Does alcohol cue inhibitory control training survive a context shift?

Inhibitory control training (ICT) is a novel psychological intervention that aims to improve inhibitory control in response to alcohol-related cues through associative learning. Laboratory studies have demonstrated reductions in alcohol consumption following ICT compared with control/sham training, but it is unclear if these effects are robust to a change of context. In a preregistered study, we examined whether the effects of ICT would survive a context shift from a neutral context to a seminaturalistic bar setting. In a mixed design, 60 heavy drinkers (40 female) were randomly allocated to receive either ICT or control/sham training in a neutral laboratory over 2 sessions. We developed a novel variation of ICT that used multiple stop signals to establish direct stimulus–stop associations. The effects of ICT/control were measured once in the same context and once following a shift to a novel (alcohol-related) context. Our dependent variables were ad libitum alcohol consumption following training, change in inhibitory control processes, and change in alcohol value. ICT did not reduce alcohol consumption in either context compared with the control group. Furthermore, we demonstrated no effects of ICT on inhibitory control processes or alcohol value. Bayesian analyses demonstrated overall support for the null hypotheses. This study failed to find any effects of ICT on alcohol consumption or candidate psychological mechanisms. These findings illustrate the difficulty in training alcohol-inhibition associations and add to a growing body of literature suggesting that ICT holds little evidential value as a psychological intervention for alcohol use disorders

Does alcohol cue inhibitory control training survive a context shift?

Inhibitory control training (ICT) is a novel psychological intervention that aims to improve inhibitory control in response to alcohol-related cues through associative learning. Laboratory studies have demonstrated reductions in alcohol consumption following ICT compared with control/sham training, but it is unclear if these effects are robust to a change of context. In a preregistered study, we examined whether the effects of ICT would survive a context shift from a neutral context to a seminaturalistic bar setting. In a mixed design, 60 heavy drinkers (40 female) were randomly allocated to receive either ICT or control/sham training in a neutral laboratory over 2 sessions. We developed a novel variation of ICT that used multiple stop signals to establish direct stimulus–stop associations. The effects of ICT/control were measured once in the same context and once following a shift to a novel (alcohol-related) context. Our dependent variables were ad libitum alcohol consumption following training, change in inhibitory control processes, and change in alcohol value. ICT did not reduce alcohol consumption in either context compared with the control group. Furthermore, we demonstrated no effects of ICT on inhibitory control processes or alcohol value. Bayesian analyses demonstrated overall support for the null hypotheses. This study failed to find any effects of ICT on alcohol consumption or candidate psychological mechanisms. These findings illustrate the difficulty in training alcohol-inhibition associations and add to a growing body of literature suggesting that ICT holds little evidential value as a psychological intervention for alcohol use disorders. (PsycInfo Database Record (c) 2020 APA, all rights reserved

Polychromatic solitons in a quadratic medium

We introduce the simplest model to describe parametric interactions in a quadratically nonlinear optical medium with the fundamental harmonic containing two components with (slightly) different carrier frequencies [which is a direct analog of wavelength-division multiplexed (WDM) models, well known in media with cubic nonlinearity]. The model takes a closed form with three different second-harmonic components, and it is formulated in the spatial domain. We demonstrate that the model supports both polychromatic solitons (PCSs), with all the components present in them, and two types of mutually orthogonal simple solitons, both types being stable in a broad parametric region. An essential peculiarity of PCS is that its power is much smaller than that of a simple (usual) soliton (taken at the same values of control parameters), which may be an advantage for experimental generation of PCSs. Collisions between the orthogonal simple solitons are simulated in detail, leading to the conclusion that the collisions are strongly inelastic, converting the simple solitons into polychromatic ones, and generating one or two additional PCSs. A collision velocity at which the inelastic effects are strongest is identified, and it is demonstrated that the collision may be used as a basis to design a simple all-optical XOR logic gate.Comment: 9 pages, 8 figures, accepted to Phys. Rev.

Resonant nonlinear magneto-optical effects in atoms

In this article, we review the history, current status, physical mechanisms, experimental methods, and applications of nonlinear magneto-optical effects in atomic vapors. We begin by describing the pioneering work of Macaluso and Corbino over a century ago on linear magneto-optical effects (in which the properties of the medium do not depend on the light power) in the vicinity of atomic resonances, and contrast these effects with various nonlinear magneto-optical phenomena that have been studied both theoretically and experimentally since the late 1960s. In recent years, the field of nonlinear magneto-optics has experienced a revival of interest that has led to a number of developments, including the observation of ultra-narrow (1-Hz) magneto-optical resonances, applications in sensitive magnetometry, nonlinear magneto-optical tomography, and the possibility of a search for parity- and time-reversal-invariance violation in atoms.Comment: 51 pages, 23 figures, to appear in Rev. Mod. Phys. in Oct. 2002, Figure added, typos corrected, text edited for clarit

Analysis of host responses to Mycobacterium tuberculosis antigens in a multi-site study of subjects with different TB and HIV infection states in sub-Saharan Africa.

BACKGROUND: Tuberculosis (TB) remains a global health threat with 9 million new cases and 1.4 million deaths per year. In order to develop a protective vaccine, we need to define the antigens expressed by Mycobacterium tuberculosis (Mtb), which are relevant to protective immunity in high-endemic areas. METHODS: We analysed responses to 23 Mtb antigens in a total of 1247 subjects with different HIV and TB status across 5 geographically diverse sites in Africa (South Africa, The Gambia, Ethiopia, Malawi and Uganda). We used a 7-day whole blood assay followed by IFN-γ ELISA on the supernatants. Antigens included PPD, ESAT-6 and Ag85B (dominant antigens) together with novel resuscitation-promoting factors (rpf), reactivation proteins, latency (Mtb DosR regulon-encoded) antigens, starvation-induced antigens and secreted antigens. RESULTS: There was variation between sites in responses to the antigens, presumably due to underlying genetic and environmental differences. When results from all sites were combined, HIV- subjects with active TB showed significantly lower responses compared to both TST(-) and TST(+) contacts to latency antigens (Rv0569, Rv1733, Rv1735, Rv1737) and the rpf Rv0867; whilst responses to ESAT-6/CFP-10 fusion protein (EC), PPD, Rv2029, TB10.3, and TB10.4 were significantly higher in TST(+) contacts (LTBI) compared to TB and TST(-) contacts fewer differences were seen in subjects with HIV co-infection, with responses to the mitogen PHA significantly lower in subjects with active TB compared to those with LTBI and no difference with any antigen. CONCLUSIONS: Our multi-site study design for testing novel Mtb antigens revealed promising antigens for future vaccine development. The IFN-γ ELISA is a cheap and useful tool for screening potential antigenicity in subjects with different ethnic backgrounds and across a spectrum of TB and HIV infection states. Analysis of cytokines other than IFN-γ is currently on-going to determine correlates of protection, which may be useful for vaccine efficacy trials

Altered Neurocircuitry in the Dopamine Transporter Knockout Mouse Brain

The plasma membrane transporters for the monoamine neurotransmitters dopamine, serotonin, and norepinephrine modulate the dynamics of these monoamine neurotransmitters. Thus, activity of these transporters has significant consequences for monoamine activity throughout the brain and for a number of neurological and psychiatric disorders. Gene knockout (KO) mice that reduce or eliminate expression of each of these monoamine transporters have provided a wealth of new information about the function of these proteins at molecular, physiological and behavioral levels. In the present work we use the unique properties of magnetic resonance imaging (MRI) to probe the effects of altered dopaminergic dynamics on meso-scale neuronal circuitry and overall brain morphology, since changes at these levels of organization might help to account for some of the extensive pharmacological and behavioral differences observed in dopamine transporter (DAT) KO mice. Despite the smaller size of these animals, voxel-wise statistical comparison of high resolution structural MR images indicated little morphological change as a consequence of DAT KO. Likewise, proton magnetic resonance spectra recorded in the striatum indicated no significant changes in detectable metabolite concentrations between DAT KO and wild-type (WT) mice. In contrast, alterations in the circuitry from the prefrontal cortex to the mesocortical limbic system, an important brain component intimately tied to function of mesolimbic/mesocortical dopamine reward pathways, were revealed by manganese-enhanced MRI (MEMRI). Analysis of co-registered MEMRI images taken over the 26 hours after introduction of Mn^(2+) into the prefrontal cortex indicated that DAT KO mice have a truncated Mn^(2+) distribution within this circuitry with little accumulation beyond the thalamus or contralateral to the injection site. By contrast, WT littermates exhibit Mn^(2+) transport into more posterior midbrain nuclei and contralateral mesolimbic structures at 26 hr post-injection. Thus, DAT KO mice appear, at this level of anatomic resolution, to have preserved cortico-striatal-thalamic connectivity but diminished robustness of reward-modulating circuitry distal to the thalamus. This is in contradistinction to the state of this circuitry in serotonin transporter KO mice where we observed more robust connectivity in more posterior brain regions using methods identical to those employed here

Technologies of sleep research

Sleep is investigated in many different ways, many different species and under many different circumstances. Modern sleep research is a multidisciplinary venture. Therefore, this review cannot give a complete overview of all techniques used in sleep research and sleep medicine. What it will try to do is to give an overview of widely applied techniques and exciting new developments. Electroencephalography has been the backbone of sleep research and sleep medicine since its first application in the 1930s. The electroencephalogram is still used but now combined with many different techniques monitoring body and brain temperature, changes in brain and blood chemistry, or changes in brain functioning. Animal research has been very important for progress in sleep research and sleep medicine. It provides opportunities to investigate the sleeping brain in ways not possible in healthy volunteers. Progress in genomics has brought new insights in sleep regulation, the best example being the discovery of hypocretin/orexin deficiency as the cause of narcolepsy. Gene manipulation holds great promise for the future since it is possible not only to investigate the functions of different genes under normal conditions, but also to mimic human pathology in much greater detail

Sleep-wake sensitive mechanisms of adenosine release in the basal forebrain of rodents : an in vitro study

Adenosine acting in the basal forebrain is a key mediator of sleep homeostasis. Extracellular adenosine concentrations increase during wakefulness, especially during prolonged wakefulness and lead to increased sleep pressure and subsequent rebound sleep. The release of endogenous adenosine during the sleep-wake cycle has mainly been studied in vivo with microdialysis techniques. The biochemical changes that accompany sleep-wake status may be preserved in vitro. We have therefore used adenosine-sensitive biosensors in slices of the basal forebrain (BFB) to study both depolarization-evoked adenosine release and the steady state adenosine tone in rats, mice and hamsters. Adenosine release was evoked by high K+, AMPA, NMDA and mGlu receptor agonists, but not by other transmitters associated with wakefulness such as orexin, histamine or neurotensin. Evoked and basal adenosine release in the BFB in vitro exhibited three key features: the magnitude of each varied systematically with the diurnal time at which the animal was sacrificed; sleep deprivation prior to sacrifice greatly increased both evoked adenosine release and the basal tone; and the enhancement of evoked adenosine release and basal tone resulting from sleep deprivation was reversed by the inducible nitric oxide synthase (iNOS) inhibitor, 1400 W. These data indicate that characteristics of adenosine release recorded in the BFB in vitro reflect those that have been linked in vivo to the homeostatic control of sleep. Our results provide methodologically independent support for a key role for induction of iNOS as a trigger for enhanced adenosine release following sleep deprivation and suggest that this induction may constitute a biochemical memory of this state

A Diffractive Study of Parametric Process in Nonlinear Photonic Crystals

We report a general description of quasi-phase-matched parametric process in nonlinear photonic crystals (NLPC) by extending the conventional X-ray diffraction theory in solids. Under the virtual wave approximation, phase-matching resonance is equivalent to the diffraction of the scattered virtual wave. Hence a modified NLPC Ewald construction can be built up, which illustrates the nature of the accident for the diffraction of the virtual wave in NLPC and further reveals the complete set of diffractions of the virtual wave for both of the air-dielectric and dielectric-dielectric contacts. We show the two basic linear sequences, the anti-stacking and para-stacking linear sequences, in one-dimension (1D) NLPC and present a general rule for multiple phase-matching resonances in 1D NLPC. The parameters affecting the NLPC structure factor are investigated, which indicate that not only the Ewald construction but also the relative NLPC atom size together determine whether a diffraction of the virtual wave can occur in 2D NLPC. The results also show that 1D NLPC is a better choice than 2D NLPC for a single parametric process

Portal Vein Embolization is Associated with Reduced Liver Failure and Mortality in High-Risk Resections for Perihilar Cholangiocarcinoma

Background Preoperative portal vein embolization (PVE) is frequently used to improve future liver remnant volume (FLRV) and to reduce the risk of liver failure after major liver resection. Objective This paper aimed to assess postoperative outcomes after PVE and resection for suspected perihilar cholangiocarcinoma (PHC) in an international, multicentric cohort. Methods Patients undergoing resection for suspected PHC across 20 centers worldwide, from the year 2000, were included. Liver failure, biliary leakage, and hemorrhage were classified according to the respective International Study Group of Liver Surgery criteria. Using propensity scoring, two equal cohorts were generated using matching parameters, i.e. age, sex, American Society of Anesthesiologists classification, jaundice, type of biliary drainage, baseline FLRV, resection type, and portal vein resection. Results A total of 1667 patients were treated for suspected PHC during the study period. In 298 patients who underwent preoperative PVE, the overall incidence of liver failure and 90-day mortality was 27% and 18%, respectively, as opposed to 14% and 12%, respectively, in patients without PVE (p < 0.001 and p = 0.005). After propensity score matching, 98 patients were enrolled in each cohort, resulting in similar baseline and operative characteristics. Liver failure was lower in the PVE group (8% vs. 36%, p < 0.001), as was biliary leakage (10% vs. 35%, p < 0.01), intra-abdominal abscesses (19% vs. 34%, p = 0.01), and 90-day mortality (7% vs. 18%, p = 0.03). Conclusion PVE before major liver resection for PHC is associated with a lower incidence of liver failure, biliary leakage, abscess formation, and mortality. These results demonstrate the importance of PVE as an integral component in the surgical treatment of PHC