Theory of Multidimensional Solitons

We review a number of topics germane to higher-dimensional solitons in Bose-Einstein condensates. For dark solitons, we discuss dark band and planar solitons; ring dark solitons and spherical shell solitons; solitary waves in restricted geometries; vortex rings and rarefaction pulses; and multi-component Bose-Einstein condensates. For bright solitons, we discuss instability, stability, and metastability; bright soliton engineering, including pulsed atom lasers; solitons in a thermal bath; soliton-soliton interactions; and bright ring solitons and quantum vortices. A thorough reference list is included.Comment: review paper, to appear as Chapter 5a in "Emergent Nonlinear Phenomena in Bose-Einstein Condensates: Theory and Experiment," edited by P. G. Kevrekidis, D. J. Frantzeskakis, and R. Carretero-Gonzalez (Springer-Verlag

Differential Effects of Attention-, Compassion-, and Socio-Cognitively Based Mental Practices on Self-Reports of Mindfulness and Compassion

Research on the effects of mindfulness- and compassion-based interventions is flourishing along with self-report scales to assess facets of these broad concepts. However, debates remain as to which mental practices are most appropriate to develop the attentional, cognitive, and socio-affective facets of mindfulness and compassion. One crucial question is whether present-moment, attention-focused mindfulness practices are sufficient to induce a cascade of changes across the different proposed facets of mindfulness, including nonjudgmental acceptance, as well as compassion or whether explicit socio-affective training is required. Here, we address these questions in the context of a 9-month longitudinal study (the ReSource Project) by examining the differential effects of three different 3-month mental training modules on subscales of mindfulness and compassion questionnaires. The “Presence” module, which aimed at cultivating present-moment-focused attention and body awareness, led to increases in the observing, nonreacting, and presence subscales, but not to increases in acceptance or nonjudging. These latter facets benefitted from specific cultivation through the socio-cognitive “Perspective” module and socio-affective, compassion-based “Affect” module, respectively. These modules also led to further increases in scores on the subscales affected by the Presence module. Moreover, scores on the compassion scales were uniquely influenced by the Affect module. Thus, whereas a present-moment attention-focused training, as implemented in many mindfulness-based programs, was indeed able to increase attentional facets of mindfulness, only socio-cognitive and compassion-based practices led to broad changes in ethical-motivational qualities like a nonjudgmental attitude, compassion, and self-compassion

Inhibition of the inositol kinase Itpkb augments calcium signaling in lymphocytes and reveals a novel strategy to treat autoimmune disease

Emerging approaches to treat immune disorders target positive regulatory kinases downstream of antigen receptors with small molecule inhibitors. Here we provide evidence for an alternative approach in which inhibition of the negative regulatory inositol kinase Itpkb in mature T lymphocytes results in enhanced intracellular calcium levels following antigen receptor activation leading to T cell death. Using Itpkb conditional knockout mice and LMW Itpkb inhibitors these studies reveal that Itpkb through its product IP4 inhibits the Orai1/Stim1 calcium channel on lymphocytes. Pharmacological inhibition or genetic deletion of Itpkb results in elevated intracellular Ca2+ and induction of FasL and Bim resulting in T cell apoptosis. Deletion of Itpkb or treatment with Itpkb inhibitors blocks T-cell dependent antibody responses in vivo and prevents T cell driven arthritis in rats. These data identify Itpkb as an essential mediator of T cell activation and suggest Itpkb inhibition as a novel approach to treat autoimmune disease

Evaluating the drivers of and obstacles to the willingness to use cognitive enhancement drugs: the influence of drug characteristics, social environment, and personal characteristics

Sattler S, Mehlkop G, Graeff P, Sauer C. Evaluating the drivers of and obstacles to the willingness to use cognitive enhancement drugs: the influence of drug characteristics, social environment, and personal characteristics. Substance Abuse Treatment, Prevention, and Policy. 2014;9(1): 8.Background The use of cognitive enhancement (CE) by means of pharmaceutical agents has been the subject of intense debate both among scientists and in the media. This study investigates several drivers of and obstacles to the willingness to use prescription drugs non-medically for augmenting brain capacity. Methods We conducted a web-based study among 2,877 students from randomly selected disciplines at German universities. Using a factorial survey, respondents expressed their willingness to take various hypothetical CE-drugs; the drugs were described by five experimentally varied characteristics and the social environment by three varied characteristics. Personal characteristics and demographic controls were also measured. Results We found that 65.3% of the respondents staunchly refused to use CE-drugs. The results of a multivariate negative binomial regression indicated that respondents’ willingness to use CE-drugs increased if the potential drugs promised a significant augmentation of mental capacity and a high probability of achieving this augmentation. Willingness decreased when there was a high probability of side effects and a high price. Prevalent CE-drug use among peers increased willingness, whereas a social environment that strongly disapproved of these drugs decreased it. Regarding the respondents’ characteristics, pronounced academic procrastination, high cognitive test anxiety, low intrinsic motivation, low internalization of social norms against CE-drug use, and past experiences with CE-drugs increased willingness. The potential severity of side effects, social recommendations about using CE-drugs, risk preferences, and competencies had no measured effects upon willingness. Conclusions These findings contribute to understanding factors that influence the willingness to use CE-drugs. They support the assumption of instrumental drug use and may contribute to the development of prevention, policy, and educational strategies

Resolution of inflammation: a new therapeutic frontier

Dysregulated inflammation is a central pathological process in diverse disease states. Traditionally, therapeutic approaches have sought to modulate the pro- or anti-inflammatory limbs of inflammation, with mixed success. However, insight into the pathways by which inflammation is resolved has highlighted novel opportunities to pharmacologically manipulate these processes — a strategy that might represent a complementary (and perhaps even superior) therapeutic approach. This Review discusses the state of the art in the biology of resolution of inflammation, highlighting the opportunities and challenges for translational research in this field

How informative is a negative finding in a small pharmacogenetic study?

Many pharmacogenetic studies fail to yield any statistically significant associations. Such negative findings may be due to the absence of, or inadequate statistical power to test for, an effect at the genetic variants tested. In many instances, sample sizes are small, making it unclear how to interpret the absence of statistically significant findings. We demonstrate that the amount of information that can be drawn from a negative study is improved by incorporating statistical power and the added context of well-validated pharmacogenetic effects into the interpretation process. This approach permits clearer inferences to be made about the possible range of genetic effects that may be present in, or are likely absent from, small drug studies

Three-Dimensional, Tomographic Super-Resolution Fluorescence Imaging of Serially Sectioned Thick Samples

Three-dimensional fluorescence imaging of thick tissue samples with near-molecular resolution remains a fundamental challenge in the life sciences. To tackle this, we developed tomoSTORM, an approach combining single-molecule localization-based super-resolution microscopy with array tomography of structurally intact brain tissue. Consecutive sections organized in a ribbon were serially imaged with a lateral resolution of 28 nm and an axial resolution of 40 nm in tissue volumes of up to 50 µm×50 µm×2.5 µm. Using targeted expression of membrane bound (m)GFP and immunohistochemistry at the calyx of Held, a model synapse for central glutamatergic neurotransmission, we delineated the course of the membrane and fine-structure of mitochondria. This method allows multiplexed super-resolution imaging in large tissue volumes with a resolution three orders of magnitude better than confocal microscopy

Midterm results after arterial switch operation for transposition of the great arteries: a single centre experience

BACKGROUND: The arterial switch operation (ASO) has become the surgical approach of choice for d-transposition of the great arteries (d-TGA). There is, however an increased incidence of midterm and longterm adverse sequelae in some survivors. In order to evaluate operative risk and midterm outcome in this population, we reviewed patients who underwent ASO for TGA at our centre. METHODS: In this retrospective study 52 consecutive patients with TGA who underwent ASO between 04/1991 and 12/1999 were included. To analyze the predictors for mortality and adverse events (coronary stenoses, distortion of the pulmonary arteries, dilatation of the neoaortic root, and aortic regurgitation), a multivariate analysis was performed. The follow-up time was ranged from 1–10 years (mean 5 years, cumulative 260 patient-years). RESULTS: All over mortality rate was 15.4% and was only observed in the early postoperative period till 1994. The predictors for poor operative survival were low APGAR-score, older age at surgery, and necessity of associated surgical procedures. Late re-operations were necessary in 6 patients (13.6%) and included a pulmonary artery patch enlargement due to supravalvular stenosis (n = 3), coronary revascularisation due to coronary stenosis in a coronary anatomy type E, aortic valve replacement due to neoaortic valve regurgitation (n = 2), and patch-plasty of a pulmonary vein due to obstruction (n = 1). The dilatation of neoaortic root was not observed in the follow up. CONCLUSIONS: ASO remains the procedure of choice for TGA with acceptable early and late outcome in terms of overall survival and freedom of reoperation. Although ASO is often complex and may be associated with morbidity, most patients survived without major complications even in a small centre

Relationship between atomoxetine plasma concentration, treatment response and tolerability in attention-deficit/hyperactivity disorder and comorbid oppositional defiant disorder

The purpose of this study was to examine whether atomoxetine plasma concentration predicts attention-deficit/hyperactivity disorder (ADHD) or oppositional defiant disorder (ODD) response. This post-hoc analysis assessed the relationship between atomoxetine plasma concentration and ADHD and ODD symptoms in patients (with ADHD and comorbid ODD) aged 6–12 years. Patients were randomly assigned to atomoxetine 1.2 mg/kg/day (n = 156) or placebo (n = 70) for 8 weeks (Study Period II). At the end of 8 weeks, ODD non-remitters (score >9 on the SNAP-IV ODD subscale and CGI-I > 2) with atomoxetine plasma concentration <800 ng/ml at 2 weeks were re-randomized to either atomoxetine 1.2 mg/kg/day or 2.4 mg/kg/day for an additional 4 weeks (Study Period III). ODD remitters and non-remitters with plasma atomoxetine ≥800 ng/ml remained on 1.2 mg/kg/day atomoxetine for 4 weeks. Patients who received atomoxetine, completed Study Period II, and entered Study Period III were included in these analyses. All the groups demonstrated improvement on the SNAP-IV ODD and ADHD-combined subscales (P < .001). At the end of Study Periods II and III, ODD and ADHD improvement was significantly greater in the remitter group compared with the non-remitter groups. Symptom improvement was numerically greater in the non-remitter (2.4 mg/kg/day compared with the non-remitter 1.2 mg/kg/day) group. Atomoxetine plasma concentration was not indicative of ODD and ADHD improvement after 12 weeks of treatment. ADHD and ODD symptoms improved in all the groups with longer duration on atomoxetine. Results suggest atomoxetine plasma concentration does not predict ODD and ADHD symptom improvement. However, a higher atomoxetine dose may benefit some patients