Touching proteins with virtual bare hands : visualizing protein–drug complexes and their dynamics in self-made virtual reality using gaming hardware

The ability to precisely visualize the atomic geometry of the interactions between a drug and its protein target in structural models is critical in predicting the correct modifications in previously identified inhibitors to create more effective next generation drugs. It is currently common practice among medicinal chemists while attempting the above to access the information contained in three-dimensional structures by using two-dimensional projections, which can preclude disclosure of useful features. A more accessible and intuitive visualization of the three-dimensional configuration of the atomic geometry in the models can be achieved through the implementation of immersive virtual reality (VR). While bespoke commercial VR suites are available, in this work, we present a freely available software pipeline for visualising protein structures through VR. New consumer hardware, such as the HTC Vive and the Oculus Rift utilized in this study, are available at reasonable prices. As an instructive example, we have combined VR visualization with fast algorithms for simulating intramolecular motions of protein flexibility, in an effort to further improve structure-led drug design by exposing molecular interactions that might be hidden in the less informative static models. This is a paradigmatic test case scenario for many similar applications in computer-aided molecular studies and design

Effectiveness of two web-based cognitive bias modification interventions targeting approach and attentional bias in gambling problems:Study protocol for a pilot randomised controlled trial

BACKGROUND: Disordered gamblers have phenotypical and pathological similarities to those with substance use disorders (SUD), including exaggerated automatic cognitive processing of motivationally salient gambling cues in the environment (i.e., attentional and approach bias). Cognitive bias modification (CBM) is a family of computerised interventions that have proved effective in successfully re-training these automatic cognitive biases in SUD. CBM interventions can, in principle, be administered online, thus showing potential of being a low-cost, low-threshold addition to conventional treatments. This paper presents the design of a pilot randomised controlled trial exploring the effectiveness of two web-based CBM interventions targeting attentional and approach bias towards gambling cues in a sample of Dutch and Belgian problematic and pathological gamblers. METHODS/DESIGN: Participants (N = 182) are community-recruited adults experiencing gambling problems, who have gambled at least twice in the past 6 months and are motivated to change their gambling behaviour. After a baseline assessment session, participants are randomly assigned to one of four experimental conditions (attentional or approach bias training, or the placebo version of the two trainings) and complete six sessions of training. At baseline and before each training session, participants receive automated personalised feedback on their gambling motives and reasons to quit or reduce gambling. The post-intervention, 1-month, and 3-month follow-up assessments will examine changes in gambling behaviour, with frequency and expenditure as primary outcomes, and depressive symptoms and gambling-related attentional and approach biases as secondary outcomes. Secondary analyses will explore possible moderators (interference control capacity and trait impulsivity) and mediators (change in cognitive bias) of training effects on the primary outcomes. DISCUSSION: This study is the first to explore the effectiveness of an online CBM intervention for gambling problems. The results of this study can be extremely valuable for developing e-health interventions for gambling problems and further understanding the role of motivational implicit cognitive processes underlying problematic gambling behaviour. TRIAL REGISTRATION: Netherlands Trial Register, NTR5096 . Registered on 11 March 2015

Is attention deficit/hyperactivity disorder among men associated with initiation or escalation of substance use at 15-month follow-up? A longitudinal study involving young Swiss men.

Young adults with attention deficit/hyperactivity disorder (ADHD) show higher substance use disorder (SUD) prevalence relative to non-ADHD controls; few longitudinal studies have examined the course of substance use with reference to conduct disorder (CD). We compared initiation and escalation of substance use at 15-month follow-up in men screened positive or negative for ADHD (ADHD(+) versus ADHD(-) ), controlling for CD presence in early adolescence. Participants were recruited during August 2010 and November 2011 from the census of all young men who have to pass mandatory army conscription from three of six Swiss Army recruitment centres. A two-wave data collection was performed via questionnaires at baseline and 15-month follow-up as a part of the longitudinal Cohort Study on Substance Use Risk Factors. Recruitment centres in Lausanne, Windisch and Mels, responsible for 21 cantons in German- and French-speaking areas of Switzerland. Consecutive sample of 5103 male Swiss Army conscripts who provided informed consent and responded to questionnaires at baseline and 15-month follow-up. Their mean age was 20.0 (standard deviation = 1.21) years at baseline. ADHD and CD were assessed using the adult ADHD Self-Report Scale and the MINI International Neuropsychiatric Interview Plus, respectively, at baseline, and substance use was measured via self-administered substance use questionnaires at baseline and follow-up. Compared with the ADHD(-) group, the ADHD(+) group (n = 215, 4.2%) showed heavier baseline substance use and increased likelihood of alcohol (χ(2)  = 53.96; P < 0.001), tobacco (χ(2)  = 21.73; P < 0.001) and cannabis use disorders (χ(2)  = 48.43; P < 0.001). The extent of alcohol, tobacco and cannabis use in the two groups remained stable from baseline to follow-up (no escalation). The ADHD(+) group was more likely to initiate substance use compared with the ADHD(-) group (higher initiation rates), particularly with amphetamines [odds ratio (OR) = 3.81; 95% confidence interval (CI) = 2.20-6.60; P < 0.001] and non-medical use of ADHD medication (OR = 4.45; 95% CI = 2.06-9.60; P < 0.001). CD was associated with initiation of substance use but did not mediate the associations between ADHD and substance use, revealing that the impact of ADHD on substance use was independent of CD. For men in their early 20s, attention deficit/hyperactivity disorder is a risk factor for continued heavier but not escalating use of alcohol, tobacco and cannabis when already consuming these substances, compared with young men with no ADHD. It is also a risk factor for initiating the use of cannabis, stimulants, hallucinogens and sedatives, independent of conduct disorder in early adolescence

Substance Misuse Education for Physicians: Why Older People are Important.

This perspective article focuses on the need for training and education for undergraduate medical students on substance-related disorders, and describes initiatives undertaken in the United Kingdom (UK), Netherlands, United States (US), and Norway to develop the skills, knowledge, and attitudes needed by future doctors to treat patients adequately. In addition, we stress that in postgraduate training, further steps should be taken to develop Addiction Medicine as a specialized and transverse medical domain. Alcohol use disorder is a growing public health problem in the geriatric population, and one that is likely to continue to increase as the baby boomer generation ages. Prescription drug misuse is a major concern, and nicotine misuse remains problematic in a substantial minority. Thus, Addiction Medicine training should address the problems for this specific population. In recent years, several countries have started an Addiction Medicine specialty. Although addiction psychiatry has been a subspecialty in the UK and US for more than 20 years, in most countries it has been a more recent development. Additional courses on addiction should be integrated into the curriculum at both undergraduate and postgraduate levels, as well as form part of the continuous training of other medical specialists. It is recommended that further research and mapping of what is currently taught in medical programs be undertaken, so as to enhance medical education in addiction and improve treatment services

Tight Kernel Bounds for Problems on Graphs with Small Degeneracy

In this paper we consider kernelization for problems on d-degenerate graphs, i.e. graphs such that any subgraph contains a vertex of degree at most $d$. This graph class generalizes many classes of graphs for which effective kernelization is known to exist, e.g. planar graphs, H-minor free graphs, and H-topological-minor free graphs. We show that for several natural problems on d-degenerate graphs the best known kernelization upper bounds are essentially tight.Comment: Full version of ESA 201

Julian of Norwich and her children today: Editions, translations and versions of her revelations

The viability of such concepts as "authorial intention," "the original text," "critical edition" and, above all, "scholarly editorial objectivity" is not what it was, and a study of the textual progeny of the revelations of Julian of Norwich--editions, versions, translations and selections--does little to rehabilitate them. Rather it tends to support the view that a history of reading is indeed a history of misreading or, more positively, that texts can have an organic life of their own that allows them to reproduce and evolve quite independently of their author. Julian's texts have had a more robustly continuous life than those of any other Middle English mystic. Their history--in manuscript and print, in editions more or less approximating Middle English and in translations more or less approaching Modern English--is virtually unbroken since the fifteenth century. But on this perilous journey, many and strange are the clutches into which she and her textual progeny have fallen