between January 18, 2010 and June 6, 2013. These patients (aged ≥65 years) had been admitted from nursing homes for unilateral hip fracture surgery. After surgery, 179 patients were included in this study. On the first day of hospitalization, all enrolled patients were examined for cognitive impairment (assessed by MMSE) and delirium (assessed by CAM). Delirium was also assessed on the tenth postoperative day. The prevalence of delirium was 10 % in patients allocated to a liberal blood transfusion strategy (LB) and 21 % in the group with a restrictive blood transfusion strategy (RB). LB prevents development of delirium on day 10, compared to RB, odds ratio 0.41 (95 % CI 0.17-0.96), p = 0.04. Development of POD on day 10 increased the risk of 90-day death, hazard ratio 3.14 (95 % CI 1.72-5.78), p < 0.001. In nursing home residents undergoing surgery for hip fracture, maintaining hemoglobin level above 11.3 g/dL reduces the rate of POD on day 10 compared to a RB. Development of POD is associated with increased mortality.

  8. Effectiveness of treat-to-target strategy for LDL-cholesterol control in type 2 diabetes: post-hoc analysis of data from the MIND.IT study.

    Science.gov (United States)

    Ardigò, Diego; Vaccaro, Olga; Cavalot, Franco; Rivellese, Albarosa Angela; Franzini, Laura; Miccoli, Roberto; Patti, Lidia; Boemi, Massimo; Trovati, Mariella; Zavaroni, Ivana

    2014-04-01

    The paper presents a post-hoc analysis of the intensity of dyslipidaemia care operated in the first 2 years of Multiple-Intervention-in-type-2-Diabetes.ITaly (MIND.IT) study. MIND.IT is a multicentric, randomized, two-parallel arm trial involving 1461 type 2 diabetic patients at high cardiovascular (CV) risk. The study compares the usual care (UC) of CV prevention with a multifactorial intensive care (IC) approach aiming at achieving target values for the main CV risk factors according to a step-wise treat-to-target approach. Proportion of patients on target for low-density lipoprotein cholesterol (LDL-C) was about 10% at baseline and increased significantly more with IC than UC (43 vs. 27%; p < 0.001). However, the majority (57%) of patients, in this intended intensively treated cohort, failed to achieve the proposed target. Average LDL-C decreased from 144 ± 35 to 108 ± 31 mg/dl with IC and from 142 ± 28 to 118 ± 32 with UC (p-for-interaction <0.0001). IC was associated with a significantly greater increase in statin prescription and lower withdrawal from treatment than UC (43 vs. 11% and 28 vs. 61%, respectively; both p < 0.001). However, the new treatments were characterized in both groups by the use of low starting doses (≤ 10 mg of atorvastatin, equivalent dose in more than 90% of patients) without increase in case of missed target. The application of a multifactorial treat-to-target intervention is associated with a significant improvement in LDL-C beyond usual practice. However, the change in LDL-C appears to be more related to an increased number of treated patients and a decreased treatment withdrawal than to a true treat-to-target approach.

  9. Costs and health resources utilization following switching to pregabalin in individuals with gabapentin-refractory neuropathic pain: a post hoc analysis.

    Science.gov (United States)

    Navarro, Ana; Saldaña, María T; Pérez, Concepción; Masramón, Xavier; Rejas, Javier

    2012-06-01

    To analyze the changes in pain severity and associated costs resulting from resource utilization and reduced productivity in patients with gabapentin-refractory peripheral neuropathic pain who switched to pregabalin therapy in primary care settings in Spain. This is a post hoc analysis of a 12-week, multicentre, noninterventional cost-of-illness study. Patients were included in the study if they were over 18 years of age and had a diagnosis of chronic, treatment-refractory peripheral neuropathic pain. The analysis included all pregabalin-naïve patients who had previously shown an inadequate response to gabapentin and switched to pregabalin. Severity of pain before and after treatment with pregabalin, alone or as an add-on therapy, was assessed using the Short-Form McGill Pain Questionnaire (SF-MPQ) and its related visual analogue scale (VA). Healthcare resource utilization, productivity (including lost-workday equivalents [LWDE]), and related costs were assessed at baseline and after pregabalin treatment. A total of 174 patients switched to pregabalin had significant and clinically relevant reductions in pain severity (mean [SD] change on SF-MPQ VA scale, -31.9 [22.1]; P use [in pregabalin add-on group], ancillary tests, and unscheduled medical visits) were observed at the end of trial. Additionally, there were substantial improvements in productivity, including a reduction in the number of LWDE following pregabalin treatment (-18.9 [26.0]; P < 0.0001). These changes correlated with substantial reductions in both direct (-652.9 ± 1622.4 €; P < 0.0001) and indirect healthcare costs (-851.6 [1259.6] €; P < 0.0001). The cost of care in patients with gabapentin-refractory peripheral neuropathic pain appeared to be significantly reduced after switching to pregabalin treatment, alone or in combination with other analgesic drugs, in a real-life setting. © 2011 The Authors. Pain Practice © 2011 World Institute of Pain.

  10. The longitudinal interplay between negative and positive symptom trajectories in patients under antipsychotic treatment: a post hoc analysis of data from a randomized, 1-year pragmatic trial.

    Science.gov (United States)

    Chen, Lei; Johnston, Joseph A; Kinon, Bruce J; Stauffer, Virginia; Succop, Paul; Marques, Tiago R; Ascher-Svanum, Haya

    2013-11-28

    Schizophrenia is a highly heterogeneous disorder with positive and negative symptoms being characteristic manifestations of the disease. While these two symptom domains are usually construed as distinct and orthogonal, little is known about the longitudinal pattern of negative symptoms and their linkage with the positive symptoms. This study assessed the temporal interplay between these two symptom domains and evaluated whether the improvements in these symptoms were inversely correlated or independent with each other. This post hoc analysis used data from a multicenter, randomized, open-label, 1-year pragmatic trial of patients with schizophrenia spectrum disorder who were treated with first- and second-generation antipsychotics in the usual clinical settings. Data from all treatment groups were pooled resulting in 399 patients with complete data on both the negative and positive subscale scores from the Positive and Negative Syndrome Scale (PANSS). Individual-based growth mixture modeling combined with interplay matrix was used to identify the latent trajectory patterns in terms of both the negative and positive symptoms. Pearson correlation coefficients were calculated to examine the relationship between the changes of these two symptom domains within each combined trajectory pattern. We identified four distinct negative symptom trajectories and three positive symptom trajectories. The trajectory matrix formed 11 combined trajectory patterns, which evidenced that negative and positive symptom trajectories moved generally in parallel. Correlation coefficients for changes in negative and positive symptom subscale scores were positive and statistically significant (P negative and positive symptoms (n = 70, 18%), (2) mild and sustained improvement in negative and positive symptoms (n = 237, 59%), and (3) no improvement in either negative or positive symptoms (n = 82, 21%). This study of symptom trajectories over 1 year shows that changes in negative

  11. Estimated medical expenditure and risk of job loss among rheumatoid arthritis patients undergoing tofacitinib treatment: post hoc analyses of two randomized clinical trials.

    Science.gov (United States)

    Rendas-Baum, Regina; Kosinski, Mark; Singh, Amitabh; Mebus, Charles A; Wilkinson, Bethany E; Wallenstein, Gene V

    2017-08-01

    RA causes high disability levels and reduces health-related quality of life, triggering increased costs and risk of unemployment. Tofacitinib is an oral Janus kinase inhibitor for the treatment of RA. These post hoc analyses of phase 3 data aimed to assess monthly medical expenditure (MME) and risk of job loss for tofacitinib treatment vs placebo. Data analysed were from two randomized phase 3 studies of RA patients (n = 1115) with inadequate response to MTX or TNF inhibitors (TNFi) receiving tofacitinib 5 or 10 mg twice daily, adalimumab (one study only) or placebo, in combination with MTX. Short Form 36 version 2 Health Survey physical and mental component summary scores were translated into predicted MME via an algorithm and concurrent inability to work and job loss risks at 6, 12 and 24 months, using Medical Outcomes Study data. MME reduction by month 3 was $100 greater for tofacitinib- than placebo-treated TNFi inadequate responders (P 20 and 6% reductions from baseline, respectively. By month 3 of tofacitinib treatment, the odds of inability to work decreased ⩾16%, and risk of future job loss decreased ∼20% (P tofacitinib- than placebo-treated MTX inadequate responders (P tofacitinib treatment, the odds of inability to work decreased ⩾31% and risk of future job loss decreased ⩾25% (P Tofacitinib treatment had a positive impact on estimated medical expenditure and risk of job loss for RA patients with inadequate response to MTX or TNFi. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Rheumatology.

  12. Relationship between response to aripiprazole once-monthly and paliperidone palmitate on work readiness and functioning in schizophrenia: A post-hoc analysis of the QUALIFY study.

    Directory of Open Access Journals (Sweden)

    Steven G Potkin

    Full Text Available Schizophrenia is a chronic disease with negative impact on patients' employment status and quality of life. This post-hoc analysis uses data from the QUALIFY study to elucidate the relationship between work readiness and health-related quality of life and functioning. QUALIFY was a 28-week, randomized study (NCT01795547 comparing the treatment effectiveness of aripiprazole once-monthly 400 mg and paliperidone palmitate once-monthly using the Heinrichs-Carpenter Quality-of-Life Scale as the primary endpoint. Also, patients' capacity to work and work readiness (Yes/No was assessed with the Work Readiness Questionnaire. We categorized patients, irrespective of treatment, by work readiness at baseline and week 28: No to Yes (n = 41, Yes to Yes (n = 49, or No at week 28 (n = 118. Quality-of-Life Scale total, domains, and item scores were assessed with a mixed model of repeated measures. Patients who shifted from No to Yes in work readiness showed robust improvements on Quality-of-Life Scale total scores, significantly greater than patients not ready to work at week 28 (least squares mean difference: 11.6±2.6, p<0.0001. Scores on Quality-of-Life Scale instrumental role domain and items therein-occupational role, work functioning, work levels, work satisfaction-significantly improved in patients shifting from No to Yes in work readiness (vs patients No at Week 28. Quality-of-Life Scale total scores also significantly predicted work readiness at week 28. Overall, these results highlight a strong association between improvements in health-related quality of life and work readiness, and suggest that increasing patients' capacity to work is an achievable and meaningful goal in the treatment of impaired functioning in schizophrenia.

  13. Relationship of Glucose Variability With Glycated Hemoglobin and Daily Mean Glucose: A Post Hoc Analysis of Data From 5 Phase 3 Studies.

    Science.gov (United States)

    Luo, Junxiang; Qu, Yongming; Zhang, Qianyi; Chang, Annette M; Jacober, Scott J

    2018-03-01

    The association of glucose variability (GV) with other glycemic measures is emerging as a topic of interest. The aim of this analysis is to study the correlation between GV and measures of glycemic control, such as glycated hemoglobin (HbA1c) and daily mean glucose (DMG). Data from 5 phase 3 trials were pooled into 3 analysis groups: type 2 diabetes (T2D) treated with basal insulin only, T2D treated with basal-bolus therapy, and type 1 diabetes (T1D). A generalized boosted model was used post hoc to assess the relationship of the following variables with glycemic control parameters (HbA1c and DMG): within-day GV, between-day GV (calculated using self-monitored blood glucose and fasting blood glucose [FBG]), hypoglycemia rate, and certain baseline characteristics. Within-day GV (calculated using standard deviation [SD]) was found to have a significant influence on endpoints HbA1c and DMG in all 3 patient groups. Between-day GV from FBG (calculated using SD), within-day GV (calculated using coefficient of variation), and hypoglycemia rate were found to significantly influence the endpoint HbA1c in the T2D basal-only group. Lower within-day GV was significantly associated with improvement in DMG and HbA1c. This finding suggests that GV could be a marker in the early phases of new antihyperglycemic therapy development for predicting clinical outcomes in terms of HbA1c and DMG.

  14. C/EBPα creates elite cells for iPSC reprogramming by upregulating Klf4 and increasing the levels of Lsd1 and Brd4

    DEFF Research Database (Denmark)

    Di Stefano, Bruno; Collombet, Samuel; Jakobsen, Janus Schou

    2016-01-01

    reprogrammed into iPSCs by the Yamanaka factors OSKM. Here we show that C/EBPα post-transcriptionally increases the abundance of several hundred proteins, including Lsd1, Hdac1, Brd4, Med1 and Cdk9, components of chromatin-modifying complexes present at super-enhancers. Lsd1 was found to be required for B cell...

  15. Apolipoprotein A-IV concentrations and clinical outcomes in haemodialysis patients with type 2 diabetes mellitus--a post hoc analysis of the 4D Study.

    Science.gov (United States)

    Kollerits, B; Krane, V; Drechsler, C; Lamina, C; März, W; Ritz, E; Wanner, C; Kronenberg, F

    2012-12-01

    Apolipoprotein A-IV (apoA-IV) is an anti-atherogenic and anti-oxidative plasma glycoprotein involved in reverse cholesterol transport. The aim of this study was to examine the association between apoA-IV and all-cause mortality, cardiovascular endpoints and parameters of protein-energy wasting and nutrition in haemodialysis patients. This post hoc analysis was performed in the German Diabetes Dialysis Study (4D Study) evaluating atorvastatin in 1255 haemodialysis patients with type 2 diabetes mellitus, followed for a median of 4 years. The association between apoA-IV and relevant outcomes was analysed using Cox proportional hazards regression analyses. Body mass index (BMI) was used as a marker of protein-energy wasting. In addition, a definition of extended wasting was applied, combining median values of BMI, serum albumin, creatinine and sensitive C-reactive protein, to classify patients. Mean (±SD) apoA-IV concentration was 49.8 ± 14.2 mg dL(-1). Age- and gender-adjusted apoA-IV concentrations were strongly associated with the presence of congestive heart failure at baseline [odds ratio = 0.81, 95% confidence interval (CI) 0.74-0.88 per 10 mg dL(-1) increase; P 1). During the prospective follow-up, the strongest association was found for all-cause mortality [hazard ratio (HR) = 0.89, 95% CI 0.85-0.95, P = 0.001), which was mainly because of patients with BMI > 23 kg m(-2) (HR = 0.87, 95% CI 0.82-0.94, P 1) and those in the nonwasting group according to the extended definition (HR = 0.89, 95% CI 0.84-0.96, P = 0.001). This association remained significant after additionally adjusting for parameters associated with apoA-IV at baseline. Further associations were observed for sudden cardiac death. ApoA-IV was less strongly associated with atherogenic events such as myocardial infarction. Low apoA-IV levels seem to be a risk predictor of all-cause mortality and sudden cardiac death. This association might be modified by nutritional status. © 2012 The Association

  16. Effectiveness and tolerability of second-line therapy with vildagliptin versus other oral agents in type 2 diabetes (EDGE): post-hoc subanalysis of the Belgian data.

    Science.gov (United States)

    Hoste, J; Daci, E; Mathieu, C

    2014-06-01

    To assess the efficacy and safety of vildagliptin versus other oral glucose-lowering drugs added to antidiabetic monotherapy in Belgian patients with type 2 diabetes mellitus, in comparison to the global EDGE study results. This is a pre-specified post-hoc subanalysis of the Belgian patient cohort from a worldwide 1-year observational study that compared the effectiveness and tolerability of vildagliptin to other oral antidiabetic agents in type 2 diabetes patients failing monotherapy with oral glucose-lowering agents (EDGE). A total of 1793 Belgian patients were enrolled. Physicians could add any oral antidiabetic drug and patients entered either into the vildagliptin or the comparator cohort. The primary effectiveness and tolerability endpoint was defined as the proportion of patients having a treatment response (HbA1c reduction from baseline to month 12 endpoint >0·3%) without hypoglycemia, weight gain, peripheral oedema, or gastrointestinal side-effects. In the Belgian population, 37·8% of patients in the vildagliptin group and 32·8% in the comparator group had a decrease in HbA1c of >0·3% without the predefined tolerability issues of hypoglycemia, weight gain, oedema or, gastrointestinal complaints (primary endpoint), resulting in an unadjusted odds ratio of 1·24 (95% CI: 0·96-1·61). Mean HbA1c change from baseline was -0·81% in the vildagliptin cohort and -0·75% in the comparator cohort. Overall, vildagliptin was well tolerated with similarly low incidences of total adverse events (14·9% versus 14·5% in the compactor group) and serious adverse events (2·7% versus 2·5% in the comparator group). In this EDGE subgroup of Belgian patients with type 2 diabetes who do not achieve the glycemic targets with monotherapy, a similar trend as in the global EDGE study was observed. Adding vildagliptin as a second oral glucose-lowering agent resulted in lowering HbA1c to <7% without weight gain, hypoglycemia or peripheral oedema in a higher proportion of

  17. Impact of time of initiation of once-monthly paliperidone palmitate in hospitalized Asian patients with acute exacerbation of schizophrenia: a post hoc analysis from the PREVAIL study

    Directory of Open Access Journals (Sweden)

    Li H

    2018-04-01

    Full Text Available Huafang Li,1,2 Yan Li,1,2 Yu Feng,3 Jianmin Zhuo,4 Ibrahim Turkoz,5 Maju Mathews,5 Wilson Tan3 1Shanghai Mental Health Centre, Shanghai Jiao Tong University School of Medicine, Shanghai, China; 2Shanghai Key Laboratory of Psychotic Disorders, Shanghai, China; 3Janssen Pharmaceutical Companies of Johnson and Johnson, Singapore; 4Janssen China Research and Development, Shanghai, China; 5Janssen Research & Development LLC, Titusville, NJ, USA Purpose: To evaluate the differences in efficacy and safety outcomes in acute exacerbating schizophrenia patients between 2 subgroups (≤1 week and >1 week, differing in time interval from hospitalization to time of initiation of once-monthly paliperidone palmitate. Patients and methods: PREVAIL was a multicenter, single-arm, open-label, prospective Phase IV study in hospitalized Asian patients (either sex, aged 18–65 years diagnosed with schizophrenia (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. Change from baseline to week 13 in primary (Positive and Negative Syndrome Scale [PANSS] total score, secondary endpoints (PANSS responder rate, PANSS subscale, PANSS Marder factor, Clinical Global Impression-Severity, and Personal and Social Performance scale scores, readiness for hospital discharge questionnaire and safety were assessed in this post hoc analysis. Results: Significant mean reduction from baseline to week 13 in the PANSS total score, 30% PANSS responder rates (P≤0.01, PANSS subscales (positive and general psychopathology; all P≤0.01, PANSS Marder factor (positive symptoms, uncontrolled hostility, and excitement and anxiety/depression; all P≤0.01, Personal and Social Performance scale scores (P≤0.05 and Clinical Global Impression-Severity categorical summary (P≤0.05 were significantly greater in the ≤1 week subgroup versus >1 week subgroup (P≤0.05. The readiness for hospital discharge questionnaire improved over time for the overall study population, but

  18. Enzalutamide in Japanese patients with chemotherapy-naïve, metastatic castration-resistant prostate cancer: A post-hoc analysis of the placebo-controlled PREVAIL trial.

    Science.gov (United States)

    Kimura, Go; Yonese, Junji; Fukagai, Takashi; Kamba, Tomomi; Nishimura, Kazuo; Nozawa, Masahiro; Mansbach, Hank; Theeuwes, Ad; Beer, Tomasz M; Tombal, Bertrand; Ueda, Takeshi

    2016-05-01

    To evaluate the treatment effects, safety and pharmacokinetics of enzalutamide in Japanese patients. This was a post-hoc analysis of the phase 3, double-blind, placebo-controlled PREVAIL trial. Asymptomatic or mildly symptomatic chemotherapy-naïve patients with metastatic castration-resistant prostate cancer progressing on androgen deprivation therapy were randomized one-to-one to 160 mg/day oral enzalutamide or placebo until discontinuation on radiographic progression or skeletal-related event and initiation of subsequent antineoplastic therapy. Coprimary end-points were centrally assessed radiographic progression-free survival and overall survival. Secondary end-points were investigator-assessed radiographic progression-free survival, time to initiation of chemotherapy, time to prostate-specific antigen progression, prostate-specific antigen response (≥50% decline) and time to skeletal-related event. Of 1717 patients, 61 were enrolled in Japan (enzalutamide, n = 28; placebo, n = 33); hazard ratios (95% confidence interval) of 0.30 for centrally assessed radiographic progression-free survival (0.03-2.95), 0.59 for overall survival (0.20-1.8), 0.46 for time to chemotherapy (0.22-0.96) and 0.36 for time to prostate-specific antigen progression (0.17-0.75) showed the treatment benefit of enzalutamide over the placebo. Prostate-specific antigen responses were observed in 60.7% of enzalutamide-treated men versus 21.2% of placebo-treated men. Plasma concentrations of enzalutamide were higher in Japanese patients: the geometric mean ratio of Japanese/non-Japanese patients was 1.126 (90% confidence interval 1.018-1.245) at 13 weeks. Treatment-related adverse events grade ≥3 occurred in 3.6% of enzalutamide- and 6.1% of placebo-treated Japanese patients. Treatment effects and safety in Japanese patients were generally consistent with the overall results from PREVAIL. © 2016 The Authors. International Journal of Urology published by John Wiley & Sons Australia, Ltd on

  19. Effect of sacubitril/valsartan versus enalapril on glycaemic control in patients with heart failure and diabetes: a post-hoc analysis from the PARADIGM-HF trial.

    Science.gov (United States)

    Seferovic, Jelena P; Claggett, Brian; Seidelmann, Sara B; Seely, Ellen W; Packer, Milton; Zile, Michael R; Rouleau, Jean L; Swedberg, Karl; Lefkowitz, Martin; Shi, Victor C; Desai, Akshay S; McMurray, John J V; Solomon, Scott D

    2017-05-01

    Diabetes is an independent risk factor for heart failure progression. Sacubitril/valsartan, a combination angiotensin receptor-neprilysin inhibitor, improves morbidity and mortality in patients with heart failure with reduced ejection fraction (HFrEF), compared with the angiotensin-converting enzyme inhibitor enalapril, and improves peripheral insulin sensitivity in obese hypertensive patients. We aimed to investigate the effect of sacubitril/valsartan versus enalapril on HbA 1c and time to first-time initiation of insulin or oral antihyperglycaemic drugs in patients with diabetes and HFrEF. In a post-hoc analysis of the PARADIGM-HF trial, we included 3778 patients with known diabetes or an HbA 1c ≥6·5% at screening out of 8399 patients with HFrEF who were randomly assigned to treatment with sacubitril/valsartan or enalapril. Of these patients, most (98%) had type 2 diabetes. We assessed changes in HbA 1c , triglycerides, HDL cholesterol and BMI in a mixed effects longitudinal analysis model. Time to initiation of oral antihyperglycaemic drugs or insulin in subjects previously not treated with these agents were compared between treatment groups. There were no significant differences in HbA 1c concentrations between randomised groups at screening. During the first year of follow-up, HbA 1c concentrations decreased by 0·16% (SD 1·40) in the enalapril group and 0·26% (SD 1·25) in the sacubitril/valsartan group (between-group reduction 0·13%, 95% CI 0·05-0·22, p=0·0023). HbA 1c concentrations were persistently lower in the sacubitril/valsartan group than in the enalapril group over the 3-year follow-up (between-group reduction 0·14%, 95% CI 0·06-0·23, p=0·0055). New use of insulin was 29% lower in patients receiving sacubitril/valsartan (114 [7%] patients) compared with patients receiving enalapril (153 [10%]; hazard ratio 0·71, 95% CI 0·56-0·90, p=0·0052). Similarly, fewer patients were started on oral antihyperglycaemic therapy (0·77, 0·58-1·02

  20. Effect of fenofibrate on uric acid and gout in type 2 diabetes: a post-hoc analysis of the randomised, controlled FIELD study.

    Science.gov (United States)

    Waldman, Boris; Ansquer, Jean-Claude; Sullivan, David R; Jenkins, Alicia J; McGill, Neil; Buizen, Luke; Davis, Timothy M E; Best, James D; Li, Liping; Feher, Michael D; Foucher, Christelle; Kesaniemi, Y Antero; Flack, Jeffrey; d'Emden, Michael C; Scott, Russell S; Hedley, John; Gebski, Val; Keech, Anthony C

    2018-04-01

    Gout is a painful disorder and is common in type 2 diabetes. Fenofibrate lowers uric acid and reduces gout attacks in small, short-term studies. Whether fenofibrate produces sustained reductions in uric acid and gout attacks is unknown. In the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) trial, participants aged 50-75 years with type 2 diabetes were randomly assigned to receive either co-micronised fenofibrate 200 mg once per day or matching placebo for a median of 5 years follow-up. We did a post-hoc analysis of recorded on-study gout attacks and plasma uric acid concentrations according to treatment allocation. The outcomes of this analysis were change in uric acid concentrations and risk of on-study gout attacks. The FIELD study is registered with ISRCTN, number ISRCTN64783481. Between Feb 23, 1998, and Nov 3, 2000, 9795 patients were randomly assigned to fenofibrate (n=4895) or placebo (n=4900) in the FIELD study. Uric acid concentrations fell by 20·2% (95% CI 19·9-20·5) during the 6-week active fenofibrate run-in period immediately pre-randomisation (a reduction of 0·06 mmol/L or 1 mg/dL) and remained -20·1% (18·5-21·7, puric acid concentration higher than 0·36 mmol/L and 13·9% in those with baseline uric acid concentration higher than 0·42 mmol/L, compared with 3·4% and 5·7%, respectively, in the fenofibrate group. Risk reductions were similar among men and women and those with dyslipidaemia, on diuretics, and with elevated uric acid concentrations. For participants with elevated baseline uric acid concentrations despite taking allopurinol at study entry, there was no heterogeneity of the treatment effect of fenofibrate on gout risk. Taking account of all gout events, fenofibrate treatment halved the risk (HR 0·48, 95% CI 0·37-0·60; puric acid concentrations by 20%, and almost halved first on-study gout events over 5 years of treatment. Fenofibrate could be a useful adjunct for preventing gout in diabetes. None. Copyright

  1. Treatment with macrolides and glucocorticosteroids in severe community-acquired pneumonia: A post-hoc exploratory analysis of a randomized controlled trial.

    Directory of Open Access Journals (Sweden)

    Adrian Ceccato

    Full Text Available Systemic corticosteroids have anti-inflammatory effects, whereas macrolides also have immunomodulatory activity in addition to their primary antimicrobial actions. We aimed to evaluate the potential interaction effect between corticosteroids and macrolides on the systemic inflammatory response in patients with severe community-acquired pneumonia to determine if combining these two immunomodulating agents was harmful, or possibly beneficial.We performed a post-hoc exploratory analysis of a randomized clinical trial conducted in three tertiary hospitals in Spain. This trial included patients with severe community-acquired pneumonia with high inflammatory response (C-reactive protein [CRP] >15 mg/dL who were randomized to receive methylprednisolone 0.5 mg/kg/tpd or placebo. The choice of antibiotic treatment was at the physician's discretion. One hundred and six patients were classified into four groups according to antimicrobial therapy combination (β-lactam plus macrolide or β-lactam plus fluoroquinolone and corticosteroid arm (placebo or corticosteroids. The primary outcome was treatment failure (composite outcome of early treatment failure, or of late treatment failure, or of both early and late treatment failure.The methylprednisolone with β-lactam plus macrolide group had more elderly patients, with comorbidities, and higher pneumonia severity index (PSI risk class V, but a lower proportion of intensive care unit admission, compared to the other groups. We found non differences in treatment failure between groups (overall p = 0.374; however, a significant difference in late treatment failure was observed (4 patients in the placebo with β-lactam plus macrolide group (31% vs. 9 patients in the placebo with β-lactam plus fluoroquinolone group (24% vs. 0 patients in the methylprednisolone with β-lactam plus macrolide group (0% vs. 2 patients [5%] in the methylprednisolone with β-lactam plus fluoroquinolone group overall p = 0.009. We found

  2. Indomethacin reduces glomerular and tubular damage markers but not renal inflammation in chronic kidney disease patients: a post-hoc analysis.

    Directory of Open Access Journals (Sweden)

    Martin H de Borst

    Full Text Available Under specific conditions non-steroidal anti-inflammatory drugs (NSAIDs may be used to lower therapy-resistant proteinuria. The potentially beneficial anti-proteinuric, tubulo-protective, and anti-inflammatory effects of NSAIDs may be offset by an increased risk of (renal side effects. We investigated the effect of indomethacin on urinary markers of glomerular and tubular damage and renal inflammation. We performed a post-hoc analysis of a prospective open-label crossover study in chronic kidney disease patients (n = 12 with mild renal function impairment and stable residual proteinuria of 4.7±4.1 g/d. After a wash-out period of six wks without any RAAS blocking agents or other therapy to lower proteinuria (untreated proteinuria (UP, patients subsequently received indomethacin 75 mg BID for 4 wks (NSAID. Healthy subjects (n = 10 screened for kidney donation served as controls. Urine and plasma levels of total IgG, IgG4, KIM-1, beta-2-microglobulin, H-FABP, MCP-1 and NGAL were determined using ELISA. Following NSAID treatment, 24 h -urinary excretion of glomerular and proximal tubular damage markers was reduced in comparison with the period without anti-proteinuric treatment (total IgG: UP 131[38-513] vs NSAID 38[17-218] mg/24 h, p<0.01; IgG4: 50[16-68] vs 10[1-38] mg/24 h, p<0.001; beta-2-microglobulin: 200[55-404] vs 50[28-110] ug/24 h, p = 0.03; KIM-1: 9[5]-[14] vs 5[2]-[9] ug/24 h, p = 0.01. Fractional excretions of these damage markers were also reduced by NSAID. The distal tubular marker H-FABP showed a trend to reduction following NSAID treatment. Surprisingly, NSAID treatment did not reduce urinary excretion of the inflammation markers MCP-1 and NGAL, but did reduce plasma MCP-1 levels, resulting in an increased fractional MCP-1 excretion. In conclusion, the anti-proteinuric effect of indomethacin is associated with reduced urinary excretion of glomerular and tubular damage markers, but not with reduced excretion of renal

  3. Onset of efficacy and tolerability following the initiation dosing of long-acting paliperidone palmitate: post-hoc analyses of a randomized, double-blind clinical trial

    Directory of Open Access Journals (Sweden)

    Fu Dong-Jing

    2011-05-01

    Full Text Available Abstract Background Paliperidone palmitate is a long-acting injectable atypical antipsychotic for the acute and maintenance treatment of adults with schizophrenia. The recommended initiation dosing regimen is 234 mg on Day 1 and 156 mg on Day 8 via intramuscular (deltoid injection; followed by 39 to 234 mg once-monthly thereafter (deltoid or gluteal. These post-hoc analyses addressed two commonly encountered clinical issues regarding the initiation dosing: the time to onset of efficacy and the associated tolerability. Methods In a 13-week double-blind trial, 652 subjects with schizophrenia were randomized to paliperidone palmitate 39, 156, or 234 mg (corresponding to 25, 100, or 150 mg equivalents of paliperidone, respectively or placebo (NCT#00590577. Subjects randomized to paliperidone palmitate received 234 mg on Day 1, followed by their randomized fixed dose on Day 8, and monthly thereafter, with no oral antipsychotic supplementation. The onset of efficacy was defined as the first timepoint where the paliperidone palmitate group showed significant improvement in the Positive and Negative Syndrome Scale (PANSS score compared to placebo (Analysis of Covariance [ANCOVA] models and Last Observation Carried Forward [LOCF] methodology without adjusting for multiplicity using data from the Days 4, 8, 22, and 36 assessments. Adverse event (AE rates and relative risks (RR with 95% confidence intervals (CI versus placebo were determined. Results Paliperidone palmitate 234 mg on Day 1 was associated with greater improvement than placebo on Least Squares (LS mean PANSS total score at Day 8 (p = 0.037. After the Day 8 injection of 156 mg, there was continued PANSS improvement at Day 22 (p ≤ 0.007 vs. placebo and Day 36 (p Conclusions Significantly greater symptom improvement was observed by Day 8 with paliperidone palmitate (234 mg on Day 1 compared to placebo; this effect was maintained after the 156 mg Day 8 injection, with a trend towards a dose

  4. Prognostic Significance of Creatinine Increases During an Acute Heart Failure Admission in Patients With and Without Residual Congestion: A Post Hoc Analysis of the PROTECT Data.

    Science.gov (United States)

    Metra, Marco; Cotter, Gad; Senger, Stefanie; Edwards, Christopher; Cleland, John G; Ponikowski, Piotr; Cursack, Guillermo C; Milo, Olga; Teerlink, John R; Givertz, Michael M; O'Connor, Christopher M; Dittrich, Howard C; Bloomfield, Daniel M; Voors, Adriaan A; Davison, Beth A

    2018-05-01

    The importance of a serum creatinine increase, traditionally considered worsening renal function (WRF), during admission for acute heart failure has been recently debated, with data suggesting an interaction between congestion and creatinine changes. In post hoc analyses, we analyzed the association of WRF with length of hospital stay, 30-day death or cardiovascular/renal readmission and 90-day mortality in the PROTECT study (Placebo-Controlled Randomized Study of the Selective A1 Adenosine Receptor Antagonist Rolofylline for Patients Hospitalized With Acute Decompensated Heart Failure and Volume Overload to Assess Treatment Effect on Congestion and Renal Function). Daily creatinine changes from baseline were categorized as WRF (an increase of 0.3 mg/dL or more) or not. Daily congestion scores were computed by summing scores for orthopnea, edema, and jugular venous pressure. Of the 2033 total patients randomized, 1537 patients had both available at study day 14. Length of hospital stay was longer and 30-day cardiovascular/renal readmission or death more common in patients with WRF. However, these were driven by significant associations in patients with concomitant congestion at the time of assessment of renal function. The mean difference in length of hospital stay because of WRF was 3.51 (95% confidence interval, 1.29-5.73) more days ( P =0.0019), and the hazard ratio for WRF on 30-day death or heart failure hospitalization was 1.49 (95% confidence interval, 1.06-2.09) times higher ( P =0.0205), in significantly congested than nonsignificantly congested patients. A similar trend was observed with 90-day mortality although not statistically significant. In patients admitted for acute heart failure, WRF defined as a creatinine increase of ≥0.3 mg/dL was associated with longer length of hospital stay, and worse 30- and 90-day outcomes. However, effects were largely driven by patients who had residual congestion at the time of renal function assessment. URL: https

  5. Evaluation of patient-rated stiffness associated with fibromyalgia: a post-hoc analysis of 4 pooled, randomized clinical trials of duloxetine.

    Science.gov (United States)

    Bennett, Robert; Russell, I Jon; Choy, Ernest; Spaeth, Michael; Mease, Philip; Kajdasz, Daniel; Walker, Daniel; Wang, Fujun; Chappell, Amy

    2012-04-01

    Patients with fibromyalgia (FM) rate stiffness as one of the most troublesome symptoms of the disorder. However, there are few published studies that have focused on better understanding the nature of stiffness in FM. The primary objectives of these analyses were to characterize the distribution of stiffness severity in patients at baseline, evaluate changes in stiffness after 12 weeks of treatment with duloxetine, and determine which outcomes were correlated with stiffness. These were post-hoc analyses of 3-month data from 4 randomized, double-blind, placebo-controlled studies that assessed efficacy of duloxetine in adults with FM. Severity of stiffness was assessed by using the Fibromyalgia Impact Questionnaire (FIQ) on a scale from 0 (no stiffness) to 10 (most severe stiffness). The association between changes in stiffness and other measures was evaluated by using Pearson's correlation coefficient. The FIQ total score and items, the Brief Pain Inventory (BPI-modified short form), the Clinical Global Impression-Severity scale, the Multidimensional Fatigue Inventory, the 17-item Hamilton Depression Rating Scale, the Sheehan Disability Scale, the 36-item Short-Form Health Survey, and the EuroQoL Questionnaire-5 Dimensions were evaluated in the correlation analyses. Stepwise linear regression was used to identify the variables that were most highly predictive of the changes in FIQ stiffness. The analysis included 1332 patients (mean age, 50.2 years; 94.7% female; and 87.8% white). The mean (SD) baseline FIQ stiffness score was 7.7 (2.0), and this score correlated with baseline BPI pain score and FIQ function. Duloxetine significantly improved the FIQ stiffness score compared with placebo (P FIQ pain and interference scores, FIQ nonrefreshing sleep, FIQ anxiety, 36-item Short-Form Health Survey bodily pain, and Sheehan Disability Scale total score. Variables related to severity of pain, pain interfering with daily activities, and physical functioning were predictors

  6. LSD enhances the emotional response to music.

    Science.gov (United States)

    Kaelen, M; Barrett, F S; Roseman, L; Lorenz, R; Family, N; Bolstridge, M; Curran, H V; Feilding, A; Nutt, D J; Carhart-Harris, R L

    2015-10-01

    There is renewed interest in the therapeutic potential of psychedelic drugs such as lysergic acid diethylamide (LSD). LSD was used extensively in the 1950s and 1960s as an adjunct in psychotherapy, reportedly enhancing emotionality. Music is an effective tool to evoke and study emotion and is considered an important element in psychedelic-assisted psychotherapy; however, the hypothesis that psychedelics enhance the emotional response to music has yet to be investigated in a modern placebo-controlled study. The present study sought to test the hypothesis that music-evoked emotions are enhanced under LSD. Ten healthy volunteers listened to five different tracks of instrumental music during each of two study days, a placebo day followed by an LSD day, separated by 5-7 days. Subjective ratings were completed after each music track and included a visual analogue scale (VAS) and the nine-item Geneva Emotional Music Scale (GEMS-9). Results demonstrated that the emotional response to music is enhanced by LSD, especially the emotions "wonder", "transcendence", "power" and "tenderness". These findings reinforce the long-held assumption that psychedelics enhance music-evoked emotion, and provide tentative and indirect support for the notion that this effect can be harnessed in the context of psychedelic-assisted psychotherapy. Further research is required to test this link directly.

  7. [The substance experience, a history of LSD].

    Science.gov (United States)

    Beck, François; Bonnet, Nicolas

    2013-04-01

    This article reviews the recent knowledge on LSD stemming from various disciplines among which pharmacology, sociology and epidemiology. The d-lysergic acid diethylamide (LSD) is a particularly powerful hallucinogenic substance. It produces distortions and hearing, visual and tactile hallucinations. Rarely used (only 1.7% of people aged 15-64 years old have tried it in their lifetime), this very powerful drug generates a strong apprehension within the general population, but the ethnographical studies show that its image seems rather good among illicit drug users. This representation relies both on the proper effects of this substance and also on the history of LSD very closely linked to the counterculture characteristic of the years 1960-1970. © 2013 médecine/sciences – Inserm / SRMS.

  8. Interaction of electron neutrino with LSD detector

    Science.gov (United States)

    Ryazhskaya, O. G.; Semenov, S. V.

    2016-06-01

    The interaction of electron neutrino flux, originating in the rotational collapse mechanism on the first stage of Supernova burst, with the LSD detector components, such as 56Fe (a large amount of this metal is included in as shielding material) and liquid scintillator barNnH2n+2, is being investigated. Both charged and neutral channels of neutrino reaction with 12barN and 56Fe are considered. Experimental data, giving the possibility to extract information for nuclear matrix elements calculation are used. The number of signals, produced in LSD by the neutrino pulse of Supernova 1987A is determined. The obtained results are in good agreement with experimental data.

  9. Supporting Structure of the LSD Wave in an Energy Absorption Perspective

    International Nuclear Information System (INIS)

    Fukui, Akihiro; Hatai, Keigo; Cho, Shinatora; Arakawa, Yoshihiro; Komurasaki, Kimiya

    2008-01-01

    In Repetitively Pulsed (RP) Laser Propulsion, laser energy irradiated to a vehicle is converted to blast wave enthalpy during the Laser Supported Detonation (LSD) regime. Based on the measured post-LSD electron number density profiles by two-wavelength Mach Zehnder interferometer in a line-focusing optics, electron temperature and absorption coefficient were estimated assuming Local Thermal Equilibrium. A 10J/pulse CO 2 laser was used. As a result, laser absorption was found completed in the layer between the shock wave and the electron density peak. Although the LSD-termination timing was not clear from the shock-front/ionization-front separation in the shadowgraph images, there observed drastic changes in the absorption layer thickness from 0.2 mm to 0.5 mm and in the peak heating rate from 12-17x10 13 kW/m 3 to 5x10 13 kW/m 3 at the termination

  10. Response of cluster headache to psilocybin and LSD.

    Science.gov (United States)

    Sewell, R Andrew; Halpern, John H; Pope, Harrison G

    2006-06-27

    The authors interviewed 53 cluster headache patients who had used psilocybin or lysergic acid diethylamide (LSD) to treat their condition. Twenty-two of 26 psilocybin users reported that psilocybin aborted attacks; 25 of 48 psilocybin users and 7 of 8 LSD users reported cluster period termination; 18 of 19 psilocybin users and 4 of 5 LSD users reported remission period extension. Research on the effects of psilocybin and LSD on cluster headache may be warranted.

  11. LSD Flashbacks: An Overview of the Literature for Counselors.

    Science.gov (United States)

    Silling, S. Marc

    1980-01-01

    Surveyed the literature to delineate the etiology of LSD flashbacks. Concluded that adverse experiences while using LSD are predictive of flashbacks; physiological effects of LSD use may linger after the drug has been metabolized; and individuals who have flashbacks are highly suggestive and play a flashback "role."

  12. LC-ESI-MS/MS on an ion trap for the determination of LSD, iso-LSD, nor-LSD and 2-oxo-3-hydroxy-LSD in blood, urine and vitreous humor.

    Science.gov (United States)

    Favretto, Donata; Frison, Giampietro; Maietti, Sergio; Ferrara, Santo Davide

    2007-07-01

    A method has been developed for the simultaneous determination of lysergic acid diethylamide (LSD), its epimer iso-LSD, and its main metabolites nor-LSD and 2-oxo-3-hydroxy LSD in blood, urine, and, for the first time, vitreous humor samples. The method is based on liquid/liquid extraction and liquid chromatography-multiple mass spectrometry detection in an ion trap mass spectrometer, in positive ion electrospray ionization conditions. Five microliter of sample are injected and analysis time is 12 min. The method is specific, selective and sensitive, and achieves limits of quantification of 20 pg/ml for both LSD and nor-LSD in blood, urine, and vitreous humor. No significant interfering substance or ion suppression was identified for LSD, iso-LSD, and nor-LSD. The interassay reproducibilities for LSD at 20 pg/ml and 2 ng/ml in urine were 8.3 and 5.6%, respectively. Within-run precision using control samples at 20 pg/ml and 2 ng/ml was 6.9 and 3.9%. Mean recoveries of two concentrations spiked into drug free samples were in the range 60-107% in blood, 50-105% in urine, and 65-105% in vitreous humor. The method was successfully applied to the forensic determination of postmortem LSD levels in the biological fluids of a multi drug abuser; for the first time, LSD could be detected in vitreous humor.

  13. Mobile ad hoc networking

    CERN Document Server

    John Wiley & Sons

    2004-01-01

    "Assimilating the most up-to-date information on research and development activities in this rapidly growing area, Mobile Ad Hoc Networking covers physical, data link, network, and transport layers, as well as application, security, simulation, and power management issues in sensor, local area, personal, and mobile ad hoc networks. Each of the book's sixteen chapters has been written by a top expert and discusses in-depth the most important topics in the field. Mobile Ad Hoc Networking is an excellent reference and guide for professionals seeking an in-depth examination of topics that also provides a comprehensive overview of the current state-of-the-art."--Jacket.

  14. Post hoc analysis of Japanese patients from the placebo-controlled PREVAIL trial of enzalutamide in patients with chemotherapy-naive, metastatic castration-resistant prostate cancer-updated results.

    Science.gov (United States)

    Kimura, Go; Ueda, Takeshi

    2017-03-01

    A post hoc analysis of interim results from PREVAIL, a Phase III, double-blind, placebo-controlled trial of men with metastatic castration-resistant prostate cancer, demonstrated that the treatment effects, safety and pharmacokinetics of enzalutamide in Japanese patients were generally consistent with those of the overall population. A recent longer term analysis of PREVAIL demonstrated continued benefit of enzalutamide treatment over placebo. Here, we report results from a post hoc analysis of Japanese patients enrolled in PREVAIL at the prespecified number of deaths for the final analysis. In Japanese patients, enzalutamide reduced the risk of death by 35% (hazard ratio, 0.65; 95% confidence interval, 0.28-1.51) and the risk of investigator-assessed radiographic progression or death by 60% (hazard ratio, 0.40; 95% confidence interval, 0.18-0.90). These results show that treatment effects and safety in Japanese patients in the final analysis of PREVAIL continued to be generally consistent with those of the overall population. © The Author 2016. Published by Oxford University Press.

  15. Post hoc analysis of Japanese patients from the placebo-controlled PREVAIL trial of enzalutamide in patients with chemotherapy-naive, metastatic castration-resistant prostate cancer—updated results

    Science.gov (United States)

    Ueda, Takeshi

    2017-01-01

    Abstract A post hoc analysis of interim results from PREVAIL, a Phase III, double-blind, placebo-controlled trial of men with metastatic castration-resistant prostate cancer, demonstrated that the treatment effects, safety and pharmacokinetics of enzalutamide in Japanese patients were generally consistent with those of the overall population. A recent longer term analysis of PREVAIL demonstrated continued benefit of enzalutamide treatment over placebo. Here, we report results from a post hoc analysis of Japanese patients enrolled in PREVAIL at the prespecified number of deaths for the final analysis. In Japanese patients, enzalutamide reduced the risk of death by 35% (hazard ratio, 0.65; 95% confidence interval, 0.28–1.51) and the risk of investigator-assessed radiographic progression or death by 60% (hazard ratio, 0.40; 95% confidence interval, 0.18–0.90). These results show that treatment effects and safety in Japanese patients in the final analysis of PREVAIL continued to be generally consistent with those of the overall population. PMID:28003320

  16. The Ex hoc Architecture

    DEFF Research Database (Denmark)

    2006-01-01

    Developed in the LIWAS project which develops technology for measuring road surfaces and communicating this data in an ad hoc environment. The communication part is built upon OOVM Resilient technology....

  17. The LSD1-Type Zinc Finger Motifs of Pisum sativa LSD1 Are a Novel Nuclear Localization Signal and Interact with Importin Alpha

    OpenAIRE

    He, Shanping; Huang, Kuowei; Zhang, Xu; Yu, Xiangchun; Huang, Ping; An, Chengcai

    2011-01-01

    BACKGROUND: Genetic studies of the Arabidopsis mutant lsd1 highlight the important role of LSD1 in the negative regulation of plant programmed cell death (PCD). Arabidopsis thaliana LSD1 (AtLSD1) contains three LSD1-type zinc finger motifs, which are involved in the protein-protein interaction. METHODOLOGY/PRINCIPAL FINDINGS: To further understand the function of LSD1, we have analyzed cellular localization and functional localization domains of Pisum sativa LSD1 (PsLSD1), which is a homolog ...

  18. Crystal Structure of an LSD-Bound Human Serotonin Receptor.

    Science.gov (United States)

    Wacker, Daniel; Wang, Sheng; McCorvy, John D; Betz, Robin M; Venkatakrishnan, A J; Levit, Anat; Lansu, Katherine; Schools, Zachary L; Che, Tao; Nichols, David E; Shoichet, Brian K; Dror, Ron O; Roth, Bryan L

    2017-01-26

    The prototypical hallucinogen LSD acts via serotonin receptors, and here we describe the crystal structure of LSD in complex with the human serotonin receptor 5-HT 2B . The complex reveals conformational rearrangements to accommodate LSD, providing a structural explanation for the conformational selectivity of LSD's key diethylamide moiety. LSD dissociates exceptionally slow from both 5-HT 2B R and 5-HT 2A R-a major target for its psychoactivity. Molecular dynamics (MD) simulations suggest that LSD's slow binding kinetics may be due to a "lid" formed by extracellular loop 2 (EL2) at the entrance to the binding pocket. A mutation predicted to increase the mobility of this lid greatly accelerates LSD's binding kinetics and selectively dampens LSD-mediated β-arrestin2 recruitment. This study thus reveals an unexpected binding mode of LSD; illuminates key features of its kinetics, stereochemistry, and signaling; and provides a molecular explanation for LSD's actions at human serotonin receptors. PAPERCLIP. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Acute LSD effects on response inhibition neural networks.

    Science.gov (United States)

    Schmidt, A; Müller, F; Lenz, C; Dolder, P C; Schmid, Y; Zanchi, D; Lang, U E; Liechti, M E; Borgwardt, S

    2017-10-02

    Recent evidence shows that the serotonin 2A receptor (5-hydroxytryptamine2A receptor, 5-HT2AR) is critically involved in the formation of visual hallucinations and cognitive impairments in lysergic acid diethylamide (LSD)-induced states and neuropsychiatric diseases. However, the interaction between 5-HT2AR activation, cognitive impairments and visual hallucinations is still poorly understood. This study explored the effect of 5-HT2AR activation on response inhibition neural networks in healthy subjects by using LSD and further tested whether brain activation during response inhibition under LSD exposure was related to LSD-induced visual hallucinations. In a double-blind, randomized, placebo-controlled, cross-over study, LSD (100 µg) and placebo were administered to 18 healthy subjects. Response inhibition was assessed using a functional magnetic resonance imaging Go/No-Go task. LSD-induced visual hallucinations were measured using the 5 Dimensions of Altered States of Consciousness (5D-ASC) questionnaire. Relative to placebo, LSD administration impaired inhibitory performance and reduced brain activation in the right middle temporal gyrus, superior/middle/inferior frontal gyrus and anterior cingulate cortex and in the left superior frontal and postcentral gyrus and cerebellum. Parahippocampal activation during response inhibition was differently related to inhibitory performance after placebo and LSD administration. Finally, activation in the left superior frontal gyrus under LSD exposure was negatively related to LSD-induced cognitive impairments and visual imagery. Our findings show that 5-HT2AR activation by LSD leads to a hippocampal-prefrontal cortex-mediated breakdown of inhibitory processing, which might subsequently promote the formation of LSD-induced visual imageries. These findings help to better understand the neuropsychopharmacological mechanisms of visual hallucinations in LSD-induced states and neuropsychiatric disorders.

  20. Lsd1 Ablation Triggers Metabolic Reprogramming of Brown Adipose Tissue

    Directory of Open Access Journals (Sweden)

    Delphine Duteil

    2016-10-01

    Full Text Available Previous work indicated that lysine-specific demethylase 1 (Lsd1 can positively regulate the oxidative and thermogenic capacities of white and beige adipocytes. Here we investigate the role of Lsd1 in brown adipose tissue (BAT and find that BAT-selective Lsd1 ablation induces a shift from oxidative to glycolytic metabolism. This shift is associated with downregulation of BAT-specific and upregulation of white adipose tissue (WAT-selective gene expression. This results in the accumulation of di- and triacylglycerides and culminates in a profound whitening of BAT in aged Lsd1-deficient mice. Further studies show that Lsd1 maintains BAT properties via a dual role. It activates BAT-selective gene expression in concert with the transcription factor Nrf1 and represses WAT-selective genes through recruitment of the CoREST complex. In conclusion, our data uncover Lsd1 as a key regulator of gene expression and metabolic function in BAT.

  1. Modelling of increased homocysteine in ischaemic stroke: post-hoc cross-sectional matched case-control analysis in young patients Aumento de homocisteína em acidente vascular cerebral isquêmico: análise post-hoc com casos controles em pacientes jovens

    Directory of Open Access Journals (Sweden)

    Penka A. Atanassova

    2007-03-01

    Full Text Available BACKGROUND & PURPOSE: Hyperhomocysteinaemia has been postulated to participate in pathogenesis of ischaemic stroke (IS. However, especially in young adults, there is possibility of significantly increased IS risk due to increased ‘normal’ homocysteinaemia, i.e., ‘hidden’ (‘pathologically dormant’ prevalence within a healthy, normally-defined range. We performed a post-hoc modelling investigation on plasma total homocysteinaemia (THCY in gender- and age-matched young patients in the acute IS phase. We evaluated relationships between THCY and prevalence of other potential risk factors in 41 patients vs. 41 healthy controls. METHOD: We used clinical methods, instrumental and neuroimmaging procedures, risk factors examination, total plasma homocysteine measurements and other laboratory and statistical modelling techniques. RESULTS: IS patients and healthy controls were similar not only for matching variables, but also for smoking, main vitamin status, serum creatinine and lipid profile. Patients with IS, however, had lower vitamin B6 levels and higher THCY, fibrinogen and triglycerides (TGL. At multivariate stepwise logistic regression only increased THCY and TGL were significantly and independently associated with the risk for stroke (72% model accuracy, p model=0.001. An increase of THCY with 1.0 µmol/L was associated with 22% higher risk of ischaemic stroke [adjusted OR=1.22 (95%CI 1.03?1.44]. In this way, novel lower cut-off value for HCY of 11.58 µmol/L in younger patients has been revealed (ROC AUC= 0.67, 95CI% 0.55-0.78, p=0.009. CONCLUSION: The new THCY cut-off clearly discriminated between absence and presence of IS (sensitivity>63%, specificity>68% irrespectively of age and gender and may be applied to better evaluate and more precisely define, as earlier as possible, the young patients at increased IS risk.OBJETIVO: Hiperhomocisteinemia tem sido postulada como um dos fatores de risco na patogênese do acidente vascular

  2. Dynamic ad hoc networks

    CERN Document Server

    Rashvand, Habib

    2013-01-01

    Motivated by the exciting new application paradigm of using amalgamated technologies of the Internet and wireless, the next generation communication networks (also called 'ubiquitous', 'complex' and 'unstructured' networking) are changing the way we develop and apply our future systems and services at home and on local, national and global scales. Whatever the interconnection - a WiMAX enabled networked mobile vehicle, MEMS or nanotechnology enabled distributed sensor systems, Vehicular Ad hoc Networking (VANET) or Mobile Ad hoc Networking (MANET) - all can be classified under new networking s

  3. Clinical response to eliglustat in treatment-naïve patients with Gaucher disease type 1: Post-hoc comparison to imiglucerase-treated patients enrolled in the International Collaborative Gaucher Group Gaucher Registry

    Directory of Open Access Journals (Sweden)

    Jennifer Ibrahim

    2016-09-01

    Full Text Available Eliglustat is a recently approved oral therapy in the United States and Europe for adults with Gaucher disease type 1 who are CYP2D6 extensive, intermediate, or poor metabolizers (>90% of patients that has been shown to decrease spleen and liver volume and increase hemoglobin concentrations and platelet counts in untreated adults with Gaucher disease type 1 and maintain these parameters in patients previously stabilized on enzyme replacement therapy. In a post-hoc analysis, we compared the results of eliglustat treatment in treatment-naïve patients in two clinical studies with the results of imiglucerase treatment among a cohort of treatment-naïve patients with comparable baseline hematologic and visceral parameters in the International Collaborative Gaucher Group Gaucher Registry. Organ volumes and hematologic parameters improved from baseline in both treatment groups, with a time course and degree of improvement in eliglustat-treated patients similar to imiglucerase-treated patients.

  4. Clinical response to eliglustat in treatment-naïve patients with Gaucher disease type 1: Post-hoc comparison to imiglucerase-treated patients enrolled in the International Collaborative Gaucher Group Gaucher Registry.

    Science.gov (United States)

    Ibrahim, Jennifer; Underhill, Lisa H; Taylor, John S; Angell, Jennifer; Peterschmitt, M Judith

    2016-09-01

    Eliglustat is a recently approved oral therapy in the United States and Europe for adults with Gaucher disease type 1 who are CYP2D6 extensive, intermediate, or poor metabolizers (> 90% of patients) that has been shown to decrease spleen and liver volume and increase hemoglobin concentrations and platelet counts in untreated adults with Gaucher disease type 1 and maintain these parameters in patients previously stabilized on enzyme replacement therapy. In a post-hoc analysis, we compared the results of eliglustat treatment in treatment-naïve patients in two clinical studies with the results of imiglucerase treatment among a cohort of treatment-naïve patients with comparable baseline hematologic and visceral parameters in the International Collaborative Gaucher Group Gaucher Registry. Organ volumes and hematologic parameters improved from baseline in both treatment groups, with a time course and degree of improvement in eliglustat-treated patients similar to imiglucerase-treated patients.

  5. Bardoxolone Methyl Improves Kidney Function in Patients with Chronic Kidney Disease Stage 4 and Type 2 Diabetes: Post-Hoc Analyses from Bardoxolone Methyl Evaluation in Patients with Chronic Kidney Disease and Type 2 Diabetes Study

    Science.gov (United States)

    Chin, Melanie P.; Bakris, George L.; Block, Geoffrey A.; Chertow, Glenn M.; Goldsberry, Angie; Inker, Lesley A.; Heerspink, Hiddo J.L.; O'Grady, Megan; Pergola, Pablo E.; Wanner, Christoph; Warnock, David G.; Meyer, Colin J.

    2018-01-01

    Background Increases in measured inulin clearance, measured creatinine clearance, and estimated glomerular filtration rate (eGFR) have been observed with bardoxolone methyl in 7 studies enrolling approximately 2,600 patients with type 2 diabetes (T2D) and chronic kidney disease (CKD). The largest of these studies was Bardoxolone Methyl Evaluation in Patients with Chronic Kidney Disease and Type 2 Diabetes (BEACON), a multinational, randomized, double-blind, placebo-controlled phase 3 trial which enrolled patients with T2D and CKD stage 4. The BEACON trial was terminated after preliminary analyses showed that patients randomized to bardoxolone methyl experienced significantly higher rates of heart failure events. We performed post-hoc analyses to characterize changes in kidney function induced by bardoxolone methyl. Methods Patients in ­BEACON (n = 2,185) were randomized 1: 1 to receive once-daily bardoxolone methyl (20 mg) or placebo. We compared the effects of bardoxolone methyl and placebo on a post-hoc composite renal endpoint consisting of ≥30% decline from baseline in eGFR, eGFR <15 mL/min/1.73 m2, and end-stage renal disease (ESRD) events (provision of dialysis or kidney transplantation). Results Consistent with prior studies, patients randomized to bardoxolone methyl experienced mean increases in eGFR that were sustained through study week 48. Moreover, increases in eGFR from baseline were sustained 4 weeks after cessation of treatment. Patients randomized to bardoxolone methyl were significantly less likely to experience the composite renal endpoint (hazards ratio 0.48 [95% CI 0.36–0.64]; p < 0.0001). Conclusions Bardoxolone methyl preserves kidney function and may delay the onset of ESRD in patients with T2D and stage 4 CKD. PMID:29402767

  6. Post-hoc analysis of MCI186-17, the extension study to MCI186-16, the confirmatory double-blind, parallel-group, placebo-controlled study of edaravone in amyotrophic lateral sclerosis.

    Science.gov (United States)

    Takahashi, Fumihiro; Takei, Koji; Tsuda, Kikumi; Palumbo, Joseph

    2017-10-01

    In the 24-week double-blind study of edaravone in ALS (MCI186-16), edaravone did not show a statistically significant difference versus placebo for the primary efficacy endpoint. For post-hoc analyses, two subpopulations were identified in which edaravone might be expected to show efficacy: the efficacy-expected subpopulation (EESP), defined by scores of ≥2 points on all 12 items of the ALS Functional Rating Scale-Revised (ALSFRS-R) and a percent predicted forced vital capacity (%FVC) ≥80% at baseline; and the definite/probable EESP 2 years (dpEESP2y) subpopulation which, in addition to EESP criteria, had definite or probable ALS diagnosed by El Escorial revised criteria, and disease duration of ≤2 years. In the 36-week extension study of MCI186-16, a 24-week double-blind comparison followed by 12 weeks of open-label edaravone (MCI186-17; NCT00424463), analyses of ALSFRS-R scores of the edaravone-edaravone group and edaravone-placebo group for the full analysis set (FAS) and EESP, as prospectively defined, were reported in a previous article. Here we additionally report results in patients who met dpEESP2y criteria at the baseline of MCI186-16. In the dpEESP2y, the difference in ALSFRS-R changes from 24 to 48 weeks between the edaravone-edaravone and edaravone-placebo groups was 2.79 (p = 0.0719), which was greater than the differences previously reported for the EESP and the FAS. The pattern of adverse events in the dpEESP2y did not show any additional safety findings to those from the earlier prospective study. In conclusion, this post-hoc analysis suggests a potential effect of edaravone between 24 and 48 weeks in patients meeting dpEESP2y criteria at baseline.

  7. Clinical Outcomes from Androgen Signaling-directed Therapy after Treatment with Abiraterone Acetate and Prednisone in Patients with Metastatic Castration-resistant Prostate Cancer: Post Hoc Analysis of COU-AA-302.

    Science.gov (United States)

    Smith, Matthew R; Saad, Fred; Rathkopf, Dana E; Mulders, Peter F A; de Bono, Johann S; Small, Eric J; Shore, Neal D; Fizazi, Karim; Kheoh, Thian; Li, Jinhui; De Porre, Peter; Todd, Mary B; Yu, Margaret K; Ryan, Charles J

    2017-07-01

    In the COU-AA-302 trial, abiraterone acetate plus prednisone significantly increased overall survival for patients with chemotherapy-naïve metastatic castration-resistant prostate cancer (mCRPC). Limited information exists regarding response to subsequent androgen signaling-directed therapies following abiraterone acetate plus prednisone in patients with mCRPC. We investigated clinical outcomes associated with subsequent abiraterone acetate plus prednisone (55 patients) and enzalutamide (33 patients) in a post hoc analysis of COU-AA-302. Prostate-specific antigen (PSA) response was assessed. Median time to PSA progression was estimated using the Kaplan-Meier method. The PSA response rate (≥50% PSA decline, unconfirmed) was 44% and 67%, respectively. The median time to PSA progression was 3.9 mo (range 2.6-not estimable) for subsequent abiraterone acetate plus prednisone and 2.8 mo (range 1.8-not estimable) for subsequent enzalutamide. The majority of patients (68%) received intervening chemotherapy before subsequent abiraterone acetate plus prednisone or enzalutamide. While acknowledging the limitations of post hoc analyses and high censoring (>75%) in both treatment groups, these results suggest that subsequent therapy with abiraterone acetate plus prednisone or enzalutamide for patients who progressed on abiraterone acetate is associated with limited clinical benefit. This analysis showed limited clinical benefit for subsequent abiraterone acetate plus prednisone or enzalutamide in patients with metastatic castration-resistant prostate cancer following initial treatment with abiraterone acetate plus prednisone. This analysis does not support prioritization of subsequent abiraterone acetate plus prednisone or enzalutamide following initial therapy with abiraterone acetate plus prednisone. Copyright © 2017 European Association of Urology. Published by Elsevier B.V. All rights reserved.

  8. Effects of memantine on cognition in patients with moderate to severe Alzheimer's disease: post-hoc analyses of ADAS-cog and SIB total and single-item scores from six randomized, double-blind, placebo-controlled studies.

    Science.gov (United States)

    Mecocci, Patrizia; Bladström, Anna; Stender, Karina

    2009-05-01

    The post-hoc analyses reported here evaluate the specific effects of memantine treatment on ADAS-cog single-items or SIB subscales for patients with moderate to severe AD. Data from six multicentre, randomised, placebo-controlled, parallel-group, double-blind, 6-month studies were used as the basis for these post-hoc analyses. All patients with a Mini-Mental State Examination (MMSE) score of less than 20 were included. Analyses of patients with moderate AD (MMSE: 10-19), evaluated with the Alzheimer's disease Assessment Scale (ADAS-cog) and analyses of patients with moderate to severe AD (MMSE: 3-14), evaluated using the Severe Impairment Battery (SIB), were performed separately. The mean change from baseline showed a significant benefit of memantine treatment on both the ADAS-cog (p ADAS-cog single-item analyses showed significant benefits of memantine treatment, compared to placebo, for mean change from baseline for commands (p < 0.001), ideational praxis (p < 0.05), orientation (p < 0.01), comprehension (p < 0.05), and remembering test instructions (p < 0.05) for observed cases (OC). The SIB subscale analyses showed significant benefits of memantine, compared to placebo, for mean change from baseline for language (p < 0.05), memory (p < 0.05), orientation (p < 0.01), praxis (p < 0.001), and visuospatial ability (p < 0.01) for OC. Memantine shows significant benefits on overall cognitive abilities as well as on specific key cognitive domains for patients with moderate to severe AD. (c) 2009 John Wiley & Sons, Ltd.

  9. Anti-hypertensive drug treatment of patients with and the metabolic syndrome and obesity: a review of evidence, meta-analysis, post hoc and guidelines publications.

    Science.gov (United States)

    Owen, Jonathan G; Reisin, Efrain

    2015-06-01

    Epidemiological studies have shown an increasing prevalence of obesity and the metabolic syndrome worldwide. Lifestyle modifications that include dietary changes, weight reduction, and exercise are the cornerstones in the treatment of this pathology. However, adherence to this approach often meets with failure in clinical practice; therefore, drug therapy should not be delayed. The ideal pharmacological antihypertensive regimen should target the underlying mechanisms involved in this syndrome, including sympathetic activation, increased renal tubular sodium reabsorption, and overexpression of the renin-angiotensin-aldosterone system by the adipocyte. Few prospective trials have been conducted in the search of the ideal antihypertensive regimen in patients with obesity and the metabolic syndrome. We summarize previously published ad hoc studies, prospective studies, and guideline publications regarding the treatment of hypertension in patients with obesity and the metabolic syndrome. We conclude that the optimal antihypertensive drug therapy in these patients has not been defined. Though caution exists regarding the use of thiazide diuretics due to potential metabolic derangements, there is insufficient data to show worsened cardiovascular or renal outcomes in patients treated with these drugs. In regard to beta blockers, the risk of accelerating conversion to diabetes and worsening of inflammatory mediators described in patients treated with traditional beta blockers appears much less pronounced or absent when using the vasodilating beta blockers. Renin-angiotensin-aldosterone system (RAAS) inhibition with an ACE or an ARB and treatment with calcium channel blockers appears safe and well tolerated in obesity-related hypertension and in patients with metabolic syndrome. Future prospective pharmacological studies in this population are needed.

  10. LSD: Still with Us after All These Years.

    Science.gov (United States)

    Henderson, Leigh A., Ed.; Glass, William J., Ed.

    This volume offers insight for parents, counselors, and educators as to why young people in the 1990s are using LSD--its appeal, the experience, and where kids are getting it. Current studies and anecdotes are woven with recent statistics to create a clear picture of contemporary LSD use. The introduction offers some history and background on the…

  11. LSD Dimensions: Use and Reuse of Linked Statistical Data

    NARCIS (Netherlands)

    Meroño-Peñuela, Albert

    2014-01-01

    RDF Data Cube (QB) has boosted the publication of Linked Statistical Data (LSD) on the Web, making them linkable to other related datasets and concepts following the Linked Data paradigm. In this demo we present LSD Dimensions, a web based application that monitors the usage of dimensions and codes

  12. LSD1 is Required for Hair Cell Regeneration in Zebrafish.

    Science.gov (United States)

    He, Yingzi; Tang, Dongmei; Cai, Chengfu; Chai, Renjie; Li, Huawei

    2016-05-01

    Lysine-specific demethylase 1 (LSD1/KDM1A) plays an important role in complex cellular processes such as differentiation, proliferation, apoptosis, and cell cycle progression. It has recently been demonstrated that during development, downregulation of LSD1 inhibits cell proliferation, modulates the expression of cell cycle regulators, and reduces hair cell formation in the zebrafish lateral line, which suggests that LSD1-mediated epigenetic regulation plays a key role in the development of hair cells. However, the role of LSD1 in hair cell regeneration after hair cell loss remains poorly understood. Here, we demonstrate the effect of LSD1 on hair cell regeneration following neomycin-induced hair cell loss. We show that the LSD1 inhibitor trans-2-phenylcyclopropylamine (2-PCPA) significantly decreases the regeneration of hair cells in zebrafish after neomycin damage. In addition, immunofluorescent staining demonstrates that 2-PCPA administration suppresses supporting cell proliferation and alters cell cycle progression. Finally, in situ hybridization shows that 2-PCPA significantly downregulates the expression of genes related to Wnt/β-catenin and Fgf activation. Altogether, our data suggest that downregulation of LSD1 significantly decreases hair cell regeneration after neomycin-induced hair cell loss through inactivation of the Wnt/β-catenin and Fgf signaling pathways. Thus, LSD1 plays a critical role in hair cell regeneration and might represent a novel biomarker and potential therapeutic approach for the treatment of hearing loss.

  13. LSD1/KDM1 isoform LSD1+8a contributes to neural differentiation in small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Takanobu Jotatsu

    2017-03-01

    Full Text Available Small cell lung cancer (SCLC is an aggressive neuroendocrine tumor characterized by rapid progression. The mechanisms that lead to a shift from initial therapeutic sensitivity to ultimate therapeutic resistance are poorly understood. Although the SCLC genomic landscape led to the discovery of promising agents targeting genetic alterations that were already under investigation, results have been disappointing. Achievements in targeted therapeutics have not been observed for over 30 years. Therefore, the underlying disease biology and novel targets urgently require a better understanding. Epigenetic regulation is deeply involved in the cellular plasticity that could shift tumor cells to the malignant phenotype. We have focused on a histone modifier, LSD1, that is overexpressed in SCLC and is a potent therapeutic target. Interestingly, the LSD1 splice variant LSD1+8a, the expression of which has been reported to be restricted to neural tissue, was detected and was involved in the expression of neuroendocrine marker genes in SCLC cell lines. Cells with high expression of LSD1+8a were resistant to CDDP and LSD1 inhibitor. Moreover, suppression of LSD1+8a inhibited cell proliferation, indicating that LSD1+8a could play a critical role in SCLC. These findings suggest that LSD1+8a should be considered a novel therapeutic target in SCLC.

  14. The association of the effect of lithium in the maintenance treatment of bipolar disorder with lithium plasma levels : a post hoc analysis of a double-blind study comparing switching to lithium or placebo in patients who responded to quetiapine (Trial 144)

    NARCIS (Netherlands)

    Nolen, Willem A.; Weisler, Richard H.

    Nolen WA, Weisler RH. The association of the effect of lithium in the maintenance treatment of bipolar disorder with lithium plasma levels: a post hoc analysis of a double-blind study comparing switching to lithium or placebo in patients who responded to quetiapine (Trial 144). Bipolar Disord 2012:

  15. Characterization of behavioral and endocrine effects of LSD on zebrafish.

    Science.gov (United States)

    Grossman, Leah; Utterback, Eli; Stewart, Adam; Gaikwad, Siddharth; Chung, Kyung Min; Suciu, Christopher; Wong, Keith; Elegante, Marco; Elkhayat, Salem; Tan, Julia; Gilder, Thomas; Wu, Nadine; Dileo, John; Cachat, Jonathan; Kalueff, Allan V

    2010-12-25

    Lysergic acid diethylamide (LSD) is a potent hallucinogenic drug that strongly affects animal and human behavior. Although adult zebrafish (Danio rerio) are emerging as a promising neurobehavioral model, the effects of LSD on zebrafish have not been investigated previously. Several behavioral paradigms (the novel tank, observation cylinder, light-dark box, open field, T-maze, social preference and shoaling tests), as well as modern video-tracking tools and whole-body cortisol assay were used to characterize the effects of acute LSD in zebrafish. While lower doses (5-100 microg/L) did not affect zebrafish behavior, 250 microg/L LSD increased top dwelling and reduced freezing in the novel tank and observation cylinder tests, also affecting spatiotemporal patterns of activity (as assessed by 3D reconstruction of zebrafish traces and ethograms). LSD evoked mild thigmotaxis in the open field test, increased light behavior in the light-dark test, reduced the number of arm entries and freezing in the T-maze and social preference test, without affecting social preference. In contrast, LSD affected zebrafish shoaling (increasing the inter-fish distance in a group), and elevated whole-body cortisol levels. Overall, our findings show sensitivity of zebrafish to LSD action, and support the use of zebrafish models to study hallucinogenic drugs of abuse. Copyright (c) 2010 Elsevier B.V. All rights reserved.

  16. Development and validation of an LC-MS/MS method to quantify lysergic acid diethylamide (LSD), iso-LSD, 2-oxo-3-hydroxy-LSD, and nor-LSD and identify novel metabolites in plasma samples in a controlled clinical trial.

    Science.gov (United States)

    Dolder, Patrick C; Liechti, Matthias E; Rentsch, Katharina M

    2018-02-01

    Lysergic acid diethylamide (LSD) is a widely used recreational drug. The aim of this study was to develop and validate a liquid chromatography tandem mass spectrometry (LC-MS/MS) method for the quantification of LSD, iso-LSD, 2-oxo-3-hydroxy LSD (O-H-LSD), and nor-LSD in plasma samples from 24 healthy subjects after controlled administration of 100 μg LSD in a clinical trial. In addition, metabolites that have been recently described in in vitro studies, including lysergic acid monoethylamide (LAE), lysergic acid ethyl-2-hydroxyethylamide (LEO), 2-oxo-LSD, trioxylated-LSD, and 13/14-hydroxy-LSD, should be identified. Separation of LSD and its metabolites was achieved on a reversed phase chromatography column after turbulent-flow online extraction. For the identification and quantification, a triple-stage quadrupole LC-MS/MS instrument was used. The validation data showed slight matrix effects for LSD, iso-LSD, O-H-LSD, or nor-LSD. Mean intraday and interday accuracy and precision were 105%/4.81% and 105%/4.35% for LSD, 98.7%/5.75% and 99.4%/7.21% for iso-LSD, 106%/4.54% and 99.4%/7.21% for O-H-LSD, and 107%/5.82% and 102%/5.88% for nor-LSD, respectively. The limit of quantification was 0.05 ng/mL for LSD, iso-LSD, and nor-LSD and 0.1 ng/mL for O-H-LSD. The limit of detection was 0.01 ng/mL for all compounds. The method described herein was accurate, precise, and the calibration range within the range of expected plasma concentrations. LSD was quantified in the plasma samples of the 24 subjects of the clinical trial, whereas iso-LSD, O-H-LSD, nor-LSD, LAE, LEO, 13/14-hydroxy-LSD, and 2-oxo-LSD could only sporadically be detected but were too low for quantification. © 2017 Wiley Periodicals, Inc.

  17. Does the effect of one-day simulation team training in obstetric emergencies decline within one year? A post-hoc analysis of a multicentre cluster randomised controlled trial.

    Science.gov (United States)

    van de Ven, J; Fransen, A F; Schuit, E; van Runnard Heimel, P J; Mol, B W; Oei, S G

    2017-09-01

    Does the effect of one-day simulation team training in obstetric emergencies decline within one year? A post-hoc analysis of a multicentre cluster randomised controlled trial. J van de Ven, AF Fransen, E Schuit, PJ van Runnard Heimel, BW Mol, SG Oei OBJECTIVE: To investigate whether the effect of a one-day simulation-based obstetric team training on patient outcome changes over time. Post-hoc analysis of a multicentre, open, randomised controlled trial that evaluated team training in obstetrics (TOSTI study).We studied women with a singleton pregnancy beyond 24 weeks of gestation in 24 obstetric units. Included obstetric units were randomised to either a one-day, multi-professional simulation-based team training focusing on crew resource management in a medical simulation centre (12 units) or to no team training (12 units). We assessed whether outcomes differed between both groups in each of the first four quarters following the team training and compared the effect of team training over quarters. Primary outcome was a composite outcome of low Apgar score, severe postpartum haemorrhage, trauma due to shoulder dystocia, eclampsia and hypoxic-ischemic encephalopathy. During a one year period after the team training the rate of obstetric complications, both on the composite level and the individual component level, did not differ between any of the quarters. For trauma due to shoulder dystocia team training led to a significant decrease in the first quarter (0.06% versus 0.26%, OR 0.19, 95% CI 0.03 to 0.98) but in the subsequent quarters no significant reductions were observed. Similar results were found for invasive treatment for severe postpartum haemorrhage where a significant increase was only seen in the first quarter (0.4% versus 0.03%, OR 19, 95% CI 2.5-147), and not thereafter. The beneficial effect of a one-day, simulation-based, multiprofessional, obstetric team training seems to decline after three months. If team training is further evaluated or

  18. Reversal learning enhanced by lysergic acid diethylamide (LSD)

    Science.gov (United States)

    King, A.R.; Martin, I.L.; Arabella Melville, K.

    1974-01-01

    1 Small doses of lysergic acid diethylamide (LSD) (12.5-50 μg/kg) consistently facilitated learning of a brightness discrimination reversal. 2 2-Bromo-lysergic acid diethylamide (BOL-148), a structural analogue of LSD, with similar peripheral anti-5-hydroxytrypamine activity but no psychotomimetic properties, had no effect in this learning situation at a similar dose (25 μg/kg). 3 LSD, but not BOL-148, caused a small but significant increase in brain 5-hydroxytryptamine levels, but had no effect on the levels of catecholamines in the brain at 25 μg/kg. PMID:4458849

  19. Development and validation of an LC-MS/MS method to quantify lysergic acid diethylamide (LSD), iso-LSD, 2-oxo-3-hydroxy-LSD, and nor-LSD and identify novel metabolites in plasma samples in a controlled clinical trial

    OpenAIRE

    Dolder, Patrick C.; Liechti, Matthias E.; Rentsch, Katharina M.

    2018-01-01

    Lysergic acid diethylamide (LSD) is a widely used recreational drug. The aim of this study was to develop and validate a liquid chromatography tandem mass spectrometry (LC-MS/MS) method for the quantification of LSD, iso-LSD, 2-oxo-3-hydroxy LSD (O-H-LSD), and nor-LSD in plasma samples from 24 healthy subjects after controlled administration of 100 μg LSD in a clinical trial. In addition, metabolites that have been recently described in in vitro studies, including lysergic acid monoethylamide...

  20. Validation of previously reported predictors for radiation-induced hypothyroidism in nasopharyngeal cancer patients treated with intensity-modulated radiation therapy, a post hoc analysis from a Phase III randomized trial.

    Science.gov (United States)

    Lertbutsayanukul, Chawalit; Kitpanit, Sarin; Prayongrat, Anussara; Kannarunimit, Danita; Netsawang, Buntipa; Chakkabat, Chakkapong

    2018-05-10

    This study aimed to validate previously reported dosimetric parameters, including thyroid volume, mean dose, and percentage thyroid volume, receiving at least 40, 45 and 50 Gy (V40, V45 and V50), absolute thyroid volume spared (VS) from 45, 50 and 60 Gy (VS45, VS50 and VS60), and clinical factors affecting the development of radiation-induced hypothyroidism (RHT). A post hoc analysis was performed in 178 euthyroid nasopharyngeal cancer (NPC) patients from a Phase III study comparing sequential versus simultaneous-integrated boost intensity-modulated radiation therapy. RHT was determined by increased thyroid-stimulating hormone (TSH) with or without reduced free thyroxin, regardless of symptoms. The median follow-up time was 42.5 months. The 1-, 2- and 3-year freedom from RHT rates were 78.4%, 56.4% and 43.4%, respectively. The median latency period was 21 months. The thyroid gland received a median mean dose of 53.5 Gy. Female gender, smaller thyroid volume, higher pretreatment TSH level (≥1.55 μU/ml) and VS60 treatment planning.

  1. Effect of aripiprazole 2 to 15 mg/d on health-related quality of life in the treatment of irritability associated with autistic disorder in children: a post hoc analysis of two controlled trials.

    Science.gov (United States)

    Varni, James W; Handen, Benjamin L; Corey-Lisle, Patricia K; Guo, Zhenchao; Manos, George; Ammerman, Diane K; Marcus, Ronald N; Owen, Randall; McQuade, Robert D; Carson, William H; Mathew, Suja; Mankoski, Raymond

    2012-04-01

    There are limited published data on the impact of treatment on the health-related quality of life (HRQOL) in individuals with autistic disorder. The aim of this study was to evaluate the impact of aripiprazole on HRQOL in the treatment of irritability in pediatric patients (aged 6-17 years) with autistic disorder. This post hoc analysis assessed data from two 8-week, double-blind, randomized, placebo-controlled studies that compared the efficacy of aripiprazole (fixed-dose study, 5, 10, and 15 mg/d; flexible-dose study, 2-15 mg/d) with placebo in the treatment of irritability associated with autistic disorder. HRQOL was assessed at baseline and week 8 using 3 Pediatric Quality of Life Inventory (PedsQL™) scales. Clinically relevant improvement in HRQOL was determined using an accepted distribution-based criterion-1 standard error of measurement. In total, 316 patients were randomly assigned to receive treatment with aripiprazole (fixed-dose study, 166; flexible-dose study, 47) or placebo (fixed-dose study, 52; flexible-dose study, 51). Aripiprazole was associated with significantly greater improvement than placebo in PedsQL combined-scales total score (difference, 7.8; 95% CI, 3.8-11.8; P autistic disorder. Copyright © 2012 Elsevier HS Journals, Inc. All rights reserved.

  2. Physicians Experience with and Expectations of the Safety and Tolerability of WHO-Step III Opioids for Chronic (Low Back Pain: Post Hoc Analysis of Data from a German Cross-Sectional Physician Survey

    Directory of Open Access Journals (Sweden)

    Michael A. Ueberall

    2015-01-01

    Full Text Available Objective. To describe physicians’ daily life experience with WHO-step III opioids in the treatment of chronic (low back pain (CLBP. Methods. Post hoc analysis of data from a cross-sectional online survey with 4.283 Germany physicians. Results. With a reported median use in 17% of affected patients, WHO-step III opioids play a minor role in treatment of CLBP in daily practice associated with a broad spectrum of positive and negative effects. If prescribed, potent opioids were reported to show clinically relevant effects (such as ≥50% pain relief in approximately 3 of 4 patients (median 72%. Analgesic effects reported are frequently related with adverse events (AEs. Only 20% of patients were reported to remain free of any AE. Most frequently reported AE was constipation (50%, also graded highest for AE-related daily life restrictions (median 46%. Specific AE countermeasures were reported to be necessary in approximately half of patients (median 45%; nevertheless AE-related premature discontinuation rates reported were high (median 22%. Fentanyl/morphine were the most/least prevalently prescribed potent opioids mentioned (median 20 versus 8%. Conclusion. Overall, use of WHO-step III opioids for CLBP is low. AEs, especially constipation, are commonly reported and interfere significantly with analgesic effects in daily practice. Nevertheless, beneficial effects outweigh related AEs in most patients with CLBP.

  3. Morning pulse pressure is associated more strongly with elevated albuminuria than systolic blood pressure in patients with type 2 diabetes mellitus: post hoc analysis of a cross-sectional multicenter study.

    Science.gov (United States)

    Ushigome, Emi; Fukui, Michiaki; Hamaguchi, Masahide; Matsumoto, Shinobu; Mineoka, Yusuke; Nakanishi, Naoko; Senmaru, Takafumi; Yamazaki, Masahiro; Hasegawa, Goji; Nakamura, Naoto

    2013-09-01

    Recently, focus has been directed toward pulse pressure as a potentially independent risk factor for micro- and macrovascular disease. This study was designed to examine the relationship between pulse pressure taken at home and elevated albuminuria in patients with type 2 diabetes. This study is a post hoc analysis of a cross-sectional multicenter study. Home blood pressure measurements were performed for 14 consecutive days in 858 patients with type 2 diabetes. We investigated the relationship between systolic blood pressure or pulse pressure in the morning or in the evening and urinary albumin excretion using univariate and multivariate analyses. Furthermore, we measured area under the receiver-operating characteristic curve (AUC) to compare the ability to identify elevated albuminuria, defined as urinary albumin excretion equal to or more than 30 mg/g creatinine, of systolic blood pressure or pulse pressure. Morning systolic blood pressure (β=0.339, Ppressure (β=0.378, PAUC for elevated albuminuria in morning systolic blood pressure and morning pulse pressure were 0.668 (0.632-0.705; PAUC of morning pulse pressure was significantly greater than that of morning systolic blood pressure (P=0.040). Our findings implicate that morning pulse pressure is associated with elevated albuminuria in patients with type 2 diabetes, which suggests that lowering morning pulse pressure could prevent the development and progression of diabetic nephropathy. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  4. Analysis of psilocin, bufotenine and LSD in hair.

    Science.gov (United States)

    Martin, Rafaela; Schürenkamp, Jennifer; Gasse, Angela; Pfeiffer, Heidi; Köhler, Helga

    2015-03-01

    A method for the simultaneous extraction of the hallucinogens psilocin, bufotenine, lysergic acid diethylamide (LSD) as well as iso-LSD, nor-LSD and O-H-LSD from hair with hydrochloride acid and methanol is presented. Clean-up of the hair extracts is performed with solid phase extraction using a mixed-mode cation exchanger. Extracts are measured with liquid chromatography coupled with electrospray tandem mass spectrometry. The method was successfully validated according to the guidelines of the 'Society of Toxicological and Forensic Chemistry' (GTFCh). To obtain reference material hair was soaked in a solution of the analytes in dimethyl sulfoxide/methanol to allow incorporation into the hair. These fortified hair samples were used for method development and can be employed as quality controls. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  5. Does rectal indomethacin eliminate the need for prophylactic pancreatic stent placement in patients undergoing high-risk ERCP? Post hoc efficacy and cost-benefit analyses using prospective clinical trial data.

    Science.gov (United States)

    Elmunzer, B Joseph; Higgins, Peter D R; Saini, Sameer D; Scheiman, James M; Parker, Robert A; Chak, Amitabh; Romagnuolo, Joseph; Mosler, Patrick; Hayward, Rodney A; Elta, Grace H; Korsnes, Sheryl J; Schmidt, Suzette E; Sherman, Stuart; Lehman, Glen A; Fogel, Evan L

    2013-03-01

    A recent large-scale randomized controlled trial (RCT) demonstrated that rectal indomethacin administration is effective in addition to pancreatic stent placement (PSP) for preventing post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) in high-risk cases. We performed a post hoc analysis of this RCT to explore whether rectal indomethacin can replace PSP in the prevention of PEP and to estimate the potential cost savings of such an approach. We retrospectively classified RCT subjects into four prevention groups: (1) no prophylaxis, (2) PSP alone, (3) rectal indomethacin alone, and (4) the combination of PSP and indomethacin. Multivariable logistic regression was used to adjust for imbalances in the prevalence of risk factors for PEP between the groups. Based on these adjusted PEP rates, we conducted an economic analysis comparing the costs associated with PEP prevention strategies employing rectal indomethacin alone, PSP alone, or the combination of both. After adjusting for risk using two different logistic regression models, rectal indomethacin alone appeared to be more effective for preventing PEP than no prophylaxis, PSP alone, and the combination of indomethacin and PSP. Economic analysis revealed that indomethacin alone was a cost-saving strategy in 96% of Monte Carlo trials. A prevention strategy employing rectal indomethacin alone could save approximately $150 million annually in the United States compared with a strategy of PSP alone, and $85 million compared with a strategy of indomethacin and PSP. This hypothesis-generating study suggests that prophylactic rectal indomethacin could replace PSP in patients undergoing high-risk ERCP, potentially improving clinical outcomes and reducing healthcare costs. A RCT comparing rectal indomethacin alone vs. indomethacin plus PSP is needed.

  6. Crystal Structure of an LSD-Bound Human Serotonin Receptor

    Energy Technology Data Exchange (ETDEWEB)

    Wacker, Daniel; Wang, Sheng; McCorvy, John D.; Betz, Robin M.; Venkatakrishnan, A.J.; Levit, Anat; Lansu, Katherine; Schools, Zachary L.; Che, Tao; Nichols, David E.; Shoichet, Brian K.; Dror, Ron O.; Roth, Bryan L. (UNCSM); (UNC); (Stanford); (Stanford-MED); (UCSF)

    2017-01-01

    The prototypical hallucinogen LSD acts via serotonin receptors, and here we describe the crystal structure of LSD in complex with the human serotonin receptor 5-HT2B. The complex reveals conformational rearrangements to accommodate LSD, providing a structural explanation for the conformational selectivity of LSD’s key diethylamide moiety. LSD dissociates exceptionally slow from both 5-HT2BR and 5-HT2AR—a major target for its psychoactivity. Molecular dynamics (MD) simulations suggest that LSD’s slow binding kinetics may be due to a “lid” formed by extracellular loop 2 (EL2) at the entrance to the binding pocket. A mutation predicted to increase the mobility of this lid greatly accelerates LSD’s binding kinetics and selectively dampens LSD-mediated β-arrestin2 recruitment. This study thus reveals an unexpected binding mode of LSD; illuminates key features of its kinetics, stereochemistry, and signaling; and provides a molecular explanation for LSD’s actions at human serotonin receptors.

  7. Transrepressive function of TLX requires the histone demethylase LSD1.

    Science.gov (United States)

    Yokoyama, Atsushi; Takezawa, Shinichiro; Schüle, Roland; Kitagawa, Hirochika; Kato, Shigeaki

    2008-06-01

    TLX is an orphan nuclear receptor (also called NR2E1) that regulates the expression of target genes by functioning as a constitutive transrepressor. The physiological significance of TLX in the cytodifferentiation of neural cells in the brain is known. However, the corepressors supporting the transrepressive function of TLX have yet to be identified. In this report, Y79 retinoblastoma cells were subjected to biochemical techniques to purify proteins that interact with TLX, and we identified LSD1 (also called KDM1), which appears to form a complex with CoREST and histone deacetylase 1. LSD1 interacted with TLX directly through its SWIRM and amine oxidase domains. LSD1 potentiated the transrepressive function of TLX through its histone demethylase activity as determined by a luciferase assay using a genomically integrated reporter gene. LSD1 and TLX were recruited to a TLX-binding site in the PTEN gene promoter, accompanied by the demethylation of H3K4me2 and deacetylation of H3. Knockdown of either TLX or LSD1 derepressed expression of the endogenous PTEN gene and inhibited cell proliferation of Y79 cells. Thus, the present study suggests that LSD1 is a prime corepressor for TLX.

  8. Masses and fission barriers of nuclei in the LSD model

    Energy Technology Data Exchange (ETDEWEB)

    Pomorski, Krzysztof

    2009-07-01

    Recently developed Lublin-Strasbourg Drop (LSD) model together with the microscopic corrections taken r is very successful in describing many features of nuclei. In addition to the classical liquid drop model the LSD contains the curvature term proportional to the A{sup 1/3}. The r.m.s. deviation of the LSD binding energies of 2766 isotopes with Z,N>7 from the experimental ones is 0.698 MeV only. It turns out that the LSD model gives also a satisfactory prediction of the fission barrier heights. In addition, it was found in that taking into account the deformation dependence of the congruence energy proposed by Myers and Swiatecki significantly approaches the LSD-model barrier-heights to the experimental data in the case of light isotopes while the fission barriers for heavy nuclei remain nearly unchanged and agree well with experiment. It was also shown in that the saddle point masses of transactinides from {sup 232}Th to {sup 250}Cf evaluated using the LSD differ by less than 0.67 MeV from the experimental data.

  9. Simultaneous determination of LSD and 2-oxo-3-hydroxy LSD in hair and urine by LC-MS/MS and its application to forensic cases.

    Science.gov (United States)

    Jang, Moonhee; Kim, Jihyun; Han, Inhoi; Yang, Wonkyung

    2015-11-10

    Lysergic acid diethylamide (LSD) is administered in low dosages, which makes its detection in biological matrices a major challenge in forensic toxicology. In this study, two sensitive and reliable methods based on liquid chromatography-tandem mass spectrometry (LC-MS/MS) were established and validated for the simultaneous determination of LSD and its metabolite, 2-oxo-3-hydroxy-LSD (O-H-LSD), in hair and urine. Target analytes in hair were extracted using methanol at 38°C for 15h and analyzed by LC-MS/MS. For urine sample preparation, liquid-liquid extraction was performed. Limits of detection (LODs) in hair were 0.25pg/mg for LSD and 0.5pg/mg for O-H-LSD. In urine, LODs were 0.01 and 0.025ng/ml for LSD and O-H-LSD, respectively. Method validation results showed good linearity and acceptable precision and accuracy. The developed methods were applied to authentic specimens from two legal cases of LSD ingestion, and allowed identification and quantification of LSD and O-H-LSD in the specimens. In the two cases, LSD concentrations in hair were 1.27 and 0.95pg/mg; O-H-LSD was detected in one case, but its concentration was below the limit of quantification. In urine samples collected from the two suspects 8 and 3h after ingestion, LSD concentrations were 0.48 and 2.70ng/ml, respectively, while O-H-LSD concentrations were 4.19 and 25.2ng/ml, respectively. These methods can be used for documenting LSD intake in clinical and forensic settings. Copyright © 2015 Elsevier B.V. All rights reserved.

  10. Wireless Ad Hoc Networks

    Directory of Open Access Journals (Sweden)

    Hong-Chuan Yang

    2007-01-01

    Full Text Available We study the energy-efficient configuration of multihop paths with automatic repeat request (ARQ mechanism in wireless ad hoc networks. We adopt a cross-layer design approach and take both the quality of each radio hop and the battery capacity of each transmitting node into consideration. Under certain constraints on the maximum tolerable transmission delay and the required packet delivery ratio, we solve optimization problems to jointly schedule the transmitting power of each transmitting node and the retransmission limit over each hop. Numerical results demonstrate that the path configuration methods can either significantly reduce the average energy consumption per packet delivery or considerably extend the average lifetime of the multihop route.

  11. Post hoc analyses of the impact of previous medication on the efficacy of lisdexamfetamine dimesylate in the treatment of attention-deficit/hyperactivity disorder in a randomized, controlled trial

    Directory of Open Access Journals (Sweden)

    Coghill DR

    2014-10-01

    Full Text Available David R Coghill,1 Tobias Banaschewski,2 Michel Lecendreux,3 César Soutullo,4 Alessandro Zuddas,5 Ben Adeyi,6 Shaw Sorooshian7 1Division of Neuroscience, University of Dundee, Dundee, UK; 2Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany; 3Paediatric Sleep Centre and National Reference Centre for Orphan Diseases: Narcolepsy, Idiopathic Hypersomnia and Kleine-Levin Syndrome, Robert-Debré University Hospital, Paris, France; 4Child and Adolescent Psychiatry Unit, Department of Psychiatry and Medical Psychology, University of Navarra Clinic, Pamplona, Spain; 5Department of Biomedical Sciences, Section of Neuroscience and Clinical Pharmacology, University of Cagliari, Cagliari, Italy; 6Shire, Wayne, PA, USA; 7Shire, Eysins, Switzerland Background: Following the approval of lisdexamfetamine dimesylate (LDX in several European countries for the treatment of attention-deficit/hyperactivity disorder (ADHD in children and adolescents with an inadequate response to methylphenidate (MPH treatment, the aim of the present analysis was to establish the response to LDX in subgroups of patients with different ADHD medication histories. Methods: This was a post hoc subgroup analysis of data from a 7-week, European, double-blind, dose-optimized, Phase III study. Patients aged 6–17 years were randomized 1:1:1 to LDX, placebo, or osmotic-release oral system methylphenidate (OROS-MPH. OROS-MPH was included as a reference arm rather than as a direct comparator. Efficacy was assessed in patients categorized according to their ADHD medication history using the ADHD Rating Scale IV and Clinical Global Impressions-Improvement (CGI-I scores. Results: The difference between active drug and placebo in least-squares mean change from baseline to endpoint in ADHD Rating Scale IV total score (95% confidence interval was similar between the overall study population (n

  12. Dark Classics in Chemical Neuroscience: Lysergic Acid Diethylamide (LSD).

    Science.gov (United States)

    Nichols, David E

    2018-03-01

    Lysergic acid diethylamide (LSD) is one of the most potent psychoactive agents known, producing dramatic alterations of consciousness after submilligram (≥20 μg) oral doses. Following the accidental discovery of its potent psychoactive effects in 1943, it was supplied by Sandoz Laboratories as an experimental drug that might be useful as an adjunct for psychotherapy, or to give psychiatrists insight into the mental processes in their patients. The finding of serotonin in the mammalian brain in 1953, and its structural resemblance to LSD, quickly led to ideas that serotonin in the brain might be involved in mental disorders, initiating rapid research interest in the neurochemistry of serotonin. LSD proved to be physiologically very safe and nonaddictive, with a very low incidence of adverse events when used in controlled experiments. Widely hailed by psychiatry as a breakthrough in the 1950s and early 1960s, clinical research with LSD ended by about 1970, when it was formally placed into Schedule 1 of the Controlled Substances Act of 1970 following its growing popularity as a recreational drug. Within the past 5 years, clinical research with LSD has begun in Europe, but there has been none in the United States. LSD is proving to be a powerful tool to help understand brain dynamics when combined with modern brain imaging methods. It remains to be seen whether therapeutic value for LSD can be confirmed in controlled clinical trials, but promising results have been obtained in small pilot trials of depression, anxiety, and addictions using psilocybin, a related psychedelic molecule.

  13. Effects of non-invasive vagus nerve stimulation on attack frequency over time and expanded response rates in patients with chronic cluster headache: a post hoc analysis of the randomised, controlled PREVA study.

    Science.gov (United States)

    Gaul, Charly; Magis, Delphine; Liebler, Eric; Straube, Andreas

    2017-12-01

    In the PREVention and Acute treatment of chronic cluster headache (PREVA) study, attack frequency reductions from baseline were significantly more pronounced with non-invasive vagus nerve stimulation plus standard of care (nVNS + SoC) than with SoC alone. Given the intensely painful and frequent nature of chronic cluster headache attacks, additional patient-centric outcomes, including the time to and level of therapeutic response, were evaluated in a post hoc analysis of the PREVA study. After a 2-week baseline phase, 97 patients with chronic cluster headache entered a 4-week randomised phase to receive nVNS + SoC (n = 48) or SoC alone (n = 49). All 92 patients who continued into a 4-week extension phase received nVNS + SoC. Compared with SoC alone, nVNS + SoC led to a significantly lower mean weekly attack frequency by week 2 of the randomised phase; the attack frequency remained significantly lower in the nVNS + SoC group through week 3 of the extension phase (P cluster headache attack frequency within 2 weeks after its addition to SoC and was associated with significantly higher ≥25%, ≥50%, and ≥75% response rates than SoC alone. The rapid decrease in weekly attack frequency justifies a 4-week trial period to identify responders to nVNS, with a high degree of confidence, among patients with chronic cluster headache.

  14. Predictive value of {sup 18}F-FDG PET/CT in adults with T-cell lymphoblastic lymphoma. Post hoc analysis of results from the GRAALL-LYSA LLO3 trial

    Energy Technology Data Exchange (ETDEWEB)

    Becker, Stephanie; Vera, Pierre [Centre Henri-Becquerel, Department of Nuclear Medicine, Rouen (France); University of Rouen, QuantIF-LITIS (EA [Equipe d' Accueil] 4108), Faculty of Medicine, Rouen (France); Vermeulin, Thomas [Rouen University Hospital, Department of Biostatistics, Rouen (France); Cottereau, Anne-Segolene [Hopital Tenon, AP-HP, Department of Nuclear Medicine, Paris (France); Boissel, Nicolas [Universite Paris Diderot, Department of Hematology, Hopital Saint-Louis, AP-HP, Paris (France); Lepretre, Stephane [Centre Henri Becquerel and Normandie Univ UNIROUEN, Inserm U1245 and Department of Hematology, Rouen (France)

    2017-11-15

    We examined whether FDG PET can be used to predict outcome in patients with lymphoblastic lymphoma (LL). This was a retrospective post hoc analysis of data from the GRAAL-LYSA LL03 trial, in which the treatment of LL using an adapted paediatric-like acute lymphoblastic leukaemia protocol was evaluated. PET data acquired at baseline and after induction were analysed. Maximum standardized uptake values (SUV{sub max}), total metabolic tumour volume and total lesion glycolysis were measured at baseline. The relative changes in SUV{sub max} from baseline (ΔSUV{sub max}) and the Deauville score were determined after induction. The population analysed comprised 36 patients with T-type LL. SUV{sub max} using a cut-off value of ≤8.76 vs. >8.76 was predictive of 3-year event-free survival (31.6% vs. 80.4%; p = 0.013) and overall survival (35.0% vs. 83.7%; p = 0.028). ΔSUV{sub max} using a cut-off value of ≤80% vs. >80% tended also to be predictive of 3-year event-free survival (40.0% vs. 76.0%; p = 0.054) and overall survival (49.2% vs. 85.6%; p = 0.085). Total metabolic tumour volume, baseline total lesion glycolysis and response according to the Deauville score were not predictive of outcome. A low initial SUV{sub max} was predictive of worse outcomes in our series of patients with T-type LL. Although relatively few patients were included, the study also suggested that ΔSUV{sub max} may be useful for predicting therapeutic efficacy. (orig.)

  15. The Effect of Sitagliptin on the Regression of Carotid Intima-Media Thickening in Patients with Type 2 Diabetes Mellitus: A Post Hoc Analysis of the Sitagliptin Preventive Study of Intima-Media Thickness Evaluation

    Directory of Open Access Journals (Sweden)

    Tomoya Mita

    2017-01-01

    Full Text Available Background. The effect of dipeptidyl peptidase-4 (DPP-4 inhibitors on the regression of carotid IMT remains largely unknown. The present study aimed to clarify whether sitagliptin, DPP-4 inhibitor, could regress carotid intima-media thickness (IMT in insulin-treated patients with type 2 diabetes mellitus (T2DM. Methods. This is an exploratory analysis of a randomized trial in which we investigated the effect of sitagliptin on the progression of carotid IMT in insulin-treated patients with T2DM. Here, we compared the efficacy of sitagliptin treatment on the number of patients who showed regression of carotid IMT of ≥0.10 mm in a post hoc analysis. Results. The percentages of the number of the patients who showed regression of mean-IMT-CCA (28.9% in the sitagliptin group versus 16.4% in the conventional group, P = 0.022 and left max-IMT-CCA (43.0% in the sitagliptin group versus 26.2% in the conventional group, P = 0.007, but not right max-IMT-CCA, were higher in the sitagliptin treatment group compared with those in the non-DPP-4 inhibitor treatment group. In multiple logistic regression analysis, sitagliptin treatment significantly achieved higher target attainment of mean-IMT-CCA ≥0.10 mm and right and left max-IMT-CCA ≥0.10 mm compared to conventional treatment. Conclusions. Our data suggested that DPP-4 inhibitors were associated with the regression of carotid atherosclerosis in insulin-treated T2DM patients. This study has been registered with the University Hospital Medical Information Network Clinical Trials Registry (UMIN000007396.

  16. Influence of complete administration of adjuvant chemotherapy cycles on overall and disease-free survival in locally advanced rectal cancer: post hoc analysis of a randomized, multicenter, non-inferiority, phase 3 trial.

    Science.gov (United States)

    Sandra-Petrescu, Flavius; Herrle, Florian; Burkholder, Iris; Kienle, Peter; Hofheinz, Ralf-Dieter

    2018-04-03

    A randomized trial demonstrated that capecitabine is at least as effective as fluorouracil in the adjuvant treatment of patients with locally advanced rectal cancer. However, not all patients receive all planned cycles of chemotherapy. Therefore it is of interest how complete or partial administration of chemotherapy influences oncological outcome. A post hoc analysis of a trial with 401 randomized patients, nine being excluded because of missing data, was performed. 392 patients (197 - capecitabine, 195 - fluorouracil) could be analyzed regarding the number of administered adjuvant chemotherapy cycles. In the subgroup of 361 patients with an overall survival of at least six months, five-year overall and disease-free survival were analyzed in respect to completion (complete vs. incomplete) of chemotherapy cycles. Survival rates and curves were calculated and compared using the log-rank test. The effect of completion of chemotherapy was adjusted for relevant confounding factors. Two hundred fifty-one (64.0%) of analyzed patients received all postoperative scheduled cycles. Five-year overall survival was significantly better in these patients compared to the incomplete group (76.0 vs. 60.6%, p cycles. Five-year overall survival was also significantly better than in the incomplete group (76.0 vs. 66.4%, p = 0.0073). Five-year disease free survival was numerically better (64.9 vs. 58.7%, p = 0.0646; HR [not all cycles vs. all cycles] = 1.42 95% CI: [0.98, 2.07]). Cox regression models show a non-significant better OS (p = 0.061) and DFS (p = 0.083), if chemotherapy cycles were administered completely. Complete administration of chemotherapy cycles was associated with improved five-year overall and disease-free survival in patients with locally advanced rectal cancer.

  17. Effects of vilazodone on suicidal ideation and behavior in adults with major depressive disorder or generalized anxiety disorder: post-hoc analysis of randomized, double-blind, placebo-controlled trials.

    Science.gov (United States)

    Thase, Michael E; Edwards, John; Durgam, Suresh; Chen, Changzheng; Chang, Cheng-Tao; Mathews, Maju; Gommoll, Carl P

    2017-09-01

    Treatment-emergent suicidal ideation and behavior are ongoing concerns with antidepressants. Vilazodone, currently approved for the treatment of major depressive disorder (MDD) in adults, has also been evaluated in generalized anxiety disorder (GAD). Post-hoc analyses of vilazodone trials were carried out to examine its effects on suicidal ideation and behavior in adults with MDD or GAD. Data were pooled from vilazodone trials in MDD (four studies) and GAD (three studies). The incidence of suicide-related events was analyzed on the basis of treatment-emergent adverse event reporting and Columbia-Suicide Severity Rating Scale (C-SSRS) monitoring. Treatment-emergent suicidal ideation was analyzed on the basis of a C-SSRS category shift from no suicidal ideation/behavior (C-SSRS=0) at baseline to suicide ideation (C-SSRS=1-5) during treatment. In pooled safety populations (MDD, n=2233; GAD, n=1475), suicide-related treatment-emergent adverse events occurred in less than 1% of vilazodone-treated and placebo-treated patients. Incidences of C-SSRS suicidal ideation were as follows: MDD (vilazodone=19.9%, placebo=24.7%); GAD (vilazodone=7.7%, placebo=9.4%). Shifts from no suicidal ideation/behavior at baseline to suicidal ideation during treatment were as follows: MDD (vilazodone=9.4%, placebo=10.3%); GAD (vilazodone=4.4%, placebo=6.1%). Data from placebo-controlled studies indicate little or no risk of treatment-emergent suicidal ideation or behavior with vilazodone in adults with MDD or GAD. Nevertheless, all patients should be monitored for suicidal thoughts and behaviors during antidepressant treatment.

  18. The paradoxical psychological effects of lysergic acid diethylamide (LSD).

    Science.gov (United States)

    Carhart-Harris, R L; Kaelen, M; Bolstridge, M; Williams, T M; Williams, L T; Underwood, R; Feilding, A; Nutt, D J

    2016-05-01

    Lysergic acid diethylamide (LSD) is a potent serotonergic hallucinogen or psychedelic that modulates consciousness in a marked and novel way. This study sought to examine the acute and mid-term psychological effects of LSD in a controlled study. A total of 20 healthy volunteers participated in this within-subjects study. Participants received LSD (75 µg, intravenously) on one occasion and placebo (saline, intravenously) on another, in a balanced order, with at least 2 weeks separating sessions. Acute subjective effects were measured using the Altered States of Consciousness questionnaire and the Psychotomimetic States Inventory (PSI). A measure of optimism (the Revised Life Orientation Test), the Revised NEO Personality Inventory, and the Peter's Delusions Inventory were issued at baseline and 2 weeks after each session. LSD produced robust psychological effects; including heightened mood but also high scores on the PSI, an index of psychosis-like symptoms. Increased optimism and trait openness were observed 2 weeks after LSD (and not placebo) and there were no changes in delusional thinking. The present findings reinforce the view that psychedelics elicit psychosis-like symptoms acutely yet improve psychological wellbeing in the mid to long term. It is proposed that acute alterations in mood are secondary to a more fundamental modulation in the quality of cognition, and that increased cognitive flexibility subsequent to serotonin 2A receptor (5-HT2AR) stimulation promotes emotional lability during intoxication and leaves a residue of 'loosened cognition' in the mid to long term that is conducive to improved psychological wellbeing.

  19. Altered network hub connectivity after acute LSD administration

    Directory of Open Access Journals (Sweden)

    Felix Müller

    Full Text Available LSD is an ambiguous substance, said to mimic psychosis and to improve mental health in people suffering from anxiety and depression. Little is known about the neuronal correlates of altered states of consciousness induced by this substance. Limited previous studies indicated profound changes in functional connectivity of resting state networks after the administration of LSD. The current investigation attempts to replicate and extend those findings in an independent sample. In a double-blind, randomized, cross-over study, 100 μg LSD and placebo were orally administered to 20 healthy participants. Resting state brain activity was assessed by functional magnetic resonance imaging. Within-network and between-network connectivity measures of ten established resting state networks were compared between drug conditions. Complementary analysis were conducted using resting state networks as sources in seed-to-voxel analyses. Acute LSD administration significantly decreased functional connectivity within visual, sensorimotor and auditory networks and the default mode network. While between-network connectivity was widely increased and all investigated networks were affected to some extent, seed-to-voxel analyses consistently indicated increased connectivity between networks and subcortical (thalamus, striatum and cortical (precuneus, anterior cingulate cortex hub structures. These latter observations are consistent with findings on the importance of hubs in psychopathological states, especially in psychosis, and could underlay therapeutic effects of hallucinogens as proposed by a recent model. Keywords: LSD, fMRI, Functional connectivity, Networks, Hubs

  20. Immunoassay screening of lysergic acid diethylamide (LSD) and its confirmation by HPLC and fluorescence detection following LSD ImmunElute extraction.

    Science.gov (United States)

    Grobosch, T; Lemm-Ahlers, U

    2002-04-01

    In all, 3872 urine specimens were screened for lysergic acid diethylamide (LSD) using the CEDIA DAU LSD assay. Forty-eight samples, mainly from psychiatric patients or drug abusers, were found to be LSD positive, but only 13 (27%) of these could be confirmed by high-performance liquid chromatography with fluorescence detection (HPLC-FLD) following immunoaffinity extraction (IAE). Additional analysis for LSD using the DPC Coat-a-Count RIA was performed to compare the two immunoassay screening methods. Complete agreement between the DPC RIA assay and HPLC-FLD results was observed at concentrations below a cutoff concentration of 500 pg/mL. Samples that were LSD positive in the CEDIA DAU assay but not confirmed by HPLC-FLD were also investigated for interfering compounds using REMEDI HS drug-profiling system. REMEDI HS analysis identified 15 compounds (parent drugs and metabolites) that are believed to cross-react in the CEDIA DAU LSD assay: ambroxol, prilocaine, pipamperone, diphenhydramine, metoclopramide, amitriptyline, doxepine, atracurium, bupivacaine, doxylamine, lidocaine, mepivacaine, promethazine, ranitidine, and tramadole. The IAE/HPLC-FLD combination is rapid, easy to perform and reliable. It can reduce costs when standard, rather than more advanced, HPLC equipment is used, especially for labs that perform analyses for LSD infrequently. The chromatographic analysis of LSD, nor-LSD, and iso-LSD is not influenced by any of the tested cross-reacting compounds even at a concentration of 100 ng/mL.

  1. Health-related quality of life effects of enzalutamide in patients with metastatic castration-resistant prostate cancer: an in-depth post hoc analysis of EQ-5D data from the PREVAIL trial.

    Science.gov (United States)

    Devlin, Nancy; Herdman, Michael; Pavesi, Marco; Phung, De; Naidoo, Shevani; Beer, Tomasz M; Tombal, Bertrand; Loriot, Yohann; Ivanescu, Cristina; Parli, Teresa; Balk, Mark; Holmstrom, Stefan

    2017-06-23

    The effect of enzalutamide on health-related quality of life (HRQoL) in the PREVAIL trial in chemotherapy-naïve men with metastatic castration-resistant prostate cancer was analyzed using the generic EQ-5D instrument. Patients received oral enzalutamide 160 mg/day (n = 872) or placebo (n = 845). EQ-5D index and EQ-5D visual analogue scale (EQ-5D VAS) scores were evaluated at baseline, week 13, and every 12 weeks until week 61 due to sample size reduction thereafter. Changes on individual dimensions were assessed, and Paretian Classification of Health Change (PCHC) and time-to-event analyses were conducted. With enzalutamide, EQ-5D index and EQ-5D VAS scores declined more slowly versus placebo and time to diverge from full health was prolonged. Average decline in EQ-5D index (-0.042 vs. -0.070; P < .0001) and EQ-5D VAS (-1.3 vs. -4.4; P < .0001) was significantly smaller with enzalutamide. There were significant (P < .05) between-group differences favoring enzalutamide in Pain/Discomfort to week 37, Anxiety/Depression at week 13, and Usual Activities at week 25, but no significant differences for Mobility and Self-care. The PCHC analysis showed more enzalutamide patients reporting improvement than placebo patients at weeks 13, 25, and 49 (all P < .05) and week 37 (P = .0512). Enzalutamide was superior (P ≤ .0003) to placebo for time to diverge from full health and time to first deterioration on Pain/Discomfort and Anxiety/Depression dimensions. This in-depth post hoc analysis showed that enzalutamide delayed HRQoL deterioration and had beneficial effects on several HRQoL domains, including Pain/Discomfort and the proportion of patients in full health, compared with placebo, and may help to support future analyses of this type. NCT01212991.

  2. Post hoc analyses of East Asian patients from the randomized placebo-controlled PREVAIL trial of enzalutamide in patients with chemotherapy-naïve, metastatic castration-resistant prostate cancer.

    Science.gov (United States)

    Kim, Choung Soo; Choi, Young Deuk; Lee, Sang Eun; Lee, Hyun Moo; Ueda, Takeshi; Yonese, Junji; Fukagai, Takashi; Chiong, Edmund; Lau, Weber; Abhyankar, Sarang; Theeuwes, Ad; Tombal, Bertrand; Beer, Tomasz M; Kimura, Go

    2017-07-01

    Enzalutamide is an androgen receptor (AR) inhibitor that acts on different steps in the AR signaling pathway. In PREVAIL, an international, phase III, double-blind, placebo-controlled trial, enzalutamide significantly reduced the risk of radiographic progression by 81% (hazard ratio [HR], 0.19; P PREVAIL trial, we performed a post hoc analysis of the Japanese, Korean, and Singaporean patients. PREVAIL enrolled patients with asymptomatic or mildly symptomatic chemotherapy-naïve metastatic castration-resistant prostate cancer who had progressed on androgen deprivation therapy. During the study, patients received enzalutamide (160 mg/d) or placebo (1:1) until death or discontinuation because of radiographic progression or skeletal-related event and initiation of subsequent therapy. Centrally assessed radiographic progression-free survival (rPFS) and overall survival (OS) were coprimary endpoints. The secondary endpoints of the PREVAIL trial were investigator-assessed rPFS, time to initiation of chemotherapy, time to prostate-specific antigen (PSA) progression, and PSA response (≥50% decline). Of 1717 patients, 148 patients were enrolled at sites in East Asia (enzalutamide 73, placebo 75). Treatment effect of enzalutamide versus placebo was consistent with that for the overall population as indicated by the HRs (95% confidence interval) of 0.38 (0.10-1.44) for centrally assessed rPFS, 0.59 (0.29-1.23) for OS, 0.33 (0.19-0.60) for time to chemotherapy, and 0.32 (0.20-0.50) for time to PSA progression. In East Asian patients, PSA responses were observed in 68.5% and 14.7% of enzalutamide- and placebo-treated patients, respectively. The enzalutamide plasma concentration ratio (East Asian:non-Asian patients) was 1.12 (90% confidence interval, 1.05-1.20) at 13 weeks. Treatment-related adverse events grade ≥ 3 occurred in 1.4% and 2.7% of enzalutamide- and placebo-treated East Asian patients, respectively. Treatment effects and safety of enzalutamide in East Asian

  3. The relationship of renal function to outcome: A post hoc analysis from the EdoxabaN versus warfarin in subjectS UndeRgoing cardiovErsion of Atrial Fibrillation (ENSURE-AF) study.

    Science.gov (United States)

    Lip, Gregory Y H; Al-Saady, Naab; Ezekowitz, Michael D; Banach, Maciej; Goette, Andreas

    2017-11-01

    The ENSURE-AF study (NCT 02072434) of anticoagulation for electrical cardioversion in nonvalvular atrial fibrillation (NVAF) showed comparable low rates of bleeding and thromboembolism between the edoxaban and the enoxaparin-warfarin treatment arms. This post hoc analysis investigated the relationship between renal function and clinical outcomes. ENSURE-AF was a multicenter, PROBE evaluation trial of edoxaban 60 mg, or dose reduced to 30 mg/d for weight≤60 kg, creatinine clearance (CrCl; Cockcroft-Gault) ≤50 mL/min, or concomitant P-glycoprotein inhibitors compared with therapeutically monitored enoxaparin-warfarin in 2,199 NVAF patients undergoing electrical cardioversion. Efficacy and safety outcomes and time in therapeutic range in the warfarin arm were analyzed in relation to CrCl in prespecified ranges ≥15 and ≤30, >30 and ≤50, >50 and warfarin. Mean age was 64.3±10 and 64.2±11 years. Mean time in therapeutic range was progressively lower with reducing CrCl strata, being 66.8% in those with CrCl >30 to ≤50 compared with 71.8% in those with CrCl ≥80. The odds ratios for the primary efficacy and safety end points were comparable for the different predefined renal function strata; given the small numbers, the 95% CI included 1.0. In the subset of those with CrCl ≥95, the odds ratios showed consistency with the other CrCl strata. When CrCl was assessed as a continuous variable, there was a nonsignificant trend toward higher major or clinically relevant nonmajor bleeding with reducing CrCl levels, with no significant differences between the 2 treatment arms. When we assessed CrCl at baseline compared with end of treatment, there were no significant differences in CrCl change between the edoxaban and enoxaparin-warfarin arms. The proportions with worsening of renal function (defined as a decrease of >20% from baseline) were similar in the 2 treatment arms. Given the small number of events in ENSURE-AF, no effect of renal (dys)function was

  4. 21 CFR 862.3580 - Lysergic acid diethylamide (LSD) test system.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Lysergic acid diethylamide (LSD) test system. 862... Test Systems § 862.3580 Lysergic acid diethylamide (LSD) test system. (a) Identification. A lysergic acid diethylamide (LSD) test system is a device intended to measure lysergic acid diethylamide, a...

  5. Lysine-specific demethylase 1 (LSD1) destabilizes p62 and inhibits autophagy in gynecologic malignancies.

    Science.gov (United States)

    Chao, Angel; Lin, Chiao-Yun; Chao, An-Ning; Tsai, Chia-Lung; Chen, Ming-Yu; Lee, Li-Yu; Chang, Ting-Chang; Wang, Tzu-Hao; Lai, Chyong-Huey; Wang, Hsin-Shih

    2017-09-26

    Lysine-specific demethylase 1 (LSD1) - also known as KDM1A - is the first identified histone demethylase. LSD1 is highly expressed in numerous human malignancies and has recently emerged as a target for anticancer drugs. Owing to the presence of several functional domains, we speculated that LSD1 could have additional functions other than histone demethylation. P62 - also termed sequestasome 1 (SQSTM1) - plays a key role in malignant transformation, apoptosis, and autophagy. Here, we show that a high LSD1 expression promotes tumorigenesis in gynecologic malignancies. Notably, LSD1 inhibition with either siRNA or pharmacological agents activates autophagy. Mechanistically, LSD1 decreases p62 protein stability in a demethylation-independent manner. Inhibition of LSD1 reduces both tumor growth and p62 protein degradation in vivo . The combination of LSD1 inhibition and p62 knockdown exerts additive anticancer effects. We conclude that LSD1 destabilizes p62 and inhibits autophagy in gynecologic cancers. LSD1 inhibition reduces malignant cell growth and activates autophagy. The combinations of LSD1 inhibition and autophagy blockade display additive inhibitory effect on cancer cell viability. A better understanding of the role played by p62 will shed more light on the anticancer effects of LSD1 inhibitors.

  6. AN ANIMAL MODEL OF SCHIZOPHRENIA BASED ON CHRONIC LSD ADMINISTRATION: OLD IDEA, NEW RESULTS

    OpenAIRE

    Marona-Lewicka, Danuta; Nichols, Charles D.; Nichols, David E.

    2011-01-01

    Many people who take LSD experience a second temporal phase of LSD intoxication that is qualitatively different, and was described by Daniel Freedman as “clearly a paranoid state.” We have previously shown that the discriminative stimulus effects of LSD in rats also occur in two temporal phases, with initial effects mediated by activation of 5-HT2A receptors (LSD30), and the later temporal phase mediated by dopamine D2-like receptors (LSD90). Surprisingly, we have now found that non-competiti...

  7. LSD Acutely Impairs Fear Recognition and Enhances Emotional Empathy and Sociality.

    Science.gov (United States)

    Dolder, Patrick C; Schmid, Yasmin; Müller, Felix; Borgwardt, Stefan; Liechti, Matthias E

    2016-10-01

    Lysergic acid diethylamide (LSD) is used recreationally and has been evaluated as an adjunct to psychotherapy to treat anxiety in patients with life-threatening illness. LSD is well-known to induce perceptual alterations, but unknown is whether LSD alters emotional processing in ways that can support psychotherapy. We investigated the acute effects of LSD on emotional processing using the Face Emotion Recognition Task (FERT) and Multifaceted Empathy Test (MET). The effects of LSD on social behavior were tested using the Social Value Orientation (SVO) test. Two similar placebo-controlled, double-blind, random-order, crossover studies were conducted using 100 μg LSD in 24 subjects and 200 μg LSD in 16 subjects. All of the subjects were healthy and mostly hallucinogen-naive 25- to 65-year-old volunteers (20 men, 20 women). LSD produced feelings of happiness, trust, closeness to others, enhanced explicit and implicit emotional empathy on the MET, and impaired the recognition of sad and fearful faces on the FERT. LSD enhanced the participants' desire to be with other people and increased their prosocial behavior on the SVO test. These effects of LSD on emotion processing and sociality may be useful for LSD-assisted psychotherapy.

  8. Neurotoxicity and LSD treatment: a follow-up study of 151 patients in Denmark.

    Science.gov (United States)

    Larsen, Jens Knud

    2016-06-01

    LSD was introduced in psychiatry in the 1950s. Between 1960 and 1973, nearly 400 patients were treated with LSD in Denmark. By 1964, one homicide, two suicides and four suicide attempts had been reported. In 1986 the Danish LSD Damages Law was passed after complaints by only one patient. According to the Law, all 154 applicants received financial compensation for LSD-inflicted harm. The Danish State Archives has preserved the case material of 151 of the 154 applicants. Most of the patients suffered from severe side effects of the LSD treatment many years afterwards. In particular, two-thirds of the patients had flashbacks. With the recent interest in LSD therapy, we should consider the neurotoxic potential of LSD. © The Author(s) 2016.

  9. Antiplatelet therapy and the effects of B vitamins in patients with previous stroke or transient ischaemic attack: a post-hoc subanalysis of VITATOPS, a randomised, placebo-controlled trial.

    Science.gov (United States)

    Hankey, Graeme J; Eikelboom, John W; Yi, Qilong; Lees, Kennedy R; Chen, Christopher; Xavier, Denis; Navarro, Jose C; Ranawaka, Udaya K; Uddin, Wasim; Ricci, Stefano; Gommans, John; Schmidt, Reinhold

    2012-06-01

    Previous studies have suggested that any benefits of folic acid-based therapy to lower serum homocysteine in prevention of cardiovascular events might be offset by concomitant use of antiplatelet therapy. We aimed to establish whether there is an interaction between antiplatelet therapy and the effects of folic acid-based homocysteine-lowering therapy on major vascular events in patients with stroke or transient ischaemic attack enrolled in the vitamins to prevent stroke (VITATOPS) trial. In the VITATOPS trial, 8164 patients with recent stroke or transient ischaemic attack were randomly allocated to double-blind treatment with one tablet daily of placebo or B vitamins (2 mg folic acid, 25 mg vitamin B(6), and 500 μg vitamin B(12)) and followed up for a median 3·4 years (IQR 2·0-5·5) for the primary composite outcome of stroke, myocardial infarction, or death from vascular causes. In our post-hoc analysis of the interaction between antiplatelet therapy and the effects of treatment with B vitamins on the primary outcome, we used Cox proportional hazards regression before and after adjusting for imbalances in baseline prognostic factors in participants who were and were not taking antiplatelet drugs at baseline and in participants assigned to receive B vitamins or placebo. We also assessed the interaction in different subgroups of patients and different secondary outcomes. The VITATOPS trial is registered with ClinicalTrials.gov, number NCT00097669, and Current Controlled Trials, number ISRCTN74743444. At baseline, 6609 patients were taking antiplatelet therapy and 1463 were not. Patients not receiving antiplatelet therapy were more likely to be younger, east Asian, and disabled, to have a haemorrhagic stroke or cardioembolic ischaemic stroke, and to have a history of hypertension or atrial fibrillation. They were less likely to be smokers and to have a history of peripheral artery disease, hypercholesterolaemia, diabetes, ischaemic heart disease, and a

  10. Effect of ELOM-080 on exacerbations and symptoms in COPD patients with a chronic bronchitis phenotype – a post-hoc analysis of a randomized, double-blind, placebo-controlled clinical trial

    Directory of Open Access Journals (Sweden)

    Beeh KM

    2016-11-01

    Full Text Available Kai-Michael Beeh,1 Jutta Beier,1 Henning Candler,2 Thomas Wittig2 1Insaf Respiratory Research Institute, Wiesbaden, Germany; 2G. Pohl-Boskamp GmbH & Co KG, Hohenlockstedt, Germany Background: Treating symptoms and preventing exacerbations are key components of chronic obstructive pulmonary disease (COPD long-term management. Recently, a more tailored treatment approach has been proposed, in particular for two well-established clinical phenotypes, frequent exacerbators and chronic bronchitis-dominant COPD. ELOM-080 has demonstrated clinical efficacy in treating symptoms and preventing exacerbations in subjects with chronic bronchitis. However, little is known about the potential effects of ELOM-080 in COPD patients. Aim: To evaluate the effect on exacerbation, cough sputum, and general state of health of long-term treatment with ELOM-080 in COPD patients with an exacerbation history and chronic bronchitis. Methods: We performed a post-hoc analysis of a randomized, double-blinded, placebo-controlled parallel-group clinical trial of a 6-month treatment with ELOM-080 (3×300 mg in patients with chronic bronchitis and concomitant COPD. The primary outcome was the proportion of subjects with at least one exacerbation over the 6-month study period. Secondary outcomes included the total number of exacerbations (ie, cumulative occurrence of exacerbations during the study period and the proportion of acute exacerbations necessitating an antibiotic treatment, monthly evaluations of sputum and cough symptoms, and the general state of health and a safety analysis. Results: Of 260 randomized subjects, 64 patients fulfilled the inclusion criteria for COPD (ELOM-080: 35, placebo: 29. Compared to placebo, ELOM-080 reduced the percentage of subjects with at least one exacerbation (29% versus 55%, P=0.031 and a reduction in the overall occurrence of exacerbations (ELOM-080: 10, placebo: 21, P=0.012 during the winter season. The percentage of asymptomatic or

  11. AN ANIMAL MODEL OF SCHIZOPHRENIA BASED ON CHRONIC LSD ADMINISTRATION: OLD IDEA, NEW RESULTS

    Science.gov (United States)

    Marona-Lewicka, Danuta; Nichols, Charles D.; Nichols, David E.

    2011-01-01

    Many people who take LSD experience a second temporal phase of LSD intoxication that is qualitatively different, and was described by Daniel Freedman as “clearly a paranoid state.” We have previously shown that the discriminative stimulus effects of LSD in rats also occur in two temporal phases, with initial effects mediated by activation of 5-HT2A receptors (LSD30), and the later temporal phase mediated by dopamine D2-like receptors (LSD90). Surprisingly, we have now found that non-competitive NMDA antagonists produced full substitution in LSD90 rats, but only in older animals, whereas in LSD30, or in younger animals, these drugs did not mimic LSD. Chronic administration of low doses of LSD (>3 months, 0.16 mg/kg every other day) induces a behavioral state characterized by hyperactivity and hyperirritability, increased locomotor activity, anhedonia, and impairment in social interaction that persists at the same magnitude for at least three months after cessation of LSD treatment. These behaviors, which closely resemble those associated with psychosis in humans, are not induced by withdrawal from LSD; rather, they are the result of neuroadaptive changes occurring in the brain during the chronic administration of LSD. These persistent behaviors are transiently reversed by haloperidol and olanzapine, but are insensitive to MDL-100907. Gene expression analysis data show that chronic LSD treatment produced significant changes in multiple neurotransmitter system-related genes, including those for serotonin and dopamine. Thus, we propose that chronic treatment of rats with low doses of LSD can serve as a new animal model of psychosis that may mimic the development and progression of schizophrenia, as well as model the established disease better than current acute drug administration models utilizing amphetamine or NMDA antagonists such as PCP. PMID:21352832

  12. An animal model of schizophrenia based on chronic LSD administration: old idea, new results.

    Science.gov (United States)

    Marona-Lewicka, Danuta; Nichols, Charles D; Nichols, David E

    2011-09-01

    Many people who take LSD experience a second temporal phase of LSD intoxication that is qualitatively different, and was described by Daniel Freedman as "clearly a paranoid state." We have previously shown that the discriminative stimulus effects of LSD in rats also occur in two temporal phases, with initial effects mediated by activation of 5-HT(2A) receptors (LSD30), and the later temporal phase mediated by dopamine D2-like receptors (LSD90). Surprisingly, we have now found that non-competitive NMDA antagonists produced full substitution in LSD90 rats, but only in older animals, whereas in LSD30, or in younger animals, these drugs did not mimic LSD. Chronic administration of low doses of LSD (>3 months, 0.16 mg/kg every other day) induces a behavioral state characterized by hyperactivity and hyperirritability, increased locomotor activity, anhedonia, and impairment in social interaction that persists at the same magnitude for at least three months after cessation of LSD treatment. These behaviors, which closely resemble those associated with psychosis in humans, are not induced by withdrawal from LSD; rather, they are the result of neuroadaptive changes occurring in the brain during the chronic administration of LSD. These persistent behaviors are transiently reversed by haloperidol and olanzapine, but are insensitive to MDL-100907. Gene expression analysis data show that chronic LSD treatment produced significant changes in multiple neurotransmitter system-related genes, including those for serotonin and dopamine. Thus, we propose that chronic treatment of rats with low doses of LSD can serve as a new animal model of psychosis that may mimic the development and progression of schizophrenia, as well as model the established disease better than current acute drug administration models utilizing amphetamine or NMDA antagonists such as PCP. Copyright © 2011 Elsevier Ltd. All rights reserved.

  13. agradecimento aos consultores ad hoc

    Directory of Open Access Journals (Sweden)

    REA Editor

    2012-02-01

    Full Text Available Agradecemos aos professores Nildo Viana (UFG e Flavio Sofiati (UFG, organizadores do DOSSIÊ JUVENTUDE & SOCIEDADE, e aos Consultores Ad hoc pela leitura e apreciação crítica dos artigos submetidos e publicados nesta edição.

  14. Identification of downstream metastasis-associated target genes regulated by LSD1 in colon cancer cells.

    Science.gov (United States)

    Chen, Jiang; Ding, Jie; Wang, Ziwei; Zhu, Jian; Wang, Xuejian; Du, Jiyi

    2017-03-21

    This study aims to identify downstream target genes regulated by lysine-specific demethylase 1 (LSD1) in colon cancer cells and investigate the molecular mechanisms of LSD1 influencing invasion and metastasis of colon cancer. We obtained the expression changes of downstream target genes regulated by small-interfering RNA-LSD1 and LSD1-overexpression via gene expression profiling in two human colon cancer cell lines. An Affymetrix Human Transcriptome Array 2.0 was used to identify differentially expressed genes (DEGs). We screened out LSD1-target gene associated with proliferation, metastasis, and invasion from DEGs via Gene Ontology and Pathway Studio. Subsequently, four key genes (CABYR, FOXF2, TLE4, and CDH1) were computationally predicted as metastasis-related LSD1-target genes. ChIp-PCR was applied after RT-PCR and Western blot validations to detect the occupancy of LSD1-target gene promoter-bound LSD1. A total of 3633 DEGs were significantly upregulated, and 4642 DEGs were downregulated in LSD1-silenced SW620 cells. A total of 4047 DEGs and 4240 DEGs were upregulated and downregulated in LSD1-overexpressed HT-29 cells, respectively. RT-PCR and Western blot validated the microarray analysis results. ChIP assay results demonstrated that LSD1 might be negative regulators for target genes CABYR and CDH1. The expression level of LSD1 is negatively correlated with mono- and dimethylation of histone H3 lysine4(H3K4) at LSD1- target gene promoter region. No significant mono-methylation and dimethylation of H3 lysine9 methylation was detected at the promoter region of CABYR and CDH1. LSD1- depletion contributed to the upregulation of CABYR and CDH1 through enhancing the dimethylation of H3K4 at the LSD1-target genes promoter. LSD1- overexpression mediated the downregulation of CABYR and CDH1expression through decreasing the mono- and dimethylation of H3K4 at LSD1-target gene promoter in colon cancer cells. CABYR and CDH1 might be potential LSD1-target genes in colon

  15. Neural correlates of the LSD experience revealed by multimodal neuroimaging.

    Science.gov (United States)

    Carhart-Harris, Robin L; Muthukumaraswamy, Suresh; Roseman, Leor; Kaelen, Mendel; Droog, Wouter; Murphy, Kevin; Tagliazucchi, Enzo; Schenberg, Eduardo E; Nest, Timothy; Orban, Csaba; Leech, Robert; Williams, Luke T; Williams, Tim M; Bolstridge, Mark; Sessa, Ben; McGonigle, John; Sereno, Martin I; Nichols, David; Hellyer, Peter J; Hobden, Peter; Evans, John; Singh, Krish D; Wise, Richard G; Curran, H Valerie; Feilding, Amanda; Nutt, David J

    2016-04-26

    Lysergic acid diethylamide (LSD) is the prototypical psychedelic drug, but its effects on the human brain have never been studied before with modern neuroimaging. Here, three complementary neuroimaging techniques: arterial spin labeling (ASL), blood oxygen level-dependent (BOLD) measures, and magnetoencephalography (MEG), implemented during resting state conditions, revealed marked changes in brain activity after LSD that correlated strongly with its characteristic psychological effects. Increased visual cortex cerebral blood flow (CBF), decreased visual cortex alpha power, and a greatly expanded primary visual cortex (V1) functional connectivity profile correlated strongly with ratings of visual hallucinations, implying that intrinsic brain activity exerts greater influence on visual processing in the psychedelic state, thereby defining its hallucinatory quality. LSD's marked effects on the visual cortex did not significantly correlate with the drug's other characteristic effects on consciousness, however. Rather, decreased connectivity between the parahippocampus and retrosplenial cortex (RSC) correlated strongly with ratings of "ego-dissolution" and "altered meaning," implying the importance of this particular circuit for the maintenance of "self" or "ego" and its processing of "meaning." Strong relationships were also found between the different imaging metrics, enabling firmer inferences to be made about their functional significance. This uniquely comprehensive examination of the LSD state represents an important advance in scientific research with psychedelic drugs at a time of growing interest in their scientific and therapeutic value. The present results contribute important new insights into the characteristic hallucinatory and consciousness-altering properties of psychedelics that inform on how they can model certain pathological states and potentially treat others.

  16. Alterations of consciousness and mystical-type experiences after acute LSD in humans.

    Science.gov (United States)

    Liechti, Matthias E; Dolder, Patrick C; Schmid, Yasmin

    2017-05-01

    Lysergic acid diethylamide (LSD) is used recreationally and in clinical research. Acute mystical-type experiences that are acutely induced by hallucinogens are thought to contribute to their potential therapeutic effects. However, no data have been reported on LSD-induced mystical experiences and their relationship to alterations of consciousness. Additionally, LSD dose- and concentration-response functions with regard to alterations of consciousness are lacking. We conducted two placebo-controlled, double-blind, cross-over studies using oral administration of 100 and 200 μg LSD in 24 and 16 subjects, respectively. Acute effects of LSD were assessed using the 5 Dimensions of Altered States of Consciousness (5D-ASC) scale after both doses and the Mystical Experience Questionnaire (MEQ) after 200 μg. On the MEQ, 200 μg LSD induced mystical experiences that were comparable to those in patients who underwent LSD-assisted psychotherapy but were fewer than those reported for psilocybin in healthy subjects or patients. On the 5D-ASC scale, LSD produced higher ratings of blissful state, insightfulness, and changed meaning of percepts after 200 μg compared with 100 μg. Plasma levels of LSD were not positively correlated with its effects, with the exception of ego dissolution at 100 μg. Mystical-type experiences were infrequent after LSD, possibly because of the set and setting used in the present study. LSD may produce greater or different alterations of consciousness at 200 μg (i.e., a dose that is currently used in psychotherapy in Switzerland) compared with 100 μg (i.e., a dose used in imaging studies). Ego dissolution may reflect plasma levels of LSD, whereas more robustly induced effects of LSD may not result in such associations.

  17. LSD-based analysis of high-resolution stellar spectra

    Science.gov (United States)

    Tsymbal, V.; Tkachenko, A.; Van, Reeth T.

    2014-11-01

    We present a generalization of the method of least-squares deconvolution (LSD), a powerful tool for extracting high S/N average line profiles from stellar spectra. The generalization of the method is effected by extending it towards the multiprofile LSD and by introducing the possibility to correct the line strengths from the initial mask. We illustrate the new approach by two examples: (a) the detection of astroseismic signatures from low S/N spectra of single stars, and (b) disentangling spectra of multiple stellar objects. The analysis is applied to spectra obtained with 2-m class telescopes in the course of spectroscopic ground-based support for space missions such as CoRoT and Kepler. Usually, rather high S/N is required, so smaller telescopes can only compete successfully with more advanced ones when one can apply a technique that enables a remarkable increase in the S/N of the spectra which they observe. Since the LSD profiles have a potential for reconstruction what is common in all the spectral profiles, it should have a particular practical application to faint stars observed with 2-m class telescopes and whose spectra show remarkable LPVs.

  18. Medicinal chemistry insights in the discovery of novel LSD1 inhibitors.

    Science.gov (United States)

    Wang, Xueshun; Huang, Boshi; Suzuki, Takayoshi; Liu, Xinyong; Zhan, Peng

    2015-01-01

    LSD1 is an epigenetic modulator associated with transcriptional regulation of genes involved in a broad spectrum of key cellular processes, and its activity is often altered under pathological conditions. LSD1 inhibitors are considered to be candidates for therapy of cancer, viral diseases and neurodegeneration. Many LSD1 inhibitors with various scaffolds have been disclosed, and a few potent molecules are in different stages of clinical development. In this review, we summarize recent biological findings on the roles of LSD1 and the current understanding of the clinical significance of LSD1, and focus on the medicinal chemistry strategies used in the design and development of LSD1 inhibitors as drug-like epigenetic modulators since 2012, including a brief consideration of structure-activity relationships.

  19. Acute effects of LSD on amygdala activity during processing of fearful stimuli in healthy subjects

    OpenAIRE

    Mueller, F.; Lenz, C.; Dolder, P. C.; Harder, S.; Schmid, Y.; Lang, U. E.; Liechti, M. E.; Borgwardt, S.

    2017-01-01

    Lysergic acid diethylamide (LSD) induces profound changes in various mental domains, including perception, self-awareness and emotions. We used functional magnetic resonance imaging (fMRI) to investigate the acute effects of LSD on the neural substrate of emotional processing in humans. Using a double-blind, randomised, cross-over study design, placebo or 100 μg LSD were orally administered to 20 healthy subjects before the fMRI scan, taking into account the subjective and pharmacological pea...

  20. ERRα induces H3K9 demethylation by LSD1 to promote cell invasion

    OpenAIRE

    Carnesecchi, Julie; Forcet, Christelle; Zhang, Ling; Tribollet, Violaine; Barenton, Bruno; Boudra, Rafik; Cerutti, Catherine; Billas, Isabelle M. L.; Sérandour, Aurélien A.; Carroll, Jason S.; Beaudoin, Claude; Vanacker, Jean-Marc

    2017-01-01

    Dynamic demethylation of histone residues plays a crucial role in the regulation of gene expression. Lysine Specific Demethylase 1 (LSD1) can remove both transcriptionally permissive and repressive histone marks. How these activities are controlled is not clearly understood. Here, we show that the estrogen-related receptor α (ERRα) induces LSD1 to erase repressive marks in vitro. Through such a mechanism, LSD1 and ERRα commonly activate a set of transcriptional targets that include genes invo...

  1. Dreamlike effects of LSD on waking imagery in humans depend on serotonin 2A receptor activation.

    Science.gov (United States)

    Kraehenmann, Rainer; Pokorny, Dan; Vollenweider, Leonie; Preller, Katrin H; Pokorny, Thomas; Seifritz, Erich; Vollenweider, Franz X

    2017-07-01

    Accumulating evidence indicates that the mixed serotonin and dopamine receptor agonist lysergic acid diethylamide (LSD) induces an altered state of consciousness that resembles dreaming. This study aimed to test the hypotheses that LSD produces dreamlike waking imagery and that this imagery depends on 5-HT2A receptor activation and is related to subjective drug effects. Twenty-five healthy subjects performed an audiorecorded guided mental imagery task 7 h after drug administration during three drug conditions: placebo, LSD (100 mcg orally) and LSD together with the 5-HT2A receptor antagonist ketanserin (40 mg orally). Cognitive bizarreness of guided mental imagery reports was quantified as a standardised formal measure of dream mentation. State of consciousness was evaluated using the Altered State of Consciousness (5D-ASC) questionnaire. LSD, compared with placebo, significantly increased cognitive bizarreness (p < 0.001). The LSD-induced increase in cognitive bizarreness was positively correlated with the LSD-induced loss of self-boundaries and cognitive control (p < 0.05). Both LSD-induced increases in cognitive bizarreness and changes in state of consciousness were fully blocked by ketanserin. LSD produced mental imagery similar to dreaming, primarily via activation of the 5-HT2A receptor and in relation to loss of self-boundaries and cognitive control. Future psychopharmacological studies should assess the differential contribution of the D2/D1 and 5-HT1A receptors to cognitive bizarreness.

  2. Ad-hoc networking towards seamless communications

    CERN Document Server

    Gavrilovska, Liljana

    2006-01-01

    Ad-Hoc Networking Towards Seamless Communications is dedicated to an area that attracts growing interest in academia and industry and concentrates on wireless ad hoc networking paradigm. The persistent efforts to acquire the ability to establish dynamic wireless connections from anywhere to anyone with any device without prerequisite imbedded infrastructure move the communications boundaries towards ad-hoc networks. Recently, ad hoc networking has attracted growing interest due to advances in wireless communications, and developed framework for running IP based protocols. The expected degree of penetration of these networks will depend on the successful resolution of the key features. Ad-hoc networks pose many complex and open problems for researchers. Ad-Hoc Networking Towards Seamless Communications reveals the state-of-the-art in wireless ad-hoc networking and discusses some of the key research topics that are expected to promote and accelerate the commercial applications of these networks (e.g., MAC, rout...

  3. LSD1 dual function in mediating epigenetic corruption of the vitamin D signaling in prostate cancer.

    Science.gov (United States)

    Battaglia, Sebastiano; Karasik, Ellen; Gillard, Bryan; Williams, Jennifer; Winchester, Trisha; Moser, Michael T; Smiraglia, Dominic J; Foster, Barbara A

    2017-01-01

    Lysine-specific demethylase 1A (LSD1) is a key regulator of the androgen (AR) and estrogen receptors (ER), and LSD1 levels correlate with tumor aggressiveness. Here, we demonstrate that LSD1 regulates vitamin D receptor (VDR) activity and is a mediator of 1,25(OH) 2 -D 3 (vitamin D) action in prostate cancer (PCa). Athymic nude mice were xenografted with CWR22 cells and monitored weekly after testosterone pellet removal. Expression of LSD1 and VDR (IHC) were correlated with tumor growth using log-rank test. TRAMP tumors and prostates from wild-type (WT) mice were used to evaluate VDR and LSD1 expression via IHC and western blotting. The presence of VDR and LSD1 in the same transcriptional complex was evaluated via immunoprecipitation (IP) using nuclear cell lysate. The effect of LSD1 and 1,25(OH) 2 -D 3 on cell viability was evaluated in C4-2 and BC1A cells via trypan blue exclusion. The role of LSD1 in VDR-mediated gene transcription was evaluated for Cdkn1a , E2f1 , Cyp24a1 , and S100g via qRT-PCR-TaqMan and via chromatin immunoprecipitation assay. Methylation of Cdkn1a TSS was measured via bisulfite sequencing, and methylation of a panel of cancer-related genes was quantified using methyl arrays. The Cancer Genome Atlas data were retrieved to identify genes whose status correlates with LSD1 and DNA methyltransferase 1 (DNMT1). Results were correlated with patients' survival data from two separate cohorts of primary and metastatic PCa. LSD1 and VDR protein levels are elevated in PCa tumors and correlate with faster tumor growth in xenograft mouse models. Knockdown of LSD1 reduces PCa cell viability, and gene expression data suggest a dual coregulatory role of LSD1 for VDR, acting as a coactivator and corepressor in a locus-specific manner. LSD1 modulates VDR-dependent transcription by mediating the recruitment of VDR and DNMT1 at the TSS of VDR-targeted genes and modulates the epigenetic status of transcribed genes by altering H3K4me2 and H3K9Ac and DNA

  4. d-Lysergic Acid Diethylamide (LSD) as a Model of Psychosis: Mechanism of Action and Pharmacology.

    Science.gov (United States)

    De Gregorio, Danilo; Comai, Stefano; Posa, Luca; Gobbi, Gabriella

    2016-11-23

    d-Lysergic Acid Diethylamide (LSD) is known for its hallucinogenic properties and psychotic-like symptoms, especially at high doses. It is indeed used as a pharmacological model of psychosis in preclinical research. The goal of this review was to understand the mechanism of action of psychotic-like effects of LSD. We searched Pubmed, Web of Science, Scopus, Google Scholar and articles' reference lists for preclinical studies regarding the mechanism of action involved in the psychotic-like effects induced by LSD. LSD's mechanism of action is pleiotropic, primarily mediated by the serotonergic system in the Dorsal Raphe, binding the 5-HT 2A receptor as a partial agonist and 5-HT 1A as an agonist. LSD also modulates the Ventral Tegmental Area, at higher doses, by stimulating dopamine D₂, Trace Amine Associate receptor 1 (TAAR₁) and 5-HT 2A . More studies clarifying the mechanism of action of the psychotic-like symptoms or psychosis induced by LSD in humans are needed. LSD's effects are mediated by a pleiotropic mechanism involving serotonergic, dopaminergic, and glutamatergic neurotransmission. Thus, the LSD-induced psychosis is a useful model to test the therapeutic efficacy of potential novel antipsychotic drugs, particularly drugs with dual serotonergic and dopaminergic (DA) mechanism or acting on TAAR₁ receptors.

  5. Radioimmunoassay of lysergic acid diethylamide (LSD) in serum and urine by using antisera of different specificities

    International Nuclear Information System (INIS)

    Ratcliffe, W.A.; Fletcher, S.M.; Moffat, A.C.; Ratcliffe, J.G.; Harland, W.A.; Levitt, T.E.

    1977-01-01

    We raised high-titre antisera to two LSD-bovine serum albumin conjugates, one linked via the indole nitrogen, the other via the amide side-chain. The antisera were specific for different parts of the LSD molecule, as demonstrated by cross-reactivity studies with LSD, its metabolites, ergot alkaloids, and closely related compounds. The antisera were used to develop a double-antibody radioimmunoassay with a detection limit of about 0.4 μg of LSD per liter of unextracted urine or serum. We saw no nonspecific interference by urine, serum, or from a series of commonly used drugs. There was good correlation between immunoassay values obtained with the two antisera (r = 0.91). However, the antiserum linked via the indole nitrogen gave consistently higher results for samples from persons who had taken LSD, owing to greater cross-reactivity with LSD metabolites. Radioimmunoassay by use of two such antisera is a more specific screening procedure for LSD abuse than has been available previously. In addition, antisera cross-reacting with LSD metabolites allow measurement of these compounds, for which there is no satisfactory method at the concentrations found in biological fluids in man

  6. Increased Global Functional Connectivity Correlates with LSD-Induced Ego Dissolution

    NARCIS (Netherlands)

    Tagliazucchi, E.; Roseman, Leor; Kaelen, Mendel; Orban, Csaba; Muthukumaraswamy, Suresh D; Murphy, Kevin; Laufs, Helmut; Leech, Robert; McGonigle, John; Crossley, Nicolas; Bullmore, Edward; Williams, Tim; Bolstridge, Mark; Feilding, Amanda; Nutt, David J; Carhart-Harris, Robin

    2016-01-01

    Lysergic acid diethylamide (LSD) is a non-selective serotonin-receptor agonist that was first synthesized in 1938 and identified as (potently) psychoactive in 1943. Psychedelics have been used by indigenous cultures for millennia [1]; however, because of LSD's unique potency and the timing of its

  7. Ad hoc Sensor Networks to Support Maritime Interdiction Operations

    OpenAIRE

    Osmundson, John; Bordetsky, Alex

    2014-01-01

    Networking sensors, decision centers, and boarding parties supports success in Maritime Interdiction Operations. Led by a team from Naval Post-graduate School (NPS), experiments were conducted in 2012 to test the use of ad-hoc, self-forming communication networks to link sensors, people, and decision centers. The experiments involved international participants and successfully shared valuable biometric and radiological sensor data between boarding parties and decis...

  8. LSD Increases Primary Process Thinking via Serotonin 2A Receptor Activation

    Science.gov (United States)

    Kraehenmann, Rainer; Pokorny, Dan; Aicher, Helena; Preller, Katrin H.; Pokorny, Thomas; Bosch, Oliver G.; Seifritz, Erich; Vollenweider, Franz X.

    2017-01-01

    Rationale: Stimulation of serotonin 2A (5-HT2A) receptors by lysergic acid diethylamide (LSD) and related compounds such as psilocybin has previously been shown to increase primary process thinking – an ontologically and evolutionary early, implicit, associative, and automatic mode of thinking which is typically occurring during altered states of consciousness such as dreaming. However, it is still largely unknown whether LSD induces primary process thinking under placebo-controlled, standardized experimental conditions and whether these effects are related to subjective experience and 5-HT2A receptor activation. Therefore, this study aimed to test the hypotheses that LSD increases primary process thinking and that primary process thinking depends on 5-HT2A receptor activation and is related to subjective drug effects. Methods: Twenty-five healthy subjects performed an audio-recorded mental imagery task 7 h after drug administration during three drug conditions: placebo, LSD (100 mcg orally) and LSD together with the 5-HT2A receptor antagonist ketanserin (40 mg orally). The main outcome variable in this study was primary index (PI), a formal measure of primary process thinking in the imagery reports. State of consciousness was evaluated using the Altered State of Consciousness (5D-ASC) rating scale. Results: LSD, compared with placebo, significantly increased primary index (p LSD-induced increase in primary index was positively correlated with LSD-induced disembodiment (p LSD-induced increases in primary index and changes in state of consciousness were fully blocked by ketanserin. Conclusion: LSD induces primary process thinking via activation of 5-HT2A receptors and in relation to disembodiment and blissful state. Primary process thinking appears to crucially organize inner experiences during both dreams and psychedelic states of consciousness. PMID:29167644

  9. LSD Increases Primary Process Thinking via Serotonin 2A Receptor Activation

    Directory of Open Access Journals (Sweden)

    Rainer Kraehenmann

    2017-11-01

    Full Text Available Rationale: Stimulation of serotonin 2A (5-HT2A receptors by lysergic acid diethylamide (LSD and related compounds such as psilocybin has previously been shown to increase primary process thinking – an ontologically and evolutionary early, implicit, associative, and automatic mode of thinking which is typically occurring during altered states of consciousness such as dreaming. However, it is still largely unknown whether LSD induces primary process thinking under placebo-controlled, standardized experimental conditions and whether these effects are related to subjective experience and 5-HT2A receptor activation. Therefore, this study aimed to test the hypotheses that LSD increases primary process thinking and that primary process thinking depends on 5-HT2A receptor activation and is related to subjective drug effects.Methods: Twenty-five healthy subjects performed an audio-recorded mental imagery task 7 h after drug administration during three drug conditions: placebo, LSD (100 mcg orally and LSD together with the 5-HT2A receptor antagonist ketanserin (40 mg orally. The main outcome variable in this study was primary index (PI, a formal measure of primary process thinking in the imagery reports. State of consciousness was evaluated using the Altered State of Consciousness (5D-ASC rating scale.Results: LSD, compared with placebo, significantly increased primary index (p < 0.001, Bonferroni-corrected. The LSD-induced increase in primary index was positively correlated with LSD-induced disembodiment (p < 0.05, Bonferroni-corrected, and blissful state (p < 0.05, Bonferroni-corrected on the 5D-ASC. Both LSD-induced increases in primary index and changes in state of consciousness were fully blocked by ketanserin.Conclusion: LSD induces primary process thinking via activation of 5-HT2A receptors and in relation to disembodiment and blissful state. Primary process thinking appears to crucially organize inner experiences during both dreams and

  10. LC-mS analysis of human urine specimens for 2-oxo-3-hydroxy LSD: method validation for potential interferants and stability study of 2-oxo-3-hydroxy LSD under various storage conditions.

    Science.gov (United States)

    Klette, Kevin L; Horn, Carl K; Stout, Peter R; Anderson, Cynthia J

    2002-01-01

    2-Oxo-3-hydroxy lysergic acid diethylamide (O-H-LSD), a major LSD metabolite, has previously been demonstrated to be a superior marker for identifying LSD use compared with the parent drug, LSD. Specifically, O-H-LSD analyzed using liquid chromatography-mass spectrometry has been reported to be present in urine at concentrations 16 to 43 times greater than LSD. To further support forensic application of this procedure, the specificity of the assay was assessed using compounds that have structural and chemical properties similar to O-H-LSD, common over-the-counter products, prescription drugs and some of their metabolites, and other drugs of abuse. Of the wide range of compounds studied, none were found to interfere with the detection of O-H-LSD or the internal standard 2-oxo-3-hydroxy lysergic acid methyl propylamide. The stability of O-H-LSD was investigated from 0 to 9 days at various temperatures, pH conditions, and exposures to fluorescent light. Additionally, the effect of long-term frozen storage and pH was investigated from 0 to 60 days. There was no significant loss of O-H-LSD under both refrigerated and frozen conditions within the normal human physiological pH range of urine (4.6-8.4). However, significant loss of O-H-LSD was observed in samples prepared at pH 4.6-8.4 and stored at room temperature or higher (24-50 degrees C).

  11. Hallucinogens as discriminative stimuli in animals: LSD, phenethylamines, and tryptamines.

    Science.gov (United States)

    Winter, J C

    2009-04-01

    Although man's first encounters with hallucinogens predate written history, it was not until the rise of the sister disciplines of organic chemistry and pharmacology in the nineteenth century that scientific studies became possible. Mescaline was the first to be isolated and its chemical structure determined. Since then, additional drugs have been recovered from their natural sources and synthetic chemists have contributed many more. Given their profound effects upon human behavior and the need for verbal communication to access many of these effects, some see humans as ideal subjects for study of hallucinogens. However, if we are to determine the mechanisms of action of these agents, establish hypotheses testable in human subjects, and explore the mechanistic links between hallucinogens and such apparently disparate topics as idiopathic psychosis, transcendental states, drug abuse, stress disorders, and cognitive dysfunction, studies in animals are essential. Stimulus control by hallucinogens has provided an intuitively attractive approach to the study of these agents in nonverbal species. The intent of this review is to provide a brief account of events from the time of the first demonstration of hallucinogen-induced stimulus control to the present. In general, the review is limited to lysergic acid diethylamide (LSD) and the hallucinogenic derivatives of phenethylamine and tryptamine. The pharmacological basis for stimulus control by LSD and hallucinogenic phenethylamines and tryptamines is serotonergic in nature. The 5-HT(2A) receptor appears to be the primary site of action with significant modulation by other serotonergic sites including 5-HT(2C) and 5-HT(1A) receptors. Interactions with other neurotransmitters, especially glutamate and dopamine, are under active investigation. Most studies to date have been conducted in the rat but transgenic mice offer interesting possibilities. Hallucinogen-induced stimulus control provides a unique behavioral tool for the

  12. The 5-HT1A Receptor and the Stimulus Effects of LSD in the Rat

    Science.gov (United States)

    Reissig, C.J.; Eckler, J.R.; Rabin, R.A.; Winter, J.C.

    2005-01-01

    Rationale It has been suggested that the 5-HT1A receptor plays a significant modulatory role in the stimulus effects of the indoleamine hallucinogen lysergic acid diethylamide (LSD). Objectives The present study sought to characterize the effects of several compounds with known affinity for the 5-HT1A receptor on the discriminative stimulus effects of LSD. Methods 12 Male F-344 rats were trained in a two-lever, fixed ratio10, food reinforced task with LSD (0.1 mg/kg; IP; 15 min pretreatment) as a discriminative stimulus. Combination and substitution tests with the 5-HT1A agonists, 8-OH-DPAT, buspirone, gepirone, and ipsapirone, with LSD-induced stimulus control were then performed. The effects of these 5-HT1A ligands were also tested in the presence of the selective 5-HT1A receptor antagonist, WAY-100,635 (0.3 mg/kg; SC; 30 min. pretreatment). Results In combination tests stimulus control by LSD was increased by all 5-HT1A receptor ligands with agonist properties. Similarly, in tests of antagonism, the increase in drug-appropriate responding caused by stimulation of the 5-HT1A receptor was abolished by administration of WAY-100,635. Conclusions These data, obtained using a drug discrimination model of the hallucinogenic effects of LSD, provide support for the hypothesis that the 5-HT1A receptor has a significant modulatory role in the stimulus effects of LSD. PMID:16025319

  13. Acute effects of LSD on amygdala activity during processing of fearful stimuli in healthy subjects.

    Science.gov (United States)

    Mueller, F; Lenz, C; Dolder, P C; Harder, S; Schmid, Y; Lang, U E; Liechti, M E; Borgwardt, S

    2017-04-04

    Lysergic acid diethylamide (LSD) induces profound changes in various mental domains, including perception, self-awareness and emotions. We used functional magnetic resonance imaging (fMRI) to investigate the acute effects of LSD on the neural substrate of emotional processing in humans. Using a double-blind, randomised, cross-over study design, placebo or 100 μg LSD were orally administered to 20 healthy subjects before the fMRI scan, taking into account the subjective and pharmacological peak effects of LSD. The plasma levels of LSD were determined immediately before and after the scan. The study (including the a priori-defined study end point) was registered at ClinicalTrials.gov before study start (NCT02308969). The administration of LSD reduced reactivity of the left amygdala and the right medial prefrontal cortex relative to placebo during the presentation of fearful faces (PLSD-induced amygdala response to fearful stimuli and the LSD-induced subjective drug effects (PLSD modulates the engagement of brain regions that mediate emotional processing.

  14. Did you get any help? A post-hoc secondary analysis of a randomized controlled trial of psychoeducation for patients with antisocial personality disorder in outpatient substance abuse treatment programs

    OpenAIRE

    Thylstrup, Birgitte; Schr?der, Sidsel; Fridell, Mats; Hesse, Morten

    2017-01-01

    Background People in treatment for substance use disorder commonly have comorbid personality disorders, including antisocial personality disorder. Little is known about treatments that specifically address comorbid antisocial personality disorder. Methods Self-rated help received for antisocial personality disorder was assessed during follow-ups at 3, 9 and 15 months post-randomization of a randomized trial of psychoeducation for people with comorbid substance use and antisocial personality d...

  15. Complex discriminative stimulus properties of (+)lysergic acid diethylamide (LSD) in C57Bl/6J mice.

    Science.gov (United States)

    Benneyworth, Michael A; Smith, Randy L; Barrett, Robert J; Sanders-Bush, Elaine

    2005-06-01

    The drug discrimination procedure is the most frequently used in vivo model of hallucinogen activity. Historically, most drug discrimination studies have been conducted in the rat. With the development of genetically modified mice, a powerful new tool has become available for investigating the mechanisms of drug-induced behavior. The current paper is part of an ongoing effort to determine the utility of the drug discrimination technique for evaluating hallucinogenic drugs in mice. To establish the training procedures and characterize the stimulus properties of (+)lysergic acid diethylamide (LSD) in mice. Using a two-lever drug discrimination procedure, C57Bl/6J mice were trained to discriminate 0.45 mg/kg LSD vs saline on a VI30 sec schedule of reinforcement, with vanilla-flavored Ensure serving as the reinforcer. As in rats, acquisition was orderly, but the training dose was nearly five-fold higher for mice than rats. LSD lever selection was dose-dependent. Time-course studies revealed a rapid loss of the LSD stimulus effects. The 5-HT(2A/2C) receptor agonist, 2,5-dimethoxy-4-bromoamphetamine [(-)DOB] (1.0 mg/kg), substituted fully for LSD and the 5-HT(1A) receptor agonist, 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT) (1.6 mg/kg), substituted partially for LSD. Pretreatment with the 5-HT(2A) receptor-selective antagonist, MDL 100907, or the 5-HT(1A)-selective antagonist WAY 100635, showed that each antagonist only partially blocked LSD discrimination. Substitution of 1.0 mg/kg (-)DOB for LSD was fully blocked by pretreatment with MDL 100907 but unaltered by WAY 100635 pretreatment. These data suggest that in mice the stimulus effects of LSD have both a 5-HT(2A) receptor and a 5-HT(1A) receptor component.

  16. Queueing Models for Mobile Ad Hoc Networks

    NARCIS (Netherlands)

    de Haan, Roland

    2009-01-01

    This thesis presents models for the performance analysis of a recent communication paradigm: \\emph{mobile ad hoc networking}. The objective of mobile ad hoc networking is to provide wireless connectivity between stations in a highly dynamic environment. These dynamics are driven by the mobility of

  17. Context discovery in ad-hoc networks

    NARCIS (Netherlands)

    Liu, F.

    2011-01-01

    With the rapid development of wireless technology and portable devices, mobile ad-hoc networks (MANETs) are more and more present in our daily life. Ad-hoc networks are often composed of mobile and battery-supplied devices, like laptops, mobile phones, and PDAs. With no requirement for

  18. A review of lysergic acid diethylamide (LSD) in the treatment of addictions: historical perspectives and future prospects.

    Science.gov (United States)

    Liester, Mitchell B

    2014-01-01

    Lysergic acid diethylamide (LSD) is a semisynthetic compound with strong psychoactive properties. Chemically related to serotonin, LSD was initially hypothesized to produce a psychosislike state. Later, LSD was reported to have benefits in the treatment of addictions. However, widespread indiscriminate use and reports of adverse affects resulted in the classification of LSD as an illicit drug with no accepted medical use. This article reviews LSD's storied history from its discovery, to its use as a research tool, followed by its widespread association with the counterculture movement of the 1960s, and finally to its rebirth as a medicine with potential benefits in the treatment of addictions. LSD's pharmacology, phenomenology, effects at neurotransmitter receptors, and effects on patterns of gene expression are reviewed. Based upon a review of the literature, it is concluded that further research into LSD's potential as a treatment for addictions is warranted.

  19. Correlations between background events of the LSD 23.02.87 detector and Baksan telescope registered

    International Nuclear Information System (INIS)

    Alekseev, E.N.; Alekseeva, L.N.; Zakidyshev, V.N.

    1989-01-01

    After publishing the results of analysis of time correlations between events of the LSD installation and two gravitational antennas detected in the time range 1:45-3:45 UT on 23.02.87 the exchange of experimental data between LSD and the Baksan telescope was performed. Joint analysis of data from the LSD and Baksan telescope installations recorded in 1:45-3:45 UT on 23.02.87 has shown the presence of correlation between natural radioactivity and high-energy cosmic muons

  20. Reversal learning enhanced by lysergic acid diethylamide (LSD): concomitant rise in brain 5-hydroxytryptamine levels.

    Science.gov (United States)

    King, A R; Martin, I L; Melville, K A

    1974-11-01

    1 Small doses of lysergic acid diethylamide (LSD) (12.5-50 mug/kg) consistently facilitated learning of a brightness discrimination reversal.2 2-Bromo-lysergic acid diethylamide (BOL-148), a structural analogue of LSD, with similar peripheral anti-5-hydroxytrypamine activity but no psychotomimetic properties, had no effect in this learning situation at a similar dose (25 mug/kg).3 LSD, but not BOL-148, caused a small but significant increase in brain 5-hydroxytryptamine levels, but had no effect on the levels of catecholamines in the brain at 25 mug/kg.

  1. Development and validation of an ultra-fast and sensitive microflow liquid chromatography-tandem mass spectrometry (MFLC-MS/MS) method for quantification of LSD and its metabolites in plasma and application to a controlled LSD administration study in humans.

    Science.gov (United States)

    Steuer, Andrea E; Poetzsch, Michael; Stock, Lorena; Eisenbeiss, Lisa; Schmid, Yasmin; Liechti, Matthias E; Kraemer, Thomas

    2017-05-01

    Lysergic acid diethylamide (LSD) is a semi-synthetic hallucinogen that has gained popularity as a recreational drug and has been investigated as an adjunct to psychotherapy. Analysis of LSD represents a major challenge in forensic toxicology due to its instability, low drug concentrations, and short detection windows in biological samples. A new, fast, and sensitive microflow liquid chromatography (MFLC) tandem mass spectrometry method for the validated quantification of LSD, iso-LSD, 2-oxo 3-hydroxy-LSD (oxo-HO-LSD), and N-desmethyl-LSD (nor-LSD) was developed in plasma and applied to a controlled pharmacokinetic (PK) study in humans to test whether LSD metabolites would offer for longer detection windows. Five hundred microlitres of plasma were extracted by solid phase extraction. Analysis was performed on a Sciex Eksigent MFLC system coupled to a Sciex 5500 QTrap. The method was validated according to (inter)-national guidelines. MFLC allowed for separation of the mentioned analytes within 3 minutes and limits of quantification of 0.01 ng/mL. Validation criteria were fulfilled for all analytes. PK data could be calculated for LSD, iso-LSD, and oxo-HO-LSD in all participants. Additionally, hydroxy-LSD (HO-LSD) and HO-LSD glucuronide could be qualitatively detected and PK determined in 11 and 8 subjects, respectively. Nor-LSD was only sporadically detected. Elimination half-lives of iso-LSD (median 12 h) and LSD metabolites (median 9, 7.4, 12, and 11 h for oxo-HO-LSD, HO-LSD, HO-LSD-gluc, and nor-LSD, respectively) exceeded those of LSD (median 4.2 h). However, screening for metabolites to increase detection windows in plasma seems not to be constructive due to their very low concentrations. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  2. Lysergic acid diethylamide (LSD) for alcoholism: meta-analysis of randomized controlled trials.

    Science.gov (United States)

    Krebs, Teri S; Johansen, Pål-Ørjan

    2012-07-01

    Assessments of lysergic acid diethylamide (LSD) in the treatment of alcoholism have not been based on quantitative meta-analysis. Hence, we performed a meta-analysis of randomized controlled trials in order to evaluate the clinical efficacy of LSD in the treatment of alcoholism. Two reviewers independently extracted the data, pooling the effects using odds ratios (ORs) by a generic inverse variance, random effects model. We identified six eligible trials, including 536 participants. There was evidence for a beneficial effect of LSD on alcohol misuse (OR, 1.96; 95% CI, 1.36-2.84; p = 0.0003). Between-trial heterogeneity for the treatment effects was negligible (I² = 0%). Secondary outcomes, risk of bias and limitations are discussed. A single dose of LSD, in the context of various alcoholism treatment programs, is associated with a decrease in alcohol misuse.

  3. LSD, 5-HT (serotonin), and the evolution of a behavioral assay.

    Science.gov (United States)

    Appel, James B; West, William B; Buggy, James

    2004-01-01

    Research in our laboratory, supported by NIDA and facilitated by Roger Brown, has indicated that serotonergic neuronal systems are involved in the discriminative stimulus effects of LSD. However, the only compounds that fully antagonize the LSD cue act at both serotonin (5-HT) and dopamine (DA) receptors. In addition, substitution for LSD in standard drug vs. no-drug (DND) discriminations does not necessarily predict either similar mechanisms of action or hallucinogenic potency because 'false positives' occur when animals are given drugs such as lisuride (LHM), quipazine, or, possibly, yohimbine. These effects can be greatly reduced by using drug vs. drug (D-D), drug vs. drug vs. no drug (D-ND), or drug vs. ' other' drug (saline, cocaine, pentobarbital) training procedures. Additional studies, in which drugs were administered directly into the cerebral ventricles or specific brain areas, suggest that structures containing terminal fields of serotonergic neurons might be involved in the stimulus effects of LSD.

  4. ERRα protein is stabilized by LSD1 in a demethylation-independent manner.

    Directory of Open Access Journals (Sweden)

    Julie Carnesecchi

    Full Text Available The LSD1 histone demethylase is highly expressed in breast tumors where it constitutes a factor of poor prognosis and promotes traits of cancer aggressiveness such as cell invasiveness. Recent work has shown that the Estrogen-Related Receptor α (ERRα induces LSD1 to demethylate the Lys 9 of histone H3. This results in the transcriptional activation of a number of common target genes, several of which being involved in cellular invasion. High expression of ERRα protein is also a factor of poor prognosis in breast tumors. Here we show that, independently of its demethylase activities, LSD1 protects ERRα from ubiquitination, resulting in overexpression of the latter protein. Our data also suggests that the elevation of LSD1 mRNA and protein in breast cancer (as compared to normal tissue may be a key event to increase ERRα protein, independently of its corresponding mRNA.

  5. ERRα protein is stabilized by LSD1 in a demethylation-independent manner.

    Science.gov (United States)

    Carnesecchi, Julie; Cerutti, Catherine; Vanacker, Jean-Marc; Forcet, Christelle

    2017-01-01

    The LSD1 histone demethylase is highly expressed in breast tumors where it constitutes a factor of poor prognosis and promotes traits of cancer aggressiveness such as cell invasiveness. Recent work has shown that the Estrogen-Related Receptor α (ERRα) induces LSD1 to demethylate the Lys 9 of histone H3. This results in the transcriptional activation of a number of common target genes, several of which being involved in cellular invasion. High expression of ERRα protein is also a factor of poor prognosis in breast tumors. Here we show that, independently of its demethylase activities, LSD1 protects ERRα from ubiquitination, resulting in overexpression of the latter protein. Our data also suggests that the elevation of LSD1 mRNA and protein in breast cancer (as compared to normal tissue) may be a key event to increase ERRα protein, independently of its corresponding mRNA.

  6. Lsd1 regulates skeletal muscle regeneration and directs the fate of satellite cells.

    Science.gov (United States)

    Tosic, Milica; Allen, Anita; Willmann, Dominica; Lepper, Christoph; Kim, Johnny; Duteil, Delphine; Schüle, Roland

    2018-01-25

    Satellite cells are muscle stem cells required for muscle regeneration upon damage. Of note, satellite cells are bipotent and have the capacity to differentiate not only into skeletal myocytes, but also into brown adipocytes. Epigenetic mechanisms regulating fate decision and differentiation of satellite cells during muscle regeneration are not yet fully understood. Here, we show that elevated levels of lysine-specific demethylase 1 (Kdm1a, also known as Lsd1) have a beneficial effect on muscle regeneration and recovery after injury, since Lsd1 directly regulates key myogenic transcription factor genes. Importantly, selective Lsd1 ablation or inhibition in Pax7-positive satellite cells, not only delays muscle regeneration, but changes cell fate towards brown adipocytes. Lsd1 prevents brown adipocyte differentiation of satellite cells by repressing expression of the novel pro-adipogenic transcription factor Glis1. Together, downregulation of Glis1 and upregulation of the muscle-specific transcription program ensure physiological muscle regeneration.

  7. Chronic LSD alters gene expression profiles in the mPFC relevant to schizophrenia.

    Science.gov (United States)

    Martin, David A; Marona-Lewicka, Danuta; Nichols, David E; Nichols, Charles D

    2014-08-01

    Chronic administration of lysergic acid diethylamide (LSD) every other day to rats results in a variety of abnormal behaviors. These build over the 90 day course of treatment and can persist at full strength for at least several months after cessation of treatment. The behaviors are consistent with those observed in animal models of schizophrenia and include hyperactivity, reduced sucrose-preference, and decreased social interaction. In order to elucidate molecular changes that underlie these aberrant behaviors, we chronically treated rats with LSD and performed RNA-sequencing on the medial prefrontal cortex (mPFC), an area highly associated with both the actions of LSD and the pathophysiology of schizophrenia and other psychiatric illnesses. We observed widespread changes in the neurogenetic state of treated animals four weeks after cessation of LSD treatment. QPCR was used to validate a subset of gene expression changes observed with RNA-Seq, and confirmed a significant correlation between the two methods. Functional clustering analysis indicates differentially expressed genes are enriched in pathways involving neurotransmission (Drd2, Gabrb1), synaptic plasticity (Nr2a, Krox20), energy metabolism (Atp5d, Ndufa1) and neuropeptide signaling (Npy, Bdnf), among others. Many processes identified as altered by chronic LSD are also implicated in the pathogenesis of schizophrenia, and genes affected by LSD are enriched with putative schizophrenia genes. Our results provide a relatively comprehensive analysis of mPFC transcriptional regulation in response to chronic LSD, and indicate that the long-term effects of LSD may bear relevance to psychiatric illnesses, including schizophrenia. Copyright © 2014 Elsevier Ltd. All rights reserved.

  8. Interaction between LSD and dopamine D2/3 binding sites in pig brain.

    Science.gov (United States)

    Minuzzi, Luciano; Nomikos, George G; Wade, Mark R; Jensen, Svend B; Olsen, Aage K; Cumming, Paul

    2005-06-15

    The psychoactive properties of the hallucinogen LSD have frequently been attributed to high affinity interactions with serotonin 5HT2 receptors in brain. Possible effects of LSD on dopamine D2/3 receptor availability have not previously been investigated in living brain. Therefore, we used PET to map the binding potential (pB) of [11C]raclopride in brain of three pigs, first in a baseline condition, and again at 1 and 4 h after administration of LSD (2.5 microg/kg, i.v.). There was a progressive treatment effect in striatum, where the pB was significantly reduced by 19% at 4 h after LSD administration. Concomitant maps of cerebral blood flow did not reveal significant changes in perfusion during this interval. Subsequent in vitro studies showed that LSD displaced [3H]raclopride (2 nM) from pig brain cryostat sections with an IC50 of 275 nM according to a one-site model. Fitting of a two-site model to the data suggested the presence of a component of the displacement curves with a subnanomolar IC50, comprising 20% of the total [3H]raclopride binding. In microdialysis experiments, LSD at similar and higher doses did not evoke changes in the interstitial concentration of dopamine or its acidic metabolites in rat striatum. Together, these results are consistent with a direct interaction between LSD and a portion of dopamine D2/3 receptors in pig brain, possibly contributing to the psychopharmacology of LSD. (c) 2005 Wiley-Liss, Inc.

  9. Lysergic acid diethylamide (LSD) administration selectively downregulates serotonin2 receptors in rat brain.

    Science.gov (United States)

    Buckholtz, N S; Zhou, D F; Freedman, D X; Potter, W Z

    1990-04-01

    A dosage regimen of lysergic acid diethylamide (LSD) that reliably produces behavioral tolerance in rats was evaluated for effects on neurotransmitter receptor binding in rat brain using a variety of radioligands selective for amine receptor subtypes. Daily administration of LSD [130 micrograms/kg (0.27 mumol/kg) intraperitoneally (IP)] for 5 days produced a decrease in serotonin2 (5-hydroxytryptamine2, 5-HT2) binding in cortex (measured 24 hours after the last drug administration) but did not affect binding to other receptor systems (5-HT1A, 5-HT1B, beta-adrenergic, alpha 1- or alpha 2-adrenergic, D2-dopaminergic) or to a recognition site for 5-HT uptake. The decrease was evident within 3 days of LSD administration but was not demonstrable after the first LSD dose. Following 5 days of LSD administration the decrease was still present 48 hours, but not 96 hours, after the last administration. The indole hallucinogen psilocybin [1.0 mg/kg (3.5 mumol/kg) for 8 days] also produced a significant decrease in 5HT2 binding, but neither the nonhallucinogenic analog bromo-LSD [1.3 mg/kg (2.4 mumol/kg) for 5 days] nor mescaline [10 mg/kg (40.3 mumol/kg) for 5 or 10 days] affected 5-HT2 binding. These observations suggest that LSD and other indole hallucinogens may act as 5-HT2 agonists at postsynaptic 5-HT2 receptors. Decreased 5-HT2 binding strikingly parallels the development and loss of behavioral tolerance seen with repeated LSD administration, but the decreased binding per se cannot explain the gamut of behavioral tolerance and cross-tolerance phenomena among the indole and phenylethylamine hallucinogens.

  10. Did you get any help? A post-hoc secondary analysis of a randomized controlled trial of psychoeducation for patients with antisocial personality disorder in outpatient substance abuse treatment programs.

    Science.gov (United States)

    Thylstrup, Birgitte; Schrøder, Sidsel; Fridell, Mats; Hesse, Morten

    2017-01-09

    People in treatment for substance use disorder commonly have comorbid personality disorders, including antisocial personality disorder. Little is known about treatments that specifically address comorbid antisocial personality disorder. Self-rated help received for antisocial personality disorder was assessed during follow-ups at 3, 9 and 15 months post-randomization of a randomized trial of psychoeducation for people with comorbid substance use and antisocial personality disorder (n = 175). Randomization to psychoeducation was associated with increased perceived help for antisocial personality disorder. Perceived help for antisocial personality disorder was in turn associated with more days abstinent and higher treatment satisfaction at the 3-month follow-up, and reduced risk of dropping out of treatment after the 3-month follow-up, and perceived help mediated the effects of random assignment on days abstinent at 3-month. Brief psychoeducation for antisocial personality disorder increased patients' self-rated help for antisocial personality disorder in substance abuse treatment, and reporting having received help for antisocial personality disorder was in turn associated with better short-term outcomes, e.g., days abstinent, dropout from treatment and treatment satisfaction. ISRCTN registry, ISRCTN67266318 , retrospectively registered 17/7/2012.

  11. High titers of both rheumatoid factor and anti-CCP antibodies at baseline in patients with rheumatoid arthritis are associated with increased circulating baseline TNF level, low drug levels, and reduced clinical responses: a post hoc analysis of the RISING study.

    Science.gov (United States)

    Takeuchi, Tsutomu; Miyasaka, Nobuyuki; Inui, Takashi; Yano, Toshiro; Yoshinari, Toru; Abe, Tohru; Koike, Takao

    2017-09-02

    Although both rheumatoid factor (RF) and anticyclic citrullinated peptide antibodies (anti-CCP) are useful for diagnosing rheumatoid arthritis (RA), the impact of these autoantibodies on the efficacy of tumor necrosis factor (TNF) inhibitors has been controversial. The aim of this post hoc analysis of a randomized double-blind study (the RISING study) was to investigate the influences of RF and anti-CCP on the clinical response to infliximab in patients with RA. Methotrexate-refractory patients with RA received 3 mg/kg of infliximab from weeks 0 to 6 and then 3, 6, or 10 mg/kg every 8 weeks from weeks 14 to 46. In this post hoc analysis, patients were stratified into three classes on the basis of baseline RF/anti-CCP titers: "low/low-C" (RF < 55 IU/ml, anti-CCP < 42 U/ml), "high/high-C" (RF ≥ 160 IU/ml, anti-CCP ≥ 100 U/ml), and "middle-C" (neither low/low-C nor high/high-C). Baseline plasma TNF level, serum infliximab level, and disease activity were compared between the three classes. Baseline RF and anti-CCP titers showed significant correlations with baseline TNF and infliximab levels in weeks 2-14. Comparison of the three classes showed that baseline TNF level was lowest in the low/low-C group and highest in the high/high-C group (median 0.73 versus 1.15 pg/ml), that infliximab levels at week 14 were highest in the low/low-C group and lowest in the high/high-C group (median 1.0 versus 0.1 μg/ml), and that Disease Activity Score in 28 joints based on C-reactive protein at week 14 was lowest in the low/low-C group and highest in the high/high-C group (median 3.17 versus 3.82). A similar correlation was observed at week 54 in the 3 mg/kg dosing group, but not in the 6 or 10 mg/kg group. Significant decreases in both RF and anti-CCP were observed during infliximab treatment. RF/anti-CCP titers correlated with TNF level. This might explain the association of RF/anti-CCP with infliximab level and clinical response in patients with RA

  12. Effects of LSD on grooming behavior in serotonin transporter heterozygous (Sert⁺/⁻) mice.

    Science.gov (United States)

    Kyzar, Evan J; Stewart, Adam Michael; Kalueff, Allan V

    2016-01-01

    Serotonin (5-HT) plays a crucial role in the brain, modulating mood, cognition and reward. The serotonin transporter (SERT) is responsible for the reuptake of 5-HT from the synaptic cleft and regulates serotonin signaling in the brain. In humans, SERT genetic variance is linked to the pathogenesis of various psychiatric disorders, including anxiety, autism spectrum disorders (ASD) and obsessive-compulsive disorder (OCD). Rodent self-grooming is a complex, evolutionarily conserved patterned behavior relevant to stress, ASD and OCD. Genetic ablation of mouse Sert causes various behavioral deficits, including increased anxiety and grooming behavior. The hallucinogenic drug lysergic acid diethylamide (LSD) is a potent serotonergic agonist known to modulate human and animal behavior. Here, we examined heterozygous Sert(+/-) mouse behavior following acute administration of LSD (0.32 mg/kg). Overall, Sert(+/-) mice displayed a longer duration of self-grooming behavior regardless of LSD treatment. In contrast, LSD increased serotonin-sensitive behaviors, such as head twitching, tremors and backwards gait behaviors in both Sert(+/+) and Sert(+/-) mice. There were no significant interactions between LSD treatment and Sert gene dosage in any of the behavioral domains measured. These results suggest that Sert(+/-) mice may respond to the behavioral effects of LSD in a similar manner to wild-type mice. Copyright © 2015 Elsevier B.V. All rights reserved.

  13. Transrepressive Function of TLX Requires the Histone Demethylase LSD1 ▿ †

    Science.gov (United States)

    Yokoyama, Atsushi; Takezawa, Shinichiro; Schüle, Roland; Kitagawa, Hirochika; Kato, Shigeaki

    2008-01-01

    TLX is an orphan nuclear receptor (also called NR2E1) that regulates the expression of target genes by functioning as a constitutive transrepressor. The physiological significance of TLX in the cytodifferentiation of neural cells in the brain is known. However, the corepressors supporting the transrepressive function of TLX have yet to be identified. In this report, Y79 retinoblastoma cells were subjected to biochemical techniques to purify proteins that interact with TLX, and we identified LSD1 (also called KDM1), which appears to form a complex with CoREST and histone deacetylase 1. LSD1 interacted with TLX directly through its SWIRM and amine oxidase domains. LSD1 potentiated the transrepressive function of TLX through its histone demethylase activity as determined by a luciferase assay using a genomically integrated reporter gene. LSD1 and TLX were recruited to a TLX-binding site in the PTEN gene promoter, accompanied by the demethylation of H3K4me2 and deacetylation of H3. Knockdown of either TLX or LSD1 derepressed expression of the endogenous PTEN gene and inhibited cell proliferation of Y79 cells. Thus, the present study suggests that LSD1 is a prime corepressor for TLX. PMID:18391013

  14. d-Lysergic Acid Diethylamide (LSD as a Model of Psychosis: Mechanism of Action and Pharmacology

    Directory of Open Access Journals (Sweden)

    Danilo De Gregorio

    2016-11-01

    Full Text Available d-Lysergic Acid Diethylamide (LSD is known for its hallucinogenic properties and psychotic-like symptoms, especially at high doses. It is indeed used as a pharmacological model of psychosis in preclinical research. The goal of this review was to understand the mechanism of action of psychotic-like effects of LSD. We searched Pubmed, Web of Science, Scopus, Google Scholar and articles’ reference lists for preclinical studies regarding the mechanism of action involved in the psychotic-like effects induced by LSD. LSD’s mechanism of action is pleiotropic, primarily mediated by the serotonergic system in the Dorsal Raphe, binding the 5-HT2A receptor as a partial agonist and 5-HT1A as an agonist. LSD also modulates the Ventral Tegmental Area, at higher doses, by stimulating dopamine D2, Trace Amine Associate receptor 1 (TAAR1 and 5-HT2A. More studies clarifying the mechanism of action of the psychotic-like symptoms or psychosis induced by LSD in humans are needed. LSD’s effects are mediated by a pleiotropic mechanism involving serotonergic, dopaminergic, and glutamatergic neurotransmission. Thus, the LSD-induced psychosis is a useful model to test the therapeutic efficacy of potential novel antipsychotic drugs, particularly drugs with dual serotonergic and dopaminergic (DA mechanism or acting on TAAR1 receptors.

  15. ERRα induces H3K9 demethylation by LSD1 to promote cell invasion

    Science.gov (United States)

    Carnesecchi, Julie; Forcet, Christelle; Zhang, Ling; Tribollet, Violaine; Barenton, Bruno; Boudra, Rafik; Cerutti, Catherine; Billas, Isabelle M. L.; Sérandour, Aurélien A.; Carroll, Jason S.; Beaudoin, Claude; Vanacker, Jean-Marc

    2017-01-01

    Lysine Specific Demethylase 1 (LSD1) removes mono- and dimethyl groups from lysine 4 of histone H3 (H3K4) or H3K9, resulting in repressive or activating (respectively) transcriptional histone marks. The mechanisms that control the balance between these two antagonist activities are not understood. We here show that LSD1 and the orphan nuclear receptor estrogen-related receptor α (ERRα) display commonly activated genes. Transcriptional activation by LSD1 and ERRα involves H3K9 demethylation at the transcriptional start site (TSS). Strikingly, ERRα is sufficient to induce LSD1 to demethylate H3K9 in vitro. The relevance of this mechanism is highlighted by functional data. LSD1 and ERRα coregulate several target genes involved in cell migration, including the MMP1 matrix metallo-protease, also activated through H3K9 demethylation at the TSS. Depletion of LSD1 or ERRα reduces the cellular capacity to invade the extracellular matrix, a phenomenon that is rescued by MMP1 reexpression. Altogether our results identify a regulatory network involving a direct switch in the biochemical activities of a histone demethylase, leading to increased cell invasion. PMID:28348226

  16. ERRα induces H3K9 demethylation by LSD1 to promote cell invasion.

    Science.gov (United States)

    Carnesecchi, Julie; Forcet, Christelle; Zhang, Ling; Tribollet, Violaine; Barenton, Bruno; Boudra, Rafik; Cerutti, Catherine; Billas, Isabelle M L; Sérandour, Aurélien A; Carroll, Jason S; Beaudoin, Claude; Vanacker, Jean-Marc

    2017-04-11

    Lysine Specific Demethylase 1 (LSD1) removes mono- and dimethyl groups from lysine 4 of histone H3 (H3K4) or H3K9, resulting in repressive or activating (respectively) transcriptional histone marks. The mechanisms that control the balance between these two antagonist activities are not understood. We here show that LSD1 and the orphan nuclear receptor estrogen-related receptor α (ERRα) display commonly activated genes. Transcriptional activation by LSD1 and ERRα involves H3K9 demethylation at the transcriptional start site (TSS). Strikingly, ERRα is sufficient to induce LSD1 to demethylate H3K9 in vitro. The relevance of this mechanism is highlighted by functional data. LSD1 and ERRα coregulate several target genes involved in cell migration, including the MMP1 matrix metallo-protease, also activated through H3K9 demethylation at the TSS. Depletion of LSD1 or ERRα reduces the cellular capacity to invade the extracellular matrix, a phenomenon that is rescued by MMP1 reexpression. Altogether our results identify a regulatory network involving a direct switch in the biochemical activities of a histone demethylase, leading to increased cell invasion.

  17. Crystal structure of histone demethylase LSD1 and tranylcypromine at 2.25 A

    International Nuclear Information System (INIS)

    Mimasu, Shinya; Sengoku, Toru; Fukuzawa, Seketsu; Umehara, Takashi; Yokoyama, Shigeyuki

    2008-01-01

    Transcriptional activity and chromatin structure accessibility are correlated with the methylation of specific histone residues. Lysine-specific demethylase 1 (LSD1) is the first discovered histone demethylase, which demethylates Lys4 or Lys9 of histone H3, using FAD. Among the known monoamine oxidase inhibitors, tranylcypromine (Parnate) showed the most potent inhibitory effect on LSD1. Recently, the crystal structure of LSD1 and tranylcypromine was solved at 2.75 A, revealing a five-membered ring fused to the flavin of LSD1. In this study, we refined the crystal structure of the LSD1-tranylcypromine complex to 2.25 A. The five-membered ring model did not fit completely with the electron density, giving R work /R free values of 0.226/0.254. On the other hand, the N(5) adduct gave the lowest R work /R free values of 0.218/0.248, among the tested models. These results imply that the LSD1-tranylcypromine complex is not completely composed of the five-membered adduct, but partially contains an intermediate, such as the N(5) adduct

  18. LSD treatment in Scandinavia: emphasizing indications and short-term treatment outcomes of 151 patients in Denmark.

    Science.gov (United States)

    Larsen, Jens Knud

    2017-10-01

    New research has suggested the clinical use of lysergic acid diethylamide (LSD) and psilocybin in selected patient populations. However, concerns about the clinical use of LSD were advanced in a large Danish follow-up study that assessed 151 LSD-treated psychiatric patients approximately 25 years after their treatment in the 1960s. The purpose of the present study was to give a retrospective account of the short-term outcome of LSD treatment in these 151 Danish psychiatric patients. The LSD case material in the Danish State Archives consists of medical case records of 151 LSD-treated patients, who complained and received economic compensation with the LSD Damages Law. The author carefully read and reviewed the LSD case material. LSD was used to treat a wide spectrum of mental disorders. Independent of diagnoses, 52 patients improved, and 48 patients worsened acutely with the LSD treatment. In a subgroup of 82 neurotic patients, the LSD dose-index (number of treatments multiplied by the maximal LSD dose) indicated the risk of acute worsening. In another subgroup of 19 patients with obsessive-compulsive neurosis, five patients later underwent psychosurgery. A small subgroup of 12 patients was treated with psilocybin. The long-term outcome was poor in most of the patients. Despite the significant limitations to a retrospective design, this database warrants caution in mental health patients. The use of LSD and psilocybin in mental health patients may be associated with serious short- and long-term side effects. Until further trials with rigorous designs have cleared these drugs of their potential harms, their clinical utility in these groups of patients has not been fully clarified.

  19. Development and validation of a rapid turboflow LC-MS/MS method for the quantification of LSD and 2-oxo-3-hydroxy LSD in serum and urine samples of emergency toxicological cases.

    Science.gov (United States)

    Dolder, Patrick C; Liechti, Matthias E; Rentsch, Katharina M

    2015-02-01

    Lysergic acid diethylamide (LSD) is a widely used recreational drug. The aim of the present study is to develop a quantitative turboflow LC-MS/MS method that can be used for rapid quantification of LSD and its main metabolite 2-oxo-3-hydroxy LSD (O-H-LSD) in serum and urine in emergency toxicological cases without time-consuming extraction steps. The method was developed on an ion-trap LC-MS/MS instrument coupled to a turbulent-flow extraction system. The validation data showed no significant matrix effects and no ion suppression has been observed in serum and urine. Mean intraday accuracy and precision for LSD were 101 and 6.84%, in urine samples and 97.40 and 5.89% in serum, respectively. For O-H-LSD, the respective values were 97.50 and 4.99% in urine and 107 and 4.70% in serum. Mean interday accuracy and precision for LSD were 100 and 8.26% in urine and 101 and 6.56% in serum, respectively. For O-H-LSD, the respective values were 101 and 8.11% in urine and 99.8 and 8.35% in serum, respectively. The lower limit of quantification for LSD was determined to be 0.1 ng/ml. LSD concentrations in serum were expected to be up to 8 ng/ml. 2-Oxo-3-hydroxy LSD concentrations in urine up to 250 ng/ml. The new method was accurate and precise in the range of expected serum and urine concentrations in patients with a suspected LSD intoxication. Until now, the method has been applied in five cases with suspected LSD intoxication where the intake of the drug has been verified four times with LSD concentrations in serum in the range of 1.80-14.70 ng/ml and once with a LSD concentration of 1.25 ng/ml in urine. In serum of two patients, the O-H-LSD concentration was determined to be 0.99 and 0.45 ng/ml. In the urine of a third patient, the O-H-LSD concentration was 9.70 ng/ml.

  20. Anti-citrullinated peptide antibodies are the strongest predictor of clinically relevant radiographic progression in rheumatoid arthritis patients achieving remission or low disease activity: A post hoc analysis of a nationwide cohort in Japan.

    Directory of Open Access Journals (Sweden)

    Tomohiro Koga

    Full Text Available To determine prognostic factors of clinically relevant radiographic progression (CRRP in patients with rheumatoid arthritis (RA achieving remission or low disease activity (LDA in clinical practice.Using data from a nationwide, multicenter, prospective study in Japan, we evaluated 198 biological disease-modifying antirheumatic drug (bDMARD-naïve RA patients who were in remission or had LDA at study entry after being treated with conventional synthetic DMARDs (csDMARDs. CRRP was defined as the yearly progression of modified total Sharp score (mTSS >3.0 U. We performed a multiple logistic regression analysis to explore the factors to predict CRRP at 1 year. We used receiver operating characteristic (ROC curve to estimate the performance of relevant variables for predicting CRRP.The mean Disease Activity Score in 28 joints-erythrocyte sedimentation rate (DAS28-ESR was 2.32 ± 0.58 at study entry. During the 1-year observation, remission or LDA persisted in 72% of the patients. CRRP was observed in 7.6% of the patients. The multiple logistic regression analysis revealed that the independent variables to predict the development of CRRP were: anti-citrullinated peptide antibodies (ACPA positivity at baseline (OR = 15.2, 95%CI 2.64-299, time-integrated DAS28-ESR during the 1 year post-baseline (7.85-unit increase, OR = 1.83, 95%CI 1.03-3.45, and the mTSS at baseline (13-unit increase, OR = 1.22, 95%CI 1.06-1.42.ACPA positivity was the strongest independent predictor of CRRP in patients with RA in remission or LDA. Physicians should recognize ACPA as a poor-prognosis factor regarding the radiographic outcome of RA, even among patients showing a clinically favorable response to DMARDs.

  1. Cytoarchitecture of the human lateral occipital cortex: mapping of two extrastriate areas hOc4la and hOc4lp.

    Science.gov (United States)

    Malikovic, Aleksandar; Amunts, Katrin; Schleicher, Axel; Mohlberg, Hartmut; Kujovic, Milenko; Palomero-Gallagher, Nicola; Eickhoff, Simon B; Zilles, Karl

    2016-05-01

    The microstructural correlates of the functional segregation of the human lateral occipital cortex are largely unknown. Therefore, we analyzed the cytoarchitecture of this region in ten human post-mortem brains using an observer-independent and statistically testable parcellation method to define the position and extent of areas in the lateral occipital cortex. Two new cytoarchitectonic areas were found: an anterior area hOc4la and a posterior area hOc4lp. hOc4la was located behind the anterior occipital sulcus in rostral and ventral portions of this region where it occupies the anterior third of the middle and inferior lateral occipital gyri. hOc4lp was found in caudal and dorsal portions of this region where it extends along the superior and middle lateral occipital gyri. The cytoarchitectonic areas were registered to 3D reconstructions of the corresponding brains, which were subsequently spatially normalized to the Montreal Neurological Institute reference space. Continuous probabilistic maps of both areas based on the analysis of ten brains were generated to characterize their inter-subject variability in location and size. The maps of hOc4la and hOc4lp were then used as seeds for meta-analytic connectivity modeling and quantitative functional decoding to identify their co-activation patterns and assignment to functional domains. Convergent evidence from their location, topography, size, functional domains and connectivity indicates that hOc4la and hOc4lp are the potential anatomical correlates of the functionally defined lateral occipital areas LO-1 and LO-2.

  2. Research of Ad Hoc Networks Access Algorithm

    Science.gov (United States)

    Xiang, Ma

    With the continuous development of mobile communication technology, Ad Hoc access network has become a hot research, Ad Hoc access network nodes can be used to expand capacity of multi-hop communication range of mobile communication system, even business adjacent to the community, improve edge data rates. When the ad hoc network is the access network of the internet, the gateway discovery protocol is very important to choose the most appropriate gateway to guarantee the connectivity between ad hoc network and IP based fixed networks. The paper proposes a QoS gateway discovery protocol which uses the time delay and stable route to the gateway selection conditions. And according to the gateway discovery protocol, it also proposes a fast handover scheme which can decrease the handover time and improve the handover efficiency.

  3. Model checking mobile ad hoc networks

    NARCIS (Netherlands)

    Ghassemi, Fatemeh; Fokkink, Wan

    2016-01-01

    Modeling arbitrary connectivity changes within mobile ad hoc networks (MANETs) makes application of automated formal verification challenging. We use constrained labeled transition systems as a semantic model to represent mobility. To model check MANET protocols with respect to the underlying

  4. Automated extraction of lysergic acid diethylamide (LSD) and N-demethyl-LSD from blood, serum, plasma, and urine samples using the Zymark RapidTrace with LC/MS/MS confirmation.

    Science.gov (United States)

    de Kanel, J; Vickery, W E; Waldner, B; Monahan, R M; Diamond, F X

    1998-05-01

    A forensic procedure for the quantitative confirmation of lysergic acid diethylamide (LSD) and the qualitative confirmation of its metabolite, N-demethyl-LSD, in blood, serum, plasma, and urine samples is presented. The Zymark RapidTrace was used to perform fully automated solid-phase extractions of all specimen types. After extract evaporation, confirmations were performed using liquid chromatography (LC) followed by positive electrospray ionization (ESI+) mass spectrometry/mass spectrometry (MS/MS) without derivatization. Quantitation of LSD was accomplished using LSD-d3 as an internal standard. The limit of quantitation (LOQ) for LSD was 0.05 ng/mL. The limit of detection (LOD) for both LSD and N-demethyl-LSD was 0.025 ng/mL. The recovery of LSD was greater than 95% at levels of 0.1 ng/mL and 2.0 ng/mL. For LSD at 1.0 ng/mL, the within-run and between-run (different day) relative standard deviation (RSD) was 2.2% and 4.4%, respectively.

  5. Chronic intraventricular administration of lysergic acid diethylamide (LSD) affects the sensitivity of cortical cells to monocular deprivation.

    Science.gov (United States)

    McCall, M A; Tieman, D G; Hirsch, H V

    1982-11-04

    In kittens, but not in adult cats, depriving one eye of pattern vision by suturing the lids shut (monocular deprivation or MD) for one week reduces the proportion of binocular units in the visual cortex. A sensitivity of cortical units in adult cats to MD can be produced by infusing exogenous monoamines into the visual cortex. Since LSD interacts with monoamines, we have examined the effects of chronic administration of LSD on the sensitivity to MD for cortical cells in adult cats. Cats were assigned randomly to one of four conditions: MD/LSD, MD/No-LSD, No-MD/LSD, No-MD/No-LSD. An osmotic minipump delivered either LSD or the vehicle solution alone during a one-week period of MD. The animals showed no obvious anomalies during the administration of the drug. After one week the response properties of single units in area 17 of the visual cortex were studied without knowledge of the contents of the individual minipumps. With the exception of ocular dominance, the response properties of units recorded in all animals did not differ from normal. In the control animals (MD/No-LSD, No-MD/LSD, No-MD/No-LSD) the average proportion of binocular cells was 78%; similar to that observed for normal adult cats. However, in the experimental animals, which received LSD during the period of MD, only 52% of the cells were binocular. Our results suggest that chronic intraventricular administration of LSD affects either directly or indirectly the sensitivity of cortical neurons to MD.

  6. Increased Global Functional Connectivity Correlates with LSD-Induced Ego Dissolution.

    Science.gov (United States)

    Tagliazucchi, Enzo; Roseman, Leor; Kaelen, Mendel; Orban, Csaba; Muthukumaraswamy, Suresh D; Murphy, Kevin; Laufs, Helmut; Leech, Robert; McGonigle, John; Crossley, Nicolas; Bullmore, Edward; Williams, Tim; Bolstridge, Mark; Feilding, Amanda; Nutt, David J; Carhart-Harris, Robin

    2016-04-25

    Lysergic acid diethylamide (LSD) is a non-selective serotonin-receptor agonist that was first synthesized in 1938 and identified as (potently) psychoactive in 1943. Psychedelics have been used by indigenous cultures for millennia [1]; however, because of LSD's unique potency and the timing of its discovery (coinciding with a period of major discovery in psychopharmacology), it is generally regarded as the quintessential contemporary psychedelic [2]. LSD has profound modulatory effects on consciousness and was used extensively in psychological research and psychiatric practice in the 1950s and 1960s [3]. In spite of this, however, there have been no modern human imaging studies of its acute effects on the brain. Here we studied the effects of LSD on intrinsic functional connectivity within the human brain using fMRI. High-level association cortices (partially overlapping with the default-mode, salience, and frontoparietal attention networks) and the thalamus showed increased global connectivity under the drug. The cortical areas showing increased global connectivity overlapped significantly with a map of serotonin 2A (5-HT2A) receptor densities (the key site of action of psychedelic drugs [4]). LSD also increased global integration by inflating the level of communication between normally distinct brain networks. The increase in global connectivity observed under LSD correlated with subjective reports of "ego dissolution." The present results provide the first evidence that LSD selectively expands global connectivity in the brain, compromising the brain's modular and "rich-club" organization and, simultaneously, the perceptual boundaries between the self and the environment. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. Ad Hoc Access Gateway Selection Algorithm

    Science.gov (United States)

    Jie, Liu

    With the continuous development of mobile communication technology, Ad Hoc access network has become a hot research, Ad Hoc access network nodes can be used to expand capacity of multi-hop communication range of mobile communication system, even business adjacent to the community, improve edge data rates. For mobile nodes in Ad Hoc network to internet, internet communications in the peer nodes must be achieved through the gateway. Therefore, the key Ad Hoc Access Networks will focus on the discovery gateway, as well as gateway selection in the case of multi-gateway and handover problems between different gateways. This paper considers the mobile node and the gateway, based on the average number of hops from an average access time and the stability of routes, improved gateway selection algorithm were proposed. An improved gateway selection algorithm, which mainly considers the algorithm can improve the access time of Ad Hoc nodes and the continuity of communication between the gateways, were proposed. This can improve the quality of communication across the network.

  8. Quantification of LSD in illicit samples by high performance liquid chromatography

    Directory of Open Access Journals (Sweden)

    Pablo Alves Marinho

    2010-12-01

    Full Text Available In the present study, a method using high performance liquid chromatography to quantify LSD, in blotter papers seized in Minas Gerais, was optimized and validated. Linearity, precision, recovery, limits of detection and quantification, and selectivity were the parameters used to evaluate performance. The samples were extracted with methanol:water (1: 1 in an ultra-sound bath. The linearity between 0.05 and 20.00 μg/mL (0.5 and 200.0μg of LSD/blotter was observed with satisfactory mean intra and inter assay precision (RSDr = 4.4% and RSD R = 6.4%, respectively and with mean recoveries of 83.4% and 84.9% to the levels of 1.00 and 20.00 μg/mL (10 and 200μg LSD/blotter. The limits of detection and quantification were 0.01 and 0.05 μg/mL, respectively (0.1 and 0.5 μg of LSD/blotter. The samples of blotters (n =22 were analyzed and the mean value of 67.55 μg of LSD/blotter (RSD=27.5% was found. Thus, the method used showed satisfactory analytical performance, and proved suitable as an analytical tool for LSD determination in illicit samples seized by police forces.No presente trabalho, um método utilizando cromatografia líquida de alta eficiência foi otimizado e validado para quantificar o LSD em selos apreendidos em Minas Gerais. A linearidade, precisão, recuperação, limites de detecção e quantificação e seletividade foram os parâmetros de desempenho avaliados. As amostras foram extraídas com metanol: água (1:1 em banho de ultra-som. A linearidade entre 0,05 a 20,00 mg/mL (0,5 a 200 μg LSD/blotter foi observada com precisão média, intra e inter ensaio, satisfatória (RSDr = 4,4% e RSD R = 6,4%, respectivamente e com recuperações médias de 83,4% e 84,9% para os níveis de LSD de 1,00 e 20,00 mg/mL (10 e 200 μg LSD/selo. Os limites de detecção e quantificação encontrados foram de 0,01 e 0,05 mg/mL, respectivamente (0,1 e 0,5 μg LSD/selo. As amostras de selos (n = 22 foram analisadas e o valor médio encontrado foi de 67

  9. The 11th Annual Mediterranean Ad Hoc Networking Workshop (Med-Hoc-Net 2012)

    NARCIS (Netherlands)

    Pitsillides, A.; Douligeris, C.; Vassiliou, V.; Heijenk, Geert; Cavalcante de Oliveira, J.

    Message from the General Chairs Welcome to the 2012 Mediterranean Ad Hoc Networking Workshop in Ayia Napa, Cyprus. We are excited to host Med-Hoc-Net. As a major annual international workshop, following recent successful workshops in Sicily (2006), Corfu (2007), Palma de Mallorca (2008), Haifa

  10. LSD Flashbacks - The Appearance of New Visual Imagery Not Experienced During Initial Intoxication: Two Case Reports.

    Science.gov (United States)

    G Lerner, Arturo; Goodman, Craig; Rudinski, Dmitri; Lev-Ran, Shaul

    2014-01-01

    A side effect associated with the use of synthetic hallucinogens such as lysergic acid diethylamide-(LSD) is the partial or total recurrence of perceptual disturbances which previously appeared during intoxication, despite absence of recent use. These are commonly referred to as "flashbacks" or Hallucinogen Persisting Perception Disorder (HPPD). Here we present two cases of patients with a prior history of LSD use who turned to psychiatric consultation following brief episodes of HPPD. Surprisingly, in both cases new visual imagery appeared during episodes of flashbacks which was not experienced during primary LSD use. Both subjects reported the ability to discern between LSD-associated visual disturbances and new visual imagery. This phenomenon did not cause functional impairment and in both cases caused gradual concern due to its persistence. Both patients refused medical treatment and continued psychiatric follow-up. At one year follow-up both patients reported almost complete spontaneous remission. To the best of our knowledge these are the first reported cases of LSD-related benign flashbacks in which new imagery is experienced. Reasons for this reversible and apparently harmless side effect are proposed. Conclusions from case reports should be taken with caution.

  11. Efficacy and enlightenment: LSD psychotherapy and the Drug Amendments of 1962.

    Science.gov (United States)

    Oram, Matthew

    2014-04-01

    The decline in therapeutic research with lysergic acid diethylamide (LSD) in the United States over the course of the 1960s has commonly been attributed to the growing controversy surrounding its recreational use. However, research difficulties played an equal role in LSD psychotherapy's demise, as they frustrated researchers' efforts to clearly establish the efficacy of treatment. Once the Kefauver Harris Drug Amendments of 1962 introduced the requirement that proof of efficacy be established through controlled clinical trials before a drug could be approved to market, the value of clinical research became increasingly dependent on the scientific rigor of the trial's design. LSD psychotherapy's complex method of utilizing drug effects to catalyze a psychological treatment clashed with the controlled trial methodology on both theoretical and practical levels, making proof of efficacy difficult to obtain. Through a close examination of clinical trials performed after 1962, this article explores how the new emphasis on controlled clinical trials frustrated the progress of LSD psychotherapy research by focusing researchers' attention on trial design to the detriment of their therapeutic method. This analysis provides a new perspective on the death of LSD psychotherapy and explores the implications of the Drug Amendments of 1962.

  12. LSD1 activates a lethal prostate cancer gene network independently of its demethylase function.

    Science.gov (United States)

    Sehrawat, Archana; Gao, Lina; Wang, Yuliang; Bankhead, Armand; McWeeney, Shannon K; King, Carly J; Schwartzman, Jacob; Urrutia, Joshua; Bisson, William H; Coleman, Daniel J; Joshi, Sunil K; Kim, Dae-Hwan; Sampson, David A; Weinmann, Sheila; Kallakury, Bhaskar V S; Berry, Deborah L; Haque, Reina; Van Den Eeden, Stephen K; Sharma, Sunil; Bearss, Jared; Beer, Tomasz M; Thomas, George V; Heiser, Laura M; Alumkal, Joshi J

    2018-05-01

    Medical castration that interferes with androgen receptor (AR) function is the principal treatment for advanced prostate cancer. However, clinical progression is universal, and tumors with AR-independent resistance mechanisms appear to be increasing in frequency. Consequently, there is an urgent need to develop new treatments targeting molecular pathways enriched in lethal prostate cancer. Lysine-specific demethylase 1 (LSD1) is a histone demethylase and an important regulator of gene expression. Here, we show that LSD1 promotes the survival of prostate cancer cells, including those that are castration-resistant, independently of its demethylase function and of the AR. Importantly, this effect is explained in part by activation of a lethal prostate cancer gene network in collaboration with LSD1's binding protein, ZNF217. Finally, that a small-molecule LSD1 inhibitor-SP-2509-blocks important demethylase-independent functions and suppresses castration-resistant prostate cancer cell viability demonstrates the potential of LSD1 inhibition in this disease.

  13. Interaction of D-LSD with binding sites in brain: a study in vivo and in vitro

    International Nuclear Information System (INIS)

    Ebersole, B.L.J.

    1985-01-01

    The localization of [ 3 H]-d-lysergic acid diethylamide ([ 3 H]LSD) binding sites in the mouse brain was compared in vivo and in vitro. Radioautography of brain sections incubated with [ 3 H]LSD in vitro revealed substantial specific [ 3 H]LSD binding in cortical layers III-IV and areas CA1 and dentate gyrus in hippocampus. In contrast, in brain sections from animals that received [ 3 H]LSD in vivo, binding in hippocampus was scant and diffuse, although the pattern of labeling in cortex was similar to that seen in vitro. The low specific binding in hippocampus relative to cortex was confirmed by homogenate filtration studies of brain areas from mice that received injections of [ 3 H]LSD. Time-course studies established that peak specific binding at ten minutes was the same in cortex and hippocampus. At all times, binding in hippocampus was about one-third of that in cortex; in contrast, the concentration of free [ 3 H]LSD did not vary between regions. This finding was unexpected, because binding studies in vitro in membrane preparations indicated that the density and affinity of [ 3 H]LSD binding sites were similar in both brain regions. Saturation binding studies in vivo showed that the lower amount of [ 3 H]LSD binding in hippocampus was attributable to a lower density of sites labeled by [ 3 H]LSD. The pharmacological identify of [ 3 H]LSD binding sites in vivo may be relevant to the hallucinogenic properties of LSD and of other related hallucinogens

  14. Ad hoc networks telecommunications and game theory

    CERN Document Server

    Benslama, Malek; Batatia, Hadj

    2015-01-01

    Random SALOHA and CSMA protocols that are used to access MAC in ad hoc networks are very small compared to the multiple and spontaneous use of the transmission channel. So they have low immunity to the problems of packet collisions. Indeed, the transmission time is the critical factor in the operation of such networks. The simulations demonstrate the positive impact of erasure codes on the throughput of the transmission in ad hoc networks. However, the network still suffers from the intermittency and volatility of its efficiency throughout its operation, and it switches quickly to the satura

  15. Vehicular ad hoc network security and privacy

    CERN Document Server

    Lin, X

    2015-01-01

    Unlike any other book in this area, this book provides innovative solutions to security issues, making this book a must read for anyone working with or studying security measures. Vehicular Ad Hoc Network Security and Privacy mainly focuses on security and privacy issues related to vehicular communication systems. It begins with a comprehensive introduction to vehicular ad hoc network and its unique security threats and privacy concerns and then illustrates how to address those challenges in highly dynamic and large size wireless network environments from multiple perspectives. This book is richly illustrated with detailed designs and results for approaching security and privacy threats.

  16. Prohibited or regulated? LSD psychotherapy and the United States Food and Drug Administration.

    Science.gov (United States)

    Oram, Matthew

    2016-09-01

    Over the 1950s and early 1960s, the use of the hallucinogenic drug lysergic acid diethylamide (LSD) to facilitate psychotherapy was a promising field of psychiatric research in the USA. However, during the 1960s, research began to decline, before coming to a complete halt in the mid-1970s. This has commonly been explained through the increase in prohibitive federal regulations during the 1960s that aimed to curb the growing recreational use of the drug. However, closely examining the Food and Drug Administration's regulation of LSD research in the 1960s will reveal that not only was LSD research never prohibited, but that the administration supported research to a greater degree than has been recognized. Instead, the decline in research reflected more complex changes in the regulation of pharmaceutical research and development. © The Author(s) 2016.

  17. Approach for domestic preparation of standard material (LSD spike) for isotope dilution mass spectrometry

    International Nuclear Information System (INIS)

    Ishikawa, Fumitaka; Sumi, Mika; Chiba, Masahiko; Suzuki, Toru; Abe, Tomoyuki; Kuno, Yusuke

    2008-01-01

    The accountancy analysis of the nuclear fuel material at Plutonium Fuel Development Center of JAEA is performed by isotope dilution mass spectrometry (IDMS; Isotope Dilution Mass Spectrometry). IDMS requires the standard material called LSD spike (Large Size Dried spike) which is indispensable for the accountancy in the facilities where the nuclear fuel materials are handled. Although the LSD spike and Pu source material have been supplied from foreign countries, the transportation for such materials has been getting more difficult recently. This difficulty may affect the operation of nuclear facilities in the future. Therefore, research and development of the domestic LSD spike and base material has been performed at JAEA. Certification for such standard nuclear materials including spikes produced in Japan is being studied. This report presents the current status and the future plan for the technological development. (author)

  18. Connectome-harmonic decomposition of human brain activity reveals dynamical repertoire re-organization under LSD.

    Science.gov (United States)

    Atasoy, Selen; Roseman, Leor; Kaelen, Mendel; Kringelbach, Morten L; Deco, Gustavo; Carhart-Harris, Robin L

    2017-12-15

    Recent studies have started to elucidate the effects of lysergic acid diethylamide (LSD) on the human brain but the underlying dynamics are not yet fully understood. Here we used 'connectome-harmonic decomposition', a novel method to investigate the dynamical changes in brain states. We found that LSD alters the energy and the power of individual harmonic brain states in a frequency-selective manner. Remarkably, this leads to an expansion of the repertoire of active brain states, suggestive of a general re-organization of brain dynamics given the non-random increase in co-activation across frequencies. Interestingly, the frequency distribution of the active repertoire of brain states under LSD closely follows power-laws indicating a re-organization of the dynamics at the edge of criticality. Beyond the present findings, these methods open up for a better understanding of the complex brain dynamics in health and disease.

  19. Possible role of biochemiluminescent photons for lysergic acid diethylamide (LSD)-induced phosphenes and visual hallucinations.

    Science.gov (United States)

    Kapócs, Gábor; Scholkmann, Felix; Salari, Vahid; Császár, Noémi; Szőke, Henrik; Bókkon, István

    2017-01-01

    Today, there is an increased interest in research on lysergic acid diethylamide (LSD) because it may offer new opportunities in psychotherapy under controlled settings. The more we know about how a drug works in the brain, the more opportunities there will be to exploit it in medicine. Here, based on our previously published papers and investigations, we suggest that LSD-induced visual hallucinations/phosphenes may be due to the transient enhancement of bioluminescent photons in the early retinotopic visual system in blind as well as healthy people.

  20. Application of directional solidification ingot (LSD) in forging of PWR reactor vessel heads

    International Nuclear Information System (INIS)

    Benhamou, C.; Poitrault, I.

    1985-09-01

    Creusot-Loire Industrie uses this type of ingot for manufacture of Framatome 1300 and 1450 MW 4-loop PWR reactor vessel heads. This type of ingot offers a number advantages: improved internal soundness; greater chemical, structural and mechanical homogeneity of the finished part; simplified forging process. After a brief description of the pouring and solidification processes, this paper presents an analysis of the results of examinations performed on the prototype forging, as well as review of results obtained during industrial fabrication of dished heads from LSD ingots. The advantages of the LSD ingot over conventional ingots are discussed in conclusion

  1. Verification measurements of the IRMM-1027 and the IAEA large-sized dried (LSD) spikes

    International Nuclear Information System (INIS)

    Jakopic, R.; Aregbe, Y.; Richter, S.

    2017-01-01

    In the frame of the accountancy measurements of the fissile materials, reliable determinations of the plutonium and uranium content in spent nuclear fuel are required to comply with international safeguards agreements. Large-sized dried (LSD) spikes of enriched "2"3"5U and "2"3"9Pu for isotope dilution mass spectrometry (IDMS) analysis are routinely applied in reprocessing plants for this purpose. A correct characterisation of these elements is a pre-requirement for achieving high accuracy in IDMS analyses. This paper will present the results of external verification measurements of such LSD spikes performed by the European Commission and the International Atomic Energy Agency. (author)

  2. a Variant of Lsd-Slam Capable of Processing High-Speed Low-Framerate Monocular Datasets

    Science.gov (United States)

    Schmid, S.; Fritsch, D.

    2017-11-01

    We develop a new variant of LSD-SLAM, called C-LSD-SLAM, which is capable of performing monocular tracking and mapping in high-speed low-framerate situations such as those of the KITTI datasets. The methods used here are robust against the influence of erronously triangulated points near the epipolar direction, which otherwise causes tracking divergence.

  3. Interaction of electron neutrinos with 56Fe in the LSD for Eνe≤50 MeV

    International Nuclear Information System (INIS)

    Gaponov, Yu.V.; Semenov, S.V.; Ryazhskaya, O.G.

    2004-01-01

    The neutrino pulses, detected by LSD (liquid scintillator detector) on February 23, 1987, are analyzed on the base of two-stage model of supernova explosion. The number of events due to the electron neutrino interaction with 56 Fe in the LSD is calculated. The obtained results is in a agreement with experimental data [ru

  4. Return of the lysergamides. Part I: Analytical and behavioral characterization of 1-propionyl-d-lysergic acid diethylamide (1P-LSD)

    Science.gov (United States)

    Brandt, Simon D.; Kavanagh, Pierce V.; Westphal, Folker; Stratford, Alexander; Elliott, Simon P.; Hoang, Khoa; Wallach, Jason; Halberstadt, Adam L.

    2015-01-01

    1-Propionyl-d-lysergic acid diethylamide hemitartrate (1P-LSD) has become available as a ‘research chemical’ in form of blotters and powdered material. This non-controlled derivative of d-lysergic acid diethylamide (LSD) has previously not been described in the published literature despite being closely related to 1-acetyl-LSD (ALD-52), which was developed in the 1950s. This study describes the characterization of 1P-LSD in comparison with LSD using various chromatographic, mass spectrometric methods and nuclear magnetic resonance spectroscopy. An important feature common to LSD and other serotonergic hallucinogens is that they produce 5-HT2A-receptor activation and induce the head-twitch response (HTR) in rats and mice. In order to assess whether 1P-LSD displays LSD-like properties and activates the 5-HT2A receptor, male C57BL/6J mice were injected with vehicle (saline) or 1P-LSD (0.025–0.8 mg/kg, IP) and HTR assessed for 30 min using magnetometer coil recordings. It was found that 1P-LSD produced a dose-dependent increase in HTR counts, and that it had ~38% (ED50 = 349.6 nmol/kg) of the potency of LSD (ED50 = 132.8 nmol/kg). Furthermore, the HTR was abolished when 1P-LSD administration followed pre-treatment with the selective 5-HT2A receptor antagonist M100907 (0.1 mg/kg, SC), which confirms that the behavioral response is mediated by activation of the 5-HT2A receptor. These results indicate that 1P-LSD produces LSD-like effects in mice, consistent with its classification as a serotonergic hallucinogen. Nevertheless, the extent to which 1P-LSD might show psychoactive effects in humans similar to LSD remains to be investigated. PMID:26456305

  5. Intrahippocampal LSD accelerates learning and desensitizes the 5-HT(2A) receptor in the rabbit, Romano et al.

    Science.gov (United States)

    Romano, Anthony G; Quinn, Jennifer L; Li, Luchuan; Dave, Kuldip D; Schindler, Emmanuelle A; Aloyo, Vincent J; Harvey, John A

    2010-10-01

    Parenteral injections of d-lysergic acid diethylamide (LSD), a serotonin 5-HT(2A) receptor agonist, enhance eyeblink conditioning. Another hallucinogen, (±)-1(2, 5-dimethoxy-4-iodophenyl)-2-aminopropane hydrochloride (DOI), was shown to elicit a 5-HT(2A)-mediated behavior (head bobs) after injection into the hippocampus, a structure known to mediate trace eyeblink conditioning. This study aims to determine if parenteral injections of the hallucinogens LSD, d,l-2,5-dimethoxy-4-methylamphetamine, and 5-methoxy-dimethyltryptamine elicit the 5-HT(2A)-mediated behavior of head bobs and whether intrahippocampal injections of LSD would produce head bobs and enhance trace eyeblink conditioning. LSD was infused into the dorsal hippocampus just prior to each of eight conditioning sessions. One day after the last infusion of LSD, DOI was infused into the hippocampus to determine whether there had been a desensitization of the 5-HT(2A) receptor as measured by a decrease in DOI-elicited head bobs. Acute parenteral or intrahippocampal LSD elicited a 5-HT(2A) but not a 5-HT(2C)-mediated behavior, and chronic administration enhanced conditioned responding relative to vehicle controls. Rabbits that had been chronically infused with 3 or 10 nmol per side of LSD during Pavlovian conditioning and then infused with DOI demonstrated a smaller increase in head bobs relative to controls. LSD produced its enhancement of Pavlovian conditioning through an effect on 5-HT(2A) receptors located in the dorsal hippocampus. The slight, short-lived enhancement of learning produced by LSD appears to be due to the development of desensitization of the 5-HT(2A) receptor within the hippocampus as a result of repeated administration of its agonist (LSD).

  6. In vivo binding of 125I-LSD to serotonin 5-HT2 receptors in mouse brain

    International Nuclear Information System (INIS)

    Hartig, P.R.; Scheffel, U.; Frost, J.J.; Wagner, H.N. Jr.

    1985-01-01

    The binding of 125 I-LSD (2-[ 125 I]-lysergic acid diethylamide) was studied in various mouse brain regions following intravenous injection of the radioligand. The high specific activity of 125 I-LSD enabled the injection of low mass doses (14ng/kg), which are well below the threshold for induction of any known physiological effect of the probe. The highest levels of 125 I-LSD binding were found in the frontal cortex, olfactory tubercles, extra-frontal cortex and striatum while the lowest level was found in the cerebellum. Binding was saturable in the frontal cortex but increased linearly in the cerebellum with increasing doses of 125 I-LSD. Serotonergic compounds potently inhibited 125 I-LSD binding in cortical regions, olfactory tubercles, and hypothalamus but had no effect in the cerebellum. Dopaminergic compounds caused partial inhibition of binding in the striatum while adrenergic compounds were inactive. From these studies the authors conclude that 125 I-LSD labels serotonin 5-HT 2 receptor sites in cortical regions with no indication that other receptor sites are labeled. In the olfactory tubercles and hypothalamus, 125 I-LSD labeling occurs predominantly or entirely at serotonic 5-HT 2 sites. In the striatum, 125 I-LSD labels approximately equal proportions of serotonergic and dopaminergic sites. These data indicate that 125 I-LSD labels serotonin receptors in vivo and suggests that appropriate derivatives of 2I-LSD may prove useful for tomographic imaging of serotonin 5-HT 2 receptors in the mammalian cortex

  7. A placebo-controlled investigation of synaesthesia-like experiences under LSD.

    Science.gov (United States)

    Terhune, Devin B; Luke, David P; Kaelen, Mendel; Bolstridge, Mark; Feilding, Amanda; Nutt, David; Carhart-Harris, Robin; Ward, Jamie

    2016-07-29

    The induction of synaesthesia in non-synaesthetes has the potential to illuminate the mechanisms that contribute to the development of this condition and the shaping of its phenomenology. Previous research suggests that lysergic acid diethylamide (LSD) reliably induces synaesthesia-like experiences in non-synaesthetes. However, these studies suffer from a number of methodological limitations including lack of a placebo control and the absence of rigorous measures used to test established criteria for genuine synaesthesia. Here we report a pilot study that aimed to circumvent these limitations. We conducted a within-groups placebo-controlled investigation of the impact of LSD on colour experiences in response to standardized graphemes and sounds and the consistency and specificity of grapheme- and sound-colour associations. Participants reported more spontaneous synaesthesia-like experiences under LSD, relative to placebo, but did not differ across conditions in colour experiences in response to inducers, consistency of stimulus-colour associations, or in inducer specificity. Further analyses suggest that individual differences in a number of these effects were associated with the propensity to experience states of absorption in one's daily life. Although preliminary, the present study suggests that LSD-induced synaesthesia-like experiences do not exhibit consistency or inducer-specificity and thus do not meet two widely established criteria for genuine synaesthesia. Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. The upper limit of the solar antineutrino flux according to the LSD array data

    International Nuclear Information System (INIS)

    Al'etta, M.; Antonioli, P.; Badino, D.

    1997-01-01

    The analysis of the experimental data obtained at the LSD liquid scintillation detector is carried out with the aim of searching the possible flux of electron antineutrinos from Sun. The most strong at present upper limit for the electron antineutrino flux of solar origin is determined: ≤ 1.0 x 10 5 cm -2 x s -1 (the reliability level of 90%)

  9. Increased thalamic resting-state connectivity as a core driver of LSD-induced hallucinations.

    Science.gov (United States)

    Müller, F; Lenz, C; Dolder, P; Lang, U; Schmidt, A; Liechti, M; Borgwardt, S

    2017-12-01

    It has been proposed that the thalamocortical system is an important site of action of hallucinogenic drugs and an essential component of the neural correlates of consciousness. Hallucinogenic drugs such as LSD can be used to induce profoundly altered states of consciousness, and it is thus of interest to test the effects of these drugs on this system. 100 μg LSD was administrated orally to 20 healthy participants prior to fMRI assessment. Whole brain thalamic functional connectivity was measured using ROI-to-ROI and ROI-to-voxel approaches. Correlation analyses were used to explore relationships between thalamic connectivity to regions involved in auditory and visual hallucinations and subjective ratings on auditory and visual drug effects. LSD caused significant alterations in all dimensions of the 5D-ASC scale and significantly increased thalamic functional connectivity to various cortical regions. Furthermore, LSD-induced functional connectivity measures between the thalamus and the right fusiform gyrus and insula correlated significantly with subjective auditory and visual drug effects. Hallucinogenic drug effects might be provoked by facilitations of cortical excitability via thalamocortical interactions. Our findings have implications for the understanding of the mechanism of action of hallucinogenic drugs and provide further insight into the role of the 5-HT 2A -receptor in altered states of consciousness. © 2017 The Authors Acta Psychiatrica Scandinavica Published by John Wiley & Sons Ltd.

  10. [Statement on Recent Research on LSD, Marihuana, and Other Dangerous Drugs.

    Science.gov (United States)

    Yolles, Stanley F.

    The National Institute of Mental Health is continuing support of several studies designed to measure trends in the use of hallucinogens. Indications are that the evidence for persisting psychological and birth defect damage from chronic LSD use is minimal. Though they are a continuing problem, admissions to psychiatric units of persons with "bad…

  11. Supporting Dynamic Ad hoc Collaboration Capabilities

    CERN Document Server

    Agarwal, D

    2003-01-01

    Modern HENP experiments such as CMS and Atlas involve as many as 2000 collaborators around the world. Collaborations this large will be unable to meet often enough to support working closely together. Many of the tools currently available for collaboration focus on heavy-weight applications such as videoconferencing tools. While these are important, there is a more basic need for tools that support connecting physicists to work together on an ad hoc or continuous basis. Tools that support the day-to-day connectivity and underlying needs of a group of collaborators are important for providing light-weight, non-intrusive, and flexible ways to work collaboratively. Some example tools include messaging, file-sharing, and shared plot viewers. An important component of the environment is a scalable underlying communication framework. In this paper we will describe our current progress on building a dynamic and ad hoc collaboration environment and our vision for its evolution into a HENP collaboration environment.

  12. Evolutionary algorithms for mobile ad hoc networks

    CERN Document Server

    Dorronsoro, Bernabé; Danoy, Grégoire; Pigné, Yoann; Bouvry, Pascal

    2014-01-01

    Describes how evolutionary algorithms (EAs) can be used to identify, model, and minimize day-to-day problems that arise for researchers in optimization and mobile networking. Mobile ad hoc networks (MANETs), vehicular networks (VANETs), sensor networks (SNs), and hybrid networks—each of these require a designer’s keen sense and knowledge of evolutionary algorithms in order to help with the common issues that plague professionals involved in optimization and mobile networking. This book introduces readers to both mobile ad hoc networks and evolutionary algorithms, presenting basic concepts as well as detailed descriptions of each. It demonstrates how metaheuristics and evolutionary algorithms (EAs) can be used to help provide low-cost operations in the optimization process—allowing designers to put some “intelligence” or sophistication into the design. It also offers efficient and accurate information on dissemination algorithms topology management, and mobility models to address challenges in the ...

  13. Quantum load balancing in ad hoc networks

    Science.gov (United States)

    Hasanpour, M.; Shariat, S.; Barnaghi, P.; Hoseinitabatabaei, S. A.; Vahid, S.; Tafazolli, R.

    2017-06-01

    This paper presents a novel approach in targeting load balancing in ad hoc networks utilizing the properties of quantum game theory. This approach benefits from the instantaneous and information-less capability of entangled particles to synchronize the load balancing strategies in ad hoc networks. The quantum load balancing (QLB) algorithm proposed by this work is implemented on top of OLSR as the baseline routing protocol; its performance is analyzed against the baseline OLSR, and considerable gain is reported regarding some of the main QoS metrics such as delay and jitter. Furthermore, it is shown that QLB algorithm supports a solid stability gain in terms of throughput which stands a proof of concept for the load balancing properties of the proposed theory.

  14. Supporting Dynamic Ad hoc Collaboration Capabilities

    International Nuclear Information System (INIS)

    Agarwal, Deborah A.; Berket, Karlo

    2003-01-01

    Modern HENP experiments such as CMS and Atlas involve as many as 2000 collaborators around the world. Collaborations this large will be unable to meet often enough to support working closely together. Many of the tools currently available for collaboration focus on heavy-weight applications such as videoconferencing tools. While these are important, there is a more basic need for tools that support connecting physicists to work together on an ad hoc or continuous basis. Tools that support the day-to-day connectivity and underlying needs of a group of collaborators are important for providing light-weight, non-intrusive, and flexible ways to work collaboratively. Some example tools include messaging, file-sharing, and shared plot viewers. An important component of the environment is a scalable underlying communication framework. In this paper we will describe our current progress on building a dynamic and ad hoc collaboration environment and our vision for its evolution into a HENP collaboration environment

  15. LSD modulates music-induced imagery via changes in parahippocampal connectivity.

    Science.gov (United States)

    Kaelen, Mendel; Roseman, Leor; Kahan, Joshua; Santos-Ribeiro, Andre; Orban, Csaba; Lorenz, Romy; Barrett, Frederick S; Bolstridge, Mark; Williams, Tim; Williams, Luke; Wall, Matthew B; Feilding, Amanda; Muthukumaraswamy, Suresh; Nutt, David J; Carhart-Harris, Robin

    2016-07-01

    Psychedelic drugs such as lysergic acid diethylamide (LSD) were used extensively in psychiatry in the past and their therapeutic potential is beginning to be re-examined today. Psychedelic psychotherapy typically involves a patient lying with their eyes-closed during peak drug effects, while listening to music and being supervised by trained psychotherapists. In this context, music is considered to be a key element in the therapeutic model; working in synergy with the drug to evoke therapeutically meaningful thoughts, emotions and imagery. The underlying mechanisms involved in this process have, however, never been formally investigated. Here we studied the interaction between LSD and music-listening on eyes-closed imagery by means of a placebo-controlled, functional magnetic resonance imaging (fMRI) study. Twelve healthy volunteers received intravenously administered LSD (75µg) and, on a separate occasion, placebo, before being scanned under eyes-closed resting conditions with and without music-listening. The parahippocampal cortex (PHC) has previously been linked with (1) music-evoked emotion, (2) the action of psychedelics, and (3) mental imagery. Imaging analyses therefore focused on changes in the connectivity profile of this particular structure. Results revealed increased PHC-visual cortex (VC) functional connectivity and PHC to VC information flow in the interaction between music and LSD. This latter result correlated positively with ratings of enhanced eyes-closed visual imagery, including imagery of an autobiographical nature. These findings suggest a plausible mechanism by which LSD works in combination with music listening to enhance certain subjective experiences that may be useful in a therapeutic context. Copyright © 2016 Elsevier B.V. and ECNP. All rights reserved.

  16. LSD alters eyes-closed functional connectivity within the early visual cortex in a retinotopic fashion.

    Science.gov (United States)

    Roseman, Leor; Sereno, Martin I; Leech, Robert; Kaelen, Mendel; Orban, Csaba; McGonigle, John; Feilding, Amanda; Nutt, David J; Carhart-Harris, Robin L

    2016-08-01

    The question of how spatially organized activity in the visual cortex behaves during eyes-closed, lysergic acid diethylamide (LSD)-induced "psychedelic imagery" (e.g., visions of geometric patterns and more complex phenomena) has never been empirically addressed, although it has been proposed that under psychedelics, with eyes-closed, the brain may function "as if" there is visual input when there is none. In this work, resting-state functional connectivity (RSFC) data was analyzed from 10 healthy subjects under the influence of LSD and, separately, placebo. It was suspected that eyes-closed psychedelic imagery might involve transient local retinotopic activation, of the sort typically associated with visual stimulation. To test this, it was hypothesized that, under LSD, patches of the visual cortex with congruent retinotopic representations would show greater RSFC than incongruent patches. Using a retinotopic localizer performed during a nondrug baseline condition, nonadjacent patches of V1 and V3 that represent the vertical or the horizontal meridians of the visual field were identified. Subsequently, RSFC between V1 and V3 was measured with respect to these a priori identified patches. Consistent with our prior hypothesis, the difference between RSFC of patches with congruent retinotopic specificity (horizontal-horizontal and vertical-vertical) and those with incongruent specificity (horizontal-vertical and vertical-horizontal) increased significantly under LSD relative to placebo, suggesting that activity within the visual cortex becomes more dependent on its intrinsic retinotopic organization in the drug condition. This result may indicate that under LSD, with eyes-closed, the early visual system behaves as if it were seeing spatially localized visual inputs. Hum Brain Mapp 37:3031-3040, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  17. The quantitation of 2-oxo-3-hydroxy lysergic acid diethylamide (O-H-LSD) in human urine specimens, a metabolite of LSD: comparative analysis using liquid chromatography-selected ion monitoring mass spectrometry and liquid chromatography-ion trap mass spectrometry.

    Science.gov (United States)

    Poch, G K; Klette, K L; Anderson, C

    2000-04-01

    This paper compares the potential forensic application of two sensitive and rapid procedures (liquid chromatography-mass spectrometry and liquid chromatography-ion trap mass spectrometry) for the detection and quantitation of 2-oxo-3-hydroxy lysergic acid diethylamide (O-H-LSD) a major LSD metabolite. O-H-LSD calibration curves for both procedures were linear over the concentration range 0-8,000 pg/mL with correlation coefficients (r2) greater than 0.99. The observed limit of detection (LOD) and limit of quantitation (LOQ) for O-H-LSD in both procedures was 400 pg/mL. Sixty-eight human urine specimens that had previously been found to contain LSD by gas chromatography-mass spectrometry were reanalyzed by both procedures for LSD and O-H-LSD. These specimens contained a mean concentration of O-H-LSD approximately 16 times higher than the LSD concentration. Because both LC methods produce similar results, either procedure can be readily adapted to O-H-LSD analysis for use in high-volume drug-testing laboratories. In addition, the possibility of significantly increasing the LSD detection time window by targeting this major LSD metabolite for analysis may influence other drug-free workplace programs to test for LSD.

  18. AD HOC Networks for the Autonomous Car

    Science.gov (United States)

    Ron, Davidescu; Negrus, Eugen

    2017-10-01

    The future of the vehicle is made of cars, roads and infrastructures connected in a two way automated communication in a holistic system. It is a mandatory to use Encryption to maintain Confidentiality, Integrity and Availability in an ad hoc vehicle network. Vehicle to Vehicle communication, requires multichannel interaction between mobile, moving and changing parties to insure the full benefit from data sharing and real time decision making, a network of such users referred as mobile ad hoc network (MANET), however as ad hoc networks were not implemented in such a scale, it is not clear what is the best method and protocol to apply. Furthermore the visibility of secure preferred asymmetric encrypted ad hoc networks in a real time environment of dense moving autonomous vehicles has to be demonstrated, In order to evaluate the performance of Ad Hoc networks in changing conditions a simulation of multiple protocols was performed on large number of mobile nodes. The following common routing protocols were tested, DSDV is a proactive protocol, every mobile station maintains a routing table with all available destinations, DSR is a reactive routing protocol which allows nodes in the MANET to dynamically discover a source route across multiple network hops, AODV is a reactive routing protocol Instead of being proactive. It minimizes the number of broadcasts by creating routes based on demand, SAODV is a secure version of AODV, requires heavyweight asymmetric cryptographic, ARIANDE is a routing protocol that relies on highly efficient symmetric cryptography the concept is primarily based on DSR. A methodical evolution was performed in a various density of transportation, based on known communication bench mark parameters including, Throughput Vs. time, Routing Load per packets and bytes. Out of the none encrypted protocols, It is clear that in terms of performance of throughput and routing load DSR protocol has a clear advantage the high node number mode. The encrypted

  19. Advantages of analyzing postmortem brain samples in routine forensic drug screening—case series of three non-natural deaths tested positive for lysergic acid diethylamide (LSD)

    DEFF Research Database (Denmark)

    Mardal, Marie; Johansen, Sys Stybe; Thomsen, Ragnar

    2017-01-01

    Three case reports are presented, including autopsy findings and toxicological screening results, which were tested positive for the potent hallucinogenic drug lysergic acid diethylamide (LSD). LSD and its main metabolites were quantified in brain tissue and femoral blood, and furthermore hematoma...... and urine when available. LSD, its main metabolite 2-oxo-3-hydroxy-LSD (oxo-HO-LSD), and iso-LSD were quantified in biological samples according to a previously published procedure involving liquid-liquid extraction and ultra-high performance liquid chromatography − tandem mass spectrometry (UHPLC......-MS/MS). LSD was measured in the brain tissue of all presented cases at a concentration level from 0.34 −10.8 μg/kg. The concentration level in the target organ was higher than in peripheral blood. Additional psychoactive compounds were quantified in blood and brain tissue, though all below toxic concentration...

  20. Resistivity tomography of Pointe du Hoc cliffs for stability assessment

    Science.gov (United States)

    Udphuay, S.; Everett, M. E.; Warden, R.

    2008-12-01

    Pointe du Hoc WWII battlefield overlooking the English Channel in western Normandy, France, is an important cultural resource, being an integral component of the June 6 1944 D-Day invasion. Two major buildings, the forward observation post (OP) and Col. Rudder's command post (RCP), are now perched perilously close to the cliff's edge owing to six decades of cliff retreat. Geophysical surveys were carried out in March 2008 to investigate the risk of cliff failure and to inform possible geotechnical remediation strategies with a final goal toward re-opening the observation post that is now closed to visitors. The geophysical surveying is accomplished by high-resolution resistivity tomography, conducted in extreme topography and in the midst of dense cultural clutter. The results of the OP tomography indicate that the highest mass movement hazard is associated with the marine caverns at the base of the cliff at the point of strongest wave attack. These caverns occupy the future site of a sea arch which will threaten the OP building. There is a high probability of a soil wedge failure on the east facing cliff edge close to the OP building. Such a failure could damage or destroy the building. The possibility of a sudden catastrophic failure along any one of these fractures cannot be ruled out. The greatest risk at the RCP site, which is under less immediate threat, is associated with soil wedge failures at the top of the cliffs.

  1. Detection of lysergic acid diethylamide (LSD) in urine by gas chromatography-ion trap tandem mass spectrometry.

    Science.gov (United States)

    Sklerov, J H; Kalasinsky, K S; Ehorn, C A

    1999-10-01

    A confirmatory method for the detection and quantitation of lysergic acid diethylamide (LSD) is presented. The method employs gas chromatography-tandem mass spectrometry (GC-MS-MS) using an internal ionization ion trap detector for sensitive MS-MS-in-time measurements of LSD extracted from urine. Following a single-step solid-phase extraction of 5 mL of urine, underivatized LSD can be measured with limits of quantitation and detection of 80 and 20 pg/mL, respectively. Temperature-programmed on-column injections of urine extracts were linear over the concentration range 20-2000 pg/mL (r2 = 0.999). Intraday and interday coefficients of variation were LSD-positive samples in this laboratory. Comparisons with alternate GC-MS methods and extraction procedures are discussed.

  2. Development of a high specific activity radioligand, 125I-LSD, and its application to the study of serotonin receptors

    International Nuclear Information System (INIS)

    Kadan, M.J.

    1987-01-01

    125 I-Labeled receptor ligands can be synthesized with specific activities exceeding 2000 Ci/mmol, making them nearly 70-fold more sensitive in receptor site assays than (mono) tritiated ligands. We have synthesized and characterized 125 I-lysergic acid diethylamide ( 125 I-LSD), the first radioiodinated ligand for serotonin receptor studies. The introduction of 125 I at the 2 position of LSD increased both the affinity and selectivity of this compound for serotonin 5-HT 2 receptors in rat cortex. The high specific activity of 125 I-LSD and its high ratio of specific to nonspecific binding make this ligand especially useful for autoradiographic studies of serotonin receptor distribution. We have found that 125 I-LSD binds with high affinity to a class of serotonin receptors in the CNS of the marine mollusk Aplysia californica

  3. Germline mutations in lysine specific demethylase 1 (LSD1/KDM1A) confer susceptibility to multiple myeloma.

    Science.gov (United States)

    Wei, Xiaomu; Calvo-Vidal, M Nieves; Chen, Siwei; Wu, Gang; Revuelta, Maria V; Sun, Jian; Zhang, Jinghui; Walsh, Michael F; Nichols, Kim E; Joseph, Vijai; Snyder, Carrie; Vachon, Celine M; McKay, James D; Wang, Shu-Ping; Jayabalan, David S; Jacobs, Lauren M; Becirovic, Dina; Waller, Rosalie G; Artomov, Mykyta; Viale, Agnes; Patel, Jayeshkumar; Phillip, Jude M; Chen-Kiang, Selina; Curtin, Karen; Salama, Mohamed; Atanackovic, Djordje; Niesvizky, Ruben; Landgren, Ola; Slager, Susan L; Godley, Lucy A; Churpek, Jane; Garber, Judy E; Anderson, Kenneth C; Daly, Mark J; Roeder, Robert G; Dumontet, Charles; Lynch, Henry T; Mullighan, Charles G; Camp, Nicola J; Offit, Kenneth; Klein, Robert J; Yu, Haiyuan; Cerchietti, Leandro; Lipkin, Steven M

    2018-03-20

    Given the frequent and largely incurable occurrence of multiple myeloma (MM), identification of germline genetic mutations that predispose cells to MM may provide insight into disease etiology and the developmental mechanisms of its cell of origin, the plasma cell. Here we identified familial and early-onset MM kindreds with truncating mutations in lysine-specific demethylase 1 (LSD1/KDM1A), an epigenetic transcriptional repressor that primarily demethylates histone H3 on lysine 4 and regulates hematopoietic stem cell self-renewal. Additionally, we found higher rates of germline truncating and predicted deleterious missense KDM1A mutations in MM patients unselected for family history compared to controls. Both monoclonal gammopathy of unknown significance (MGUS) and MM cells have significantly lower KDM1A transcript levels compared with normal plasma cells. Transcriptome analysis of MM cells from KDM1A mutation carriers shows enrichment of pathways and MYC target genes previously associated with myeloma pathogenesis. In mice, antigen challenge followed by pharmacological inhibition of KDM1A promoted plasma cell expansion, enhanced secondary immune response, elicited appearance of serum paraprotein, and mediated upregulation of MYC transcriptional targets. These changes are consistent with the development of MGUS. Collectively, our findings show KDM1A is the first autosomal dominant MM germline predisposition gene, providing new insights into its mechanistic roles as a tumor suppressor during post-germinal center B cell differentiation. Copyright ©2018, American Association for Cancer Research.

  4. Electrochemistry and analytical determination of lysergic acid diethylamide (LSD) via adsorptive stripping voltammetry.

    Science.gov (United States)

    Merli, Daniele; Zamboni, Daniele; Protti, Stefano; Pesavento, Maria; Profumo, Antonella

    2014-12-01

    Lysergic acid diethylamide (LSD) is hardly detectable and quantifiable in biological samples because of its low active dose. Although several analytical tests are available, routine analysis of this drug is rarely performed. In this article, we report a simple and accurate method for the determination of LSD, based on adsorptive stripping voltammetry in DMF/tetrabutylammonium perchlorate, with a linear range of 1-90 ng L(-1) for deposition times of 50s. LOD of 1.4 ng L(-1) and LOQ of 4.3 ng L(-1) were found. The method can be also applied to biological samples after a simple extraction with 1-chlorobutane. Copyright © 2014 Elsevier B.V. All rights reserved.

  5. The research program of the Liquid Scintillation Detector (LSD) in the Mont Blanc Laboratory

    Science.gov (United States)

    Dadykin, V. L.; Yakushev, V. F.; Korchagin, P. V.; Korchagin, V. B.; Malgin, A. S.; Ryassny, F. G.; Ryazhskaya, O. G.; Talochkin, V. P.; Zatsepin, G. T.; Badino, G.

    1985-01-01

    A massive (90 tons) liquid scintillation detector (LSD) has been running since October 1984 in the Mont Blanc Laboratory at a depth of 5,200 hg/sq cm of standard rock. The research program of the experiment covers a variety of topics in particle physics and astrophysics. The performance of the detector, the main fields of research are presented and the preliminary results are discussed.

  6. Advantages of analyzing postmortem brain samples in routine forensic drug screening-Case series of three non-natural deaths tested positive for lysergic acid diethylamide (LSD).

    Science.gov (United States)

    Mardal, Marie; Johansen, Sys Stybe; Thomsen, Ragnar; Linnet, Kristian

    2017-09-01

    Three case reports are presented, including autopsy findings and toxicological screening results, which were tested positive for the potent hallucinogenic drug lysergic acid diethylamide (LSD). LSD and its main metabolites were quantified in brain tissue and femoral blood, and furthermore hematoma and urine when available. LSD, its main metabolite 2-oxo-3-hydroxy-LSD (oxo-HO-LSD), and iso-LSD were quantified in biological samples according to a previously published procedure involving liquid-liquid extraction and ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). LSD was measured in the brain tissue of all presented cases at a concentration level from 0.34-10.8μg/kg. The concentration level in the target organ was higher than in peripheral blood. Additional psychoactive compounds were quantified in blood and brain tissue, though all below toxic concentration levels. The cause of death in case 1 was collision-induced brain injury, while it was drowning in case 2 and 3 and thus not drug intoxication. However, the toxicological findings could help explain the decedent's inability to cope with brain injury or drowning incidents. The presented findings could help establish reference concentrations in brain samples and assist in interpretation of results from forensic drug screening in brain tissue. This is to the author's knowledge the first report of LSD, iso-LSD, and oxo-HO-LSD measured in brain tissue samples. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Melatonin exerts anti-oral cancer effect via suppressing LSD1 in patient-derived tumor xenograft models

    Science.gov (United States)

    Yang, Cheng-Yu; Lin, Chih-Kung; Tsao, Chang-Huei; Hsieh, Cheng-Chih; Lin, Gu-Jiun; Ma, Kuo-Hsing; Shieh, Yi-Shing; Sytwu, Huey-Kang; Chen, Yuan-Wu

    2017-01-01

    Aberrant activation of histone lysine-specific demethylase (LSD1) increases tumorigenicity; hence, LSD1 is considered a therapeutic target for various human cancers. Although melatonin, an endogenously produced molecule, may defend against various cancers, the precise mechanism involved in its anti-oral cancer effect remains unclear. Patient-derived tumor xenograft (PDTX) models are preclinical models that can more accurately reflect human tumor biology compared with cell line xenograft models. Here, we evaluated the anticancer activity of melatonin by using LSD1-overexpressing oral cancer PDTX models. By assessing oral squamous cell carcinoma (OSCC) tissue arrays through immunohistochemistry, we examined whether aberrant LSD1 overexpression in OSCC is associated with poor prognosis. We also evaluated the action mechanism of melatonin against OSCC with lymphatic metastases by using the PDTX models. Our results indicated that melatonin, at pharmacological concentrations, significantly suppresses cell proliferation in a dose- and time-dependent manner. The observed suppression of proliferation was accompanied by the melatonin-mediated inhibition of LSD1 in oral cancer PDTXs and oral cancer cell lines. In conclusion, we determined that the beneficial effects of melatonin in reducing oral cancer cell proliferation are associated with reduced LSD1 expression in vivo and in vitro. PMID:28422711

  8. Numerical predictions of particle dispersed two-phase flows, using the LSD and SSF models

    International Nuclear Information System (INIS)

    Avila, R.; Cervantes de Gortari, J.; Universidad Nacional Autonoma de Mexico, Mexico City. Facultad de Ingenieria)

    1988-01-01

    A modified version of a numerical scheme which is suitable to predict parabolic dispersed two-phase flow, is presented. The original version of this scheme was used to predict the test cases discussed during the 3rd workshop on TPF predictions in Belgrade, 1986. In this paper, two particle dispersion models are included which use the Lagrangian approach predicting test case 1 and 3 of the 4th workshop. For the prediction of test case 1 the Lagrangian Stochastic Deterministic model (LSD) is used providing acceptable good results of mean and turbulent quantities for both solid and gas phases; however, the computed void fraction distribution is not in agreement with the measurements at locations away from the inlet, especially near the walls. Test case 3 is predicted using both the LSD and the Stochastic Separated Flow (SSF) models. It was found that the effects of turbulence modulation are large when the LSD model is used, whereas the particles have a negligible influence on the continuous phase if the SSF model is utilized for the computations. Predictions of gas phase properties based on both models agree well with measurements; however, the agreement between calculated and measured solid phase properties is less satisfactory. (orig.)

  9. APF530 versus ondansetron, each in a guideline-recommended three-drug regimen, for the prevention of chemotherapy-induced nausea and vomiting due to anthracycline plus cyclophosphamide–based highly emetogenic chemotherapy regimens: a post hoc subgroup analysis of the Phase III randomized MAGIC trial

    Directory of Open Access Journals (Sweden)

    Schnadig ID

    2017-05-01

    Full Text Available Ian D Schnadig1, Richy Agajanian2, Christopher Dakhil3, Nashat Gabrail4, Jeffrey Vacirca5, Charles Taylor6, Sharon Wilks7, Eduardo Braun8, Michael C Mosier9, Robert B Geller10, Lee Schwartzberg11, Nicholas Vogelzang12 1Compass Oncology, US Oncology Research, Tualatin, OR, 2The Oncology Institute of Hope and Innovation, Whittier, CA, 3Cancer Center of Kansas, Wichita, KS, 4Gabrail Cancer Center, Canton, OH, 5North Shore Hematology Oncology, East Setauket, NY, 6Tulsa Cancer Institute, Tulsa, OK, 7Cancer Care Centers of South Texas, San Antonio, TX, 8Michiana Hematology Oncology, Westville, IN, 9Biostatistics, EMB Statistical Solutions, LLC, Overland Park, KS, 10Medical Affairs, Heron Therapeutics, Inc., San Diego, CA, 11West Cancer Center, Germantown, TN, 12Comprehensive Cancer Centers of Nevada, Las Vegas, NV, USA Background: APF530, a novel extended-release granisetron injection, was superior to ondansetron in a guideline-recommended three-drug regimen in preventing delayed-phase chemotherapy-induced nausea and vomiting (CINV among patients receiving highly emetogenic chemotherapy (HEC in the double-blind Phase III Modified Absorption of Granisetron In the prevention of CINV (MAGIC trial.Patients and methods: This MAGIC post hoc analysis evaluated CINV prevention efficacy and safety of APF530 versus ondansetron, each with fosaprepitant and dexamethasone, in patient subgroup receiving an anthracycline plus cyclophosphamide (AC regimen. Patients were randomized 1:1 to APF530 500 mg subcutaneously (granisetron 10 mg or ondansetron 0.15 mg/kg intravenously (IV (≤16 mg; stratification was by planned cisplatin ≥50 mg/m2 (yes/no. Patients were to receive fosaprepitant 150 mg IV and dexamethasone 12 mg IV on day 1, then dexamethasone 8 mg orally once daily on day 2 and twice daily on days 3 and 4. Patients were mostly younger females (APF530 arm, mean age 54.1 years, female, 99.3%; ondansetron arm, 53.8 years, female 98.3%. The primary

  10. Game Theory in Wireless Ad-Hoc Opportunistic Radios

    OpenAIRE

    Mumtaz, Shahid; Gameiro, Atilio

    2010-01-01

    Emerging research in game theory based power control applied to ad hoc opportunist networks shows much promise to help understand the complex interactions between OR nodes in this highly dynamic and distributed environment. Also, the employment of game theory in modeling dynamic situations for opportunist ad hoc networks where OR nodes have incomplete information has led to the application of largely unexplored games such as games of imperfect monitoring. Ad hoc security using game theory is ...

  11. Ad hoc mobile wireless networks principles, protocols and applications

    CERN Document Server

    Sarkar, Subir Kumar; Puttamadappa, C

    2007-01-01

    Ad hoc mobile wireless networks have seen increased adaptation in a variety of disciplines because they can be deployed with simple infrastructures and virtually no central administration. In particular, the development of ad hoc wireless and sensor networks provides tremendous opportunities in areas including disaster recovery, defense, health care, and industrial environments. Ad Hoc Mobile Wireless Networks: Principles, Protocols and Applications explains the concepts, mechanisms, design, and performance of these systems. It presents in-depth explanations of the latest wireless technologies

  12. Ad hoc mobile wireless networks principles, protocols, and applications

    CERN Document Server

    Sarkar, Subir Kumar

    2013-01-01

    The military, the research community, emergency services, and industrial environments all rely on ad hoc mobile wireless networks because of their simple infrastructure and minimal central administration. Now in its second edition, Ad Hoc Mobile Wireless Networks: Principles, Protocols, and Applications explains the concepts, mechanism, design, and performance of these highly valued systems. Following an overview of wireless network fundamentals, the book explores MAC layer, routing, multicast, and transport layer protocols for ad hoc mobile wireless networks. Next, it examines quality of serv

  13. Worm epidemics in wireless ad hoc networks

    Energy Technology Data Exchange (ETDEWEB)

    Nekovee, Maziar [BT Research, Polaris 134, Adastral Park, Martlesham, Suffolk IP5 3RE (United Kingdom); Centre for Computational Science, University College London, 20 Gordon Street, London WC1H 0AJ (United Kingdom)

    2007-06-15

    A dramatic increase in the number of computing devices with wireless communication capability has resulted in the emergence of a new class of computer worms which specifically target such devices. The most striking feature of these worms is that they do not require Internet connectivity for their propagation but can spread directly from device to device using a short-range radio communication technology, such as WiFi or Bluetooth. In this paper, we develop a new model for epidemic spreading of these worms and investigate their spreading in wireless ad hoc networks via extensive Monte Carlo simulations. Our studies show that the threshold behaviour and dynamics of worm epidemics in these networks are greatly affected by a combination of spatial and temporal correlations which characterize these networks, and are significantly different from the previously studied epidemics in the Internet.

  14. Worm epidemics in wireless ad hoc networks

    Science.gov (United States)

    Nekovee, Maziar

    2007-06-01

    A dramatic increase in the number of computing devices with wireless communication capability has resulted in the emergence of a new class of computer worms which specifically target such devices. The most striking feature of these worms is that they do not require Internet connectivity for their propagation but can spread directly from device to device using a short-range radio communication technology, such as WiFi or Bluetooth. In this paper, we develop a new model for epidemic spreading of these worms and investigate their spreading in wireless ad hoc networks via extensive Monte Carlo simulations. Our studies show that the threshold behaviour and dynamics of worm epidemics in these networks are greatly affected by a combination of spatial and temporal correlations which characterize these networks, and are significantly different from the previously studied epidemics in the Internet.

  15. Worm epidemics in wireless ad hoc networks

    International Nuclear Information System (INIS)

    Nekovee, Maziar

    2007-01-01

    A dramatic increase in the number of computing devices with wireless communication capability has resulted in the emergence of a new class of computer worms which specifically target such devices. The most striking feature of these worms is that they do not require Internet connectivity for their propagation but can spread directly from device to device using a short-range radio communication technology, such as WiFi or Bluetooth. In this paper, we develop a new model for epidemic spreading of these worms and investigate their spreading in wireless ad hoc networks via extensive Monte Carlo simulations. Our studies show that the threshold behaviour and dynamics of worm epidemics in these networks are greatly affected by a combination of spatial and temporal correlations which characterize these networks, and are significantly different from the previously studied epidemics in the Internet

  16. Intrusion detection in wireless ad-hoc networks

    CERN Document Server

    Chaki, Nabendu

    2014-01-01

    Presenting cutting-edge research, Intrusion Detection in Wireless Ad-Hoc Networks explores the security aspects of the basic categories of wireless ad-hoc networks and related application areas. Focusing on intrusion detection systems (IDSs), it explains how to establish security solutions for the range of wireless networks, including mobile ad-hoc networks, hybrid wireless networks, and sensor networks.This edited volume reviews and analyzes state-of-the-art IDSs for various wireless ad-hoc networks. It includes case studies on honesty-based intrusion detection systems, cluster oriented-based

  17. Changes in global brain connectivity in LSD-induced altered states of consciousness are attributable to the 5-HT2A receptor

    OpenAIRE

    Anticevic, Alan; Vollenweider, Franz; Murray, John; Krystal, John; Repovs, Grega; Staempfli, Philipp; Adkinson, Brendan; Schleifer, Charles; Ji, Jie; Burt, Joshua; Preller, Katrin

    2017-01-01

    Lysergic acid diethylamide (LSD) is a psychedelic drug with predominantly agonist activity at various serotonin (5-HT) and dopamine receptors. Despite the therapeutic and scientific interest in LSD, the specific receptor contributions to its neurobiological effects remain largely unknown. To address this knowledge gap, we conducted a double-blind, randomized, counterbalanced, cross-over study during which 24 healthy participants received either i) placebo+placebo, ii) placebo+LSD (100 microgr...

  18. Return of the lysergamides. Part I: Analytical and behavioural characterization of 1-propionyl-d-lysergic acid diethylamide (1P-LSD).

    Science.gov (United States)

    Brandt, Simon D; Kavanagh, Pierce V; Westphal, Folker; Stratford, Alexander; Elliott, Simon P; Hoang, Khoa; Wallach, Jason; Halberstadt, Adam L

    2016-09-01

    1-Propionyl-d-lysergic acid diethylamide hemitartrate (1P-LSD) has become available as a 'research chemical' in the form of blotters and powdered material. This non-controlled derivative of d-lysergic acid diethylamide (LSD) has previously not been described in the published literature despite being closely related to 1-acetyl-LSD (ALD-52), which was developed in the 1950s. This study describes the characterization of 1P-LSD in comparison with LSD using various chromatographic and mass spectrometric methods, infrared and nuclear magnetic resonance spectroscopy. An important feature common to LSD and other serotonergic hallucinogens is that they produce 5-HT2A -receptor activation and induce the head-twitch response (HTR) in rats and mice. In order to assess whether 1P-LSD displays LSD-like properties and activates the 5-HT2A receptor, male C57BL/6 J mice were injected with vehicle (saline) or 1P-LSD (0.025-0.8 mg/kg, IP) and HTR assessed for 30 min using magnetometer coil recordings. It was found that 1P-LSD produced a dose-dependent increase in HTR counts, and that it had ~38% (ED50  = 349.6 nmol/kg) of the potency of LSD (ED50  = 132.8 nmol/kg). Furthermore, HTR was abolished when 1P-LSD administration followed pretreatment with the selective 5-HT2A receptor antagonist M100907 (0.1 mg/kg, SC), which was consistent with the concept that the behavioural response was mediated by activation of the 5-HT2A receptor. These results indicate that 1P-LSD produces LSD-like effects in mice, consistent with its classification as a serotonergic hallucinogen. Nevertheless, the extent to which 1P-LSD might show psychoactive effects in humans similar to LSD remains to be investigated. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

  19. Receiver-Based Ad Hoc On Demand Multipath Routing Protocol for Mobile Ad Hoc Networks.

    Science.gov (United States)

    Al-Nahari, Abdulaziz; Mohamad, Mohd Murtadha

    2016-01-01

    Decreasing the route rediscovery time process in reactive routing protocols is challenging in mobile ad hoc networks. Links between nodes are continuously established and broken because of the characteristics of the network. Finding multiple routes to increase the reliability is also important but requires a fast update, especially in high traffic load and high mobility where paths can be broken as well. The sender node keeps re-establishing path discovery to find new paths, which makes for long time delay. In this paper we propose an improved multipath routing protocol, called Receiver-based ad hoc on demand multipath routing protocol (RB-AOMDV), which takes advantage of the reliability of the state of the art ad hoc on demand multipath distance vector (AOMDV) protocol with less re-established discovery time. The receiver node assumes the role of discovering paths when finding data packets that have not been received after a period of time. Simulation results show the delay and delivery ratio performances are improved compared with AOMDV.

  20. Decentralized position verification in geographic ad hoc routing

    NARCIS (Netherlands)

    Leinmüller, Tim; Schoch, Elmar; Kargl, Frank; Maihöfer, Christian

    Inter-vehicle communication is regarded as one of the major applications of mobile ad hoc networks (MANETs). Compared to MANETs or wireless sensor networks (WSNs), these so-called vehicular ad hoc networks (VANETs) have unique requirements on network protocols. The requirements result mainly from

  1. Assured Resource Sharing in Ad-Hoc Collaboration

    Energy Technology Data Exchange (ETDEWEB)

    Ahn, Gail-Joon [Arizona State Univ., Tempe, AZ (United States)

    2015-12-19

    The project seeks an innovative framework to enable users to access and selectively share resources in distributed environments, enhancing the scalability of information sharing. We have investigated secure sharing & assurance approaches for ad-hoc collaboration, focused on Grids, Clouds, and ad-hoc network environments.

  2. AD HOC TEAMWORK BEHAVIORS FOR INFLUENCING A FLOCK

    Directory of Open Access Journals (Sweden)

    Katie Genter

    2016-02-01

    Full Text Available Ad hoc teamwork refers to the challenge of designing agents that can influence the behavior of a team, without prior coordination with its teammates. This paper considers influencing a flock of simple robotic agents to adopt a desired behavior within the context of ad hoc teamwork. Specifically, we examine how the ad hoc agents should behave in order to orient a flock towards a target heading as quickly as possible when given knowledge of, but no direct control over, the behavior of the flock. We introduce three algorithms which the ad hoc agents can use to influence the flock, and we examine the relative importance of coordinating the ad hoc agents versus planning farther ahead when given fixed computational resources. We present detailed experimental results for each of these algorithms, concluding that in this setting, inter-agent coordination and deeper lookahead planning are no more beneficial than short-term lookahead planning.

  3. Ad hoc committee on reactor physics benchmarks

    International Nuclear Information System (INIS)

    Diamond, D.J.; Mosteller, R.D.; Gehin, J.C.

    1996-01-01

    In the spring of 1994, an ad hoc committee on reactor physics benchmarks was formed under the leadership of two American Nuclear Society (ANS) organizations. The ANS-19 Standards Subcommittee of the Reactor Physics Division and the Computational Benchmark Problem Committee of the Mathematics and Computation Division had both seen a need for additional benchmarks to help validate computer codes used for light water reactor (LWR) neutronics calculations. Although individual organizations had employed various means to validate the reactor physics methods that they used for fuel management, operations, and safety, additional work in code development and refinement is under way, and to increase accuracy, there is a need for a corresponding increase in validation. Both organizations thought that there was a need to promulgate benchmarks based on measured data to supplement the LWR computational benchmarks that have been published in the past. By having an organized benchmark activity, the participants also gain by being able to discuss their problems and achievements with others traveling the same route

  4. Spontaneous ad hoc mobile cloud computing network.

    Science.gov (United States)

    Lacuesta, Raquel; Lloret, Jaime; Sendra, Sandra; Peñalver, Lourdes

    2014-01-01

    Cloud computing helps users and companies to share computing resources instead of having local servers or personal devices to handle the applications. Smart devices are becoming one of the main information processing devices. Their computing features are reaching levels that let them create a mobile cloud computing network. But sometimes they are not able to create it and collaborate actively in the cloud because it is difficult for them to build easily a spontaneous network and configure its parameters. For this reason, in this paper, we are going to present the design and deployment of a spontaneous ad hoc mobile cloud computing network. In order to perform it, we have developed a trusted algorithm that is able to manage the activity of the nodes when they join and leave the network. The paper shows the network procedures and classes that have been designed. Our simulation results using Castalia show that our proposal presents a good efficiency and network performance even by using high number of nodes.

  5. Origin of a signal detected with the LSD detector after the accident at the chernobyl nuclear power plant

    Energy Technology Data Exchange (ETDEWEB)

    Agafonova, N. Yu., E-mail: natagafonova@gmail.com; Malgin, A. S., E-mail: malgin@lngs.infn.it [Russian Academy of Sciences, Institute for Nuclear Research (Russian Federation); Fulgione, W. [Istituto Nazionale di Fisica Nucleare, and Osservatorio Astrofisico di Torino, Istituto di Fisica dello Spazio Interplanetario (Italy)

    2013-08-15

    A rare signal was detected at 23:53 Moscow time on April 27, 1986 with the LSD low-background scintillation detector located under Mont Blanc at a distance of 1820 km from Chernobyl. To reveal the origin of this signal, we discuss the results obtained with other instruments operating within a similar program, as well as analyze the characteristics of the pulses of the signal and facts referring to the explosion of the Chernobyl reactor. A hypothesis based on detection with the LSD of gamma-quanta from {beta} decays of {sup 135}I nuclei ejected into atmosphere by the reactor explosion and carried in the underground detector camera with air of positive ventilation is considered. The explosion origin of the LSD signal indicates a new technogenic source of the background in the search for neutrino bursts from cores of collapsing stars.

  6. Enhancing action of LSD on neuronal responsiveness to serotonin in a brain structure involved in obsessive-compulsive disorder.

    Science.gov (United States)

    Zghoul, Tarek; Blier, Pierre

    2003-03-01

    Potent serotonin (5-HT) reuptake inhibitors are the only drugs that consistently exert a therapeutic action in obsessive-compulsive disorder (OCD). Given that some hallucinogens were reported to exert an anti-OCD effect outlasting their psychotomimetic action, possible modifications of neuronal responsiveness to 5-HT by LSD were examined in two rat brain structures: one associated with OCD, the orbitofrontal cortex (OFC), and another linked to depression, the hippocampus. The effects of concurrent microiontophoretic application of LSD and 5-HT were examined on neuronal firing rate in the rat OFC and hippocampus under chloral hydrate anaesthesia. In order to determine whether LSD could also exert a modification of 5-HT neuronal responsiveness upon systemic administration, after a delay when hallucinosis is presumably no longer present, it was given once daily (100 microg/kg i.p.) for 4 d and the experiments were carried out 24 h after the last dose. LSD attenuated the firing activity of OFC neurons, and enhanced the inhibitory effect of 5-HT when concomitantly ejected on the same neurons. In the hippocampus, LSD also decreased firing rate by itself but decreased the inhibitory action of 5-HT. The inhibitory action of 5-HT was significantly greater in the OFC, but smaller in the hippocampus, when examined after subacute systemic administration of LSD. It is postulated that some hallucinogens could have a beneficial action in OCD by enhancing the responsiveness to 5-HT in the OFC, and not necessarily in direct relation to hallucinosis. The latter observation may have theoretical implications for the pharmacotherapy of OCD.

  7. Method of LSD profile asymmetry for estimating the center of mass velocities of pulsating stars

    Science.gov (United States)

    Britavskiy, N.; Pancino, E.; Tsymbal, V.; Romano, D.; Cacciari, C.; Clementini, C.

    2016-05-01

    We present radial velocity analysis for 20 solar neighborhood RR Lyrae and 3 Population II Cepheids. High-resolution spectra were observed with either TNG/SARG or VLT/UVES over varying phases. To estimate the center of mass (barycentric) velocities of the program stars, we utilized two independent methods. First, the 'classic' method was employed, which is based on RR Lyrae radial velocity curve templates. Second, we provide the new method that used absorption line profile asymmetry to determine both the pulsation and the barycentric velocities even with a low number of high-resolution spectra and in cases where the phase of the observations is uncertain. This new method is based on a least squares deconvolution (LSD) of the line profiles in order to an- alyze line asymmetry that occurs in the spectra of pulsating stars. By applying this method to our sample stars we attain accurate measurements (+- 2 kms^-1) of the pulsation component of the radial velocity. This results in determination of the barycentric velocity to within 5 kms^-1 even with a low number of high- resolution spectra. A detailed investigation of LSD profile asymmetry shows the variable nature of the project factor at different pulsation phases, which should be taken into account in the detailed spectroscopic analysis of pulsating stars.

  8. Anxiety and depression symptoms in Brazilian sexual minority ecstasy and LSD users

    Directory of Open Access Journals (Sweden)

    Lysa S. Remy

    2017-11-01

    Full Text Available Abstract Background This study examined drug use patterns and psychiatric symptoms of anxiety and depression among young Brazilian sexual minority ecstasy and LSD users and compared findings with those reported for their heterosexual peers. Method This cross-sectional study employed targeted sampling and ethnographic mapping approaches via face-to-face interviews conducted at bars and electronic music festivals using an adapted, semi-structured version of the Global Appraisal of Individual Needs questionnaire. The sample comprised 240 male and female young adults who had used ecstasy and/or LSD in the 90 days prior to the interview and who were not on treatment for alcohol and drug abuse. Results Of the 240 subjects enrolled (mean age: 22.9±4.5 years, 28.7% were gay or bisexuals. Multivariate regression analysis showed that the prevalence of depression symptoms in the past 12 months in the sexual minority group was 37% higher than among heterosexuals (prevalence ratio [PR]=1.79; 95% confidence interval [95%CI] 1.03-3.11; p=0.037. Conclusion Strategies should be developed to assess and address individual needs and treatment approaches should be tailored to address depressive symptoms in young, sexual minority club drug users.

  9. An automated system for the preparation of Large Size Dried (LSD) Spikes

    Energy Technology Data Exchange (ETDEWEB)

    Verbruggen, A.; Bauwens, J.; Jakobsson, U.; Eykens, R.; Wellum, R.; Aregbe, Y. [European Commission - Joint Research Centre, Institute for Reference Materials and Measurements (IRMM), Retieseweg 211, B2440 Geel (Belgium); Van De Steene, N. [Nucomat, Mercatorstraat 206, B9100 Sint Niklaas (Belgium)

    2008-07-01

    Large size dried (LSD) spikes have been produced to fulfill the existing requirement for reliable and traceable isotopic reference materials for nuclear safeguards. A system to produce certified nuclear isotopic reference material as a U/Pu mixture in the form of large size dried spikes, comparable to those produced using traditional methods has been installed in collaboration with Nucomat, a company with a recognized reputation in design and development of integrated automated systems. The major components of the system are a robot, two balances, a dispenser and a drying unit fitted into a glove box. The robot is software driven and designed to control all movements inside the glove-box, to identify unambiguously the penicillin vials with a bar-code reader, to dispense the LSD batch solution into the vials and to weigh the amount dispensed. The system functionality has been evaluated and the performance validated by comparing the results from a series of samples dispensed and weighed by the automated system with the results by manual substitution weighing. After applying the proper correction factors to the data from the automated system balance no significant difference was observed between the two. However, an additional component of uncertainty of 3*10{sup -4} is introduced in the uncertainty budget for the certified weights provided by the automatic system. (authors)

  10. An automated system for the preparation of Large Size Dried (LSD) Spikes

    International Nuclear Information System (INIS)

    Verbruggen, A.; Bauwens, J.; Jakobsson, U.; Eykens, R.; Wellum, R.; Aregbe, Y.; Van De Steene, N.

    2008-01-01

    Large size dried (LSD) spikes have been produced to fulfill the existing requirement for reliable and traceable isotopic reference materials for nuclear safeguards. A system to produce certified nuclear isotopic reference material as a U/Pu mixture in the form of large size dried spikes, comparable to those produced using traditional methods has been installed in collaboration with Nucomat, a company with a recognized reputation in design and development of integrated automated systems. The major components of the system are a robot, two balances, a dispenser and a drying unit fitted into a glove box. The robot is software driven and designed to control all movements inside the glove-box, to identify unambiguously the penicillin vials with a bar-code reader, to dispense the LSD batch solution into the vials and to weigh the amount dispensed. The system functionality has been evaluated and the performance validated by comparing the results from a series of samples dispensed and weighed by the automated system with the results by manual substitution weighing. After applying the proper correction factors to the data from the automated system balance no significant difference was observed between the two. However, an additional component of uncertainty of 3*10 -4 is introduced in the uncertainty budget for the certified weights provided by the automatic system. (authors)

  11. Detecting Signatures of Positive Selection along Defined Branches of a Population Tree Using LSD.

    Science.gov (United States)

    Librado, Pablo; Orlando, Ludovic

    2018-06-01

    Identifying the genomic basis underlying local adaptation is paramount to evolutionary biology, and bears many applications in the fields of conservation biology, crop, and animal breeding, as well as personalized medicine. Although many approaches have been developed to detect signatures of positive selection within single populations and population pairs, the increasing wealth of high-throughput sequencing data requires improved methods capable of handling multiple, and ideally large number of, populations in a single analysis. In this study, we introduce LSD (levels of exclusively shared differences), a fast and flexible framework to perform genome-wide selection scans, along the internal and external branches of a given population tree. We use forward simulations to demonstrate that LSD can identify branches targeted by positive selection with remarkable sensitivity and specificity. We illustrate a range of potential applications by analyzing data from the 1000 Genomes Project and uncover a list of adaptive candidates accompanying the expansion of anatomically modern humans out of Africa and their spread to Europe.

  12. Advantages of analyzing postmortem brain samples in routine forensic drug screening—case series of three non-natural deaths tested positive for lysergic acid diethylamide (LSD)

    DEFF Research Database (Denmark)

    Mardal, Marie; Johansen, Sys Stybe; Thomsen, Ragnar

    2017-01-01

    Three case reports are presented, including autopsy findings and toxicological screening results, which were tested positive for the potent hallucinogenic drug lysergic acid diethylamide (LSD). LSD and its main metabolites were quantified in brain tissue and femoral blood, and furthermore hematoma...

  13. Broadcast design in cognitive radio ad hoc networks

    CERN Document Server

    Song, Yi

    2014-01-01

    This SpringerBrief investigates the special challenges of broadcast design in cognitive radio (CR) ad hoc networks. It introduces two broadcast protocols in CR ad hoc networks: a quality-of-service based broadcast protocol under blind information and a fully-distributed broadcast protocol with collision avoidance. A novel unified analytical model is also presented to analyze the performance of the broadcast protocols. This is the first book dedicated to the unique broadcast design challenges in CR ad hoc networks. The authors also discuss the recent research on the performance analysis of broa

  14. Ad hoc laser networks component technology for modular spacecraft

    Science.gov (United States)

    Huang, Xiujun; Shi, Dele; Shen, Jingshi

    2017-10-01

    Distributed reconfigurable satellite is a new kind of spacecraft system, which is based on a flexible platform of modularization and standardization. Based on the module data flow analysis of the spacecraft, this paper proposes a network component of ad hoc Laser networks architecture. Low speed control network with high speed load network of Microwave-Laser communication mode, no mesh network mode, to improve the flexibility of the network. Ad hoc Laser networks component technology was developed, and carried out the related performance testing and experiment. The results showed that ad hoc Laser networks components can meet the demand of future networking between the module of spacecraft.

  15. The hallucinogen d-lysergic acid diethylamide (d-LSD) induces the immediate-early gene c-Fos in rat forebrain.

    Science.gov (United States)

    Frankel, Paul S; Cunningham, Kathryn A

    2002-12-27

    The hallucinogen d-lysergic acid diethylamide (d-LSD) evokes dramatic somatic and psychological effects. In order to analyze the neural activation induced by this unique psychoactive drug, we tested the hypothesis that expression of the immediate-early gene product c-Fos is induced in specific regions of the rat forebrain by a relatively low, behaviorally active, dose of d-LSD (0.16 mg/kg, i.p.); c-Fos protein expression was assessed at 30 min, and 1, 2 and 4 h following d-LSD injection. A time- and region-dependent expression of c-Fos was observed with a significant increase (PLSD administration. These data demonstrate a unique pattern of c-Fos expression in the rat forebrain following a relatively low dose of d-LSD and suggest that activation of these forebrain regions contributes to the unique behavioral effects of d-LSD. Copyright 2002 Elsevier Science B.V.

  16. The hallucinogen d-lysergic diethylamide (LSD) decreases dopamine firing activity through 5-HT1A, D2 and TAAR1 receptors.

    Science.gov (United States)

    De Gregorio, Danilo; Posa, Luca; Ochoa-Sanchez, Rafael; McLaughlin, Ryan; Maione, Sabatino; Comai, Stefano; Gobbi, Gabriella

    2016-11-01

    d-lysergic diethylamide (LSD) is a hallucinogenic drug that interacts with the serotonin (5-HT) system binding to 5-HT 1 and 5-HT 2 receptors. Little is known about its potential interactions with the dopamine (DA) neurons of the ventral tegmental area (VTA). Using in-vivo electrophysiology in male adult rats, we evaluated the effects of cumulative doses of LSD on VTA DA neuronal activity, compared these effects to those produced on 5-HT neurons in the dorsal raphe nucleus (DRN), and attempted to identify the mechanism of action mediating the effects of LSD on VTA DA neurons. LSD, at low doses (5-20μg/kg, i.v.) induced a significant decrease of DRN 5-HT firing activity through 5-HT 2A and D 2 receptors. At these low doses, LSD did not alter VTA DA neuronal activity. On the contrary, at higher doses (30-120μg/kg, i.v.), LSD dose-dependently decreased VTA DA firing activity. The depletion of 5-HT with p-chlorophenylalanine did not modulate the effects of LSD on DA firing activity. The inhibitory effects of LSD on VTA DA firing activity were prevented by the D 2 receptor antagonist haloperidol (50μg/kg, i.v.) and by the 5-HT 1A receptor antagonist WAY-100,635 (500μg/kg, i.v.). Notably, pretreatment with the trace amine-associate receptor 1 (TAAR 1 ) antagonist EPPTB (5mg/kg, i.v.) blocked the inhibitory effect of LSD on VTA DA neurons. These results suggest that LSD at high doses strongly affects DA mesolimbic neuronal activity in a 5-HT independent manner and with a pleiotropic mechanism of action involving 5-HT 1A, D 2 and TAAR 1 receptors. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. Interference in wireless ad hoc networks with smart antennas

    KAUST Repository

    Alabdulmohsin, Ibrahim

    2014-01-01

    In this paper, we show that the use of directional antennas in wireless ad hoc networks can actually increase interference due to limitations of virtual carrier sensing. We derive a simple mathematical expression for interference in both physical

  18. Source Authentication for Multicast in Mobile Ad Hoc Networks

    National Research Council Canada - National Science Library

    Ramachandran, Prabha

    2003-01-01

    Recent emergence and popularity of mobile ad hoc networks in a host of current-day applications has instigated a suite of research challenges, primarily in routing and security issues for such networks...

  19. Internet-Based Mobile Ad Hoc Networking (Preprint)

    National Research Council Canada - National Science Library

    Corson, M. S; Macker, Joseph P; Cirincione, Gregory H

    1999-01-01

    Internet-based Mobile Ad Hoc Networking is an emerging technology that supports self-organizing, mobile networking infrastructures, and is one which appears well-suited for use in future commercial...

  20. Ad Hoc Human Information Nets for Asymmetric Threat Surveillance

    National Research Council Canada - National Science Library

    Thiruvathukal, George

    2003-01-01

    ...: Hybrid-Hierarchical Micro-Databases, Query Optimization, and XML for Embedded Systems. After meeting with the program manager, Tom Armour, in Washington, DC, we were able to get a better perspective on the ad hoc nature of the solicitation...

  1. A New Hybrid Channel Access Scheme for Ad Hoc Networks

    National Research Council Canada - National Science Library

    Wang, Yu; Garcia-Luna-Aceves, J. J

    2002-01-01

    Many contention-based channel access schemes have been proposed for multi-hop ad hoc networks in the recent past, and they can be divided into two categories, sender-initiated and receiver-initiated...

  2. Sensor and ad-hoc networks theoretical and algorithmic aspects

    CERN Document Server

    Makki, S Kami; Pissinou, Niki; Makki, Shamila; Karimi, Masoumeh; Makki, Kia

    2008-01-01

    This book brings together leading researchers and developers in the field of wireless sensor networks to explain the special problems and challenges of the algorithmic aspects of sensor and ad-hoc networks. The book also fosters communication not only between the different sensor and ad-hoc communities, but also between those communities and the distributed systems and information systems communities. The topics addressed pertain to the sensors and mobile environment.

  3. Optimal channel choice for collaborative ad-hoc dissemination

    DEFF Research Database (Denmark)

    Hu, Liang; Boudec, J-Y. L.; Vojnovic, M.

    2010-01-01

    Collaborative ad-hoc dissemination of information has been proposed as an efficient means to disseminate information among devices in a wireless ad-hoc network. Devices help in forwarding the information channels to the entire network, by disseminating the channels they subscribe to, plus others...... by a Metropolis-Hastings sampling algorithm. We also give a variant that accounts for battery level. This leads to a practical channel selection and re-selection algorithm that can be implemented without any central control....

  4. Self-Reported and Judged Personality, Value, and Attitudinal Patterns: A Comparison of Users and Non Users of LSD-25.

    Science.gov (United States)

    Jones, Allan P.

    This study is designed to assess the benefits of LSD use as well as to examine personality, value, and attitudinal variables in order to characterize users and non users. The main assessment tool used was the in-depth interview. Subjects were 31 male and 8 female users and a non user group matched for education and age. The user was characterized…

  5. The serotonergic system and mysticism: could LSD and the nondrug-induced mystical experience share common neural mechanisms?

    Science.gov (United States)

    Goodman, Neil

    2002-01-01

    This article aims to explore, through established scientific research and documented accounts of personal experience, the similarities between religious mystical experiences and some effects of D-lysergic diethylamide or LSD. LSD predominantly works upon the serotonergic (serotonin-using neurons) diffuse neuromodulatory system, which projects its axons to virtually all areas of the brain including the neocortex. By its normal action it modulates awareness of the environmental surroundings and filters a high proportion of this information before it can be processed, thereby only allowing the amount of information that is necessary for survival. LSD works to open this filter, and so an increased amount of somatosensory data is processed with a corresponding increase in what is deemed important. This article describes the effects and actions of LSD, and due to the similarities with the nondrug-induced mystical experience the author proposes that the two could have common modes of action upon the brain. This could lead to avenues of research into mysticism and a wealth of knowledge on consciousness and how we perceive the universe.

  6. miR-137 forms a regulatory loop with nuclear receptor TLX and LSD1 in neural stem cells.

    Science.gov (United States)

    Sun, GuoQiang; Ye, Peng; Murai, Kiyohito; Lang, Ming-Fei; Li, Shengxiu; Zhang, Heying; Li, Wendong; Fu, Chelsea; Yin, Jason; Wang, Allen; Ma, Xiaoxiao; Shi, Yanhong

    2011-11-08

    miR-137 is a brain-enriched microRNA. Its role in neural development remains unknown. Here we show that miR-137 has an essential role in controlling embryonic neural stem cell fate determination. miR-137 negatively regulates cell proliferation and accelerates neural differentiation of embryonic neural stem cells. In addition, we show that the histone lysine-specific demethylase 1 (LSD1), a transcriptional co-repressor of nuclear receptor TLX, is a downstream target of miR-137. In utero electroporation of miR-137 in embryonic mouse brains led to premature differentiation and outward migration of the transfected cells. Introducing a LSD1 expression vector lacking the miR-137 recognition site rescued miR-137-induced precocious differentiation. Furthermore, we demonstrate that TLX, an essential regulator of neural stem cell self-renewal, represses the expression of miR-137 by recruiting LSD1 to the genomic regions of miR-137. Thus, miR-137 forms a feedback regulatory loop with TLX and LSD1 to control the dynamics between neural stem cell proliferation and differentiation during neural development.

  7. An image overall complexity evaluation method based on LSD line detection

    Science.gov (United States)

    Li, Jianan; Duan, Jin; Yang, Xu; Xiao, Bo

    2017-04-01

    In the artificial world, whether it is the city's traffic roads or engineering buildings contain a lot of linear features. Therefore, the research on the image complexity of linear information has become an important research direction in digital image processing field. This paper, by detecting the straight line information in the image and using the straight line as the parameter index, establishing the quantitative and accurate mathematics relationship. In this paper, we use LSD line detection algorithm which has good straight-line detection effect to detect the straight line, and divide the detected line by the expert consultation strategy. Then we use the neural network to carry on the weight training and get the weight coefficient of the index. The image complexity is calculated by the complexity calculation model. The experimental results show that the proposed method is effective. The number of straight lines in the image, the degree of dispersion, uniformity and so on will affect the complexity of the image.

  8. Persistent effects of chronic clozapine on the cellular and behavioral responses to LSD in mice

    Science.gov (United States)

    Moreno, José L.; Holloway, Terrell; Umali, Adrienne; Rayannavar, Vinayak; Sealfon, Stuart C.

    2013-01-01

    Rationale In schizophrenia patients, optimal treatment with antipsychotics requires weeks to months of sustained drug therapy. However, single administration of antipsychotic drugs can reverse schizophrenia-like behavioral alterations in rodent models of psychosis. This raises questions about the physiological relevance of such antipsychotic-like activity. Objective This study evaluates the effects of chronic treatment with clozapine on the cellular and behavioral responses induced by the hallucinogenic serotonin 5-HT2A receptor agonist lysergic acid diethylamide (LSD) as a mouse model of psychosis. Method Mice were treated chronically (21 days) with 25 mg/kg/day clozapine. Experiments were conducted 1, 7, 14, and 21 days after the last clozapine administration. [3H]Ketanserin binding and 5-HT2A mRNA expression were determined in mouse somatosensory cortex. Head-twitch behavior, expression of c-fos, which is induced by all 5-HT2A agonists, and expression of egr-1 and egr-2, which are LSD-like specific, were assayed. Results Head-twitch response was decreased and [3H]ketanserin binding was downregulated in 1, 7, and 14 days after chronic clozapine. 5-HT2A mRNA was reduced 1 day after chronic clozapine. Induction of c-fos, but not egr-1 and egr-2, was rescued 7 days after chronic clozapine. These effects were not observed after short treatment (2 days) with clozapine or chronic haloperidol (1 mg/kg/day). Conclusion Our findings provide a murine model of chronic atypical antipsychotic drug action and suggest downregulation of the 5-HT2A receptor as a potential mechanism involved in these persistent therapeutic-like effects. PMID:22842765

  9. Positive expression of LSD1 and negative expression of E-cadherin correlate with metastasis and poor prognosis of colon cancer.

    Science.gov (United States)

    Jie, Ding; Zhongmin, Zhang; Guoqing, Liao; Sheng, Liu; Yi, Zhang; Jing, Wen; Liang, Zeng

    2013-06-01

    The first identified lysine-specific demethylase, LSD1, plays an important role in the metastatic progression of several types of cancer. The aim of this study was to investigate LSD1, E-cadherin, and N-cadherin expression in colon cancer specimens and their clinical significance. The expression of LSD1, E-cadherin, and N-cadherin in colon cancer specimens was determined by immunohistochemistry, and the relationship between the expression of the respective molecules and clinicopathological characteristics was analyzed. The positive expression rates of LSD1, E-cadherin, and N-cadherin in colon cancer specimens were 66.7 % (72/108), 85.2 % (92/108), and 41.7 % (45/108), respectively. LSD1 was significantly more highly expressed in colon cancer specimens classified as high TNM stage lesions and with distant metastasis (P colon cancer specimens classified as high TNM stage lesions and with distant metastasis (P clinical and pathological characteristics (P > 0.05). Correlation analysis revealed that LSD1 expression was negatively correlated with E-cadherin expression (r s = -0.318, P = 0.001), but not evidently correlated with N-cadherin expression (r s = 0.182, P = 0.06). Colon cancer specimens with positive LSD1 expression and negative E-cadherin expression were correlated with significantly lower overall survival. LSD1 showed a significantly higher expression, in contrast to the significantly lower expression of E-cadherin, in colon cancer specimens classified as high TNM stage lesions and with distant metastasis. Positive expression of LSD1 and negative expression of E-cadherin may be predictors of a worse colon cancer prognosis.

  10. Innovative research of AD HOC network mobility model

    Science.gov (United States)

    Chen, Xin

    2017-08-01

    It is difficult for researchers of AD HOC network to conduct actual deployment during experimental stage as the network topology is changeable and location of nodes is unfixed. Thus simulation still remains the main research method of the network. Mobility model is an important component of AD HOC network simulation. It is used to describe the movement pattern of nodes in AD HOC network (including location and velocity, etc.) and decides the movement trail of nodes, playing as the abstraction of the movement modes of nodes. Therefore, mobility model which simulates node movement is an important foundation for simulation research. In AD HOC network research, mobility model shall reflect the movement law of nodes as truly as possible. In this paper, node generally refers to the wireless equipment people carry. The main research contents include how nodes avoid obstacles during movement process and the impacts of obstacles on the mutual relation among nodes, based on which a Node Self Avoiding Obstacle, i.e. NASO model is established in AD HOC network.

  11. Routing Protocol for Mobile Ad-hoc Wireless Networks

    Directory of Open Access Journals (Sweden)

    I. M. B. Nogales

    2007-09-01

    Full Text Available Bluetooth is a cutting-edge technology used for implementing wireless ad hoc networks. In order to provide an overall scheme for mobile ad hoc networks, this paper deals with scatternet topology formation and routing algorithm to form larger ad hoc wireless Networks. Scatternet topology starts by forming a robust network, which is less susceptible to the problems posed by node mobility. Mobile topology relies on the presence of free nodes that create multiple connections with the network and on their subsequently rejoining the network. Our routing protocol is a proactive routing protocol, which is tailor made for the Bluetooth ad hoc network. The connection establishment connects nodes in a structure that simplifies packet routing and scheduling. The design allows nodes to arrive and leave arbitrarily, incrementally building the topology and healing partitions when they occur. We present simulation results that show that the algorithm presents low formation latency and also generates an efficient topology for forwarding packets along ad-hoc wireless networks.

  12. A Framework for Speech Enhancement with Ad Hoc Microphone Arrays

    DEFF Research Database (Denmark)

    Tavakoli, Vincent Mohammad; Jensen, Jesper Rindom; Christensen, Mads Græsbøll

    2016-01-01

    Speech enhancement is vital for improved listening practices. Ad hoc microphone arrays are promising assets for this purpose. Most well-established enhancement techniques with conventional arrays can be adapted into ad hoc scenarios. Despite recent efforts to introduce various ad hoc speech...... enhancement apparatus, a common framework for integration of conventional methods into this new scheme is still missing. This paper establishes such an abstraction based on inter and intra sub-array speech coherencies. Along with measures for signal quality at the input of sub-arrays, a measure of coherency...... is proposed both for sub-array selection in local enhancement approaches, and also for selecting a proper global reference when more than one sub-array are used. Proposed methods within this framework are evaluated with regard to quantitative and qualitative measures, including array gains, the speech...

  13. A Clustering Routing Protocol for Mobile Ad Hoc Networks

    Directory of Open Access Journals (Sweden)

    Jinke Huang

    2016-01-01

    Full Text Available The dynamic topology of a mobile ad hoc network poses a real challenge in the design of hierarchical routing protocol, which combines proactive with reactive routing protocols and takes advantages of both. And as an essential technique of hierarchical routing protocol, clustering of nodes provides an efficient method of establishing a hierarchical structure in mobile ad hoc networks. In this paper, we designed a novel clustering algorithm and a corresponding hierarchical routing protocol for large-scale mobile ad hoc networks. Each cluster is composed of a cluster head, several cluster gateway nodes, several cluster guest nodes, and other cluster members. The proposed routing protocol uses proactive protocol between nodes within individual clusters and reactive protocol between clusters. Simulation results show that the proposed clustering algorithm and hierarchical routing protocol provide superior performance with several advantages over existing clustering algorithm and routing protocol, respectively.

  14. Multiagent Based Information Dissemination in Vehicular Ad Hoc Networks

    Directory of Open Access Journals (Sweden)

    S.S. Manvi

    2009-01-01

    Full Text Available Vehicular Ad hoc Networks (VANETs are a compelling application of ad hoc networks, because of the potential to access specific context information (e.g. traffic conditions, service updates, route planning and deliver multimedia services (Voice over IP, in-car entertainment, instant messaging, etc.. This paper proposes an agent based information dissemination model for VANETs. A two-tier agent architecture is employed comprising of the following: 1 'lightweight', network-facing, mobile agents; 2 'heavyweight', application-facing, norm-aware agents. The limitations of VANETs lead us to consider a hybrid wireless network architecture that includes Wireless LAN/Cellular and ad hoc networking for analyzing the proposed model. The proposed model provides flexibility, adaptability and maintainability for traffic information dissemination in VANETs as well as supports robust and agile network management. The proposed model has been simulated in various network scenarios to evaluate the effectiveness of the approach.

  15. Auto-configuration protocols in mobile ad hoc networks.

    Science.gov (United States)

    Villalba, Luis Javier García; Matesanz, Julián García; Orozco, Ana Lucila Sandoval; Díaz, José Duván Márquez

    2011-01-01

    The TCP/IP protocol allows the different nodes in a network to communicate by associating a different IP address to each node. In wired or wireless networks with infrastructure, we have a server or node acting as such which correctly assigns IP addresses, but in mobile ad hoc networks there is no such centralized entity capable of carrying out this function. Therefore, a protocol is needed to perform the network configuration automatically and in a dynamic way, which will use all nodes in the network (or part thereof) as if they were servers that manage IP addresses. This article reviews the major proposed auto-configuration protocols for mobile ad hoc networks, with particular emphasis on one of the most recent: D2HCP. This work also includes a comparison of auto-configuration protocols for mobile ad hoc networks by specifying the most relevant metrics, such as a guarantee of uniqueness, overhead, latency, dependency on the routing protocol and uniformity.

  16. Effects of Data Replication on Data Exfiltration in Mobile Ad Hoc Networks Utilizing Reactive Protocols

    Science.gov (United States)

    2015-03-01

    aerial vehicle VANET vehicular ad hoc network VoIP Voice over Internet Protocol VRR Virtual Ring Routing xiii EFFECTS OF DATA REPLICATION ON DATA...ad hoc networks in mobile ad hoc networks (MANETs), vehicular ad hoc networks (VANETs), and flying ad hoc net- works (FANETs). Much of the research...metric, such as capacity, congestion , power, or combinations thereof. Caro refers to two different types of ants, FANTs and BANTs which are analogous to

  17. Multichannel MAC Layer In Mobile Ad—Hoc Network

    Science.gov (United States)

    Logesh, K.; Rao, Samba Siva

    2010-11-01

    This paper we presented the design objectives and technical challenges in Multichannel MAC protocols in Mobile Ad-hoc Network. In IEEE 802.11 a/b/g standards allow use of multiple channels, only a single channel is popularly used, due to the lack of efficient protocols that enable use of Multiple Channels. Even though complex environments in ad hoc networks require a combined control of physical (PHY) and medium access control (MAC) layers resources in order to optimize performance. And also we discuss the characteristics of cross-layer frame and give a multichannel MAC approach.

  18. Determination of lysergic acid diethylamide (LSD) in mouse blood by capillary electrophoresis/ fluorescence spectroscopy with sweeping techniques in micellar electrokinetic chromatography.

    Science.gov (United States)

    Fang, Ching; Liu, Ju-Tsung; Chou, Shiu-Huey; Lin, Cheng-Huang

    2003-03-01

    The separation and on-line concentration of lysergic acid diethylamide (LSD) in mouse blood was achieved by means of capillary electrophoresis/fluorescence spectroscopy using sodium dodecyl sulfate (SDS) as the surfactant. Techniques involving on-line sample concentration, including sweeping micellar electrokinetic chromatography (sweeping-MEKC) and cation-selective exhaustive injection-sweep-micellar electrokinetic chromatography (CSEI-sweep-MEKC) were applied; the optimum on-line concentration and separation conditions were determined. In the analysis of an actual sample, LSD was found in a blood sample from a test mouse (0.1 mg LSD fed to a 20 g mouse; approximately 1/10 to the value of LD(50)). As a result, 120 and 30 ng/mL of LSD was detected at 20 and 60 min, respectively, after ingestion of the doses.

  19. Epigenetic silencing of the DNA mismatch repair gene, MLH1, induced by hypoxic stress in a pathway dependent on the histone demethylase, LSD1

    Science.gov (United States)

    Lu, Yuhong; Wajapeyee, Narendra; Turker, Mitchell S.; Glazer, Peter M.

    2014-01-01

    SUMMARY Silencing of the MLH1 gene is frequently seen in sporadic cancers. We report that hypoxia causes decreased H3K4 methylation at the MLH1 promoter via the H3K4 demethylases, LSD1 and PLU-1, and promotes long-term silencing of the promoter in a pathway that requires LSD1. Knockdown of LSD1 or its co-repressor, CoREST, also prevents the re-silencing (and cytosine DNA methylation) of the endogenous MLH1 promoter in RKO colon cancer cells following transient reactivation by the DNA methyltransferase inhibitor 5-aza-2′-deoxycytidine (5-aza-dC). The results demonstrate that hypoxia is a critical driving force for silencing of MLH1 through chromatin modification and indicate that the LSD1/CoREST complex is essential for MLH1 silencing. PMID:25043185

  20. The histone demethylase LSD1 is required for estrogen-dependent S100A7 gene expression in human breast cancer cells

    International Nuclear Information System (INIS)

    Yu, Seung Eun; Jang, Yeun Kyu

    2012-01-01

    Highlights: ► S100A7 gene is up-regulated in response to estrogen in breast cancer cells. ► Histone demethylase LSD1 can associate physically with S100A7 gene promoters. ► E2-induced S100A7 expression requires the enzymatic activity of LSD1. ► S100A7 inhibits cell proliferation, implying its tumor suppressor-like function. -- Abstract: S100A7, a member of S100 calcium binding protein family, is highly associated with breast cancer. However, the molecular mechanism of S100A7 regulation remains unclear. Here we show that long-term treatment with estradiol stimulated S100A7 expression in MCF7 breast cancer cells at both the transcriptional and translational levels. Both treatment with a histone demethylase LSD1 inhibitor and shRNA-based knockdown of LSD1 expression significantly decreased 17β-estradiol (E2)-induced S100A7 expression. These reduced E2-mediated S100A7 expression are rescued by the overexpressed wild-type LSD1 but not by its catalytically inactive mutant. Our data showed in vivo association of LSD1 with S100A7 promoters, confirming the potential role of LSD1 in regulating S100A7 expression. S100A7 knockdown increased both normal cell growth and estrogen-induced cell proliferation, suggesting a negative influence by S100A7 on the growth of cancer cells. Together, our data suggest that estrogen-induced S100A7 expression mediated by the histone demethylase LSD1 may downregulate breast cancer cell proliferation, implying a potential tumor suppressor-like function for S100A7.

  1. Disrupted integration of sensory stimuli with information about the movement of the body as a mechanism explaining LSD-induced experience.

    Science.gov (United States)

    Juszczak, Grzegorz R

    2017-03-01

    LSD (lysergic acid diethylamide) is a model psychedelic drug used to study mechanism underlying the effects induced by hallucinogens. However, despite advanced knowledge about molecular mechanism responsible for the effects induced by LSD and other related substances acting at serotonergic 5-HT 2a receptors, we still do not understand how these drugs trigger specific sensory experiences. LSD-induced experience is characterised by perception of movement in the environment and by presence of various bodily sensations such as floating in space, merging into surroundings and movement out of the physical body (the out-of-body experience). It means that a large part of the experience induced by the LSD can be simplified to the illusory movement that can be attributed to the self or to external objects. The phenomenology of the LSD-induced experience has been combined with the fact that serotonergic neurons provide all major parts of the brain with information about the level of tonic motor activity, occurrence of external stimuli and the execution of orienting responses. Therefore, it has been proposed that LSD-induced stimulation of 5-HT 2a receptors disrupts the integration of the sensory stimuli with information about the movement of the body leading to perception of illusory movement. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. Chronic treatment with LY341495 decreases 5-HT(2A) receptor binding and hallucinogenic effects of LSD in mice.

    Science.gov (United States)

    Moreno, José L; Holloway, Terrell; Rayannavar, Vinayak; Sealfon, Stuart C; González-Maeso, Javier

    2013-03-01

    Hallucinogenic drugs, such as lysergic acid diethylamide (LSD), mescaline and psilocybin, alter perception and cognitive processes. All hallucinogenic drugs have in common a high affinity for the serotonin 5-HT(2A) receptor. Metabotropic glutamate 2/3 (mGlu2/3) receptor ligands show efficacy in modulating the cellular and behavioral responses induced by hallucinogenic drugs. Here, we explored the effect of chronic treatment with the mGlu2/3 receptor antagonist 2S-2-amino-2-(1S,2S-2-carboxycyclopropan-1-yl)-3-(xanth-9-yl)-propionic acid (LY341495) on the hallucinogenic-like effects induced by LSD (0.24mg/kg). Mice were chronically (21 days) treated with LY341495 (1.5mg/kg), or vehicle, and experiments were carried out one day after the last injection. Chronic treatment with LY341495 down-regulated [(3)H]ketanserin binding in somatosensory cortex of wild-type, but not mGlu2 knockout (KO), mice. Head-twitch behavior, and expression of c-fos, egr-1 and egr-2, which are responses induced by hallucinogenic 5-HT(2A) agonists, were found to be significantly decreased by chronic treatment with LY341495. These findings suggest that repeated blockade of the mGlu2 receptor by LY341495 results in reduced 5-HT(2A) receptor-dependent hallucinogenic effects of LSD. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  3. Serotonin 2A Receptor Signaling Underlies LSD-induced Alteration of the Neural Response to Dynamic Changes in Music.

    Science.gov (United States)

    Barrett, Frederick S; Preller, Katrin H; Herdener, Marcus; Janata, Petr; Vollenweider, Franz X

    2017-09-28

    Classic psychedelic drugs (serotonin 2A, or 5HT2A, receptor agonists) have notable effects on music listening. In the current report, blood oxygen level-dependent (BOLD) signal was collected during music listening in 25 healthy adults after administration of placebo, lysergic acid diethylamide (LSD), and LSD pretreated with the 5HT2A antagonist ketanserin, to investigate the role of 5HT2A receptor signaling in the neural response to the time-varying tonal structure of music. Tonality-tracking analysis of BOLD data revealed that 5HT2A receptor signaling alters the neural response to music in brain regions supporting basic and higher-level musical and auditory processing, and areas involved in memory, emotion, and self-referential processing. This suggests a critical role of 5HT2A receptor signaling in supporting the neural tracking of dynamic tonal structure in music, as well as in supporting the associated increases in emotionality, connectedness, and meaningfulness in response to music that are commonly observed after the administration of LSD and other psychedelics. Together, these findings inform the neuropsychopharmacology of music perception and cognition, meaningful music listening experiences, and altered perception of music during psychedelic experiences. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  4. Chronic treatment with LY341495 decreases 5-HT2A receptor binding and hallucinogenic effects of LSD in mice

    Science.gov (United States)

    Moreno, José L.; Holloway, Terrell; Rayannavar, Vinayak; Sealfon, Stuart C.; González-Maeso, Javier

    2013-01-01

    Hallucinogenic drugs, such as lysergic acid diethylamide (LSD), mescaline and psilocybin, alter perception and cognitive processes. All hallucinogenic drugs have in common a high affinity for the serotonin 5-HT2A receptor. Metabotropic glutamate 2/3 (mGlu2/3) receptor ligands show efficacy in modulating the cellular and behavioral responses induced by hallucinogenic drugs. Here, we explored the effect of chronic treatment with the mGlu2/3 receptor antagonist 2S-2-amino-2-(1S,2S-2-carboxycyclopropan-1-yl)-3-(xanth-9-yl)-propionic acid (LY341495) on the hallucinogenic-like effects induced by LSD (0.24 mg/kg). Mice were chronically (21 days) treated with LY341495 (1.5 mg/kg), or vehicle, and experiments were carried out one day after the last injection. Chronic treatment with LY341495 down-regulated [3H]ketanserin binding in somatosensory cortex of wild-type, but not mGlu2 knockout (KO), mice. Head-twitch behavior, and expression of c-fos, egr-1 and egr-2, which are responses induced by hallucinogenic 5-HT2A agonists, were found to be significantly decreased by chronic treatment with LY341495. These findings suggest that repeated blockade of the mGlu2 receptor by LY341495 results in reduced 5-HT2A receptor-dependent hallucinogenic effects of LSD. PMID:23333599

  5. SFPQ associates to LSD1 and regulates the migration of newborn pyramidal neurons in the developing cerebral cortex.

    Science.gov (United States)

    Saud, K; Cánovas, J; Lopez, C I; Berndt, F A; López, E; Maass, J C; Barriga, A; Kukuljan, M

    2017-04-01

    The development of the cerebral cortex requires the coordination of multiple processes ranging from the proliferation of progenitors to the migration and establishment of connectivity of the newborn neurons. Epigenetic regulation carried out by the COREST/LSD1 complex has been identified as a mechanism that regulates the development of pyramidal neurons of the cerebral cortex. We now identify the association of the multifunctional RNA-binding protein SFPQ to LSD1 during the development of the cerebral cortex. In vivo reduction of SFPQ dosage by in utero electroporation of a shRNA results in impaired radial migration of newborn pyramidal neurons, in a similar way to that observed when COREST or LSD1 expressions are decreased. Diminished SFPQ expression also associates to decreased proliferation of progenitor cells, while it does not affect the acquisition of neuronal fate. These results are compatible with the idea that SFPQ, plays an important role regulating proliferation and migration during the development of the cerebral cortex. Copyright © 2016 ISDN. Published by Elsevier Ltd. All rights reserved.

  6. Ad Hoc Transient Groups: Instruments for Awareness in Learning Networks

    NARCIS (Netherlands)

    Fetter, Sibren; Rajagopal, Kamakshi; Berlanga, Adriana; Sloep, Peter

    2011-01-01

    Fetter, S., Rajagopal, K., Berlanga, A. J., & Sloep, P. B. (2011). Ad Hoc Transient Groups: Instruments for Awareness in Learning Networks. In W. Reinhardt, T. D. Ullmann, P. Scott, V. Pammer, O. Conlan, & A. J. Berlanga (Eds.), Proceedings of the 1st European Workshop on Awareness and Reflection in

  7. Verification of mobile ad hoc networks : an algebraic approach

    NARCIS (Netherlands)

    Ghassemi, F.; Fokkink, W.J.; Movaghar, A.

    2011-01-01

    We introduced Computed Network Process Theory to reason about protocols for mobile ad hoc networks (MANETs). Here we explore the applicability of our framework in two regards: model checking and equational reasoning. The operational semantics of our framework is based on constrained labeled

  8. What Is the Problem of Ad Hoc Hypotheses?

    Science.gov (United States)

    Bamford, Greg

    1999-01-01

    Philosophers' attempts to convincingly explicate the received view of an ad hoc hypothesis--that it accounts for only the observations it was designed to account for--have been unsuccessful. Familiar and firmer criteria for evaluating the hypotheses or modified theories so classified are characteristically available. Contains 41 references.…

  9. Securing DSR with mobile agents in wireless ad hoc networks

    Directory of Open Access Journals (Sweden)

    Ahmed Abosamra

    2011-03-01

    Full Text Available Ad hoc wireless network consists of a set of wireless nodes communicating with each other without a pre-defined infrastructure. They communicate by forwarding packets which can reach wireless nodes that do not exist in the range of the direct radio transmission. Designing ad hoc network routing protocols is a challenging task because of its decentralized infrastructure which makes securing ad hoc networks more and more challenging. Dynamic Source Routing (DSR protocol is a popular routing protocol designed for use in wireless ad hoc networks. Mobile agent is a promising technology used in diverse fields of network applications. In this paper, we try to implement DSR using mobile agents for securing this type of wireless network. Hybrid encryption technique (symmetric key encryption/public key encryption is used to improve performance; where symmetric keys are used to encrypt routing data to authenticate and authorize node sending data, while, public keys are used for the exchange of symmetric keys between nodes. We found that DSR may be secured using mobile agents with competitive performance.

  10. ON SECURE FULL DUPLEX COMMUNICATION IN MOBILE AD HOC NETWORK

    OpenAIRE

    S. C. Dutta; Sudha Singh; D. K. Singh

    2013-01-01

    This paper is to establish Ad Hoc network in mobile phones and start fully secured full duplex communication in any situation. This type of communication will be cost effective and it will be fastest way of communication in case of any server failure or server error.

  11. The accuracy of interpreting key psychiatric terms by ad hoc ...

    African Journals Online (AJOL)

    MacFarlane et al.15 note that a greater number of people have a preference for working with ad hoc interpreters in comparison to professional interpreters ... As part of a larger study, a cross-sectional qualitative interview design was used to ..... obstacle they would face if they would receive training. They had concerns over ...

  12. Authentication and consensus overhead in vehicular ad hoc networks

    NARCIS (Netherlands)

    Petit, Jonathan; Mammeri, Zoubir

    Vehicular ad hoc networks aim at increasing passenger safety by exchanging warning messages between vehicles wirelessly. A main challenge is to resist to various malicious abuses and security attacks. However, any security mechanism comes with overhead. We analyze how the authentication algorithm

  13. Challenges of evidence acquisition in wireless ad-hoc networks

    CSIR Research Space (South Africa)

    Mutanga, MB

    2010-05-01

    Full Text Available a big challenge. Thus, the aim of this paper is to explore the challenges of acquiring live evidence in wireless ad-hoc networks. We also give some legal requirements of evidence admissibility as outlined in the Communications and Transactions Act...

  14. Analysis of Pervasive Mobile Ad Hoc Routing Protocols

    Science.gov (United States)

    Qadri, Nadia N.; Liotta, Antonio

    Mobile ad hoc networks (MANETs) are a fundamental element of pervasive networks and therefore, of pervasive systems that truly support pervasive computing, where user can communicate anywhere, anytime and on-the-fly. In fact, future advances in pervasive computing rely on advancements in mobile communication, which includes both infrastructure-based wireless networks and non-infrastructure-based MANETs. MANETs introduce a new communication paradigm, which does not require a fixed infrastructure - they rely on wireless terminals for routing and transport services. Due to highly dynamic topology, absence of established infrastructure for centralized administration, bandwidth constrained wireless links, and limited resources in MANETs, it is challenging to design an efficient and reliable routing protocol. This chapter reviews the key studies carried out so far on the performance of mobile ad hoc routing protocols. We discuss performance issues and metrics required for the evaluation of ad hoc routing protocols. This leads to a survey of existing work, which captures the performance of ad hoc routing algorithms and their behaviour from different perspectives and highlights avenues for future research.

  15. Collaboration Layer for Robots in Mobile Ad-hoc Networks

    DEFF Research Database (Denmark)

    Borch, Ole; Madsen, Per Printz; Broberg, Jacob Honor´e

    2009-01-01

    In many applications multiple robots in Mobile Ad-hoc Networks are required to collaborate in order to solve a task. This paper shows by proof of concept that a Collaboration Layer can be modelled and designed to handle the collaborative communication, which enables robots in small to medium size...

  16. VMQL: A Visual Language for Ad-Hoc Model Querying

    DEFF Research Database (Denmark)

    Störrle, Harald

    2011-01-01

    In large scale model based development, analysis level models are more like knowledge bases than engineering artifacts. Their effectiveness depends, to a large degree, on the ability of domain experts to retrieve information from them ad hoc. For large scale models, however, existing query...

  17. Ad Hoc Physical Hilbert Spaces in Quantum Mechanics

    Czech Academy of Sciences Publication Activity Database

    Fernandez, F. M.; Garcia, J.; Semorádová, Iveta; Znojil, Miloslav

    2015-01-01

    Roč. 54, č. 12 (2015), s. 4187-4203 ISSN 0020-7748 Institutional support: RVO:61389005 Keywords : quantum mechanics * physical Hilbert spaces * ad hoc inner product * singular potentials regularized * low lying energies Subject RIV: BE - Theoretical Physics Impact factor: 1.041, year: 2015

  18. TMAP ad hoc Working Group Fish Progress report 2007

    NARCIS (Netherlands)

    Bolle, L.J.; Damm, U.; Diederichs, B.; Jager, Z.; Overzee, van H.M.J.

    2007-01-01

    Building on previous work done by the TMAP ad hoc Working Group Fish, a meeting and a workshop were held in Hamburg in June and October 2007. The most important aim of both was to come to an agreement on how to proceed with the data preparations and analyses, and to facilitate the exchange of data

  19. Node counting in wireless ad-hoc networks

    NARCIS (Netherlands)

    Evers, J.H.M.; Kiss, D.; Kowalczyk, W.; Navilarekallu, T.; Renger, D.R.M.; Sella, L.; Timperio, V.; Viorel, A.; Wijk, van A.C.C.; Yzelman, A.J.; Planqué, B.; Bhulai, S.; Hulshof, J.; Kager, W.; Rot, T.

    2012-01-01

    We study wireless ad-hoc networks consisting of small microprocessors with limited memory, where the wireless communication between the processors can be highly unreliable. For this setting, we propose a number of algorithms to estimate the number of nodes in the network, and the number of direct

  20. Capacity, delay and mobility in wireless ad-hoc networks

    NARCIS (Netherlands)

    Bansal, N.; Liu, Z.

    2003-01-01

    Network throughput and packet delay are two important parameters in the design and the evaluation of routing protocols for ad-hoc networks. While mobility has been shown to increase the capacity of a network, it is not clear whether the delay can be kept low without trading off the throughput. We

  1. Access Point Security Service for wireless ad-hoc communication

    NARCIS (Netherlands)

    Scholten, Johan; Nijdam, M.

    2006-01-01

    This paper describes the design and implementation of a security solution for ad-hoc peer-to-peer communication. The security solution is based on a scenario where two wireless devices require secure communication, but share no security relationship a priori. The necessary requirements for the

  2. Modelling Mobility in Mobile AD-HOC Network Environments ...

    African Journals Online (AJOL)

    In the simulation of mobile ad-hoc networks (MANETs), the probability distribution governing the movement of nodes typically varies over time and converges to a steady state distribution, known as the stationary distribution. This paper presents and evaluates the stationary distribution for location, speed and pause time of a ...

  3. Dynamic Mobile IP routers in ad hoc networks

    NARCIS (Netherlands)

    Kock, B.A.; Schmidt, J.R.

    2005-01-01

    This paper describes a concept combining mobile IP and ad hoc routing to create a robust mobile network. In this network all nodes are mobile and globally and locally reachable under the same IP address. Essential for implementing this network are the dynamic mobile IP routers. They act as gateways

  4. Increased spontaneous MEG signal diversity for psychoactive doses of ketamine, LSD and psilocybin

    Science.gov (United States)

    Schartner, Michael M.; Carhart-Harris, Robin L.; Barrett, Adam B.; Seth, Anil K.; Muthukumaraswamy, Suresh D.

    2017-04-01

    What is the level of consciousness of the psychedelic state? Empirically, measures of neural signal diversity such as entropy and Lempel-Ziv (LZ) complexity score higher for wakeful rest than for states with lower conscious level like propofol-induced anesthesia. Here we compute these measures for spontaneous magnetoencephalographic (MEG) signals from humans during altered states of consciousness induced by three psychedelic substances: psilocybin, ketamine and LSD. For all three, we find reliably higher spontaneous signal diversity, even when controlling for spectral changes. This increase is most pronounced for the single-channel LZ complexity measure, and hence for temporal, as opposed to spatial, signal diversity. We also uncover selective correlations between changes in signal diversity and phenomenological reports of the intensity of psychedelic experience. This is the first time that these measures have been applied to the psychedelic state and, crucially, that they have yielded values exceeding those of normal waking consciousness. These findings suggest that the sustained occurrence of psychedelic phenomenology constitutes an elevated level of consciousness - as measured by neural signal diversity.

  5. Experiências com a dietilamina do ácido lisérgico (LSD 25

    Directory of Open Access Journals (Sweden)

    Paulo Luiz Vianna Guedes

    1961-03-01

    Full Text Available São relatados os resultados de 5 experiências realizadas em 3 pacientes com LSD 25, sendo salientadas as propriedades terapêuticas dêste medicamento como auxiliar da psicoterapia. Entre outras, são ressaltadas como principais qualidades: a ação regressiva sôbre o ego que facilita o aparecimento, sob forte carga afetiva, dos conflitos internos na transferência; b ação não uniforme sôbre o ego, poupando umas partes que, assim, não só assistem, mas podem, durante a experiência, analisar o material surgido; c conservação da memória que permite em dias ulteriores e fora da ação lisérgica, a análise das vivências ocorridas na experiência. O método só terá tôda sua utilidade, na opinião do autor, em mãos de médico psicanalista capacitado a lidar com material derivado do inconsciente.

  6. KDM1A/LSD1 regulates the differentiation and maintenance of spermatogonia in mice.

    Directory of Open Access Journals (Sweden)

    Dexter A Myrick

    Full Text Available The proper regulation of spermatogenesis is crucial to ensure the continued production of sperm and fertility. Here, we investigated the function of the H3K4me2 demethylase KDM1A/LSD1 during spermatogenesis in developing and adult mice. Conditional deletion of Kdm1a in the testis just prior to birth leads to fewer spermatogonia and germ cell loss before 3 weeks of age. These results demonstrate that KDM1A is required for spermatogonial differentiation, as well as germ cell survival, in the developing testis. In addition, inducible deletion of Kdm1a in the adult testis results in the abnormal accumulation of meiotic spermatocytes, as well as apoptosis and progressive germ cell loss. These results demonstrate that KDM1A is also required during adult spermatogenesis. Furthermore, without KDM1A, the stem cell factor OCT4 is ectopically maintained in differentiating germ cells. This requirement for KDM1A is similar to what has been observed in other stem cell populations, suggesting a common function. Taken together, we propose that KDM1A is a key regulator of spermatogenesis and germ cell maintenance in the mouse.

  7. Serotonergic and dopaminergic distinctions in the behavioral pharmacology of (±)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) and lysergic acid diethylamide (LSD).

    Science.gov (United States)

    Schindler, Emmanuelle A D; Dave, Kuldip D; Smolock, Elaine M; Aloyo, Vincent J; Harvey, John A

    2012-03-01

    After decades of social stigma, hallucinogens have reappeared in the clinical literature demonstrating unique benefits in medicine. The precise behavioral pharmacology of these compounds remains unclear, however. Two commonly studied hallucinogens, (±)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) and lysergic acid diethylamide (LSD), were investigated both in vivo and in vitro to determine the pharmacology of their behavioral effects in an animal model. Rabbits were administered DOI or LSD and observed for head bob behavior after chronic drug treatment or after pretreatment with antagonist ligands. The receptor binding characteristics of DOI and LSD were studied in vitro in frontocortical homogenates from naïve rabbits or ex vivo in animals receiving an acute drug injection. Both DOI- and LSD-elicited head bobs required serotonin(2A) (5-HT(2A)) and dopamine(1) (D(1)) receptor activation. Serotonin(2B/2C) receptors were not implicated in these behaviors. In vitro studies demonstrated that LSD and the 5-HT(2A/2C) receptor antagonist, ritanserin, bound frontocortical 5-HT(2A) receptors in a pseudo-irreversible manner. In contrast, DOI and the 5-HT(2A/2C) receptor antagonist, ketanserin, bound reversibly. These binding properties were reflected in ex vivo binding studies. The two hallucinogens also differed in that LSD showed modest D(1) receptor binding affinity whereas DOI had negligible binding affinity at this receptor. Although DOI and LSD differed in their receptor binding properties, activation of 5-HT(2A) and D(1) receptors was a common mechanism for eliciting head bob behavior. These findings implicate these two receptors in the mechanism of action of hallucinogens. Copyright © 2011 Elsevier Inc. All rights reserved.

  8. Role of androgen receptor and associated lysine-demethylase coregulators, LSD1 and JMJD2A, in localized and advanced human bladder cancer.

    Science.gov (United States)

    Kauffman, Eric C; Robinson, Brian D; Downes, Martin J; Powell, Leagh G; Lee, Ming Ming; Scherr, Douglas S; Gudas, Lorraine J; Mongan, Nigel P

    2011-12-01

    Bladder cancer is approximately three times more common in men as compared to women. We and others have previously investigated the contribution of androgens and the androgen receptor (AR) to bladder cancer. JMJD2A and LSD1 are recently discovered AR coregulator proteins that mediate AR-dependent transcription via recently described histone lysine-demethylation (KDM) mechanisms. We used immunohistochemistry to examine JMJD2A, LSD1, and AR expression in 72 radical cystectomy specimens, resulting in evaluation of 129 tissue samples (59 urothelial carcinoma, 70 benign). We tested levels of these proteins for statistical association with clinicopathologic variables and patient survival. Expression of these markers was also assessed in human bladder cancer cell lines. The effects of pharmacological inhibition of LSD1 on the proliferation of these bladder cancer cells was determined. JMJD2A and AR levels were significantly lower in malignant versus benign urothelium, while increased LSD1 levels were observed in malignant urothelium relative to benign. A significant reduction in all three proteins occurred with cancer stage progression, including muscle invasion (JMJD2A/LSD1/AR), extravesical extension (JMJD2A/LSD1), and lymph node metastasis (JMJD2A/AR). Lower JMJD2A intensity correlated with additional poor prognostic features, including lymphovascular invasion, concomitant carcinoma in situ and tobacco usage, and predicted significantly worse overall survival. Pharmacological inhibition of LSD1 suppressed bladder cancer cell proliferation and androgen-induced transcription. Our results support a novel role for the AR-KDM complex in bladder cancer initiation and progression, identify JMJD2A as a promising prognostic biomarker, and demonstrate targeting of the KDM activity as an effective potential approach for bladder cancer growth inhibition. Copyright © 2011 Wiley Periodicals, Inc.

  9. Proposal of interference reduction routing for ad-hoc networks

    Directory of Open Access Journals (Sweden)

    Katsuhiro Naito

    2010-10-01

    Full Text Available In this paper, we propose an interference reduction routing protocol for ad-hoc networks. The interference is one of the degradation factors in wireless communications. In the ad-hoc network, some nodes communicate simultaneously. Therefore, these communications cause interference each other, and some packets are corrupted due to interference from another node. In the proposed protocol, each node estimates required transmission power according to hello messages. Therefore, the node can transmit a data packet with minimum required transmission power. Consequently, the interference against neighbor nodes can be reduced. From simulation results, we can find that the proposed protocol can reduce the number of control messages and can improve the throughput performance.

  10. Information Sharing Modalities for Mobile Ad-Hoc Networks

    Science.gov (United States)

    de Spindler, Alexandre; Grossniklaus, Michael; Lins, Christoph; Norrie, Moira C.

    Current mobile phone technologies have fostered the emergence of a new generation of mobile applications. Such applications allow users to interact and share information opportunistically when their mobile devices are in physical proximity or close to fixed installations. It has been shown how mobile applications such as collaborative filtering and location-based services can take advantage of ad-hoc connectivity to use physical proximity as a filter mechanism inherent to the application logic. We discuss the different modes of information sharing that arise in such settings based on the models of persistence and synchronisation. We present a platform that supports the development of applications that can exploit these modes of ad-hoc information sharing and, by means of an example, show how such an application can be realised based on the supported event model.

  11. Energy management in wireless cellular and ad-hoc networks

    CERN Document Server

    Imran, Muhammad; Qaraqe, Khalid; Alouini, Mohamed-Slim; Vasilakos, Athanasios

    2016-01-01

    This book investigates energy management approaches for energy efficient or energy-centric system design and architecture and presents end-to-end energy management in the recent heterogeneous-type wireless network medium. It also considers energy management in wireless sensor and mesh networks by exploiting energy efficient transmission techniques and protocols. and explores energy management in emerging applications, services and engineering to be facilitated with 5G networks such as WBANs, VANETS and Cognitive networks. A special focus of the book is on the examination of the energy management practices in emerging wireless cellular and ad hoc networks. Considering the broad scope of energy management in wireless cellular and ad hoc networks, this book is organized into six sections covering range of Energy efficient systems and architectures; Energy efficient transmission and techniques; Energy efficient applications and services. .

  12. Secure Geographic Routing in Ad Hoc and Wireless Sensor Networks

    Directory of Open Access Journals (Sweden)

    Zahariadis Theodore

    2010-01-01

    Full Text Available Security in sensor networks is one of the most relevant research topics in resource constrained wireless devices and networks. Several attacks can be suffered in ad hoc and wireless sensor networks (WSN, which are highly susceptible to attacks, due to the limited resources of the nodes. In this paper, we propose innovative and lightweight localization techniques that allow for intrusion identification and isolation schemes and provide accurate location information. This information is used by our routing protocol which additionally incorporates a distributed trust model to prevent several routing attacks to the network. We finally evaluate our algorithms for accurate localization and for secure routing which have been implemented and tested in real ad hoc and wireless sensor networks.

  13. Capacity of Wireless Ad Hoc Networks with Opportunistic Collaborative Communications

    Directory of Open Access Journals (Sweden)

    Simeone O

    2007-01-01

    Full Text Available Optimal multihop routing in ad hoc networks requires the exchange of control messages at the MAC and network layer in order to set up the (centralized optimization problem. Distributed opportunistic space-time collaboration (OST is a valid alternative that avoids this drawback by enabling opportunistic cooperation with the source at the physical layer. In this paper, the performance of OST is investigated. It is shown analytically that opportunistic collaboration outperforms (centralized optimal multihop in case spatial reuse (i.e., the simultaneous transmission of more than one data stream is not allowed by the transmission protocol. Conversely, in case spatial reuse is possible, the relative performance between the two protocols has to be studied case by case in terms of the corresponding capacity regions, given the topology and the physical parameters of network at hand. Simulation results confirm that opportunistic collaborative communication is a promising paradigm for wireless ad hoc networks that deserves further investigation.

  14. Capacity of Wireless Ad Hoc Networks with Opportunistic Collaborative Communications

    Directory of Open Access Journals (Sweden)

    O. Simeone

    2007-03-01

    Full Text Available Optimal multihop routing in ad hoc networks requires the exchange of control messages at the MAC and network layer in order to set up the (centralized optimization problem. Distributed opportunistic space-time collaboration (OST is a valid alternative that avoids this drawback by enabling opportunistic cooperation with the source at the physical layer. In this paper, the performance of OST is investigated. It is shown analytically that opportunistic collaboration outperforms (centralized optimal multihop in case spatial reuse (i.e., the simultaneous transmission of more than one data stream is not allowed by the transmission protocol. Conversely, in case spatial reuse is possible, the relative performance between the two protocols has to be studied case by case in terms of the corresponding capacity regions, given the topology and the physical parameters of network at hand. Simulation results confirm that opportunistic collaborative communication is a promising paradigm for wireless ad hoc networks that deserves further investigation.

  15. Cognitive radio application for vehicular ad hoc networks (VANETS

    Directory of Open Access Journals (Sweden)

    Miladić Suzana D.

    2016-01-01

    Full Text Available This paper presents the application of cognitive radio technology in vehicular ad-hoc networks aimed to improve the communications between vehicles themselves as well as between vehicles and roadside infrastructure. Due to dynamic approach of spectrum access, cognitive radio is a technology that enables more efficient usage of radio-frequency spectrum. We review actual approaches and discuss research challenges related to the use of cognitive radio technology in vehicular ad hoc networks with emphasis on architecture, spectrum management as well as QoS optimization. The researching on cognitive radio application in vehicular networks is still developing and there are not many experimental platforms due to their complex setups. Some related research projects and cognitive radio realizations are provided in this paper.

  16. Psychedelics as medicines for substance abuse rehabilitation: evaluating treatments with LSD, Peyote, Ibogaine and Ayahuasca.

    Science.gov (United States)

    Winkelman, Michael

    2014-01-01

    Substances known as psychedelics, hallucinogens and entheogens have been employed in ethnomedical traditions for thousands of years, but after promising uses in the 1950's and 1960's they were largely prohibited in medical treatment and human research starting in the 1970's as part of the fallout from the war on drugs. Nonetheless, there are a number of studies which suggest that these substances have potential applications in the treatment of addictions. While these substances are generally classified as Schedule I, alleging no established medical uses and a high drug abuse potential, there is nonetheless evidence indicating they might be safe and effective tools for short term interventions in addictions treatment. Evidence suggests that the psychedelics have a much greater safety profile than the major addictive drugs, having extremely low levels of mortality, and producing little if any physical dependence. This paper reviews studies evaluating the use of LSD, peyote, ibogaine and ayahuasca in the treatment of dependencies and the possible mechanisms underlying the indications of effectiveness. Evidence suggests that these substances help assist recovery from drug dependency through a variety of therapeutic mechanisms, including a notable "after-glow" effect that in part reflects their action on the serotonin neurotransmitter system. Serotonin has been long recognized as central to the psychedelics' well-known phenomenological, physical, emotional and cognitive dynamics. These serotonin-based dynamics are directly relevant to treatment of addiction because of depressed serotonin levels found in addict populations, as well as the role of serotonin as a neuromodulators affecting many other neurotransmitter systems.

  17. A Single Dose of LSD Does Not Alter Gene Expression of the Serotonin 2A Receptor Gene (HTR2A) or Early Growth Response Genes (EGR1-3) in Healthy Subjects

    Science.gov (United States)

    Dolder, Patrick C.; Grünblatt, Edna; Müller, Felix; Borgwardt, Stefan J.; Liechti, Matthias E.

    2017-01-01

    Rationale: Renewed interest has been seen in the use of lysergic acid diethylamide (LSD) in psychiatric research and practice. The repeated use of LSD leads to tolerance that is believed to result from serotonin (5-HT) 5-HT2A receptor downregulation. In rats, daily LSD administration for 4 days decreased frontal cortex 5-HT2A receptor binding. Additionally, a single dose of LSD acutely increased expression of the early growth response genes EGR1 and EGR2 in rat and mouse brains through 5-HT2A receptor stimulation. No human data on the effects of LSD on gene expression has been reported. Therefore, we investigated the effects of single-dose LSD administration on the expression of the 5-HT2A receptor gene (HTR2A) and EGR1-3 genes. Methods: mRNA expression levels were analyzed in whole blood as a peripheral biomarker in 15 healthy subjects before and 1.5 and 24 h after the administration of LSD (100 μg) and placebo in a randomized, double-blind, placebo-controlled, cross-over study. Results: LSD did not alter the expression of the HTR2A or EGR1-3 genes 1.5 and 24 h after administration compared with placebo. Conclusion: No changes were observed in the gene expression of LSD’s primary target receptor gene or genes that are implicated in its downstream effects. Remaining unclear is whether chronic LSD administration alters gene expression in humans. PMID:28701958

  18. A framework for reactive optimization in mobile ad hoc networks

    DEFF Research Database (Denmark)

    McClary, Dan; Syrotiuk, Violet; Kulahci, Murat

    2008-01-01

    We present a framework to optimize the performance of a mobile ad hoc network over a wide range of operating conditions. It includes screening experiments to quantify the parameters and interactions among parameters influential to throughput. Profile-driven regression is applied to obtain a model....... The predictive accuracy of the model is monitored and used to update the model dynamically. The results indicate the framework may be useful for the optimization of dynamic systems of high dimension....

  19. Power control algorithms for mobile ad hoc networks

    Directory of Open Access Journals (Sweden)

    Nuraj L. Pradhan

    2011-07-01

    We will also focus on an adaptive distributed power management (DISPOW algorithm as an example of the multi-parameter optimization approach which manages the transmit power of nodes in a wireless ad hoc network to preserve network connectivity and cooperatively reduce interference. We will show that the algorithm in a distributed manner builds a unique stable network topology tailored to its surrounding node density and propagation environment over random topologies in a dynamic mobile wireless channel.

  20. A Survey on Trust Management for Mobile Ad Hoc Networks

    Science.gov (United States)

    2011-11-01

    expects, trust is dangerous implying the possible betrayal of trust. In his comments on Lagerspetz’s book titled Trust: The Tacit Demand, Lahno [24...AODV Zouridaki et al. (2005 ) [79] (2006) [80] Secure routing Direct observation [79][80] Reputation by secondhand information [80] Packet dropping...areas of signal processing, wireless communications, sensor and mobile ad hoc networks. He is co-editor of the book Wireless Sensor Networks: Signal

  1. Decentralized session initiation protocol solution in ad hoc networks

    Science.gov (United States)

    Han, Lu; Jin, Zhigang; Shu, Yantai; Dong, Linfang

    2006-10-01

    With the fast development of ad hoc networks, SIP has attracted more and more attention in multimedia service. This paper proposes a new architecture to provide SIP service for ad hoc users, although there is no centralized SIP server deployed. In this solution, we provide the SIP service by the introduction of two nodes: Designated SIP Server (DS) and its Backup Server (BDS). The nodes of ad hoc network designate DS and BDS when they join the session nodes set and when some pre-defined events occur. A new sip message type called REGISTRAR is presented so nodes can send others REGISTRAR message to declare they want to be DS. According to the IP information taken in the message, an algorithm works like the election of DR and BDR in OSPF protocol is used to vote DS and BDS SIP servers. Naturally, the DS will be replaced by BDS when the DS is down for predicable or unpredictable reasons. To facilitate this, the DS should register to the BDS and transfer a backup of the SIP users' database. Considering the possibility DS or BDS may abruptly go down, a special policy is given. When there is no DS and BDS, a new election procedure is triggered just like the startup phase. The paper also describes how SIP works normally in the decentralized model as well as the evaluation of its performance. All sessions based on SIP in ad hoc such as DS voting have been tested in the real experiments within a 500m*500m square area where about 30 random nodes are placed.

  2. Interference in wireless ad hoc networks with smart antennas

    KAUST Repository

    Alabdulmohsin, Ibrahim

    2014-08-01

    In this paper, we show that the use of directional antennas in wireless ad hoc networks can actually increase interference due to limitations of virtual carrier sensing. We derive a simple mathematical expression for interference in both physical and virtual carrier sense networks, which reveals counter-intuitively that receivers in large dense networks with directional antennas can experience larger interference than in omnidirectional networks unless the beamwidth is sufficiently small. Validity of mathematical analysis is confirmed using simulations.

  3. Report of the Ad Hoc Committee on SSC physics

    International Nuclear Information System (INIS)

    1990-04-01

    The Ad Hoc Committee on SSC Physics has reexamined the relationship between beam energy, machine luminosity, and physics capability. In the next section, the physics motivation for the SSC is reviewed in general terms. This is followed by a discussion of the ability to detect a number of specific processes as a function of the SSC energy and luminosity. The viability of various detector technologies is then assessed as a function of luminosity. The report ends with a brief summary and some conclusions

  4. MAC Protocol for Ad Hoc Networks Using a Genetic Algorithm

    Science.gov (United States)

    Elizarraras, Omar; Panduro, Marco; Méndez, Aldo L.

    2014-01-01

    The problem of obtaining the transmission rate in an ad hoc network consists in adjusting the power of each node to ensure the signal to interference ratio (SIR) and the energy required to transmit from one node to another is obtained at the same time. Therefore, an optimal transmission rate for each node in a medium access control (MAC) protocol based on CSMA-CDMA (carrier sense multiple access-code division multiple access) for ad hoc networks can be obtained using evolutionary optimization. This work proposes a genetic algorithm for the transmission rate election considering a perfect power control, and our proposition achieves improvement of 10% compared with the scheme that handles the handshaking phase to adjust the transmission rate. Furthermore, this paper proposes a genetic algorithm that solves the problem of power combining, interference, data rate, and energy ensuring the signal to interference ratio in an ad hoc network. The result of the proposed genetic algorithm has a better performance (15%) compared to the CSMA-CDMA protocol without optimizing. Therefore, we show by simulation the effectiveness of the proposed protocol in terms of the throughput. PMID:25140339

  5. MAC Protocol for Ad Hoc Networks Using a Genetic Algorithm

    Directory of Open Access Journals (Sweden)

    Omar Elizarraras

    2014-01-01

    Full Text Available The problem of obtaining the transmission rate in an ad hoc network consists in adjusting the power of each node to ensure the signal to interference ratio (SIR and the energy required to transmit from one node to another is obtained at the same time. Therefore, an optimal transmission rate for each node in a medium access control (MAC protocol based on CSMA-CDMA (carrier sense multiple access-code division multiple access for ad hoc networks can be obtained using evolutionary optimization. This work proposes a genetic algorithm for the transmission rate election considering a perfect power control, and our proposition achieves improvement of 10% compared with the scheme that handles the handshaking phase to adjust the transmission rate. Furthermore, this paper proposes a genetic algorithm that solves the problem of power combining, interference, data rate, and energy ensuring the signal to interference ratio in an ad hoc network. The result of the proposed genetic algorithm has a better performance (15% compared to the CSMA-CDMA protocol without optimizing. Therefore, we show by simulation the effectiveness of the proposed protocol in terms of the throughput.

  6. Recent development in wireless sensor and ad-hoc networks

    CERN Document Server

    Li, Xiaolong; Yang, Yeon-Mo

    2015-01-01

    Wireless Sensor Network (WSN) consists of numerous physically distributed autonomous devices used for sensing and monitoring the physical and/or environmental conditions. A WSN uses a gateway that provides wireless connectivity to the wired world as well as distributed networks. There are many open problems related to Ad-Hoc networks and its applications. Looking at the expansion of the cellular infrastructure, Ad-Hoc network may be acting as the basis of the 4th generation wireless technology with the new paradigm of ‘anytime, anywhere communications’. To realize this, the real challenge would be the security, authorization and management issues of the large scale WSNs. This book is an edited volume in the broad area of WSNs. The book covers various chapters like Multi-Channel Wireless Sensor Networks, its Coverage, Connectivity as well as Deployment. It covers comparison of various communication protocols and algorithms such as MANNET, ODMRP and ADMR Protocols for Ad hoc Multicasting, Location Based C...

  7. Auto-Configuration Protocols in Mobile Ad Hoc Networks

    Science.gov (United States)

    Villalba, Luis Javier García; Matesanz, Julián García; Orozco, Ana Lucila Sandoval; Díaz, José Duván Márquez

    2011-01-01

    The TCP/IP protocol allows the different nodes in a network to communicate by associating a different IP address to each node. In wired or wireless networks with infrastructure, we have a server or node acting as such which correctly assigns IP addresses, but in mobile ad hoc networks there is no such centralized entity capable of carrying out this function. Therefore, a protocol is needed to perform the network configuration automatically and in a dynamic way, which will use all nodes in the network (or part thereof) as if they were servers that manage IP addresses. This article reviews the major proposed auto-configuration protocols for mobile ad hoc networks, with particular emphasis on one of the most recent: D2HCP. This work also includes a comparison of auto-configuration protocols for mobile ad hoc networks by specifying the most relevant metrics, such as a guarantee of uniqueness, overhead, latency, dependency on the routing protocol and uniformity. PMID:22163814

  8. MWAHCA: a multimedia wireless ad hoc cluster architecture.

    Science.gov (United States)

    Diaz, Juan R; Lloret, Jaime; Jimenez, Jose M; Sendra, Sandra

    2014-01-01

    Wireless Ad hoc networks provide a flexible and adaptable infrastructure to transport data over a great variety of environments. Recently, real-time audio and video data transmission has been increased due to the appearance of many multimedia applications. One of the major challenges is to ensure the quality of multimedia streams when they have passed through a wireless ad hoc network. It requires adapting the network architecture to the multimedia QoS requirements. In this paper we propose a new architecture to organize and manage cluster-based ad hoc networks in order to provide multimedia streams. Proposed architecture adapts the network wireless topology in order to improve the quality of audio and video transmissions. In order to achieve this goal, the architecture uses some information such as each node's capacity and the QoS parameters (bandwidth, delay, jitter, and packet loss). The architecture splits the network into clusters which are specialized in specific multimedia traffic. The real system performance study provided at the end of the paper will demonstrate the feasibility of the proposal.

  9. MWAHCA: A Multimedia Wireless Ad Hoc Cluster Architecture

    Directory of Open Access Journals (Sweden)

    Juan R. Diaz

    2014-01-01

    Full Text Available Wireless Ad hoc networks provide a flexible and adaptable infrastructure to transport data over a great variety of environments. Recently, real-time audio and video data transmission has been increased due to the appearance of many multimedia applications. One of the major challenges is to ensure the quality of multimedia streams when they have passed through a wireless ad hoc network. It requires adapting the network architecture to the multimedia QoS requirements. In this paper we propose a new architecture to organize and manage cluster-based ad hoc networks in order to provide multimedia streams. Proposed architecture adapts the network wireless topology in order to improve the quality of audio and video transmissions. In order to achieve this goal, the architecture uses some information such as each node’s capacity and the QoS parameters (bandwidth, delay, jitter, and packet loss. The architecture splits the network into clusters which are specialized in specific multimedia traffic. The real system performance study provided at the end of the paper will demonstrate the feasibility of the proposal.

  10. Adolescent alcohol exposure alters lysine demethylase 1 (LSD1) expression and histone methylation in the amygdala during adulthood.

    Science.gov (United States)

    Kyzar, Evan J; Zhang, Huaibo; Sakharkar, Amul J; Pandey, Subhash C

    2017-09-01

    Alcohol exposure in adolescence is an important risk factor for the development of alcoholism in adulthood. Epigenetic processes are implicated in the persistence of adolescent alcohol exposure-related changes, specifically in the amygdala. We investigated the role of histone methylation mechanisms in the persistent effects of adolescent intermittent ethanol (AIE) exposure in adulthood. Adolescent rats were exposed to 2 g/kg ethanol (2 days on/off) or intermittent n-saline (AIS) during postnatal days (PND) 28-41 and used for behavioral and epigenetic studies. We found that AIE exposure caused a long-lasting decrease in mRNA and protein levels of lysine demethylase 1(Lsd1) and mRNA levels of Lsd1 + 8a (a neuron-specific splice variant) in specific amygdaloid structures compared with AIS-exposed rats when measured at adulthood. Interestingly, AIE increased histone H3 lysine 9 dimethylation (H3K9me2) levels in the central nucleus of the amygdala (CeA) and medial nucleus of the amygdala (MeA) in adulthood without producing any change in H3K4me2 protein levels. Acute ethanol challenge (2 g/kg) in adulthood attenuated anxiety-like behaviors and the decrease in Lsd1 + 8a mRNA levels in the amygdala induced by AIE. AIE caused an increase in H3K9me2 occupancy at the brain-derived neurotrophic factor exon IV promoter in the amygdala that returned to baseline after acute ethanol challenge in adulthood. These results indicate that AIE specifically modulates epizymes involved in H3K9 dimethylation in the amygdala in adulthood, which are possibly responsible for AIE-induced chromatin remodeling and adult psychopathology such as anxiety. © Published 2016. This article is a U.S. Government work and is in the public domain in the USA.

  11. Results of low energy background measurements with the Liquid Scintillation Detector (LSD) of the Mont Blanc Laboratory

    Science.gov (United States)

    Aglietta, M.; Badino, G.; Bologna, G. F.; Castagnoli, C.; Fulgione, W.; Galeotti, P.; Saavedra, O.; Trinchero, G. C.; Vernetto, S.; Dadykin, V. L.

    1985-01-01

    The 90 tons liquid scintillation detector (LSD) is fully running since October 1984, at a depth of 5,200 hg/sq cm of standard rock underground. The main goal is to search for neutrino bursts from collapsing stars. The experiment is very sensitive to detect low energy particles and has a very good signature to gamma-rays from (n,p) reaction which follows the upsilon e + p yields n + e sup + neutrino capture. The analysis of data is presented and the preliminary results on low energy measurements are discussed.

  12. Results of low energy background measurements with the liquid scintillation detector (LSD) of the Mont Blanc Laboratory

    International Nuclear Information System (INIS)

    Aglietta, M.; Badino, G.; Bologna, G.F.

    1985-01-01

    The 90 tons liquid scintillation detector (LSD) has been fully running since October 1984 at a depth of 5,200 hg/sq cm of standard rock underground. The main goal is to search for neutrino bursts from collapsing stars. The experiment is very sensitive to detect low energy particles and has a very good signature to gamma rays from (n,p) reactions which follows the upsilon e + p yields n + e sup + neutrino capture. The analysis of data is presented and the preliminary results on low energy measurements are discussed. 1 ref

  13. Effects of autoshaping procedures on 3H-8-OH-DPAT-labeled 5-HT1a binding and 125I-LSD-labeled 5-HT2a binding in rat brain.

    Science.gov (United States)

    Tomie, Arthur; Di Poce, Jason; Aguado, Allison; Janes, Amy; Benjamin, Daniel; Pohorecky, Larissa

    2003-06-13

    Effects of experience with Pavlovian autoshaping procedures on lever-press autoshaping conditioned response (CR) performance and 3H-8-OH-DPAT-labeled binding of 5-HT(1a) receptors as well as 125I-LSD-labeled binding of 5-HT(2a) receptors were evaluated in four groups of male Long-Evans hooded rats. Two groups of rats (Group Paired High CR and Group Paired Low CR) received Pavlovian autoshaping procedures wherein the presentation of a lever (conditioned stimulus, CS) was followed by the response-independent presentation of food (unconditioned stimulus, US). Rats in Group Paired High CR (n=12) showed more rapid CR acquisition and higher asymptotic levels of lever-press autoshaping CR performance relative to rats in Group Low CR (n=12). Group Omission (n=9) received autoshaping with an omission contingency, such that performing the lever-press autoshaping CR resulted in the cancellation the food US, while Group Random (n=9) received presentations of lever CS and food US randomly with respect to one another. Though Groups Omission and Random did not differ in lever-press autoshaping CR performance, Group Omission showed significantly lower levels of 3H-8-OH-DPAT-labeled 5-HT(1a) binding in post-synaptic areas (frontal cortex, septum, caudate putamen), as well as significantly higher plasma corticosterone levels than Group Random. In addition, Group Random showed higher levels of 3H-8-OH-DPAT-labeled 5-HT(1a) binding in pre-synaptic somatodendritic autoreceptors on dorsal raphe nucleus relative to each of the other three groups. Autoradiographic analysis of 125I-LSD-labeled 5-HT(2a) receptor binding revealed no significant differences between Groups Paired High CR and Paired Low CR or between Groups Omission and Random in any brain regions.

  14. Correlations between muons and low energy pulses at LSD of the Mont Blanc laboratory near the time of SN1987A explosion

    International Nuclear Information System (INIS)

    Dadykin, V.L.; Khalchukov, F.F.; Korchagin, P.V.; Korolkova, E.V.; Kudryavtsev, V.A.; Mal'gin, A.S.; Ryasny, V.G.; Ryazhskaya, O.G.; Yakushev, V.F.; Zatsepin, G.T.; Aglietta, M.; Badino, G.; Bologna, G.; Castagnoli, C.; Castellina, A.; Fulgione, W.; Galeotti, P.; Saavedra, O.; Trinchero, G.; Vernetto, S.; Turin Univ.

    1989-01-01

    We have analysed the data of LSD from February 10, 1987, to March 7, 1987, in order to search for autocorrelations between all pulses detected by LSD with energy higher than 5 MeV like those occurred at ∼ 3:00 UT on February 23, 1987, between the pulses detected by 3 neutrino telescopes and 2 gravitational wave antennae. We have found 9 pairs of correlated pulses (muon + low energy pulse) from 5:42 UT to 10:13 UT on February 23, 1987. The time differences of pulses in the pairs are less than 2 s, the first pulse in the pair being either muon or low energy pulse. The frequency of such random poissonian fluctuations is ∼1/(10 years). There are no correlations outside statistics between low energy, low energy pulses and muon, muon pulses detected by LSD during the whole time period

  15. Distributed optimization of a multisubchannel Ad Hoc cognitive radio network

    KAUST Repository

    Leith, Alex

    2012-05-01

    In this paper, we study the distributed-duality-based optimization of a multisubchannel ad hoc cognitive radio network (CRN) that coexists with a multicell primary radio network (PRN). For radio resource allocation in multiuser orthogonal frequency-division multiplexing (MU-OFDM) systems, the orthogonal-access-based exclusive subchannel assignment (ESA) technique has been a popular method, but it is suboptimal in ad hoc networks, because nonorthogonal access between multiple secondary-user links by using shared subchannel assignment (SSA) can bring a higher weighted sum rate. We utilize the Lagrangian dual composition tool and design low-complexity near-optimal SSA resource allocation methods, assuming practical discrete-rate modulation and that the CRN-to-PRN interference constraint has to strictly be satisfied. However, available SSA methods for CRNs are either suboptimal or involve high complexity and suffer from slow convergence. To address this problem, we design fast-convergence SSA duality schemes and introduce several novel methods to increase the speed of convergence and to satisfy various system constraints with low complexity. For practical implementation in ad hoc CRNs, we design distributed-duality schemes that involve only a small number of CRN local information exchanges for dual update. The effects of many system parameters are presented through simulation results, which show that the near-optimal SSA duality scheme can perform significantly better than the suboptimal ESA duality and SSA-iterative waterfilling schemes and that the performance loss of the distributed schemes is small, compared with their centralized counterparts. © 2012 IEEE.

  16. Studies on urban vehicular ad-hoc networks

    CERN Document Server

    Zhu, Hongzi

    2013-01-01

    With the advancement of wireless technology, vehicular ad hoc networks (VANETs) are emerging as a promising approach to realizing 'smart cities' and addressing many important transportation problems such as road safety, efficiency, and convenience.This brief provides an introduction to the large trace data set collected from thousands of taxis and buses in Shanghai, the largest metropolis in China. It also presents the challenges, design issues, performance modeling and evaluation of a wide spectrum of VANET research topics, ranging from realistic vehicular mobility models and opportunistic ro

  17. Throughput Capacity of Ad Hoc Networks with Route Discovery

    Directory of Open Access Journals (Sweden)

    Blum Rick S

    2007-01-01

    Full Text Available Throughput capacity of large ad hoc networks has been shown to scale adversely with the size of network . However the need for the nodes to find or repair routes has not been analyzed in this context. In this paper, we explicitly take route discovery into account and obtain the scaling law for the throughput capacity under general assumptions on the network environment, node behavior, and the quality of route discovery algorithms. We also discuss a number of possible scenarios and show that the need for route discovery may change the scaling for the throughput capacity.

  18. Wireless ad hoc and sensor networks management, performance, and applications

    CERN Document Server

    He, Jing

    2013-01-01

    Although wireless sensor networks (WSNs) have been employed across a wide range of applications, there are very few books that emphasize the algorithm description, performance analysis, and applications of network management techniques in WSNs. Filling this need, Wireless Ad Hoc and Sensor Networks: Management, Performance, and Applications summarizes not only traditional and classical network management techniques, but also state-of-the-art techniques in this area. The articles presented are expository, but scholarly in nature, including the appropriate history background, a review of current

  19. Power-Aware Intrusion Detection in Mobile Ad Hoc Networks

    Science.gov (United States)

    Şen, Sevil; Clark, John A.; Tapiador, Juan E.

    Mobile ad hoc networks (MANETs) are a highly promising new form of networking. However they are more vulnerable to attacks than wired networks. In addition, conventional intrusion detection systems (IDS) are ineffective and inefficient for highly dynamic and resource-constrained environments. Achieving an effective operational MANET requires tradeoffs to be made between functional and non-functional criteria. In this paper we show how Genetic Programming (GP) together with a Multi-Objective Evolutionary Algorithm (MOEA) can be used to synthesise intrusion detection programs that make optimal tradeoffs between security criteria and the power they consume.

  20. Mobile ad hoc networking the cutting edge directions

    CERN Document Server

    Basagni, Stefano; Giordano, Silvia; Stojmenovic, Ivan

    2013-01-01

    ""An excellent book for those who are interested in learning the current status of research and development . . . [and] who want to get a comprehensive overview of the current state-of-the-art.""-E-Streams This book provides up-to-date information on research and development in the rapidly growing area of networks based on the multihop ad hoc networking paradigm. It reviews all classes of networks that have successfully adopted this paradigm, pointing out how they penetrated the mass market and sparked breakthrough research. Covering both physical issues and applica

  1. Ad-Hoc vs. Standardized and Optimized Arthropod Diversity Sampling

    Directory of Open Access Journals (Sweden)

    Pedro Cardoso

    2009-09-01

    Full Text Available The use of standardized and optimized protocols has been recently advocated for different arthropod taxa instead of ad-hoc sampling or sampling with protocols defined on a case-by-case basis. We present a comparison of both sampling approaches applied for spiders in a natural area of Portugal. Tests were made to their efficiency, over-collection of common species, singletons proportions, species abundance distributions, average specimen size, average taxonomic distinctness and behavior of richness estimators. The standardized protocol revealed three main advantages: (1 higher efficiency; (2 more reliable estimations of true richness; and (3 meaningful comparisons between undersampled areas.

  2. Mobile agents affect worm spreading in wireless ad hoc networks

    International Nuclear Information System (INIS)

    Huang, Zi-Gang; Sun, Jin-Tu; Wang, Ying-Hai; Wang, Sheng-Jun; Xu, Xin-Jian

    2009-01-01

    Considering the dynamic nature of portable computing devices with wireless communication capability, an extended model is introduced for worm spreading in the wireless ad hoc network, with a population of mobile agents in a planar distribution, starting from an initial infected seed. The effect of agents' mobility on worm spreading is investigated via extensive Monte Carlo simulations. The threshold behavior and the dynamics of worm epidemics in the wireless networks are greatly affected by both agents' mobility and spatial and temporal correlations. The medium access control mechanism for the wireless communication promotes the sensitivity of the spreading dynamics to agents' mobility

  3. Regulation of protein quality control by UBE4B and LSD1 through p53-mediated transcription.

    Directory of Open Access Journals (Sweden)

    Goran Periz

    2015-04-01

    Full Text Available Protein quality control is essential for clearing misfolded and aggregated proteins from the cell, and its failure is associated with many neurodegenerative disorders. Here, we identify two genes, ufd-2 and spr-5, that when inactivated, synergistically and robustly suppress neurotoxicity associated with misfolded proteins in Caenorhabditis elegans. Loss of human orthologs ubiquitination factor E4 B (UBE4B and lysine-specific demethylase 1 (LSD1, respectively encoding a ubiquitin ligase and a lysine-specific demethylase, promotes the clearance of misfolded proteins in mammalian cells by activating both proteasomal and autophagic degradation machineries. An unbiased search in this pathway reveals a downstream effector as the transcription factor p53, a shared substrate of UBE4B and LSD1 that functions as a key regulator of protein quality control to protect against proteotoxicity. These studies identify a new protein quality control pathway via regulation of transcription factors and point to the augmentation of protein quality control as a wide-spectrum antiproteotoxicity strategy.

  4. Energy Efficient Probabilistic Broadcasting for Mobile Ad-Hoc Network

    Science.gov (United States)

    Kumar, Sumit; Mehfuz, Shabana

    2017-06-01

    In mobile ad-hoc network (MANETs) flooding method is used for broadcasting route request (RREQ) packet from one node to another node for route discovery. This is the simplest method of broadcasting of RREQ packets but it often results in broadcast storm problem, originating collisions and congestion of packets in the network. A probabilistic broadcasting is one of the widely used broadcasting scheme for route discovery in MANETs and provides solution for broadcasting storm problem. But it does not consider limited energy of the battery of the nodes. In this paper, a new energy efficient probabilistic broadcasting (EEPB) is proposed in which probability of broadcasting RREQs is calculated with respect to remaining energy of nodes. The analysis of simulation results clearly indicate that an EEPB route discovery scheme in ad-hoc on demand distance vector (AODV) can increase the network lifetime with a decrease in the average power consumption and RREQ packet overhead. It also decreases the number of dropped packets in the network, in comparison to other EEPB schemes like energy constraint gossip (ECG), energy aware gossip (EAG), energy based gossip (EBG) and network lifetime through energy efficient broadcast gossip (NEBG).

  5. Taxonomic and ad hoc categorization within the two cerebral hemispheres.

    Science.gov (United States)

    Shen, Yeshayahu; Aharoni, Bat-El; Mashal, Nira

    2015-01-01

    A typicality effect refers to categorization which is performed more quickly or more accurately for typical than for atypical members of a given category. Previous studies reported a typicality effect for category members presented in the left visual field/right hemisphere (RH), suggesting that the RH applies a similarity-based categorization strategy. However, findings regarding the typicality effect within the left hemisphere (LH) are less conclusive. The current study tested the pattern of typicality effects within each hemisphere for both taxonomic and ad hoc categories, using words presented to the left or right visual fields. Experiment 1 tested typical and atypical members of taxonomic categories as well as non-members, and Experiment 2 tested typical and atypical members of ad hoc categories as well as non-members. The results revealed a typicality effect in both hemispheres and in both types of categories. Furthermore, the RH categorized atypical stimuli more accurately than did the LH. Our findings suggest that both hemispheres rely on a similarity-based categorization strategy, but the coarse semantic coding of the RH seems to facilitate the categorization of atypical members.

  6. A Spontaneous Ad Hoc Network to Share WWW Access

    Directory of Open Access Journals (Sweden)

    Lloret Jaime

    2010-01-01

    Full Text Available In this paper, we propose a secure spontaneous ad-hoc network, based on direct peer-to-peer interaction, to grant a quick, easy, and secure access to the users to surf the Web. The paper shows the description of our proposal, the procedure of the nodes involved in the system, the security algorithms implemented, and the designed messages. We have taken into account the security and its performance. Although some people have defined and described the main features of spontaneous ad-hoc networks, nobody has published any design and simulation until today. Spontaneous networking will enable a more natural form of wireless computing when people physically meet in the real world. We also validate the success of our proposal through several simulations and comparisons with a regular architecture, taking into account the optimization of the resources of the devices. Finally, we compare our proposal with other caching techniques published in the related literature. The proposal has been developed with the main objective of improving the communication and integration between different study centers of low-resource communities. That is, it lets communicate spontaneous networks, which are working collaboratively and which have been created on different physical places.

  7. A Novel Routing Algorithm for Vehicular Ad Hoc Networks

    Directory of Open Access Journals (Sweden)

    Raúl Aquino Santos

    2008-01-01

    Full Text Available Este trabajo examina la importancia de las redes inalámbricas ad hoc y el algoritmo de enrutamiento con inundación basada en grupos (LORA-CBF para la comunicación inter-vehicular con la finalidad de optimizar el flujo de tráfico e incrementar la seguridad en las autopistas. Se discute el algoritmo de enrutamiento LORA-CBF y se presentan los resultados de simulaciones realizadas en OPNET de una autopista con alta movilidad vehicular. Primero, el modelo de simulación propuesto se valida a pequeña escala con resultados experimentales. Posteriormente, se emplean simulaciones de nuestro modelo comparándolos con Ad Hoc On-Demand Distance Vector (AODV y Dynamic Source Routing (DSR. Finalmente, se emplea un modelo de tráfico microscópico desarrollado en OPNET para simular la movilidad de 250 vehículos en una autopista y se aplica el algoritmo de enrutamiento LORA-CBF en un escenario vehicular.

  8. Minimizing Broadcast Expenses in Clustered Ad-hoc Networks

    Directory of Open Access Journals (Sweden)

    S. Zeeshan Hussain

    2018-01-01

    Full Text Available One way to minimize the broadcast expenses of routing protocols is to cluster the network. In clustered ad-hoc networks, all resources can be managed easily by resolving scalability issues. However, blind query broadcast is a major issue that leads to the broadcast storm problem in clustered ad-hoc networks. This query broadcast is done to carry out the route-search task that leads to the unnecessary propagation of route-query even after route has been found. Hence, this query propagation poses the problem of congestion in the network. In particular this motivates us to propose a query-control technique in such networks which works based on broadcast repealing. A huge amount of work has been devoted to propose the query control broadcasting techniques. However, such techniques used in traditional broadcasting mechanisms need to be properly extended for use in the cluster based routing architecture. In this paper, query-control technique is proposed for cluster based routing technique to reduce the broadcast expenses. Finally, we report some experiments which compare the proposed technique to other commonly used techniques including standard one-class AODV that follows TTL-sequence based broadcasting technique.

  9. LAMAN: Load Adaptable MAC for Ad Hoc Networks

    Directory of Open Access Journals (Sweden)

    Realp Marc

    2005-01-01

    Full Text Available In mobile ad hoc radio networks, mechanisms on how to access the radio channel are extremely important in order to improve network efficiency. In this paper, the load adaptable medium access control for ad hoc networks (LAMAN protocol is described. LAMAN is a novel decentralized multipacket MAC protocol designed following a cross-layer approach. Basically, this protocol is a hybrid CDMA-TDMA-based protocol that aims at throughput maximization in multipacket communication environments by efficiently combining contention and conflict-free protocol components. Such combination of components is used to adapt the nodes' access priority to changes on the traffic load while, at the same time, accounting for the multipacket reception (MPR capability of the receivers. A theoretical analysis of the system is developed presenting closed expressions of network throughput and packet delay. By simulations the validity of our analysis is shown and the performances of a LAMAN-based system and an Aloha-CDMA-based one are compared.

  10. Autonomous Power Control MAC Protocol for Mobile Ad Hoc Networks

    Directory of Open Access Journals (Sweden)

    2006-01-01

    Full Text Available Battery energy limitation has become a performance bottleneck for mobile ad hoc networks. IEEE 802.11 has been adopted as the current standard MAC protocol for ad hoc networks. However, it was developed without considering energy efficiency. To solve this problem, many modifications on IEEE 802.11 to incorporate power control have been proposed in the literature. The main idea of these power control schemes is to use a maximum possible power level for transmitting RTS/CTS and the lowest acceptable power for sending DATA/ACK. However, these schemes may degrade network throughput and reduce the overall energy efficiency of the network. This paper proposes autonomous power control MAC protocol (APCMP, which allows mobile nodes dynamically adjusting power level for transmitting DATA/ACK according to the distances between the transmitter and its neighbors. In addition, the power level for transmitting RTS/CTS is also adjustable according to the power level for DATA/ACK packets. In this paper, the performance of APCMP protocol is evaluated by simulation and is compared with that of other protocols.

  11. Discontinuation of continuous renal replacement therapy: A post hoc analysis of a prospective multicenter observational study

    NARCIS (Netherlands)

    Uchino, Shigehiko; Bellomo, Rinaldo; Morimatsu, Hiroshi; Morgera, Stanislao; Schetz, Miet; Tan, Ian; Bouman, Catherine; Macedo, Ettiene; Gibney, Noel; Tolwani, Ashita; Oudemans-van Straaten, Heleen; Ronco, Claudio; Kellum, John A.

    2009-01-01

    Objectives: To describe current practice for the discontinuation of continuous renal replacement therapy in a multinational setting and to identify variables associated with successful discontinuation. The approach to discontinue continuous renal replacement therapy may affect patient outcomes.

  12. Onychomycosis of Toenails and Post-hoc Analyses with Efinaconazole 10% Solution Once-daily Treatment

    Science.gov (United States)

    2016-01-01

    Topical treatment for toenail onychomycosis has been fraught with a long-standing reputation of poor efficaey, primarily due to physical properties of the nail unit that impede drug penetration. Newer topical agents have been formulated as Solution, which appear to provide better therapeutic response in properly selected patients. It is important to recognize the impact the effects that mitigating and concomitant factors can have on efficaey. These factors include disease severity, gender, presence of tinea pedis, and diabetes. This article reviews results achieved in Phase 3 pivotal studies with topical efinaconazole 10% Solution applied once daily for 48 weeks with a focus on how the aforementioned factors influenced therapeutic outcomes. It is important for clinicians treating patients for onychomycosis to evaluate severity, treat concomitant tinea pedis, address control of diabetes if present by encouraging involvement of the patient’s primary care physician, and consider longer treatment courses when clinically relevant. PMID:27047631

  13. Telephone audit for monitoring stroke unit facilities: a post hoc analysis from PROSIT study.

    Science.gov (United States)

    Candelise, Livia; Gattinoni, Monica; Bersano, Anna

    2015-01-01

    Although several valid approaches exist to measure the number and the quality of acute stroke units, only few studies tested their reliability. This study is aimed at establishing whether the telephone administration of the PROject of Stroke unIt ITaly (PROSIT) audit questionnaire is reliable compared with direct face-to-face interview. Forty-three medical leaders in charge of in-hospital stroke services were interviewed twice using the same PROSIT questionnaire with 2 different modalities. First, the interviewers approached the medical leaders by telephone. Thereafter, they went to the hospital site and performed a direct face-to-face interview. Six independent couples of trained researchers conducted the audit interviews. The degree of intermodality agreement was measured with kappa statistic. We found a perfect agreement for stroke units identification between the 2 different audit modalities (K = 1.00; standard error [SE], 1.525). The agreement was also very good for stroke dedicated beds (K = 1.00; SE, 1.525) and dedicated personnel (K = 1.00; SE, 1.525), which are the 2 components of stroke unit definition. The agreement was lower for declared in use process of care and availability of diagnostic investigations. The telephone audit can be used for monitoring stroke unit structures. It is more rapid, less expensive, and can repeatedly be used at appropriate intervals. However, a reliable description of the process of care and diagnostic investigations indicators should be obtained by either local site audit visit or prospective stroke register based on individual patient data. Copyright © 2015 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  14. Post Hoc Analysis of Passive Cavitation Imaging for Classification of Histotripsy-Induced Liquefaction in Vitro.

    Science.gov (United States)

    Bader, Kenneth B; Haworth, Kevin J; Maxwell, Adam D; Holland, Christy K

    2018-01-01

    Histotripsy utilizes focused ultrasound to generate bubble clouds for transcutaneous tissue liquefaction. Bubble activity maps are under development to provide image guidance and monitor treatment progress. The aim of this paper was to investigate the feasibility of using plane wave B-mode and passive cavitation images to be used as binary classifiers of histotripsy-induced liquefaction. Prostate tissue phantoms were exposed to histotripsy pulses over a range of pulse durations (5- ) and peak negative pressures (12-23 MPa). Acoustic emissions were recorded during the insonation and beamformed to form passive cavitation images. Plane wave B-mode images were acquired following the insonation to detect the hyperechoic bubble cloud. Phantom samples were sectioned and stained to delineate the liquefaction zone. Correlation between passive cavitation and plane wave B-mode images and the liquefaction zone was assessed using receiver operating characteristic (ROC) curve analysis. Liquefaction of the phantom was observed for all the insonation conditions. The area under the ROC (0.94 versus 0.82), accuracy (0.90 versus 0.83), and sensitivity (0.81 versus 0.49) was greater for passive cavitation images relative to B-mode images ( ) along the azimuth of the liquefaction zone. The specificity was greater than 0.9 for both imaging modalities. These results demonstrate a stronger correlation between histotripsy-induced liquefaction and passive cavitation imaging compared with the plane wave B-mode imaging, albeit with limited passive cavitation image range resolution.

  15. A-priori and post-hoc segmentation in the design of healthy eating campaigns

    NARCIS (Netherlands)

    Kazbare, L.; Trijp, van J.C.M.; Eskildsen, J.K.

    2010-01-01

    Nutrition-oriented public health campaigns – both communication and intervention initiatives – often target particular demographic groups, for example schoolchildren, adults at workplaces, older women, presuming that the members of these groups are homogenous with respect to healthy eating. Although

  16. Reducing consumption of confectionery foods: A post-hoc segmentation analysis using a social cognition approach.

    Science.gov (United States)

    Naughton, Paul; McCarthy, Mary; McCarthy, Sinéad

    2017-10-01

    Considering confectionary consumption behaviour this cross-sectional study used social cognition variables to identify distinct segments in terms of their motivation and efforts to decrease their consumption of such foods with the aim of informing targeted social marketing campaigns. Using Latent Class analysis on a sample of 500 adults four segments were identified: unmotivated, triers, successful actors, and thrivers. The unmotivated and triers segments reported low levels of perceived need and perceived behavioural control (PBC) in addition to high levels of habit and hedonic hunger with regards their consumption of confectionery foods. Being a younger adult was associated with higher odds of being in the unmotivated and triers segments and being female was associated with higher odds of being in the triers and successful actors segments. The findings indicate that in the absence of strong commitment to eating low amounts of confectionery foods (i.e. perceived need) people will continue to overconsume free sugars regardless of motivation to change. It is therefore necessary to identify relevant messages or 'triggers' related to sugar consumption that resonate with young adults in particular. For those motivated to change, counteracting unhealthy eating habits and the effects of hedonic hunger may necessitate changes to food environments in order to make the healthy choice more appealing and accessible. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Quantitative Research Methods in Chaos and Complexity: From Probability to Post Hoc Regression Analyses

    Science.gov (United States)

    Gilstrap, Donald L.

    2013-01-01

    In addition to qualitative methods presented in chaos and complexity theories in educational research, this article addresses quantitative methods that may show potential for future research studies. Although much in the social and behavioral sciences literature has focused on computer simulations, this article explores current chaos and…

  18. Who Should Be the Winner: A "Post Hoc" Analysis of the 2000 US Election

    Science.gov (United States)

    Wu, D. W.

    2006-01-01

    The 2000 US presidential election between Al Gore and George W. Bush has been the most intriguing and controversial in American history. Using the Florida ballot data, Wu showed that the 2000 election result could have been reversed had the "butterfly ballot effect" been eliminated. Through a combinatorial approach, Harger concluded that…

  19. Intelligent routing protocol for ad hoc wireless network

    Science.gov (United States)

    Peng, Chaorong; Chen, Chang Wen

    2006-05-01

    A novel routing scheme for mobile ad hoc networks (MANETs), which combines hybrid and multi-inter-routing path properties with a distributed topology discovery route mechanism using control agents is proposed in this paper. In recent years, a variety of hybrid routing protocols for Mobile Ad hoc wireless networks (MANETs) have been developed. Which is proactively maintains routing information for a local neighborhood, while reactively acquiring routes to destinations beyond the global. The hybrid protocol reduces routing discovery latency and the end-to-end delay by providing high connectivity without requiring much of the scarce network capacity. On the other side the hybrid routing protocols in MANETs likes Zone Routing Protocol still need route "re-discover" time when a route between zones link break. Sine the topology update information needs to be broadcast routing request on local zone. Due to this delay, the routing protocol may not be applicable for real-time data and multimedia communication. We utilize the advantages of a clustering organization and multi-routing path in routing protocol to achieve several goals at the same time. Firstly, IRP efficiently saves network bandwidth and reduces route reconstruction time when a routing path fails. The IRP protocol does not require global periodic routing advertisements, local control agents will automatically monitor and repair broke links. Secondly, it efficiently reduces congestion and traffic "bottlenecks" for ClusterHeads in clustering network. Thirdly, it reduces significant overheads associated with maintaining clusters. Fourthly, it improves clusters stability due to dynamic topology changing frequently. In this paper, we present the Intelligent Routing Protocol. First, we discuss the problem of routing in ad hoc networks and the motivation of IRP. We describe the hierarchical architecture of IRP. We describe the routing process and illustrate it with an example. Further, we describe the control manage

  20. Extending Service Area of IEEE 802.11 Ad Hoc Networks

    Science.gov (United States)

    Choi, Woo-Yong

    2012-06-01

    According to the current IEEE 802.11 wireless LAN standards, IEEE 802.11 ad hoc networks have the limitation that all STAs (Stations) are in the one-hop transmission range of each other. In this paper, to alleviate the limitation of IEEE 802.11 ad hoc networks we propose the efficient method for selecting the most appropriate pseudo AP (Access Point) from among the set of ad hoc STAs and extending the service area of IEEE 802.11 ad hoc networks by the pseudo AP's relaying the internal traffic of IEEE 802.11 ad hoc networks. Numerical examples show that the proposed method significantly extends the service area of IEEE 802.11 ad hoc networks.

  1. Tolerance to LSD and DOB induced shaking behaviour: differential adaptations of frontocortical 5-HT(2A) and glutamate receptor binding sites.

    Science.gov (United States)

    Buchborn, Tobias; Schröder, Helmut; Dieterich, Daniela C; Grecksch, Gisela; Höllt, Volker

    2015-03-15

    Serotonergic hallucinogens, such as lysergic acid diethylamide (LSD) and dimethoxy-bromoamphetamine (DOB), provoke stereotype-like shaking behaviour in rodents, which is hypothesised to engage frontocortical glutamate receptor activation secondary to serotonin2A (5-HT2A) related glutamate release. Challenging this hypothesis, we here investigate whether tolerance to LSD and DOB correlates with frontocortical adaptations of 5-HT2A and/or overall-glutamate binding sites. LSD and DOB (0.025 and 0.25 mg/kg, i.p.) induce a ketanserin-sensitive (0.5 mg/kg, i.p., 30-min pretreatment) increase in shaking behaviour (including head twitches and wet dog shakes), which with repeated application (7× in 4 ds) is undermined by tolerance. Tolerance to DOB, as indexed by DOB-sensitive [(3)H]spiroperidol and DOB induced [(35)S]GTP-gamma-S binding, is accompanied by a frontocortical decrease in 5-HT2A binding sites and 5-HT2 signalling, respectively; glutamate-sensitive [(3)H]glutamate binding sites, in contrast, remain unchanged. As to LSD, 5-HT2 signalling and 5-HT2A binding, respectively, are not or only marginally affected, yet [(3)H]glutamate binding is significantly decreased. Correlation analysis interrelates tolerance to DOB to the reduced 5-HT2A (r=.80) as well as the unchanged [(3)H]glutamate binding sites (r=.84); tolerance to LSD, as opposed, shares variance with the reduction in [(3)H]glutamate binding sites only (r=.86). Given that DOB and LSD both induce tolerance, one correlating with 5-HT2A, the other with glutamate receptor adaptations, it might be inferred that tolerance can arise at either level. That is, if a hallucinogen (like LSD in our study) fails to induce 5-HT2A (down-)regulation, glutamate receptors (activated postsynaptic to 5-HT2A related glutamate release) might instead adapt and thus prevent further overstimulation of the cortex. Copyright © 2014 Elsevier B.V. All rights reserved.

  2. Les Protocoles de routage dans les réseaux mobiles Ad Hoc ...

    African Journals Online (AJOL)

    Dans cet article nous présentons un état de l'art sur les protocoles de routage dans les réseaux mobiles Ad hoc. Mots clés : Réseaux mobiles ad hoc/, Protocoles de routage. Routing protocols in wireless mobile ad hoc networks. Abstract:The communication between users with handheld computers interconnected through ...

  3. Topology for efficient information dissemination in ad-hoc networking

    Science.gov (United States)

    Jennings, E.; Okino, C. M.

    2002-01-01

    In this paper, we explore the information dissemination problem in ad-hoc wirless networks. First, we analyze the probability of successful broadcast, assuming: the nodes are uniformly distributed, the available area has a lower bould relative to the total number of nodes, and there is zero knowledge of the overall topology of the network. By showing that the probability of such events is small, we are motivated to extract good graph topologies to minimize the overall transmissions. Three algorithms are used to generate topologies of the network with guaranteed connectivity. These are the minimum radius graph, the relative neighborhood graph and the minimum spanning tree. Our simulation shows that the relative neighborhood graph has certain good graph properties, which makes it suitable for efficient information dissemination.

  4. Undilatable Stent Neoatherosclerosis Treated with Ad Hoc Rotational Atherectomy

    Directory of Open Access Journals (Sweden)

    Michael Koutouzis

    2017-01-01

    Full Text Available A middle age woman with known ischemic heart disease and old stents in proximal left anterior descending coronary artery (LAD was admitted to Coronary Care Unit with acute coronary syndrome. The coronary angiography showed one vessel disease with significant restenosis within the previously implanted stents. The lesion was tough and remained undilatable despite high pressure balloon inflation. Eventually, the balloon ruptured creating a massive dissection of the LAD beginning immediately after the distal part of the undilatable lesion. We proceeded with a challenging ad hoc rotational atherectomy of the lesion and finally stenting of the lesion. In-stent restenosis many years after stent implantation is considered to be mainly due to neoatheromatosis compared to intimal hyperplasia, making lesion treatment more difficult and unpredictable.

  5. Optimum Combining for Rapidly Fading Channels in Ad Hoc Networks

    Directory of Open Access Journals (Sweden)

    Sonia Furman

    2003-10-01

    Full Text Available Research and technology in wireless communication systems such as radar and cellular networks have successfully implemented alternative design approaches that utilize antenna array techniques such as optimum combining, to mitigate the degradation effects of multipath in rapid fading channels. In ad hoc networks, these methods have not yet been exploited primarily due to the complexity inherent in the network's architecture. With the high demand for improved signal link quality, devices configured with omnidirectional antennas can no longer meet the growing need for link quality and spectrum efficiency. This study takes an empirical approach to determine an optimum combining antenna array based on 3 variants of interelement spacing. For rapid fading channels, the simulation results show that the performance in the network of devices retrofitted with our antenna arrays consistently exceeded those with an omnidirectional antenna. Further, with the optimum combiner, the performance increased by over 60% compared to that of an omnidirectional antenna in a rapid fading channel.

  6. Vehicular ad hoc networks standards, solutions, and research

    CERN Document Server

    Molinaro, Antonella; Scopigno, Riccardo

    2015-01-01

    This book presents vehicular ad-hoc networks (VANETs) from the their onset, gradually going into technical details, providing a clear understanding of both theoretical foundations and more practical investigation. The editors gathered top-ranking authors to provide comprehensiveness and timely content; the invited authors were carefully selected from a list of who’s who in the respective field of interest: there are as many from Academia as from Standardization and Industry sectors from around the world. The covered topics are organized around five Parts starting from an historical overview of vehicular communications and standardization/harmonization activities (Part I), then progressing to the theoretical foundations of VANETs and a description of the day-one standard-compliant solutions (Part II), hence going into details of vehicular networking and security (Part III) and to the tools to study VANETs, from mobility and channel models, to network simulators and field trial methodologies (Part IV), and fi...

  7. Making friends on the fly advances in ad hoc teamwork

    CERN Document Server

    Barrett, Samuel

    2015-01-01

    This book is devoted to the encounter and interaction of agents such as robots with other agents and describes how they cooperate with their previously unknown teammates, forming an Ad Hoc team. It presents a new algorithm, PLASTIC, that allows agents to quickly adapt to new teammates by reusing knowledge learned from previous teammates.  PLASTIC is instantiated in both a model-based approach, PLASTIC-Model, and a policy-based approach, PLASTIC-Policy.  In addition to reusing knowledge learned from previous teammates, PLASTIC also allows users to provide expert-knowledge and can use transfer learning (such as the new TwoStageTransfer algorithm) to quickly create models of new teammates when it has some information about its new teammates. The effectiveness of the algorithm is demonstrated on three domains, ranging from multi-armed bandits to simulated robot soccer games.

  8. A Hybrid Energy Efficient Protocol for Mobile Ad Hoc Networks

    Directory of Open Access Journals (Sweden)

    Niranjan Kumar Ray

    2016-01-01

    Full Text Available We proposed an energy conservation technique called Location Based Topology Control with Sleep Scheduling for ad hoc networks. It uses the feature of both topology control approach and power management approach. Like the topology control approach, it attempts to reduce the transmission power of a node, which is determined from its neighborhood location information. A node goes to sleep state based on the traffic condition as that of power management approach. In the proposed scheme, a node goes to sleep state only when its absence does not create local partition in its neighborhood. We preformed extensive simulation to compare the proposed scheme with existing ones. Simulation results show that the energy consumption is lower with increase in the network lifetime and higher throughput in the proposed scheme.

  9. Adaptive Probabilistic Broadcasting over Dense Wireless Ad Hoc Networks

    Directory of Open Access Journals (Sweden)

    Victor Gau

    2010-01-01

    Full Text Available We propose an idle probability-based broadcasting method, iPro, which employs an adaptive probabilistic mechanism to improve performance of data broadcasting over dense wireless ad hoc networks. In multisource one-hop broadcast scenarios, the modeling and simulation results of the proposed iPro are shown to significantly outperform the standard IEEE 802.11 under saturated condition. Moreover, the results also show that without estimating the number of competing nodes and changing the contention window size, the performance of the proposed iPro can still approach the theoretical bound. We further apply iPro to multihop broadcasting scenarios, and the experiment results show that within the same elapsed time after the broadcasting, the proposed iPro has significantly higher Packet-Delivery Ratios (PDR than traditional methods.

  10. Increased longevity of wireless Ad hoc network through fuzzy system

    Directory of Open Access Journals (Sweden)

    Fawzia Abdali Larki

    2014-06-01

    Full Text Available The Ad hoc network is one of the multistep-based self-organizing networks, which are dynamically changing and are taken more into account as the ways of connecting the terminals through the development of wireless communication terminals. We are faced with numerous challenges in designing a wireless network such as the dynamic topology, common and limited bandwidth, and the limited energy. The nodes are moving according to the continuous changes in the topology and the source-to-destination paths are completely broken. Therefore, the repeated route discovery enhances the delay and overload of routing. Thus, it is essential to consider the link stability while designing the path in order to choose the routing protocol. Providing the multiple paths may lead to the better performance than a path. The transmission energy control in the wireless Ad hoc networks is the option for the level of transmission energy in order to transmit each node packet in this system. Therefore, transmission energy control affects the wireless medium interface. Because of choosing the appropriate protocol, the routing operation can be improved and the energy consumption can be controlled properly as well as enhancing the durability and longevity of network. The main objective of this study is to enhance the network longevity. The proposed algorithm in this research considers the combination of 2 parameters including the rate of node energy and number of steps in Fuzzy System applied on AOMDV Protocol, which is a Multipath Routing Protocol. The results of simulation also indicate the improved performance of proposed algorithm (AOMDV-F compared to AODV and AOMDV Protocols in NS2 simulator.

  11. A case study of the intraseasonal oscillation traversing the TOGA-COARE LSD. [large-scale domain

    Science.gov (United States)

    Vincent, Dayton G.; Schrage, Jon M.; Sliwinski, L. D.

    1993-01-01

    The paper presents examination of tree intraseasonal (30-60 day) oscillations (ISOs) that occurred during the southern summer season (December 1, 1985 - February 28, 1986) traversing the Large-Scale Domain (LSD) TOGA-COARE, the region which also plays an important role in ENSO, Australian monsoon, and extratropical circulations. Data presented include Hovmoeller diagrams of 5-day running means of 250-mb velocity potential anomalies and OLR anomalies; graphs of five-day running means of OLR in precipitable water (W) per sq m, averaged over 10 x 10 deg boxes centered on 5 S and (1) 145 E, (2) 155 E, (3) 165 E, and (4) 165 D, indicating the midpoint of each ISO; and vertical profiles of zonal wind in m/s averaged over the time period that each ISO spends in the 10 x 10 deg box centered at 5 S, and 175 E and 145 E.

  12. Large-scale digitizer system (LSD) for charge and time digitization in high-energy physics experiments

    International Nuclear Information System (INIS)

    Althaus, R.F.; Kirsten, F.A.; Lee, K.L.; Olson, S.R.; Wagner, L.J.; Wolverton, J.M.

    1976-10-01

    A large-scale digitizer (LSD) system for acquiring charge and time-of-arrival particle data from high-energy-physics experiments has been developed at the Lawrence Berkeley Laboratory. The objective in this development was to significantly reduce the cost of instrumenting large-detector arrays which, for the 4π-geometry of colliding-beam experiments, are proposed with an order of magnitude increase in channel count over previous detectors. In order to achieve the desired economy (approximately $65 per channel), a system was designed in which a number of control signals for conversion, for digitization, and for readout are shared in common by all the channels in each 128-channel bin. The overall-system concept and the distribution of control signals that are critical to the 10-bit charge resolution and to the 12-bit time resolution are described. Also described is the bit-serial transfer scheme, chosen for its low component and cabling costs

  13. Hallucinogenic 5-HT2AR agonists LSD and DOI enhance dopamine D2R protomer recognition and signaling of D2-5-HT2A heteroreceptor complexes.

    Science.gov (United States)

    Borroto-Escuela, Dasiel O; Romero-Fernandez, Wilber; Narvaez, Manuel; Oflijan, Julia; Agnati, Luigi F; Fuxe, Kjell

    2014-01-03

    Dopamine D2LR-serotonin 5-HT2AR heteromers were demonstrated in HEK293 cells after cotransfection of the two receptors and shown to have bidirectional receptor-receptor interactions. In the current study the existence of D2L-5-HT2A heteroreceptor complexes was demonstrated also in discrete regions of the ventral and dorsal striatum with in situ proximity ligation assays (PLA). The hallucinogenic 5-HT2AR agonists LSD and DOI but not the standard 5-HT2AR agonist TCB2 and 5-HT significantly increased the density of D2like antagonist (3)H-raclopride binding sites and significantly reduced the pKiH values of the high affinity D2R agonist binding sites in (3)H-raclopride/DA competition experiments. Similar results were obtained in HEK293 cells and in ventral striatum. The effects of the hallucinogenic 5-HT2AR agonists on D2R density and affinity were blocked by the 5-HT2A antagonist ketanserin. In a forskolin-induced CRE-luciferase reporter gene assay using cotransfected but not D2R singly transfected HEK293 cells DOI and LSD but not TCB2 significantly enhanced the D2LR agonist quinpirole induced inhibition of CRE-luciferase activity. Haloperidol blocked the effects of both quinpirole alone and the enhancing actions of DOI and LSD while ketanserin only blocked the enhancing actions of DOI and LSD. The mechanism for the allosteric enhancement of the D2R protomer recognition and signalling observed is likely mediated by a biased agonist action of the hallucinogenic 5-HT2AR agonists at the orthosteric site of the 5-HT2AR protomer. This mechanism may contribute to the psychotic actions of LSD and DOI and the D2-5-HT2A heteroreceptor complex may thus be a target for the psychotic actions of hallunicogenic 5-HT2A agonists. Copyright © 2013 Elsevier Inc. All rights reserved.

  14. LSD1 demethylase and the methyl-binding protein PHF20L1 prevent SET7 methyltransferase-dependent proteolysis of the stem-cell protein SOX2.

    Science.gov (United States)

    Zhang, Chunxiao; Hoang, Nam; Leng, Feng; Saxena, Lovely; Lee, Logan; Alejo, Salvador; Qi, Dandan; Khal, Anthony; Sun, Hong; Lu, Fei; Zhang, Hui

    2018-03-09

    The pluripotency-controlling stem-cell protein SRY-box 2 (SOX2) plays a pivotal role in maintaining the self-renewal and pluripotency of embryonic stem cells and also of teratocarcinoma or embryonic carcinoma cells. SOX2 is monomethylated at lysine 119 (Lys-119) in mouse embryonic stem cells by the SET7 methyltransferase, and this methylation triggers ubiquitin-dependent SOX2 proteolysis. However, the molecular regulators and mechanisms controlling SET7-induced SOX2 proteolysis are unknown. Here, we report that in human ovarian teratocarcinoma PA-1 cells, methylation-dependent SOX2 proteolysis is dynamically regulated by the LSD1 lysine demethylase and a methyl-binding protein, PHD finger protein 20-like 1 (PHF20L1). We found that LSD1 not only removes the methyl group from monomethylated Lys-117 (equivalent to Lys-119 in mouse SOX2), but it also demethylates monomethylated Lys-42 in SOX2, a reaction that SET7 also regulated and that also triggered SOX2 proteolysis. Our studies further revealed that PHF20L1 binds both monomethylated Lys-42 and Lys-117 in SOX2 and thereby prevents SOX2 proteolysis. Down-regulation of either LSD1 or PHF20L1 promoted SOX2 proteolysis, which was prevented by SET7 inactivation in both PA-1 and mouse embryonic stem cells. Our studies also disclosed that LSD1 and PHF20L1 normally regulate the growth of pluripotent mouse embryonic stem cells and PA-1 cells by preventing methylation-dependent SOX2 proteolysis. In conclusion, our findings reveal an important mechanism by which the stability of the pluripotency-controlling stem-cell protein SOX2 is dynamically regulated by the activities of SET7, LSD1, and PHF20L1 in pluripotent stem cells. © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.

  15. Gaddum and LSD: the birth and growth of experimental and clinical neuropharmacology research on 5-HT in the UK

    Science.gov (United States)

    Green, A R

    2008-01-01

    The vasoconstrictor substance named serotonin was identified as 5-hydroxytryptamine (5-HT) by Maurice Rapport in 1949. In 1951, Rapport gave Gaddum samples of 5-HT substance allowing him to develop a bioassay to both detect and measure the amine. Gaddum and colleagues rapidly identified 5-HT in brain and showed that lysergic acid diethylamide (LSD) antagonized its action in peripheral tissues. Gaddum accordingly postulated that 5-HT might have a role in mood regulation. This review examines the role of UK scientists in the first 20 years following these major discoveries, discussing their role in developing assays for 5-HT in the CNS, identifying the enzymes involved in the synthesis and metabolism of 5-HT and investigating the effect of drugs on brain 5-HT. It reviews studies on the effects of LSD in humans, including Gaddum's self-administration experiments. It outlines investigations on the role of 5-HT in psychiatric disorders, including studies on the effect of antidepressant drugs on the 5-HT concentration in rodent and human brain, and the attempts to examine 5-HT biochemistry in the brains of patients with depressive illness. It is clear that a rather small group of both preclinical scientists and psychiatrists in the UK made major advances in our understanding of the role of 5-HT in the brain, paving the way for much of the knowledge now taken for granted when discussing ways that 5-HT might be involved in the control of mood and the idea that therapeutic drugs used to alleviate psychiatric illness might alter the function of cerebral 5-HT. PMID:18516072

  16. Gaddum and LSD: the birth and growth of experimental and clinical neuropharmacology research on 5-HT in the UK.

    Science.gov (United States)

    Green, A R

    2008-08-01

    The vasoconstrictor substance named serotonin was identified as 5-hydroxytryptamine (5-HT) by Maurice Rapport in 1949. In 1951, Rapport gave Gaddum samples of 5-HT substance allowing him to develop a bioassay to both detect and measure the amine. Gaddum and colleagues rapidly identified 5-HT in brain and showed that lysergic acid diethylamide (LSD) antagonized its action in peripheral tissues. Gaddum accordingly postulated that 5-HT might have a role in mood regulation. This review examines the role of UK scientists in the first 20 years following these major discoveries, discussing their role in developing assays for 5-HT in the CNS, identifying the enzymes involved in the synthesis and metabolism of 5-HT and investigating the effect of drugs on brain 5-HT. It reviews studies on the effects of LSD in humans, including Gaddum's self-administration experiments. It outlines investigations on the role of 5-HT in psychiatric disorders, including studies on the effect of antidepressant drugs on the 5-HT concentration in rodent and human brain, and the attempts to examine 5-HT biochemistry in the brains of patients with depressive illness. It is clear that a rather small group of both preclinical scientists and psychiatrists in the UK made major advances in our understanding of the role of 5-HT in the brain, paving the way for much of the knowledge now taken for granted when discussing ways that 5-HT might be involved in the control of mood and the idea that therapeutic drugs used to alleviate psychiatric illness might alter the function of cerebral 5-HT.

  17. Building Realistic Mobility Models for Mobile Ad Hoc Networks

    Directory of Open Access Journals (Sweden)

    Adrian Pullin

    2018-04-01

    Full Text Available A mobile ad hoc network (MANET is a self-configuring wireless network in which each node could act as a router, as well as a data source or sink. Its application areas include battlefields and vehicular and disaster areas. Many techniques applied to infrastructure-based networks are less effective in MANETs, with routing being a particular challenge. This paper presents a rigorous study into simulation techniques for evaluating routing solutions for MANETs with the aim of producing more realistic simulation models and thereby, more accurate protocol evaluations. MANET simulations require models that reflect the world in which the MANET is to operate. Much of the published research uses movement models, such as the random waypoint (RWP model, with arbitrary world sizes and node counts. This paper presents a technique for developing more realistic simulation models to test and evaluate MANET protocols. The technique is animation, which is applied to a realistic scenario to produce a model that accurately reflects the size and shape of the world, node count, movement patterns, and time period over which the MANET may operate. The animation technique has been used to develop a battlefield model based on established military tactics. Trace data has been used to build a model of maritime movements in the Irish Sea. Similar world models have been built using the random waypoint movement model for comparison. All models have been built using the ns-2 simulator. These models have been used to compare the performance of three routing protocols: dynamic source routing (DSR, destination-sequenced distance-vector routing (DSDV, and ad hoc n-demand distance vector routing (AODV. The findings reveal that protocol performance is dependent on the model used. In particular, it is shown that RWP models do not reflect the performance of these protocols under realistic circumstances, and protocol selection is subject to the scenario to which it is applied. To

  18. Typicality Mediates Performance during Category Verification in Both Ad-Hoc and Well-Defined Categories

    Science.gov (United States)

    Sandberg, Chaleece; Sebastian, Rajani; Kiran, Swathi

    2012-01-01

    Background: The typicality effect is present in neurologically intact populations for natural, ad-hoc, and well-defined categories. Although sparse, there is evidence of typicality effects in persons with chronic stroke aphasia for natural and ad-hoc categories. However, it is unknown exactly what influences the typicality effect in this…

  19. Ad Hoc Categories and False Memories: Memory Illusions for Categories Created On-The-Spot

    Science.gov (United States)

    Soro, Jerônimo C.; Ferreira, Mário B.; Semin, Gün R.; Mata, André; Carneiro, Paula

    2017-01-01

    Three experiments were designed to test whether experimentally created ad hoc associative networks evoke false memories. We used the DRM (Deese, Roediger, McDermott) paradigm with lists of ad hoc categories composed of exemplars aggregated toward specific goals (e.g., going for a picnic) that do not share any consistent set of features. Experiment…

  20. A peer-to-peer file search and download protocol for wireless ad-hoc networks

    NARCIS (Netherlands)

    Sözer, Hasan; Tekkalmaz, M.; Korpeoglu, I.

    Deployment of traditional peer-to-peer file sharing systems on a wireless ad-hoc network introduces several challenges. Information and workload distribution as well as routing are major problems for members of a wireless ad-hoc network, which are only aware of their immediate neighborhood. In this

  1. A flow level model for wireless multihop ad hoc network throughput

    NARCIS (Netherlands)

    Coenen, Tom Johannes Maria; van den Berg, Hans Leo; Boucherie, Richardus J.

    2005-01-01

    A flow level model for multihop wireless ad hoc networks is presented in this paper. Using a flow level view, we show the main properties and modeling challenges for ad hoc networks. Considering different scenarios, a multihop WLAN and a serial network with a TCP-like flow control protocol, we

  2. On the impact of network dynamics on a discovery protocol for ad-hoc networks

    NARCIS (Netherlands)

    Liu, F.; Heijenk, Geert

    A very promising approach to discovering services and context information in ad-hoc networks is based on the use of Attenuated Bloom filters. In this paper we analyze the impact of changes in the connectivity of an ad-hoc network on this approach. We evaluate the performance of the discovery

  3. Twenty-One at TREC-7: ad-hoc and cross-language track

    NARCIS (Netherlands)

    Hiemstra, Djoerd; Kraaij, Wessel; Voorhees, E.M; Harman, D.K.

    1999-01-01

    This paper describes the official runs of the Twenty-One group for TREC-7. The Twenty-One group participated in the ad-hoc and the cross-language track and made the following accomplishments: We developed a new weighting algorithm, which outperforms the popular Cornell version of BM25 on the ad-hoc

  4. Reliability analysis of cluster-based ad-hoc networks

    International Nuclear Information System (INIS)

    Cook, Jason L.; Ramirez-Marquez, Jose Emmanuel

    2008-01-01

    The mobile ad-hoc wireless network (MAWN) is a new and emerging network scheme that is being employed in a variety of applications. The MAWN varies from traditional networks because it is a self-forming and dynamic network. The MAWN is free of infrastructure and, as such, only the mobile nodes comprise the network. Pairs of nodes communicate either directly or through other nodes. To do so, each node acts, in turn, as a source, destination, and relay of messages. The virtue of a MAWN is the flexibility this provides; however, the challenge for reliability analyses is also brought about by this unique feature. The variability and volatility of the MAWN configuration makes typical reliability methods (e.g. reliability block diagram) inappropriate because no single structure or configuration represents all manifestations of a MAWN. For this reason, new methods are being developed to analyze the reliability of this new networking technology. New published methods adapt to this feature by treating the configuration probabilistically or by inclusion of embedded mobility models. This paper joins both methods together and expands upon these works by modifying the problem formulation to address the reliability analysis of a cluster-based MAWN. The cluster-based MAWN is deployed in applications with constraints on networking resources such as bandwidth and energy. This paper presents the problem's formulation, a discussion of applicable reliability metrics for the MAWN, and illustration of a Monte Carlo simulation method through the analysis of several example networks

  5. An ad hoc wireless sensor network for tele medicine applications

    International Nuclear Information System (INIS)

    Sheltami, Tarek R.; Mahmoud, Ashraf S.; Abu-Amara, Marwan H.

    2007-01-01

    Recent advances in embedded computing systems have led to the emergence of wireless sensor networks (SNETs), consisting of small, battery-powered motes with limited computation and radio communication capabilities. SNETs permit data gathering and computation to be deeply embedded in the physical environment. Large scale ad hoc sensor networks (ASNET), when deployed among mobile patients, can provide dynamic data query architecture to allow medical specialists to monitor patients at any place via the web or cellular network. In case of an emergency, doctors and/or nurses will be contacted automatically through their handheld personal digital assistants (PDAs) or cellular phones. In specific, the proposed network consists of sensor nodes at the first layer whose responsibility is to measure, collect and communicate, via wired or wireless interface, readings to a microcontroller presenting the second layer of architecture. Deployed microcontrollers process incoming readings and report to a central system via a wireless interface. The implemented network distinguishes between periodic sensor readings and critical or event driven readings where higher priorities is given for the latter. In this paper we implement 3 special cases for tracking and monitoring patients and doctors using SNETs. In addition, the performance of a large scale of our implementation has been tested by means of mathematical analysis. (author)

  6. A Dynamic Reputation Management System for Mobile Ad Hoc Networks

    Directory of Open Access Journals (Sweden)

    Eric Chiejina

    2015-04-01

    Full Text Available Nodes in mobile ad hoc networks (MANETs are mandated to utilize their limited energy resources in forwarding routing control and data packets for other nodes. Since a MANET lacks a centralized administration and control, a node may decide to act selfishly, either by refusing to respond to route requests from other nodes or deceitfully by responding to some route requests, but dropping the corresponding data packets that are presented for forwarding. A significant increase in the presence of these misbehaving nodes in a MANET can subsequently degrade network performance. In this paper, we propose a dynamic reputation management system for detecting and isolating misbehaving nodes in MANETs. Our model employs a novel direct monitoring technique to evaluate the reputation of a node in the network, which ensures that nodes that expend their energy in transmitting data and routing control packets for others are allowed to carry out their network activities while the misbehaving nodes are detected and isolated from the network. Simulation results show that our model is effective at curbing and mitigating the effects of misbehaving nodes in the network.

  7. Data management issues in mobile ad hoc networks.

    Science.gov (United States)

    Hara, Takahiro

    2017-01-01

    Research on mobile ad hoc networks (MANETs) has become a hot research topic since the middle 1990's. Over the first decade, most research focused on networking techniques, ignoring data management issues. We, however, realized early the importance of data management in MANETs, and have been conducting studies in this area for 15 years. In this review, we summarize some key technical issues related to data management in MANETs, and the studies we have done in addressing these issues, which include placement of data replicas, update management, and query processing with security management. The techniques proposed in our studies have been designed with deep considerations of MANET features including network partitioning, node participation/disappearance, limited network bandwidth, and energy efficiency. Our studies published in early 2000's have developed a new research field as data management in MANETs. Also, our recent studies are expected to be significant guidelines of new research directions. We conclude the review by discussing some future directions for research.

  8. On-line identification of lysergic acid diethylamide (LSD) in tablets using a combination of a sweeping technique and micellar electrokinetic chromatography/77 K fluorescence spectroscopy.

    Science.gov (United States)

    Fang, Ching; Liu, Ju-Tsung; Lin, Cheng-Huang

    2003-03-01

    This work describes a novel method for the accurate determination of lysergic acid diethylamide (LSD) in tablets. A technique involving sweeping-micellar electrokinetic chromatography (MEKC) was used for the initial on-line concentration and separation, after which a cryogenic molecular fluorescence experiment was performed at 77 K. Using this approach, not only the separation of LSD from the tablet extract was achieved, but on-line spectra were readily distinguishable and could be unambiguously assigned. The results are in agreement with analyses by gas chromatography-mass spectrometry (GC-MS). Thus, this method, which was found to be accurate, sensitive and rapid, has the potential for use as a reliable complementary method to GC-MS in such analyses.

  9. (125I)LSD labels 5-TCsub(IC) recognition sites in pig choriod plexus membranes. Comparison with (3H)mesulergine and (3H)5-HT binding

    International Nuclear Information System (INIS)

    Hoyer, D.; Srivatsa, S.; Pazos, A.; Engel, G.; Palacios, J.M.

    1986-01-01

    The mammalian choroid plexus is enriched in a newly described serotonin recognition site, the binding characteristics of ( 125 I)LSD, ( 3 H)mesulergine and ( 3 H)serotonin to pig choroid plexus membranes were compared. These ligands labelled with high affinity a similar number of sites. The binding profiles of the sites labelled with these radioligands are indistinguishable as illustrated by highly significant correlation parameters. These sites are very similar to those labelled by Nsub(I)-methyl-2-( 125 I)LSD in pig and rat choroid plexus membranes. The data demonstrate that these ligands label 5-HTsub(IC) recognition sites in the pig and rat choroid plexus membranes. (author)

  10. Does Ad Hoc Coronary Intervention Reduce Radiation Exposure? – Analysis of 568 Patients

    Energy Technology Data Exchange (ETDEWEB)

    Truffa, Márcio A. M., E-mail: marciotruffa@yahoo.com.br; Alves, Gustavo M.P.; Bernardi, Fernando; Esteves Filho, Antonio; Ribeiro, Expedito; Galon, Micheli Z.; Spadaro, André; Kajita, Luiz J.; Arrieta, Raul; Lemos, Pedro A. [Instituto do Coração - Hospital das Clínicas - Faculdade de Medicina da Universidade de São Paulo (USP), São Paulo, SP (Brazil)

    2015-11-15

    Advantages and disadvantages of ad hoc percutaneous coronary intervention have been described. However little is known about the radiation exposure of that procedure as compared with the staged intervention. To compare the radiation dose of the ad hoc percutaneous coronary intervention with that of the staged procedure The dose-area product and total Kerma were measured, and the doses of the diagnostic and therapeutic procedures were added. In addition, total fluoroscopic time and number of acquisitions were evaluated. A total of 568 consecutive patients were treated with ad hoc percutaneous coronary intervention (n = 320) or staged percutaneous coronary intervention (n = 248). On admission, the ad hoc group had less hypertension (74.1% vs 81.9%; p = 0.035), dyslipidemia (57.8% vs. 67.7%; p = 0.02) and three-vessel disease (38.8% vs. 50.4%; p = 0.015). The ad hoc group was exposed to significantly lower radiation doses, even after baseline characteristic adjustment between both groups. The ad hoc group was exposed to a total dose-area product of 119.7 ± 70.7 Gycm{sup 2}, while the staged group, to 139.2 ± 75.3 Gycm{sup 2} (p < 0.001). Ad hoc percutaneous coronary intervention reduced radiation exposure as compared with diagnostic and therapeutic procedures performed at two separate times.

  11. Does Ad Hoc Coronary Intervention Reduce Radiation Exposure? – Analysis of 568 Patients

    International Nuclear Information System (INIS)

    Truffa, Márcio A. M.; Alves, Gustavo M.P.; Bernardi, Fernando; Esteves Filho, Antonio; Ribeiro, Expedito; Galon, Micheli Z.; Spadaro, André; Kajita, Luiz J.; Arrieta, Raul; Lemos, Pedro A.

    2015-01-01

    Advantages and disadvantages of ad hoc percutaneous coronary intervention have been described. However little is known about the radiation exposure of that procedure as compared with the staged intervention. To compare the radiation dose of the ad hoc percutaneous coronary intervention with that of the staged procedure The dose-area product and total Kerma were measured, and the doses of the diagnostic and therapeutic procedures were added. In addition, total fluoroscopic time and number of acquisitions were evaluated. A total of 568 consecutive patients were treated with ad hoc percutaneous coronary intervention (n = 320) or staged percutaneous coronary intervention (n = 248). On admission, the ad hoc group had less hypertension (74.1% vs 81.9%; p = 0.035), dyslipidemia (57.8% vs. 67.7%; p = 0.02) and three-vessel disease (38.8% vs. 50.4%; p = 0.015). The ad hoc group was exposed to significantly lower radiation doses, even after baseline characteristic adjustment between both groups. The ad hoc group was exposed to a total dose-area product of 119.7 ± 70.7 Gycm 2 , while the staged group, to 139.2 ± 75.3 Gycm 2 (p < 0.001). Ad hoc percutaneous coronary intervention reduced radiation exposure as compared with diagnostic and therapeutic procedures performed at two separate times

  12. Illicit use of LSD or psilocybin, but not MDMA or nonpsychedelic drugs, is associated with mystical experiences in a dose-dependent manner.

    Science.gov (United States)

    Lyvers, Michael; Meester, Molly

    2012-01-01

    Psychedelic drugs have long been known to be capable of inducing mystical or transcendental experiences. However, given the common "recreational" nature of much present-day psychedelic use, with typical doses tending to be lower than those commonly taken in the 1960s, the extent to which illicit use of psychedelics today is associated with mystical experiences is not known. Furthermore the mild psychedelic MDMA ("Ecstasy") is more popular today than "full" psychedelics such as LSD or psilocybin, and the contribution of illicit MDMA use to mystical experiences is not known. The present study recruited 337 adults from the website and newsletter of the Multidisciplinary Association for Psychedelic Studies (MAPS), most of whom reported use of a variety of drugs both licit and illicit including psychedelics. Although only a quarter of the sample reported "spiritual" motives for using psychedelics, use of LSD and psilocybin was significantly positively related to scores on two well-known indices of mystical experiences in a dose-related manner, whereas use of MDMA, cannabis, cocaine, opiates and alcohol was not. Results suggest that even in today's context of "recreational" drug use, psychedelics such as LSD and psilocybin, when taken at higher doses, continue to induce mystical experiences in many users.

  13. Epoxide hydrolase Lsd19 for polyether formation in the biosynthesis of lasalocid A: direct experimental evidence on polyene-polyepoxide hypothesis in polyether biosynthesis.

    Science.gov (United States)

    Shichijo, Yoshihiro; Migita, Akira; Oguri, Hiroki; Watanabe, Mami; Tokiwano, Tetsuo; Watanabe, Kenji; Oikawa, Hideaki

    2008-09-17

    Polyether metabolites are an important class of natural products. Although their biosynthesis, especially construction of polyether skeletons, attracted organic chemists for many years, no experimental data on the enzymatic polyether formation has been obtained. In this study, a putative epoxide hydrolase gene lsd19 found on the biosynthetic gene cluster of an ionophore polyether lasalocid was cloned and successfully overexpressed in Escherichia coli. Using the purified Lsd19, a proposed substrate, bisepoxyprelasalocid, and its synthesized analogue were successfully converted into lasalocid A and its derivative via a 6-endo-tet cyclization mode. On the other hand, treatment of the bisepoxide with trichloroacetic acid gave isolasalocid A via a 5-exo-tet cyclization mode. Therefore, the enzymatic conversion observed in this study unambiguously showed that the bisepoxyprelasalocid is an intermediate of the lasalocid biosynthesis and that Lsd19 catalyzes the sequential cyclic ether formations involving an energetically disfavored 6-endo-tet cyclization. This is the first example of the enzymatic epoxide-opening reactions leading to a polyether natural product.

  14. Contribution to design a communication framework for vehicular ad hoc networks in urban scenarios

    OpenAIRE

    Tripp Barba, Carolina

    2013-01-01

    The constant mobility of people, the growing need to be always connected, the large number of vehicles that nowadays can be found in the roads and the advances in technology make Vehicular Ad hoc Networks (VANETs) be a major area of research. Vehicular Ad hoc Networks are a special type of wireless Mobile Ad hoc Networks (MANETs), which allow a group of mobile nodes configure a temporary network and maintain it without the need of a fixed infrastructure. A vehicular network presents some spec...

  15. Contribution to design a communication framework for vehicular ad hoc networks in urban scenarios

    OpenAIRE

    Tripp Barba, Carolina

    2013-01-01

    La movilidad constante de las personas y la creciente necesidad de estar conectados en todo momento ha hecho de las redes vehiculares un área cuyo interés ha ido en aumento. La gran cantidad de vehículos que hay en la actualidad, y los avances tecnológicos han hecho de las redes vehiculares (VANETS, Vehicular Ad hoc Networks) un gran campo de investigación. Las redes vehiculares son un tipo especial de redes móviles ad hoc inalámbricas, las cuales, al igual que las redes MANET (Mobile Ad hoc ...

  16. History of the research ad hoc committee on 'dissemination of information' and the special ad hoc committee on 'dissemination of information' of the Atomic Energy Society of Japan

    Energy Technology Data Exchange (ETDEWEB)

    Itabashi, Keizo [Japan Atomic Energy Agency, Intellectual Resources Department, Tokai, Ibaraki (Japan)

    2010-06-15

    The Research ad hoc committee on 'Dissemination of information' of the Atomic Energy Society of Japan was held 15 times from Oct. 1970 to Mar 1973. After that, The Special ad hoc committee on 'Dissemination of information' of the Atomic Energy Society of Japan was held 115 times from Apr. 1973 to Mar 2009. The history of these two committees is described. Activity report is arranged including the information on change of the member and topics of the meeting, and the minutes. Furthermore, the document list on International Nuclear Information System (INIS) from Japan is included. (author)

  17. History of the research ad hoc committee on 'dissemination of information' and the special ad hoc committee on 'dissemination of information' of the Atomic Energy Society of Japan

    International Nuclear Information System (INIS)

    Itabashi, Keizo

    2010-06-01

    The Research ad hoc committee on 'Dissemination of information' of the Atomic Energy Society of Japan was held 15 times from Oct. 1970 to Mar 1973. After that, The Special ad hoc committee on 'Dissemination of information' of the Atomic Energy Society of Japan was held 115 times from Apr. 1973 to Mar 2009. The history of these two committees is described. Activity report is arranged including the information on change of the member and topics of the meeting, and the minutes. Furthermore, the document list on International Nuclear Information System (INIS) from Japan is included. (author)

  18. Argyreia nervosa (Burm. f.): receptor profiling of lysergic acid amide and other potential psychedelic LSD-like compounds by computational and binding assay approaches.

    Science.gov (United States)

    Paulke, Alexander; Kremer, Christian; Wunder, Cora; Achenbach, Janosch; Djahanschiri, Bardya; Elias, Anderson; Schwed, J Stefan; Hübner, Harald; Gmeiner, Peter; Proschak, Ewgenij; Toennes, Stefan W; Stark, Holger

    2013-07-09

    The convolvulacea Argyreia nervosa (Burm. f.) is well known as an important medical plant in the traditional Ayurvedic system of medicine and it is used in numerous diseases (e.g. nervousness, bronchitis, tuberculosis, arthritis, and diabetes). Additionally, in the Indian state of Assam and in other regions Argyreia nervosa is part of the traditional tribal medicine (e.g. the Santali people, the Lodhas, and others). In the western hemisphere, Argyreia nervosa has been brought in attention as so called "legal high". In this context, the seeds are used as source of the psychoactive ergotalkaloid lysergic acid amide (LSA), which is considered as the main active ingredient. As the chemical structure of LSA is very similar to that of lysergic acid diethylamide (LSD), the seeds of Argyreia nervosa (Burm. f.) are often considered as natural substitute of LSD. In the present study, LSA and LSD have been compared concerning their potential pharmacological profiles based on the receptor binding affinities since our recent human study with four volunteers on p.o. application of Argyreia nervosa seeds has led to some ambiguous effects. In an initial step computer-aided in silico prediction models on receptor binding were employed to screen for serotonin, norepinephrine, dopamine, muscarine, and histamine receptor subtypes as potential targets for LSA. In addition, this screening was extended to accompany ergotalkaloids of Argyreia nervosa (Burm. f.). In a verification step, selected LSA screening results were confirmed by in vitro binding assays with some extensions to LSD. In the in silico model LSA exhibited the highest affinity with a pKi of about 8.0 at α1A, and α1B. Clear affinity with pKi>7 was predicted for 5-HT1A, 5-HT1B, 5-HT1D, 5-HT6, 5-HT7, and D2. From these receptors the 5-HT1D subtype exhibited the highest pKi with 7.98 in the prediction model. From the other ergotalkaloids, agroclavine and festuclavine also seemed to be highly affine to the 5-HT1D

  19. The effect of DAD timeout period on address autoconfiguration in wireless ad-hoc networks

    CSIR Research Space (South Africa)

    Mutanga, MB

    2011-09-01

    Full Text Available Lack of manual management mechanisms in wireless ad-hoc networks means that automatic configuration of IP addresses and other related network parameters are very crucial. Many IP address autoconfiguration mechanisms have been proposed in literature...

  20. A Tool for Visualizing Mobile Ad-Hoc Network Topology Definitions Files

    National Research Council Canada - National Science Library

    Nguyen, Binh Q

    2006-01-01

    This report documents a research and development effort that the U.S. Army Research Laboratory conducted in FY05 in support of the building of an emulated tactical mobile ad hoc network (MANET) research test bed...

  1. Accurate 3D Localization Method for Public Safety Applications in Vehicular Ad-hoc Networks

    KAUST Repository

    Ansari, Abdul Rahim; Saeed, Nasir; Haq, Mian Imtiaz Ul; Cho, Sunghyun

    2018-01-01

    Vehicular ad hoc networks (VANETs) represent a very promising research area because of their ever increasing demand, especially for public safety applications. In VANETs vehicles communicate with each other to exchange road maps and traffic

  2. DESAIN ALGORITMA DAN SIMULASI ROUTING UNTUK GATEWAY AD HOC WIRELESS NETWORKS

    Directory of Open Access Journals (Sweden)

    Nixson Meok

    2009-12-01

    Full Text Available   Routing protocol to the wireless ad hoc networks is very needed in the communication process between some terminals, to send the data packet through one or several node(s to the destination address where the network typology is always changing. Many previous works that discussed about routing ad hoc both for manet (mobile ad hoc networks and wireless networks, but the emphasis have more focus on comparing the performance of several routing ad hoc. While in this work, there is a bulding of routing algorithm model to gateway in land to the nodes that analogized as a boat that move on the sea. With the assumption that the communication inter terminals to radio band of Very High Frequency, thus algorithm that built in the simulation based on the range gap of the HF frequency. The result of this simulation will be developed as the platform to implement the service development of multiuser communication

  3. Analysis for Ad Hoc Network Attack-Defense Based on Stochastic Game Model

    Directory of Open Access Journals (Sweden)

    Yuanjie LI

    2014-06-01

    Full Text Available The attack actions analysis for Ad Hoc networks can provide a reference for the design security mechanisms. This paper presents an analysis method of security of Ad Hoc networks based on Stochastic Game Nets (SGN. This method can establish a SGN model of Ad Hoc networks and calculate to get the Nash equilibrium strategy. After transforming the SGN model into a continuous-time Markov Chain (CTMC, the security of Ad Hoc networks can be evaluated and analyzed quantitatively by calculating the stationary probability of CTMC. Finally, the Matlab simulation results show that the probability of successful attack is related to the attack intensity and expected payoffs, but not attack rate.

  4. SURVEI TEKNIK CLUSTERING ROUTING BERDASARKAN MOBILITAS PADA WIRELESS AD-HOC NETWORK

    Directory of Open Access Journals (Sweden)

    I Nyoman Trisna Wirawan

    2016-01-01

    Full Text Available Wireless ad-hoc merupakan sebuah skema jaringan yang didesain supaya mampu beroperasi tanpa membutuhkan infrastruktur tetap serta bersifat otonom. Teknik flooding pada proses path discovery dalam kasus wireless ad-hoc network dapat menimbulkan masalah beban jaringan yang berlebihan. Oleh karena itu, sebuah skema clustering diusulkan untuk mengurangi adanya flooding paket yang berlebihan dengan membagi node-node dalam jaringan menjadi beberapa bagian berdasarkan parameter tertentu. Teknik ini efektifuntuk mengurangi paket yang harus dilewatkan dalam jaringan. Namun masalah muncul ketika sebuah jaringan wireless ad-hoc harus membentuk sebuah cluster dengan mempertimbangkan beberapa parameter khusus. Parameter tersebut harus disesuaikan dengan kasus yang dihadapi. Pada tulisan ini akan dibahas secara khusus mengenai penerapan skema clustering dalam lingkungan wireless ad-hoc network, baik pada MANETdan penyesuaian skema clustering yang harus dilakukan pada VANET berdasarkan mobilitasnya.

  5. An Ad-Hoc Opportunistic Dissemination Protocol for Smartphone-based Participatory Traffic Monitoring

    NARCIS (Netherlands)

    Türkes, Okan; Seraj, Fatjon; Scholten, Johan; Meratnia, Nirvana; Havinga, Paul J.M.

    2015-01-01

    This study introduces an ad-hoc opportunistic data dissemination protocol, called VADISS, that facilitates participatory traffic monitoring applications with smartphones. As a ubiquitous alternative to existing vehicular networking methods, VADISS uses the default WiFi interfaces universally adopted

  6. Energy-Aware Broadcasting and Multicasting in Wireless Ad Hoc Networks: A Cross-Layering Approach

    National Research Council Canada - National Science Library

    Wieselthier, Jeffrey E; Nguyen, Gam D; Ephremides, Anthony

    2004-01-01

    ...) problems, especially when energy-aware operation is required. To address the specific problem of energy-aware tree construction in wireless ad hoc networks, we have developed the Broadcast Incremental Power (BIP...

  7. A Group Based Key Sharing and Management Algorithm for Vehicular Ad Hoc Networks

    Directory of Open Access Journals (Sweden)

    Zeeshan Shafi Khan

    2014-01-01

    Full Text Available Vehicular ad hoc networks (VANETs are one special type of ad hoc networks that involves vehicles on roads. Typically like ad hoc networks, broadcast approach is used for data dissemination. Blind broadcast to each and every node results in exchange of useless and irrelevant messages and hence creates an overhead. Unicasting is not preferred in ad-hoc networks due to the dynamic topology and the resource requirements as compared to broadcasting. Simple broadcasting techniques create several problems on privacy, disturbance, and resource utilization. In this paper, we propose media mixing algorithm to decide what information should be provided to each user and how to provide such information. Results obtained through simulation show that fewer number of keys are needed to share compared to simple broadcasting. Privacy is also enhanced through this approach.

  8. On-Demand Routing in Multi-hop Wireless Mobile Ad Hoc Networks

    National Research Council Canada - National Science Library

    Maltz, David A

    2001-01-01

    .... Routing protocols used in ad hoc networks must automatically adjust to environments that can vary between the extremes of high mobility with low bandwidth, and low mobility with high bandwidth...

  9. Ad-hoc Content-based Queries and Data Analysis for Virtual Observatories, Phase II

    Data.gov (United States)

    National Aeronautics and Space Administration — Aquilent, Inc. proposes to support ad-hoc, content-based query and data retrieval from virtual observatories (VxO) by developing 1) Higher Order Query Services that...

  10. Voice Communications over 802.11 Ad Hoc Networks: Modeling, Optimization and Call Admission Control

    Science.gov (United States)

    Xu, Changchun; Xu, Yanyi; Liu, Gan; Liu, Kezhong

    Supporting quality-of-service (QoS) of multimedia communications over IEEE 802.11 based ad hoc networks is a challenging task. This paper develops a simple 3-D Markov chain model for queuing analysis of IEEE 802.11 MAC layer. The model is applied for performance analysis of voice communications over IEEE 802.11 single-hop ad hoc networks. By using the model, we finish the performance optimization of IEEE MAC layer and obtain the maximum number of voice calls in IEEE 802.11 ad hoc networks as well as the statistical performance bounds. Furthermore, we design a fully distributed call admission control (CAC) algorithm which can provide strict statistical QoS guarantee for voice communications over IEEE 802.11 ad hoc networks. Extensive simulations indicate the accuracy of the analytical model and the CAC scheme.

  11. Throughput and Fairness of Collision Avoidance Protocols in Ad Hoc Networks

    National Research Council Canada - National Science Library

    Garcia-Luna-Aceves, J. J; Wang, Yu

    2004-01-01

    .... In Section 1, The authors present an analytical modeling to derive the saturation throughput of these sender-initiated collision avoidance protocols in multi-hop ad hoc networks with nodes randomly...

  12. Analysis and Enhancements of Leader Elections algorithms in Mobile Ad Hoc Networks

    OpenAIRE

    Shayeji, Mohammad H. Al; Al-Azmi, AbdulRahman R.; Al-Azmi, AbdulAziz R.; Samrajesh, M. D.

    2012-01-01

    Mobile Ad Hoc networks (MANET), distinct from traditional distributed systems, are dynamic and self-organizing networks. MANET requires a leader to coordinate and organize tasks. The challenge is to have the right election algorithm that chooses the right leader based on various factors in MANET. In this paper, we analyze four leader election algorithms used in mobile Ad Hoc Networks. Factors considered in our analysis are time complexity, message complexity, assumptions considered, fault tol...

  13. Algorithmic, LOCS and HOCS (chemistry) exam questions: performance and attitudes of college students

    Science.gov (United States)

    Zoller, Uri

    2002-02-01

    The performance of freshmen biology and physics-mathematics majors and chemistry majors as well as pre- and in-service chemistry teachers in two Israeli universities on algorithmic (ALG), lower-order cognitive skills (LOCS), and higher-order cognitive skills (HOCS) chemistry exam questions were studied. The driving force for the study was an interest in moving science and chemistry instruction from an algorithmic and factual recall orientation dominated by LOCS, to a decision-making, problem-solving and critical system thinking approach, dominated by HOCS. College students' responses to the specially designed ALG, LOCS and HOCS chemistry exam questions were scored and analysed for differences and correlation between the performance means within and across universities by the questions' category. This was followed by a combined student interview - 'speaking aloud' problem solving session for assessing the thinking processes involved in solving these types of questions and the students' attitudes towards them. The main findings were: (1) students in both universities performed consistently in each of the three categories in the order of ALG > LOCS > HOCS; their 'ideological' preference, was HOCS > algorithmic/LOCS, - referred to as 'computational questions', but their pragmatic preference was the reverse; (2) success on algorithmic/LOCS does not imply success on HOCS questions; algorithmic questions constitute a category on its own as far as students success in solving them is concerned. Our study and its results support the effort being made, worldwide, to integrate HOCS-fostering teaching and assessment strategies and, to develop HOCS-oriented science-technology-environment-society (STES)-type curricula within science and chemistry education.

  14. User-centred and context-aware identity management in mobile ad-hoc networks

    CERN Document Server

    Arabo, Abdullahi

    2013-01-01

    The emergent notion of ubiquitous computing makes it possible for mobile devices to communicate and provide services via networks connected in an ad-hoc manner. These have resulted in the proliferation of wireless technologies such as Mobile Ad-hoc Networks (MANets), which offer attractive solutions for services that need flexible setup as well as dynamic and low cost wireless connectivity. However, the growing trend outlined above also raises serious concerns over Identity Management (IM) du...

  15. The Ex Hoc Infrastructure - Enhancing Traffic Safety through LIfe WArning Systems

    DEFF Research Database (Denmark)

    Hansen, Klaus Marius; Kristensen, Lars Michael; Eskildsen, Toke

    2004-01-01

    New pervasive computing technologies for sensing and communication open up novel possibilities for enhancing traffic safety. We are currently designing and implementing the Ex Hoc infrastructure framework for communication among mobile and stationary units including vehicles. The infrastructure...... will connect sensing devices on vehicles with sensing devices on other vehicles and with stationary communication units placed alongside roads. The current application of Ex Hoc is to enable the collection and dissemination of information on road condition through LIfe Warning Systems (LIWAS) units....

  16. Cliff stability assessment using electrical resistivity tomography at the historic WWII D-Day invasion site, Pointe du Hoc, France

    Science.gov (United States)

    Everett, M. E.; Udphuay, S.; Warden, R.

    2007-05-01

    The 1944 D-Day invasion site at Pointe du Hoc, Normandy, France is an important WWII battlefield and cultural resource but is at risk from chalk cliff collapse. The American Battle Monuments Commission tasked us to evaluate the geohazard to the observation post and other cliff-side buildings of historical significance. Geophysical multi-electrode resistivity profiling is used to study cliff stability and the condition of the observation- post foundations. Preliminary 2-D geological interpretations are provided of individual profiles. The copious steel, concrete and void spaces at the site renders hydrogeological interpretation challenging but tractable. The cliff face appears to be relatively intact and well-drained. Several routes taken by groundwater into fractures within the chalk were identified mainly on the western side of the site. The eastern side is drier and somewhat sheltered from the Atlantic storms but may contain large void spaces that could efficiently transmit groundwater flow during heavy precipitation events, thereby imperiling the major antiaircraft gun emplacement occupied by Col. Rudder in the early days of the Allied invasion. The forward German observation post perched close to the sea stack, which now hosts the U.S. Ranger memorial, may be moving with the soil and not securely anchored to bedrock. A complex failure mechanism is identified as a combination of groundwater dissolution of the fractured chalk and sea wave attack at the cliff base.

  17. Handbook on theoretical and algorithmic aspects of sensor, ad hoc wireless, and peer-to-peer networks

    CERN Document Server

    Wu, Jie

    2005-01-01

    PrefaceAD HOC WIRELESS NETWORKSA Modular Cross Layer Architecture for Ad Hoc Networks, M. Conti, J. Crowcroft, G. Maselli, and G. TuriRouting Scalability in MANETs, J. Eriksson, S. Krishnamurthy and M. FaloutsosUniformly Distributed Algorithm for Virtual Backbone Routing in Ad Hoc Wireless Networks, D.S. KimMaximum Necessary Hop Count for Packet Routing in MANET, X. Chen and J. ShenEfficient Strategyproof Multicast in Selfish Wireless Networks, X.-Yang LiGeocasting in Ad Hoc and Sensor Networks, I. StojmenovicTopology Control for Ad hoc Networks: Present Solutions and Open Issues, C.-C. Shen a

  18. Phospholipase C mediates (±)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI)-, but not lysergic acid diethylamide (LSD)-elicited head bobs in rabbit medial prefrontal cortex.

    Science.gov (United States)

    Schindler, Emmanuelle A D; Harvey, John A; Aloyo, Vincent J

    2013-01-23

    The phenethylamine and indoleamine classes of hallucinogens demonstrate distinct pharmacological properties, although they share a serotonin(2A) (5-HT(2A)) receptor mechanism of action (MOA). The 5-HT(2A) receptor signals through phosphatidylinositol (PI) hydrolysis, which is initiated upon activation of phospholipase C (PLC). The role of PI hydrolysis in the effects of hallucinogens remains unclear. In order to better understand the role of PI hydrolysis in the MOA of hallucinogens, the PLC inhibitor, 1-[6-((17β-3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl]-1H-pyrrole-2,5-dione (U73122), was used to study the effects of two hallucinogens, the phenethylamine, (±)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI), and the indoleamine, lysergic acid diethylamide (LSD). PI hydrolysis was quantified through release of [3H]inositol-4-phosphate from living rabbit frontocortical tissue prisms. Head bobs were counted after hallucinogens were infused into the medial prefrontal cortex (mPFC) of rabbits. Both DOI and LSD stimulated PI hydrolysis in frontocortical tissue through activation of PLC. DOI-stimulated PI hydrolysis was blocked by 5-HT(2A/2C) receptor antagonist, ketanserin, whereas the LSD signal was blocked by 5-HT(2B/2C) receptor antagonist, SB206553. When infused into the mPFC, both DOI- and LSD-elicited head bobs. Pretreatment with U73122 blocked DOI-, but not LSD-elicited head bobs. The two hallucinogens investigated were distinct in their activation of the PI hydrolysis signaling pathway. The serotonergic receptors involved with DOI and LSD signals in frontocortical tissue were different. Furthermore, PLC activation in mPFC was necessary for DOI-elicited head bobs, whereas LSD-elicited head bobs were independent of this pathway. These novel findings urge closer investigation into the intracellular mechanism of action of these unique compounds. Published by Elsevier B.V.

  19. An implementation of traffic light system using multi-hop Ad hoc networks

    KAUST Repository

    Ansari, Imran Shafique

    2009-08-01

    In ad hoc networks nodes cooperate with each other to form a temporary network without the aid of any centralized administration. No wired base station or infrastructure is supported, and each host communicates via radio packets. Each host must act as a router, since routes are mostly multi-hop, due to the limited power transmission set by government agencies, (e.g. the Federal Communication Commission (FCC), which is 1 Watt in Industrial Scientific and Medical (ISM) band. The natures of wireless mobile ad hoc networks depend on batteries or other fatiguing means for their energy. A limited energy capacity may be the most significant performance constraint. Therefore, radio resource and power management is an important issue of any wireless network. In this paper, a design for traffic light system employing ad hoc networks is proposed. The traffic light system runs automatically based on signals sent through a multi-hop ad hoc network of \\'n\\' number of nodes utilizing the Token Ring protocol, which is efficient for this application from the energy prospective. The experiment consists of a graphical user interface that simulates the traffic lights and laptops (which have wireless network adapters) are used to run the graphical user interface and are responsible for setting up the ad hoc network between them. The traffic light system has been implemented utilizing A Mesh Driver (which allows for more than one wireless device to be connected simultaneously) and Java-based client-server programs. © 2009 IEEE.

  20. Packets Distributing Evolutionary Algorithm Based on PSO for Ad Hoc Network

    Science.gov (United States)

    Xu, Xiao-Feng

    2018-03-01

    Wireless communication network has such features as limited bandwidth, changeful channel and dynamic topology, etc. Ad hoc network has lots of difficulties in accessing control, bandwidth distribution, resource assign and congestion control. Therefore, a wireless packets distributing Evolutionary algorithm based on PSO (DPSO)for Ad Hoc Network is proposed. Firstly, parameters impact on performance of network are analyzed and researched to obtain network performance effective function. Secondly, the improved PSO Evolutionary Algorithm is used to solve the optimization problem from local to global in the process of network packets distributing. The simulation results show that the algorithm can ensure fairness and timeliness of network transmission, as well as improve ad hoc network resource integrated utilization efficiency.

  1. Service for fault tolerance in the Ad Hoc Networks based on Multi Agent Systems

    Directory of Open Access Journals (Sweden)

    Ghalem Belalem

    2011-02-01

    Full Text Available The Ad hoc networks are distributed networks, self-organized and does not require infrastructure. In such network, mobile infrastructures are subject of disconnections. This situation may concern a voluntary or involuntary disconnection of nodes caused by the high mobility in the Ad hoc network. In these problems we are trying through this work to contribute to solving these problems in order to ensure continuous service by proposing our service for faults tolerance based on Multi Agent Systems (MAS, which predict a problem and decision making in relation to critical nodes. Our work contributes to study the prediction of voluntary and involuntary disconnections in the Ad hoc network; therefore we propose our service for faults tolerance that allows for effective distribution of information in the Network by selecting some objects of the network to be duplicates of information.

  2. Energy-Aware Routing Protocol for Ad Hoc Wireless Sensor Networks

    Directory of Open Access Journals (Sweden)

    Mann Raminder P

    2005-01-01

    Full Text Available Wireless ad hoc sensor networks differ from wireless ad hoc networks from the following perspectives: low energy, lightweight routing protocols, and adaptive communication patterns. This paper proposes an energy-aware routing protocol (EARP suitable for ad hoc wireless sensor networks and presents an analysis for its energy consumption in various phases of route discovery and maintenance. Based on the energy consumption associated with route request processing, EARP advocates the minimization of route requests by allocating dynamic route expiry times. This paper introduces a unique mechanism for estimation of route expiry time based on the probability of route validity, which is a function of time, number of hops, and mobility parameters. In contrast to AODV, EARP reduces the repeated flooding of route requests by maintaining valid routes for longer durations.

  3. Analysis of DDoS Attack Effect and Protection Scheme in Wireless Mobile Ad-hoc Network

    OpenAIRE

    Ramratan Ahirwal; Leeladhar Mahour

    2012-01-01

    In Wireless mobile Ad Hoc Networks (MANET) every node functions as transmitter, router and data sink is network without infrastructure. Detecting malicious nodes in an open ad-hoc network in whichparticipating nodes have no previous security associations presents a number of challenges not faced by traditional wired networks. Traffic monitoring in wired networks is usually performed at switches,routers and gateways, but an ad-hoc network does not have these types of network elements where the...

  4. Ad Hoc Wireless Networking and Shared Computation for Autonomous Multirobot Systems

    OpenAIRE

    Bevilacqua, Riccardo; Hall, Jason S.; Horning, James; Romano, Marcello

    2009-01-01

    The article of record as published may be located at http://dx.doi.org/10.2514/1.40734 A wireless ad hoc network is introduced that enables inter-robot communication and shared computation among multiple robots with PC/104-based single board computers running the real-time application interface patched Linux operating system. Through the use of IEEE 802.11 ad hoc technology and User Datagram Protocol, each robot is able to exchange data without the need of a centralized router ...

  5. Mitigate DoS and DDoS attacks in Mobile Ad Hoc Networks

    DEFF Research Database (Denmark)

    Michalas, Antonis; Komninos, Nikos; Prasad, Neeli R.

    2011-01-01

    This paper proposes a technique to defeat Denial of Service (DoS) and Distributed Denial of Service (DDoS) attacks in Ad Hoc Networks. The technique is divided into two main parts and with game theory and cryptographic puzzles. Introduced first is a new client puzzle to prevent DoS attacks...... in DoS and DDoS attacks. Experimental results show the effectiveness of the approach for devices with limited resources and for environments like ad hoc networks where nodes must exchange information quickly....

  6. Multiplayer Game for DDoS Attacks Resilience in Ad Hoc Networks

    DEFF Research Database (Denmark)

    Mikalas, Antonis; Komninos, Nikos; Prasad, Neeli R.

    2011-01-01

    This paper proposes a multiplayer game to prevent Distributed Denial of Service attack (DDoS) in ad hoc networks. The multiplayer game is based on game theory and cryptographic puzzles. We divide requests from nodes into separate groups which decreases the ability of malicious nodes to cooperate...... with one another in order to effectively make a DDoS attack. Finally, through our experiments we have shown that the total overhead of the multiplayer game as well as the the total time that each node needs to be served is affordable for devices that have limited resources and for environments like ad hoc...

  7. Deny-by-Default Distributed Security Policy Enforcement in Mobile Ad Hoc Networks

    Science.gov (United States)

    Alicherry, Mansoor; Keromytis, Angelos D.; Stavrou, Angelos

    Mobile Ad-hoc Networks (MANETs) are increasingly employed in tactical military and civil rapid-deployment networks, including emergency rescue operations and ad hoc disaster-relief networks. However, this flexibility of MANETs comes at a price, when compared to wired and base station-based wireless networks: MANETs are susceptible to both insider and outsider attacks. This is mainly because of the lack of a well-defined defense perimeter preventing the effective use of wired defenses including firewalls and intrusion detection systems.

  8. Multicasting in Wireless Communications (Ad-Hoc Networks): Comparison against a Tree-Based Approach

    Science.gov (United States)

    Rizos, G. E.; Vasiliadis, D. C.

    2007-12-01

    We examine on-demand multicasting in ad hoc networks. The Core Assisted Mesh Protocol (CAMP) is a well-known protocol for multicast routing in ad-hoc networks, generalizing the notion of core-based trees employed for internet multicasting into multicast meshes that have much richer connectivity than trees. On the other hand, wireless tree-based multicast routing protocols use much simpler structures for determining route paths, using only parent-child relationships. In this work, we compare the performance of the CAMP protocol against the performance of wireless tree-based multicast routing protocols, in terms of two important factors, namely packet delay and ratio of dropped packets.

  9. Centralized cooperative spectrum sensing for ad-hoc disaster relief network clusters

    DEFF Research Database (Denmark)

    Pratas, Nuno; Marchetti, Nicola; Prasad, Neeli R.

    2010-01-01

    Disaster relief networks have to be highly adaptable and resilient. Cognitive radio enhanced ad-hoc architecture have been put forward as a candidate to enable such networks. Spectrum sensing is the cornerstone of the cognitive radio paradigm, and it has been the target of intensive research....... The main common conclusion was that the achievable spectrum sensing accuracy can be greatly enhanced through the use of cooperative sensing schemes. When considering applying Cognitive Radio to ad-hoc disaster relief networks, spectrum sensing cooperative schemes are paramount. A centralized cluster...

  10. Substance use -- LSD

    Science.gov (United States)

    ... from reality. Joy (euphoria, or "rush") and less inhibition, similar to being drunk from alcohol use. As ... use, the next step is getting help and support. Treatment programs use behavior change techniques through counseling ( ...

  11. A selective and sensitive method for quantitation of lysergic acid diethylamide (LSD) in whole blood by gas chromatography-ion trap tandem mass spectrometry.

    Science.gov (United States)

    Libong, Danielle; Bouchonnet, Stéphane; Ricordel, Ivan

    2003-01-01

    A gas chromatography-ion trap tandem mass spectrometry (GC-ion trap MS-MS) method for detection and quantitation of LSD in whole blood is presented. The sample preparation process, including a solid-phase extraction step with Bond Elut cartridges, was performed with 2 mL of whole blood. Eight microliters of the purified extract was injected with a cold on-column injection method. Positive chemical ionization was performed using acetonitrile as reagent gas; LSD was detected in the MS-MS mode. The chromatograms obtained from blood extracts showed the great selectivity of the method. GC-MS quantitation was performed using lysergic acid methylpropylamide as the internal standard. The response of the MS was linear for concentrations ranging from 0.02 ng/mL (detection threshold) to 10.0 ng/mL. Several parameters such as the choice of the capillary column, the choice of the internal standard and that of the ionization mode (positive CI vs. EI) were rationalized. Decomposition pathways under both ionization modes were studied. Within-day and between-day stability were evaluated.

  12. Antidepressive, anxiolytic, and antiaddictive effects of ayahuasca, psilocybin and lysergic acid diethylamide (LSD): a systematic review of clinical trials published in the last 25 years.

    Science.gov (United States)

    Dos Santos, Rafael G; Osório, Flávia L; Crippa, José Alexandre S; Riba, Jordi; Zuardi, Antônio W; Hallak, Jaime E C

    2016-06-01

    To date, pharmacological treatments for mood and anxiety disorders and for drug dependence show limited efficacy, leaving a large number of patients suffering severe and persistent symptoms. Preliminary studies in animals and humans suggest that ayahuasca, psilocybin and lysergic acid diethylamide (LSD) may have antidepressive, anxiolytic, and antiaddictive properties. Thus, we conducted a systematic review of clinical trials published from 1990 until 2015, assessing these therapeutic properties. Electronic searches were performed using the PubMed, LILACS, and SciELO databases. Only clinical trials published in peer-reviewed journals were included. Of these, 151 studies were identified, of which six met the established criteria. Reviewed studies suggest beneficial effects for treatment-resistant depression, anxiety and depression associated with life-threatening diseases, and tobacco and alcohol dependence. All drugs were well tolerated. In conclusion, ayahuasca, psilocybin and LSD may be useful pharmacological tools for the treatment of drug dependence, and anxiety and mood disorders, especially in treatment-resistant patients. These drugs may also be useful pharmacological tools to understand psychiatric disorders and to develop new therapeutic agents. However, all studies reviewed had small sample sizes, and half of them were open-label, proof-of-concept studies. Randomized, double-blind, placebo-controlled studies with more patients are needed to replicate these preliminary findings.

  13. Antidepressive, anxiolytic, and antiaddictive effects of ayahuasca, psilocybin and lysergic acid diethylamide (LSD): a systematic review of clinical trials published in the last 25 years

    Science.gov (United States)

    dos Santos, Rafael G.; Osório, Flávia L.; Crippa, José Alexandre S.; Riba, Jordi; Zuardi, Antônio W.; Hallak, Jaime E. C.

    2016-01-01

    To date, pharmacological treatments for mood and anxiety disorders and for drug dependence show limited efficacy, leaving a large number of patients suffering severe and persistent symptoms. Preliminary studies in animals and humans suggest that ayahuasca, psilocybin and lysergic acid diethylamide (LSD) may have antidepressive, anxiolytic, and antiaddictive properties. Thus, we conducted a systematic review of clinical trials published from 1990 until 2015, assessing these therapeutic properties. Electronic searches were performed using the PubMed, LILACS, and SciELO databases. Only clinical trials published in peer-reviewed journals were included. Of these, 151 studies were identified, of which six met the established criteria. Reviewed studies suggest beneficial effects for treatment-resistant depression, anxiety and depression associated with life-threatening diseases, and tobacco and alcohol dependence. All drugs were well tolerated. In conclusion, ayahuasca, psilocybin and LSD may be useful pharmacological tools for the treatment of drug dependence, and anxiety and mood disorders, especially in treatment-resistant patients. These drugs may also be useful pharmacological tools to understand psychiatric disorders and to develop new therapeutic agents. However, all studies reviewed had small sample sizes, and half of them were open-label, proof-of-concept studies. Randomized, double-blind, placebo-controlled studies with more patients are needed to replicate these preliminary findings. PMID:27354908

  14. New grid based test bed environment for carrying out ad-hoc networking experiments

    CSIR Research Space (South Africa)

    Johnson, D

    2006-09-01

    Full Text Available and the third is to do analysis on a real test bed network which has implemented the ad-hoc networking protocol. This paper concerns the third option. Most researchers who have done work on test bed environments have used either indoor Wifi inter-office links...

  15. Peer-to-peer over mobile ad hoc networks (Chapter 11)

    NARCIS (Netherlands)

    Qadri, N.N.; Liotta, A.; Pierre, S.

    2010-01-01

    In this chapter we review various approaches for the convergence of Peer-to-Peer (P2P) and Mobile Ad hoc Networks (MANETs), identifying strengths and weaknesses, and putting things in perspective. P2P and MANETs are among the most active research topics in pervasive computing. The convergence of P2P

  16. Specification and Validation of an Edge Router Discovery Protocol for Mobile Ad Hoc Networks

    DEFF Research Database (Denmark)

    Kristensen, Lars Michael; Jensen, Kurt

    2004-01-01

    We present an industrial project at Ericsson Telebit A/S where Coloured Petri Nets (CP-nets or CPNs) have been used for the design and specification of an edge router discovery protocol for mobile ad-hoc networks. The Edge Router Discovery Protocol (ERDP) supports an edge router in a stationary...

  17. An Economic Framework for Resource Allocation in Ad-hoc Grids

    NARCIS (Netherlands)

    Pourebrahimi, B.

    2009-01-01

    In this dissertation, we present an economic framework to study and develop different market-based mechanisms for resource allocation in an ad-hoc Grid. Such an economic framework helps to understand the impact of certain choices and explores what are the suitable mechanisms from Grid user/owner

  18. NDN-CRAHNs: Named Data Networking for Cognitive Radio Ad Hoc Networks

    Directory of Open Access Journals (Sweden)

    Rana Asif Rehman

    2015-01-01

    Full Text Available Named data networking (NDN is a newly proposed paradigm for future Internet, in which communication among nodes is based on data names, decoupling from their locations. In dynamic and self-organized cognitive radio ad hoc networks (CRAHNs, it is difficult to maintain end-to-end connectivity between ad hoc nodes especially in the presence of licensed users and intermittent wireless channels. Moreover, IP-based CRAHNs have several issues like scalability, inefficient-mapping, poor resource utilization, and location dependence. By leveraging the advantages of NDN, in this paper, we propose a new cross layer fine-grained architecture called named data networking for cognitive radio ad hoc networks (NDN-CRAHNs. The proposed architecture provides distinct features such as in-networking caching, security, scalability, and multipath routing. The performances of the proposed scheme are evaluated comparing to IP-based scheme in terms of average end-to-end delay and packet delivery ratio. Simulation results show that the proposed scheme is effective in terms of average contents download time and packet delivery ratios comparing to conventional cognitive radio ad hoc networks.

  19. Conflict Management in "Ad Hoc" Problem-Solving Groups: A Preliminary Investigation.

    Science.gov (United States)

    Wallace, Les; Baxter, Leslie

    Full study of small group communication must include consideration of task and socio-emotional dimensions, especially in relation to group problem solving. Thirty small groups were tested for their reactions in various "ad hoc" conflict resolution situations. Instructions to the groups were (1) no problem-solving instructions (control),…

  20. Performance analysis of differentiated resource-sharing in a wireless ad-hoc network

    NARCIS (Netherlands)

    Roijers, F.; van den Berg, H.; Mandjes, M.

    2010-01-01

    In this paper we model and analyze a relay node in a wireless ad-hoc network; the capacity available at this node is used to both transmit traffic from the source nodes (towards the relay node), and to serve traffic at the relay node (so that it can be forwarded to successor nodes). Clearly, a

  1. On the Geometrical Characteristics of Three-Dimensional Wireless Ad Hoc Networks and Their Applications

    Directory of Open Access Journals (Sweden)

    2006-01-01

    Full Text Available In a wireless ad hoc network, messages are transmitted, received, and forwarded in a finite geometrical region and the transmission of messages is highly dependent on the locations of the nodes. Therefore the study of geometrical relationship between nodes in wireless ad hoc networks is of fundamental importance in the network architecture design and performance evaluation. However, most previous works concentrated on the networks deployed in the two-dimensional region or in the infinite three-dimensional space, while in many cases wireless ad hoc networks are deployed in the finite three-dimensional space. In this paper, we analyze the geometrical characteristics of the three-dimensional wireless ad hoc network in a finite space in the framework of random graph and deduce an expression to calculate the distance probability distribution between network nodes that are independently and uniformly distributed in a finite cuboid space. Based on the theoretical result, we present some meaningful results on the finite three-dimensional network performance, including the node degree and the max-flow capacity. Furthermore, we investigate some approximation properties of the distance probability distribution function derived in the paper.

  2. Built-In Device Orientation Sensors for Ad-Hoc Pairing and Spatial Awareness

    DEFF Research Database (Denmark)

    Grønbæk, Jens Emil; O'Hara, Kenton

    Mobile devices are equipped with multiple sensors. The ubiquity of these sensors is key in their ability to support in-the-wild application and use. Building on the ubiquity we look at how we can use this existing sensing infrastructure combined with user mediation to support ad-hoc sharing with ...

  3. Ad Hoc Transient Communities to Enhance Social Interaction and Spread Tutor Responsibilities

    OpenAIRE

    Sloep, Peter; Kester, Liesbeth; Brouns, Francis; Van Rosmalen, Peter; De Vries, Fred; De Croock, Marcel; Koper, Rob

    2007-01-01

    Sloep, P.B., Kester, L. Brouns, F., Van Rosmalen, P., De Vries, F., De Croock, M., Koper, R. (2007) Ad Hoc Transient Communities to Enhance Social Interaction and Spread Tutor Responsibilities. In V. Uskov (Ed.) The Sixth IASTED International Conference on Web-based Education WBE 2007, March 14-16, Chamonix, France (pp. 549-554). Calgary, Canada: Acta Press.

  4. Ad Hoc Transient Communities to Enhance Social Interaction and Spread Tutor Responsibilities

    NARCIS (Netherlands)

    Sloep, Peter; Kester, Liesbeth; Brouns, Francis; Van Rosmalen, Peter; De Vries, Fred; De Croock, Marcel; Koper, Rob

    2007-01-01

    Sloep, P.B., Kester, L. Brouns, F., Van Rosmalen, P., De Vries, F., De Croock, M., Koper, R. (2007) Ad Hoc Transient Communities to Enhance Social Interaction and Spread Tutor Responsibilities. In V. Uskov (Ed.) The Sixth IASTED International Conference on Web-based Education WBE 2007, March 14-16,

  5. Ad Hoc Transient Communities to Enhance Social Interaction and Spread Tutor Responsibilities

    NARCIS (Netherlands)

    Sloep, Peter; Kester, Liesbeth; Brouns, Francis; Van Rosmalen, Peter; De Vries, Fred; De Croock, Marcel; Koper, Rob

    2007-01-01

    Sloep, P.B., Kester, L., Brouns, F., Van Rosmalen, P., De Vries, F., De Croock, M., Koper, R. (2007). Ad Hoc Transient Communities to Enhance Social Interaction and Spread Tutor Responsibilities. Presentation given at the Sixth IASTED International Conference on Web-based Education, 14-16 March,

  6. Neuroprotection as initial therapy in acute stroke - Third report of an Ad Hoc Consensus Group Meeting

    NARCIS (Netherlands)

    Bogousslavsky, J; De Keyser, J; Diener, HC; Fieschi, C; Hacke, W; Kaste, M; Orgogozo, JM; Pulsinelli, W; Wahlgren, NG

    1998-01-01

    Although a considerable body of scientific data is now available on neuroprotection in acute ischaemic stroke, this field is not yet established in clinical practice. At its third meeting, the European Ad Hoc Consensus Group considered the potential for neuroprotection in acute stroke and the

  7. Model-based prototyping of an interoperability protocol for mobile ad-hoc networks

    NARCIS (Netherlands)

    Kristensen, L.M.; Westergaard, M.; Norgaard, P.C.; Romijn, J.; Smith, G.; Pol, van de J.

    2005-01-01

    We present an industrial project conducted at Ericsson Danmark A/S, Telebit where formal methods in the form of Coloured Petri Nets (CP-nets or CPNs) have been used for the specification of an interoperability protocol for routing packets between fixed core networks and mobile ad-hoc networks. The

  8. BLESSED with Opportunistic Beacons: A Lightweight Data Dissemination Model for Smart Mobile Ad-Hoc Networks

    NARCIS (Netherlands)

    Türkes, Okan; Scholten, Johan; Havinga, Paul J.M.

    2015-01-01

    This paper introduces BLESSED, a universal opportunistic ad hoc networking model intended for smart mobile devices. It enables fast and lightweight data dissemination in wireless community networks through the complementary utilization of the IEEE 802.11 and Bluetooth Low Energy standards. As a

  9. Integrated Social and Quality of Service Trust Management of Mobile Groups in Ad Hoc Networks

    Science.gov (United States)

    2013-01-01

    high resiliency to malicious attacks and misbehaving nodes. Keywords—trust management; mobile ad hoc networks; QoS trust; social trust; trust...paper we address an importance issue of trust management protocol design for MANETs: trust bias minimization despite misbehaving nodes performing

  10. Ad hoc public disclosure obligations of public companies on the capital market

    Directory of Open Access Journals (Sweden)

    Marjanski Vladimir

    2012-01-01

    Full Text Available The author gives a comprehensive analysis of the obligations of public companies regarding the provision of periodical (ad hoc information to the public on the capital market. Ad hoc disclosure is to achieve a number of aims. It is one of the devices to secure the market's functional abilities. By means of regularly fulfilling this obligation, the market is provided with all the relevant information necessary to form adequate prices of market materials - i.e. securities and other financial instruments (the function of market protection. Investors are thus being able to aptly respond to modified circumstances and deliver investment decisions whether to buy or sell market materials the price of which are being changed (the function of investor protection. Due to the fact that the duty of ad hoc disclosure encompasses the obligation to reveal insider information directly affecting the emitter, ad hoc disclosure serves as a preventive measure, i.e. as a protection against illicit trade with insider information (the function of prevention against the abuse of insider information.

  11. Student Self-Assessment in HOCS Science Examinations: Is There a Problem?

    Science.gov (United States)

    Zoller, Uri; Ben-Chaim, David

    1998-06-01

    A specially-designed self-assessment questionnaire (SAQHOCS), containing higher-order cognitive skills (HOCS)-type questions, was administered to 71 biology majors, enrolled in a four-year college program. The gap between students' self-assessment marking, and that of their HOCS-biased teachers (the authors), is accounted for by the prevailing LOCS-orientation and the "testing culture"—a total separation between testing and learning—in contemporary science teaching. The majority of the students in the study evaluated themselves as capable of self-assessment, and felt reasonably confident in doing so. They were quite reserved as far as the applicability of the self-assessment method to nonalgorithmic ("correct/incorrect") questions is concerned. The results of this study suggest that the potential for student self-assessment within college science teaching and learning exists. However, still a great purposed effort in HOCS-oriented teaching and learning is required in order for the student self-assessment practice to become a routine integral component of HOCS science examinations.

  12. PUCA: A Pseudonym Scheme with User-Controlled Anonymity for Vehicular Ad-Hoc Networks (VANET)

    NARCIS (Netherlands)

    Förster, David; Kargl, Frank; Löhr, Hans

    2014-01-01

    Envisioned vehicular ad-hoc networks (VANET) standards use pseudonym certificates to provide secure and privacy-friendly message authentication. Revocation of long-term credentials is required to remove participants from the system, e.g. in case of vehicle theft. However, the current approach to

  13. A tandem queueing model for delay analysis in disconnected ad hoc networks

    NARCIS (Netherlands)

    Al Hanbali, Ahmad; de Haan, Roland; Boucherie, Richardus J.; van Ommeren, Jan C.W.

    2007-01-01

    Ad hoc network routing protocols may fail to operate in the absence of an end-to-end connection from source to destination. This deficiency can be resolved by so-called opportunistic networking which exploits the mobility of the nodes by letting them operate as relays according to the

  14. Improving the Usability of OCL as an Ad-hoc Model Querying Language

    DEFF Research Database (Denmark)

    Störrle, Harald

    2013-01-01

    from our research and make it accessible to the OCL community, we propose the OCL Query API (OQAPI), a library of query-predicates to improve the user-friendliness of OCL for ad-hoc querying. The usability of OQAPI is studied using controlled experiments. We nd considerable evidence to support our...

  15. RAILWAY INFRASTRUCTURE CAPACITY MANAGEMENT FOR AD-HOC TRAINS ON THE SŽDC NETWORK

    Directory of Open Access Journals (Sweden)

    Petr Nachtigall

    2016-09-01

    Full Text Available The paper describes basic principles of ad-hoc routes assignment. Each carrier has its own interface called information system KADR with SŽDC for capacity requests management. The paper describes all steps which must be done before train departure.

  16. Impact of mobility on the performance of relaying in ad hoc networks (Extended version)

    NARCIS (Netherlands)

    Al Hanbali, A.; Kherani, A.A.; Groenevelt, R.; Nain, P.; Altman, E.

    2007-01-01

    We consider a mobile ad hoc network consisting of three types of nodes: source, destination, and relay nodes. All the nodes are moving over a bounded region with possibly different mobility patterns. We introduce and study the notion of relay throughput, i.e. the maximum rate at which a node can

  17. Impact of Mobility on the Performance of Relaying in Ad Hoc Networks

    NARCIS (Netherlands)

    Al Hanbali, Ahmad; Kherani, A.A.; Groenevelt, R.; Nain, P.; Altman, E

    2006-01-01

    We consider a mobile ad hoc network consisting of three types of nodes: source, destination, and relay nodes. All the nodes are moving over a bounded region with possibly different mobility patterns. We introduce and study the notion of relay throughput, i.e. the maximum rate at which a node can

  18. Impact of mobility on the performance7 of relaying in ad hoc networks – Extended version

    NARCIS (Netherlands)

    Al Hanbali, Ahmad; Kherani, A.A.; Groenevelt, R.; Nain, P.; Altman, E

    2007-01-01

    We consider a mobile ad hoc network consisting of three types of nodes: source, destination, and relay nodes. All the nodes are moving over a bounded region with possibly different mobility patterns. We introduce and study the notion of relay throughput, i.e. the maximum rate at which a node can

  19. Adjusting Sensing Range to Maximize Throughput on Ad-Hoc Multi-Hop Wireless Networks

    National Research Council Canada - National Science Library

    Roberts, Christopher

    2003-01-01

    .... Such a network is referred to as a multi-hop ad-hoc network, or simply a multi-hop network. Most multi-hop network protocols use some form of carrier sensing to determine if the wireless channel is in use...

  20. Adaptive Demand-Driven Multicast Routing in Multi-Hop Wireless Ad Hoc Networks

    National Research Council Canada - National Science Library

    Jetcheva, Jorjeta G

    2004-01-01

    ...) nodes that wish to communicate. Each node in the ad hoc network acts as a router and forwards packets on behalf of other nodes, allowing nodes that are not within wireless range of each other to communicate over multi-hop paths...