Impulsivity in cocaine-dependent individuals with and without attention-deficit/hyperactivity disorder

&lt;b&gt;&lt;i&gt;Background:&lt;/i&gt;&lt;/b&gt; Cocaine-dependent individuals (CDI) display increased impulsivity. However, despite its multifactorial nature most studies in CDI have treated impulsivity monolithically. Moreover, the impact of attention-deficit/hyperactivity disorder (ADHD) has often not been taken into account. This study investigates whether CDI with ADHD (CDI+ADHD) differ from CDI without an ADHD diagnosis and healthy controls (HC) on several impulsivity measures. &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; Thirty-four CDI, 25 CDI+ADHD and 28 HC participated in this study. Trait impulsivity was assessed with the motor, attentional and non-planning subscales of the Barratt Impulsiveness Scale (BIS-11). Neurocognitive dimensions of impulsivity were examined with the stop signal task (SST), delay discounting task (DDT) and information sampling task (IST). &lt;b&gt;&lt;i&gt;Results:&lt;/i&gt;&lt;/b&gt; Relative to HC, both CDI and CDI+ADHD scored higher on all BIS-11 subscales, required more time to inhibit their responses (SST) and sampled less information before making a decision (IST). Greater discounting of delayed rewards (DDT) was only found among CDI+ADHD. Compared to CDI without ADHD, CDI+ADHD scored higher on the BIS-11 non-planning and total scale and showed higher discounting rates. &lt;b&gt;&lt;i&gt;Conclusion:&lt;/i&gt;&lt;/b&gt; CDI score higher on several indices of impulsivity relative to HC, regardless of whether they have concomitant ADHD or not. CDI+ADHD are specifically characterized by a lack of future orientation compared to CDI without ADHD.</jats:p

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

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

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 &lt; 0.001), tobacco (χ(2)  = 21.73; P &lt; 0.001) and cannabis use disorders (χ(2)  = 48.43; P &lt; 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 &lt; 0.001] and non-medical use of ADHD medication (OR = 4.45; 95% CI = 2.06-9.60; P &lt; 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

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

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

Polynomial Kernels and User Reductions for the Workflow Satisfiability Problem

The Workflow Satisfiability Problem (WSP) is a problem of practical interest that arises whenever tasks need to be performed by authorized users, subject to constraints defined by business rules. We are required to decide whether there exists a plan -- an assignment of tasks to authorized users -- such that all constraints are satisfied. The WSP is, in fact, the conservative Constraint Satisfaction Problem (i.e., for each variable, here called task, we have a unary authorization constraint) and is, thus, NP-complete. It was observed by Wang and Li (2010) that the number k of tasks is often quite small and so can be used as a parameter, and several subsequent works have studied the parameterized complexity of WSP regarding parameter k. We take a more detailed look at the kernelization complexity of WSP(\Gamma) when \Gamma\ denotes a finite or infinite set of allowed constraints. Our main result is a dichotomy for the case that all constraints in \Gamma\ are regular: (1) We are able to reduce the number n of users to n' <= k. This entails a kernelization to size poly(k) for finite \Gamma, and, under mild technical conditions, to size poly(k+m) for infinite \Gamma, where m denotes the number of constraints. (2) Already WSP(R) for some R \in \Gamma\ allows no polynomial kernelization in k+m unless the polynomial hierarchy collapses.Comment: An extended abstract appears in the proceedings of IPEC 201

PHYTOCHEMICAL SCREENING AND ANALYSIS POLYPHENOLIC ANTIOXIDANT ACTIVITY OF METHANOLIC EXTRACT OF WHITE DRAGON FRUIT (Hylocereus undatus)

White dragon fruit is a well known and widely used herbal medicine, especially in Asia, which contains several interesting bioactive constituents and possesses health promoting properties. The aim of this study was to analyze for the bioactive compounds, evaluate total phenolic contents and antioxidant capacities of methanolic extract of white dragon fruit. The antioxidant activity was determined by the 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging activity assay. Total phenolic content were determined by Folin-Ciocalteu method. Phytochemical screening of the white dragon fruit showed the presence of triterpenoid, alkaloid, flavonoid and saponin. The extract exhibited strong antioxidant activity with IC50 of 193 μg/mL, and total phenolic content of 246 μg/mL in 1 Kg dry extract

Gene signature of the post-Chernobyl papillary thyroid cancer

Purpose: Following the nuclear accidents in Chernobyl and later in Fukushima, the nuclear community has been faced with important issues concerning how to search for and diagnose biological consequences of low-dose internal radiation contamination. Although after the Chernobyl accident an increase in childhood papillary thyroid cancer (PTC) was observed, it is still not clear whether the molecular biology of PTCs associated with low-dose radiation exposure differs from that of sporadic PTC. Methods: We investigated tissue samples from 65 children/young adults with PTC using DNA microarray (Affymetrix, Human Genome U133 2.0 Plus) with the aim of identifying molecular differences between radiation-induced (exposed to Chernobyl radiation, ECR) and sporadic PTC. All participants were resident in the same region so that confounding factors related to genetics or environment were minimized. Results: There were small but significant differences in the gene expression profiles between ECR and non-ECR PTC (global test, p &lt; 0.01), with 300 differently expressed probe sets (p &lt; 0.001) corresponding to 239 genes. Multifactorial analysis of variance showed that besides radiation exposure history, the BRAF mutation exhibited independent effects on the PTC expression profile; the histological subset and patient age at diagnosis had negligible effects. Ten genes (PPME1, HDAC11, SOCS7, CIC, THRA, ERBB2, PPP1R9A, HDGF, RAD51AP1, and CDK1) from the 19 investigated with quantitative RT-PCR were confirmed as being associated with radiation exposure in an independent, validation set of samples. Conclusion: Significant, but subtle, differences in gene expression in the post-Chernobyl PTC are associated with previous low-dose radiation exposure

Vertex Cover Kernelization Revisited: Upper and Lower Bounds for a Refined Parameter

An important result in the study of polynomial-time preprocessing shows that there is an algorithm which given an instance (G,k) of Vertex Cover outputs an equivalent instance (G',k') in polynomial time with the guarantee that G' has at most 2k' vertices (and thus O((k')^2) edges) with k' <= k. Using the terminology of parameterized complexity we say that k-Vertex Cover has a kernel with 2k vertices. There is complexity-theoretic evidence that both 2k vertices and Theta(k^2) edges are optimal for the kernel size. In this paper we consider the Vertex Cover problem with a different parameter, the size fvs(G) of a minimum feedback vertex set for G. This refined parameter is structurally smaller than the parameter k associated to the vertex covering number vc(G) since fvs(G) <= vc(G) and the difference can be arbitrarily large. We give a kernel for Vertex Cover with a number of vertices that is cubic in fvs(G): an instance (G,X,k) of Vertex Cover, where X is a feedback vertex set for G, can be transformed in polynomial time into an equivalent instance (G',X',k') such that |V(G')| <= 2k and |V(G')| <= O(|X'|^3). A similar result holds when the feedback vertex set X is not given along with the input. In sharp contrast we show that the Weighted Vertex Cover problem does not have a polynomial kernel when parameterized by the cardinality of a given vertex cover of the graph unless NP is in coNP/poly and the polynomial hierarchy collapses to the third level.Comment: Published in "Theory of Computing Systems" as an Open Access publicatio