Adding tobacco to cannabis: its frequency and likely implications.

INTRODUCTION: Young cannabis users are at increased risk of later cigarette initiation and progression to nicotine addiction. The present study addresses the frequency at which mulling (adding tobacco to cannabis smoked as joints) is performed and in which way this practice varies according to cigarette smoking status. METHODS: Data were issued from the Swiss 2007 European School Survey Project on Alcohol and other Drugs (ESPAD). A total of 881 past month cannabis users (mean age 15 years, boys 60.1%) were inquired on mulling using an anonymous self-administered questionnaire. Participants were further grouped according to their cigarette smoking status (daily, occasional, former, and never-smokers). RESULTS: Four of every 5 cannabis users depicted mulling as frequently performed. The highest occurrence was found among daily cigarette smokers (DSC; 90.3%), while former cigarette smokers reported the lowest (58.9%). The multinomial logistic regression showed DSC more likely reporting mulling as frequent compared with never-smokers (risk ratio = 3.56 [95% CI 1.55-8.21]). Conclusions: Mulling appears to be a very common process among young cannabis users, especially among concomitant cigarette smokers. Nevertheless, the majority of cigarette abstainers also reported frequently adding tobacco to the cannabis they smoke. Because it may represent a significant exposition to nicotine, mulling should be taken into account when assessing substance use among adolescents and in supporting their quitting attempts.

A new poly(ortho ester)-based drug delivery system as an adjunct treatment in filtering surgery.

PURPOSE: Pharmacologic modulation of wound healing after glaucoma filtering surgery remains a major clinical challenge in ophthalmology. Poly(ortho ester) (POE) is a bioerodible and biocompatible viscous polymer potentially useful as a sustained drug delivery system that allows the frequency of intraocular injections to be reduced. The purpose of this study was to determine the efficacy of POE containing a precise amount of 5-fluorouracil (5-FU) in an experimental model of filtering surgery in the rabbit. METHODS: Trabeculectomy was performed in pigmented rabbit eyes. An ointmentlike formulation of POE containing 1% wt/wt 5-FU was injected subconjunctivally at the site of surgery, during the procedure. Intraocular pressure (IOP), bleb persistence, and ocular inflammatory reaction were monitored until postoperative day 30. Quantitative analysis of 5-FU was performed in the anterior chamber. Histologic analysis was used to assess the appearance of the filtering fistula and the polymer's biocompatibility. RESULTS: The decrease in IOP from baseline and the persistence of the filtering bleb were significantly more marked in the 5-FU-treated eyes during postoperative days 9 through 28. Corneal toxicity triggered by 5-FU was significantly lower in the group that received 5-FU in POE compared with a 5-FU tamponade. Histopathologic evaluation showed that POE was well tolerated, and no fibrosis occurred in eyes treated with POE containing 5-FU. CONCLUSIONS: In this rabbit model of trabeculectomy, the formulation based on POE and containing a precise amount of 5-FU reduced IOP and prolonged bleb persistence in a way similar to the conventional method of a 5-FU tamponade, while significantly reducing 5-FU toxicity.

Pre-stimulus beta oscillations within left posterior sylvian regions impact auditory temporal order judgment accuracy.

Both neural and behavioral responses to stimuli are influenced by the state of the brain immediately preceding their presentation, notably by pre-stimulus oscillatory activity. Using frequency analysis of high-density electroencephalogram coupled with source estimations, the present study investigated the role of pre-stimulus oscillatory activity in auditory spatial temporal order judgments (TOJ). Oscillations within the beta range (i.e. 18-23Hz) were significantly stronger before accurate than inaccurate TOJ trials. Distributed source estimations identified bilateral posterior sylvian regions as the principal contributors to pre-stimulus beta oscillations. Activity within the left posterior sylvian region was significantly stronger before accurate than inaccurate TOJ trials. We discuss our results in terms of a modulation of sensory gating mechanisms mediated by beta activity.

Decrease in luteinizing hormone pulse frequency during a five-hour peripheral Ghrelin infusion in the ovariectomized rhesus monkey

RESUME : La ghrelin est un peptide sécrété par l'estomac jouant un rôle important dans le maintien de l'homéostasie énergétique. Ses taux plasmatiques sont augmentés durant des périodes prolongées de déficit nutritionnel. Une carence énergétique étant souvent associée à une inhibition de l'axe hypothalamo-hypophyso-ovarien, nous avons postulé que l'augmentation des taux circulant de ghrelin pourrait diminuer l'activité du générateur hypothalamique de pulsations de GnRH. Le protocole expérimental impliquait des singes rhésus adultes ovariectomisés (n=6) qui dans un premier temps recevaient durant 3 heures une perfusion de solution saline physiologique afin de mesurer la sécrétion pulsatile de LH à l'état basai. L'expérience se poursuivait alors durant 5 heures par une perfusion intraveineuse de ghrelin humaine (un bolus de 100-150µg suivi par 100-150µg/h) ou le maintien de la perfusion de solution saline physiologique. Des échantillons de sang étaient prélevés toutes les 15 minutes. La perfusion de ghrelin a augmenté ses taux plasmatiques de 2.9 fois par rapport aux valeurs de base. L'administration de ghrelin a significativement diminué la fréquence des pulsations de LH (de 0.89±0.07/h à l'état basai à 0.57±0.10/h durant la perfusion de ghrelin; p<0.05, moyenne±SEM), alors que la fréquence des pulsations de LH est restée inchangée durant la perfusion de solution physiologique. L'amplitude des pulsations de LH n'a pas été modifiée. La ghrelin a également stimulé de manière significative la sécrétion de cortisol et d'hormone de croissance, mais n'a toutefois pas eu d'effet sur la sécrétion de leptin. En conclusion, la ghrelin peut inhiber l'activité du générateur de pulsations de GnRH et pourrait ainsi contribuer à l'inhibition de l'axe de la reproduction observée durant des périodes de carence nutritionnelle, comme notamment chez les patientes souffrant d'anorexie mentale. La ghrelin peut également activer l'axe hypothalamo-hypophyso-surrénalien. Le lien dans cette situation entre l'activation de l'axe surrénalien et l'inhibition de l'axe de la reproduction reste à démontrer. ABSTRACT: Ghrelin, a nutrition-related peptide secreted by the stomach, is elevated during prolonged food deprivation. Because undernutrition is often associated with a suppressed reproductive axis, we have postulated that increasing peripheral ghrelin levels will decrease the activity of the GnRH pulse generator. Adult ovariectomized rhesus monkeys (n = 6) were subjected to a 5-h iv human ghrelin (100- to 150µg bolus followed by 100-150 µg/h) or saline infusion, preceded by a 3-h saline infusion to establish baseline pulsatile LH release. Blood samples were collected at 15-min intervals throughout the experiment. Ghrelin infusion increased plasma ghrelin levels 2.9-fold of baseline. Ghrelin significantly decreased LH pulse frequency (from 0.89 ± 0.07/h in baseline to 0.57 ± 0.10/h during ghrelin infusion; P<0.05, mean ± SEM), whereas LH pulse frequency remained unchanged during saline treatment. LH pulse amplitude was not affected. Ghrelin also significantly stimulated both Cortisol and GH release, but had no effect on leptin. We conclude that ghrelin can inhibit GnRH pulse activity and may thereby mediate the suppression of the reproductive system observed in conditions of undernutrition, such as in anorexia nervosa. Ghrelin also activates the adrenal axis, but the relevance of this to the inhibition of GnRH pulse frequency remains to be established.

High capacity audio watermarking using the high frequency band of the wavelet domain

This paper proposes a novel high capacity robust audio watermarking algorithm by using the high frequency band of the wavelet decomposition at which the human auditory system (HAS) is not very sensitive to alteration. The main idea is to divide the high frequency band into frames and, for embedding, to change the wavelet samples depending on the average of relevant frame¿s samples. The experimental results show that the method has a very high capacity (about 11,000 bps), without significant perceptual distortion (ODG in [¿1 ,0] and SNR about 30dB), and provides robustness against common audio signal processing such as additive noise, filtering, echo and MPEG compression (MP3).

Feeding rate and frequency on juvenile pompano growth

The objective of this work was to evaluate the ideal feeding rate and frequency for juvenile pompano (Trachinotus marginatus). Two experiments were carried out in a completely randomized design, with three replicates each. In experiment I, 25 fish (4.8±0.6 g and 6.48±0.01 cm) were stocked in 15 tanks (50 L) during 21 days and fed 4, 8, 12, 16, and 20% body weight per day. In experiment II, 20 fish (4.1±0.1 g and 6.6±0.1 cm) were stocked in 15 tanks (40 L) during 28 days and fed 2, 6, 8, and 10 times a day. The tested feeding rates and frequencies did not influence survival. Final weight and length in experiment I were significantly lower in fish fed 4% body weight per day, whereas in experiment II only weight was significantly lower in fish fed 2 and 6 times a day. At the end of both experiments, apparent feed conversion showed significant difference, with the worst value observed for fish fed 20% body weight per day in experiment I and 2 times a day in experiment II. Juvenile pompano show better growth performance when fed 8% body weight per day and 8 times a day.

Intracellular thiol-mediated modulation of epithelial sodium channel activity.

The epithelial sodium channel ENaC is physiologically important in the kidney for the regulation of the extracellular fluid volume, and in the lungs for the maintenance of the appropriate airway surface liquid volume that lines the pulmonary epithelium. Besides the regulation of ENaC by hormones, intracellular factors such as Na(+) ions, pH, or Ca(2+) are responsible for fast adaptive responses of ENaC activity to changes in the intracellular milieu. In this study, we show that ENaC is rapidly and reversibly inhibited by internal sulfhydryl-reactive molecules such as methanethiosulfonate derivatives of different sizes, the metal cations Cd(2+) and Zn(2+), or copper(II) phenanthroline, a mild oxidizing agent that promotes the formation of disulfide bonds. At the single channel level, these agents applied intracellularly induce the appearance of long channel closures, suggesting an effect on ENaC gating. The intracellular reducing agent dithiothreitol fully reverses the rundown of ENaC activity in inside-out patches. Our observations suggest that changes in intracellular redox potential modulate ENaC activity and may regulate ENaC-mediated Na(+) transport in epithelia. Finally, substitution experiments reveal that multiple cysteine residues in the amino and carboxyl termini of ENaC subunits are responsible for this thiol-mediated inhibition of ENaC.

Robust power allocation algorithms for MIMO OFDM systems with imperfect CSI

This paper presents a Bayesian approach to the design of transmit prefiltering matrices in closed-loop schemes robust to channel estimation errors. The algorithms are derived for a multiple-input multiple-output (MIMO) orthogonal frequency division multiplexing (OFDM) system. Two different optimizationcriteria are analyzed: the minimization of the mean square error and the minimization of the bit error rate. In both cases, the transmitter design is based on the singular value decomposition (SVD) of the conditional mean of the channel response, given the channel estimate. The performance of the proposed algorithms is analyzed,and their relationship with existing algorithms is indicated. As withother previously proposed solutions, the minimum bit error rate algorithmconverges to the open-loop transmission scheme for very poor CSI estimates.

Spatial processing for frequency diversity schemes

A novel technique to obtain optimum blind spatialprocessing for frequency diversity spread spectrum (FDSS) communicationsystems is introduced. The sufficient statistics for alinear combiner, which prove ineffective due to the interferers frequencycharacteristics, are modified to yield improved detectionunder partial jamming in the spectral domain. Robustness to partialtime jamming is achieved by extending the notion of replicasover the frequency axis to a repetition over the time variable. Analysisand simulations are provided, showing the advantages of usingFDSS with spatial diversity to combat the interference when it isconfined to a narrow frequency band or short time interval relativeto the desired signal extent in either domain.

Asymptotic equivalence between the unconditional maximum likelihood and the square-law nonlinearity symbol timing estimation

This paper provides a systematic approach to theproblem of nondata aided symbol-timing estimation for linearmodulations. The study is performed under the unconditionalmaximum likelihood framework where the carrier-frequencyerror is included as a nuisance parameter in the mathematicalderivation. The second-order moments of the received signal arefound to be the sufficient statistics for the problem at hand and theyallow the provision of a robust performance in the presence of acarrier-frequency error uncertainty. We particularly focus on theexploitation of the cyclostationary property of linear modulations.This enables us to derive simple and closed-form symbol-timingestimators which are found to be based on the well-known squaretiming recovery method by Oerder and Meyr. Finally, we generalizethe OM method to the case of linear modulations withoffset formats. In this case, the square-law nonlinearity is foundto provide not only the symbol-timing but also the carrier-phaseerror.

Positive time-frequency distributions based on joint marginal constraints

This correspondence studies the formulation of members ofthe Cohen-Posch class of positive time-frequency energy distributions.Minimization of cross-entropy measures with respect to different priorsand the case of no prior or maximum entropy were considered. It isconcluded that, in general, the information provided by the classicalmarginal constraints is very limited, and thus, the final distributionheavily depends on the prior distribution. To overcome this limitation,joint time and frequency marginals are derived based on a "directioninvariance" criterion on the time-frequency plane that are directly relatedto the fractional Fourier transform.

Power quality improving with virtual flux-based voltage source line converter

Line converters have become an attractive AC/DC power conversion solution in industrial applications. Line converters are based on controllable semiconductor switches, typically insulated gate bipolar transistors. Compared to the traditional diode bridge-based power converters line converters have many advantageous characteristics, including bidirectional power flow, controllable de-link voltage and power factor and sinusoidal line current. This thesis considers the control of the lineconverter and its application to power quality improving. The line converter control system studied is based on the virtual flux linkage orientation and the direct torque control (DTC) principle. A new DTC-based current control scheme is introduced and analyzed. The overmodulation characteristics of the DTC converter are considered and an analytical equation for the maximum modulation index is derived. The integration of the active filtering features to the line converter isconsidered. Three different active filtering methods are implemented. A frequency-domain method, which is based on selective harmonic sequence elimination, anda time-domain method, which is effective in a wider frequency band, are used inharmonic current compensation. Also, a voltage feedback active filtering method, which mitigates harmonic sequences of the grid voltage, is implemented. The frequency-domain and the voltage feedback active filtering control systems are analyzed and controllers are designed. The designs are verified with practical measurements. The performance and the characteristics of the implemented active filtering methods are compared and the effect of the L- and the LCL-type line filteris discussed. The importance of the correct grid impedance estimate in the voltage feedback active filter control system is discussed and a new measurement-based method to obtain it is proposed. Also, a power conditioning system (PCS) application of the line converter is considered. A new method for correcting the voltage unbalance of the PCS-fed island network is proposed and experimentally validated.

Linear transceiver design in nonregenerative relays with channel state information

This paper deals with the design of nonregenerativerelaying transceivers in cooperative systems where channel stateinformation (CSI) is available at the relay station. The conventionalnonregenerative approach is the amplify and forward(A&F) approach, where the signal received at the relay is simplyamplified and retransmitted. In this paper, we propose an alternativelinear transceiver design for nonregenerative relaying(including pure relaying and the cooperative transmission cases),making proper use of CSI at the relay station. Specifically, wedesign the optimum linear filtering performed on the data to beforwarded at the relay. As optimization criteria, we have consideredthe maximization of mutual information (that provides aninformation rate for which reliable communication is possible) fora given available transmission power at the relay station. Threedifferent levels of CSI can be considered at the relay station: onlyfirst hop channel information (between the source and relay);first hop channel and second hop channel (between relay anddestination) information, or a third situation where the relaymay have complete cooperative channel information includingall the links: first and second hop channels and also the directchannel between source and destination. Despite the latter beinga more unrealistic situation, since it requires the destination toinform the relay station about the direct channel, it is useful as anupper benchmark. In this paper, we consider the last two casesrelating to CSI.We compare the performance so obtained with theperformance for the conventional A&F approach, and also withthe performance of regenerative relays and direct noncooperativetransmission for two particular cases: narrowband multiple-inputmultiple-output transceivers and wideband single input singleoutput orthogonal frequency division multiplex transmissions.

Modulation of pancreatic β-cell mass and insulin secretion by PPARβ/δ

SUMMARY : Peroxisome proliferator-activated receptor ß/δ protects against obesity by reducing dyslipidemia and insulin resistance via effects in various organs, including muscle, adipose tissue and liver. However, nothing is known about the function of PPARß in pancreas, a prime organ in the control of glucose homeostasis. To gain insight into so far hypothetical functions of this PPAR isotype in ß-cell function, we specifically ablated Pparß in the whole epithelial compartment of the pancreas. The mutated mice presented expanded ß-cell mass, possibly, this is due to increased burst of ß-cell proliferation at 2 weeks of age. These PPARß null pancreas mice exhibit hyperinsulinemia-hypoglycaemia starting at 4 weeks of age, due to hyperfunctionality of ß-cell. Gene expression profiling indicated a broad repressive function of PPARß impacting the vesicular and granular compartment, actin cytoskeleton, and metabolism of glucose and fatty acids. Analyses of insulin release from isolated islets revealed accelerated second-phase of glucose-stimulated insulin secretion. Higher levels of PKD and PKCS in mutated animals, in concert with F-actin disassembly, lead to an increased insulin secretion and its associated systemic effects. Enhanced palmitate potentiation of glucose-stimulated insulin secretion in PPARß mutant islets, suggests an important role of this receptor in lipid/glucose metabolism in ß-cell. Taken together, these results provide evidence for PPARß playing a repressive role on ß-cell growth and insulin exocytosis, and shed new light on its metabolic .action. RESUME : Le récepteur nucléaire PPARß (Peroxisome proliferator-activated receptor ß/δ) protège contre l'obésité en réduisant la dyslipidémie et la résistance à l'insuline dans différents organes, comme le muscle, le tissue adipeux et le foie. Cependant, il y a, à ce jour, très peu de connaissance par rapport au rôle de PPARß dans le pancréas, qui est un organe très important dans le contrôle homéostatique du glucose. Afin de comprendre le rôle de cet isotype de PPAR dans le fonctionnement des cellules beta du pancréas, nous avons invalidé le gène Pparß dans tout le compartiment pancréatique de la souris. Ces souris mutantes présentent une augmentation de la masse totale de cellules beta; Cela serait dû à une intense prolifération des cellules beta à 2 semaines après la naissance. Également, ces souris présentent une hyperinsulinémie et une hypoglycémie qui commencent à l'âge de 4 semaines; la raison de ce phénotype serait une hyperactivité des cellules beta. Le profil d'expression génique indique une fonction répressive globale de PPARß en se référant aux compartiments vésiculaire et granulaire, au cytosquelette d'actine, et au métabolisme du glucose et des acides gras. L'analyse de la sécrétion d'insuline par les cellules beta a démontré que la deuxième phase de sécrétion d'insuline après stimulation au glucose est augmentée. Les niveaux élevés de PKD et PKCS dans les îlots pancréatiques de souris mutantes, ainsi qu'une augmentation de la dépolymérisation des filaments d'active génèrent un surplus de sécrétion d'insuline après stimulation au glucose. Les îlots pancréatiques des souris mutantes secrètent plus d'insuline après stimulation au glucose et au palmitate que les îlots de souris contrôles. Ceci suggère un rôle important de PPARß dans le métabolisme des lipides et du glucose des cellules beta. En résumé, ces résultats mettent en évidence un rôle répressif de PPARß dans la croissance des cellules beta et dans l'exocytose d'insuline.