Addiction-related genes in gambling disorders:new insights from parallel human and pre-clinical models

Neurobiological research supports the characterization of disordered gambling (DG) as a behavioral addiction. Recently, an animal model of gambling behavior was developed (rat gambling task, rGT), expanding the available tools to investigate DG neurobiology. We investigated whether rGT performance and associated risk gene expression in the rat's brain could provide cross-translational understanding of the neuromolecular mechanisms of addiction in DG. We genotyped tagSNPs (single-nucleotide polymorphisms) in 38 addiction-related genes in 400 DG and 345 non-DG subjects. Genes with P<0.1 in the human association analyses were selected to be investigated in the animal arm to determine whether their mRNA expression in rats was associated with the rat's performance on the rGT. In humans, DG was significantly associated with tagSNPs in DRD3 (rs167771) and CAMK2D (rs3815072). Our results suggest that age and gender might moderate the association between CAMK2D and DG. Moderation effects could not be investigated due to sample power. In the animal arm, only the association between rGT performance and Drd3 expression remained significant after Bonferroni correction for 59 brain regions. As male rats were used, gender effects could not be investigated. Our results corroborate previous findings reporting the involvement of DRD3 receptor in addictions. To our knowledge, the use of human genetics, pre-clinical models and gene expression as a cross-translation paradigm has not previously been attempted in the field of addictions. The cross-validation of human findings in animal models is crucial for improving the translation of basic research into clinical treatments, which could accelerate neurobiological and pharmacological investigations in addictions

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

The influence of transition metal solutes on dislocation core structure and values of Peierls stress and barrier in tungsten

Several transition metals were examined to evaluate their potential for improving the ductility of tungsten. The dislocation core structure and Peierls stress and barrier of $1/2$ screw dislocations in binary tungsten-transition metal alloys (W$_{1-x}$TM$_{x}$) were investigated using first principles electronic structure calculations. The periodic quadrupole approach was applied to model the structure of $1/2$ dislocation. Alloying with transition metals was modeled using the virtual crystal approximation and the applicability of this approach was assessed by calculating the equilibrium lattice parameter and elastic constants of the tungsten alloys. Reasonable agreement was obtained with experimental data and with results obtained from the conventional supercell approach. Increasing the concentration of a transition metal from the VIIIA group, i.e. the elements in columns headed by Fe, Co and Ni, leads to reduction of the $C^\prime$ elastic constant and increase of elastic anisotropy A=$C_{44}/C^\prime$. Alloying W with a group VIIIA transition metal changes the structure of the dislocation core from symmetric to asymmetric, similar to results obtained for W$_{1-x}$Re$_{x}$ alloys in the earlier work of Romaner {\it et al} (Phys. Rev. Lett. 104, 195503 (2010))\comments{\cite{WRECORE}}. In addition to a change in the core symmetry, the values of the Peierls stress and barrier are reduced. The latter effect could lead to increased ductility in a tungsten-based alloy\comments{\cite{WRECORE}}. Our results demonstrate that alloying with any of the transition metals from the VIIIA group should have similar effect as alloying with Re.Comment: 12 pages, 8 figures, 3 table

The utilization of antidepressants and benzodiazepines among people with major depression in Canada

Objective: Although clinical guidelines recommend monotherapy with antidepressants (ADs) for major depression, polypharmacy with benzodiazepines (BDZs) remains an issue. Risks associated with such treatments include tolerance and dependence, among others. We assessed the prevalence and determinants of AD and BDZ utilization among Canadians who experienced a major depressive episode (MDE) in the previous 12 months, and determined the association of seeing a psychiatrist on the utilization of ADs and BDZs. Method: Data were drawn from the 2002 Canadian Community Health Survey: Health and Well-Being, a nationally representative sample of Canadians aged 15 years and older. Descriptive statistics quantified utilization, while logistic regression identified factors associated with utilization, such as sociodemographic characteristics or type of physician seen. Sampling weights and bootstrap variance estimations were used for all analysis. Results: The overall prevalence of AD and BDZ utilization was 49.3% of respondents who experienced an MDE in the past 12 months and reported AD use. Key determinants of utilization were younger age and unemployment in the past week (OR 2.6; P < 0.001). Being seen by a psychiatrist increased utilization (OR 2.5; P < 0.001), possibly because psychiatrists were seeing patients with severe depression. Conclusion: A large proportion of people with past-year MDEs utilized ADs and BDZs. It is unclear how much of this is appropriate given that evidence-based clinical guidelines recommend monotherapy with ADs in the treatment of major depression

Implementing complete smokefree policies in mental health inpatient settings Results from a before and after mixed-methods evaluation : results from a before and after mixed-methods evaluation

Abstract Background Tobacco smoking is extremely prevalent in people with severe mental illness (SMI) and has been recognised as the main contributor to widening health inequalities in this population. Historically, smoking has been deeply entrenched in the culture of mental health settings in the UK, and until recently, smokefree policies tended to be only partially implemented. However, recent national guidance and the government’s tobacco control plan now call for the implementation of complete smokefree policies. Many mental health Trusts across the UK are currently in the process of implementing the new guidance, but little is known about the impact of and experience with policy implementation. Methods This paper reports findings from a mixed-methods evaluation of policy implementation across 12 wards in a large mental health Trust in England. Quantitative data were collected and compared before and after implementation of NICE guidance PH48 and referred to 1) identification and treatment of tobacco dependence, 2) smoking-related incident reporting, and 3) prescribing of psychotropic medication. A qualitative exploration of the experience of inpatients was also carried out. Descriptive statistical analyses were performed, and the feasibility of collecting relevant and complete data for each quantitative component was assessed. Qualitative data were analysed using thematic framework analysis. Results Following implementation of the complete smokefree policy, increases in the numbers of patients offered smoking cessation advice (72% compared to 38%) were identified. While incident reports demonstrated a decrease in challenging behaviour during the post-PH48 period (6% compared to 23%), incidents relating to the concealment of smoking materials increased (10% compared to 2%). Patients reported encouraging changes in smoking behaviour and motivation to maintain change after discharge. However, implementation issues challenging full policy implementation, including covert facilitation of smoking by staff, were reported, and difficulties in collecting relevant and complete data for comprehensive evaluation purposes identified. Conclusions Overall, the implementation of complete smokefree policies in mental health settings may currently be undermined by partial support. Strategies to enhance support and the establishment of suitable data collection pathways to monitor progress are required

The Impact of Environmental Factors on Emergency Medicine Resident Career Choice

Objective: To evaluate the impact of environmental factors on emergency medicine (EM) resident career choice. Methods: Program directors of all U.S. EM residencies were surveyed in November 1997. A 22-item questionnaire assessed resources allocated to research, fellowship availability, academic productivity of faculty and residents, and career choices of residency graduates. Results: The response rate was 83%. The program director (mean ± SD) estimates of resident career choice were as follows: 27.8 ± 19.1% pursued academic positions with emphasis on teaching, 5.4 ± 9.8% pursued academic positions with emphasis on research, and 66.8 ± 23.1%, pursued private practice positions. In addition, 5.70 ± 6.13% of the residency graduates were estimated to seek felloship training. Univariate analyses demonstrated that increasing departmental funding for research, having substantial resource availability (defined as having at least two of the following: dedicated laboratory space; support for a laboratory research technician/assistant, a clinical research nurse or study coordinator, a statistician, or an assistant with a PhD degree), a greater number of peer-reviewed publications by residents (r = 0.22; p = 0.08), and a greater number of peer-reviewed publications by faculty (r = 0.26; p = 0.04) positively correlated with the percentage of graduates who pursue academic research careers. Using multiple regression, however, increasing intramural funding and the presence of substantial resource availability were the only variables predictive of resident pursuit of an academic research career. Conclusion: Modification of the EM training environment may influence the career choices of graduates. Specifically, greater commitment of departmental funds and support of resources for research may enhance the likelihood of a trainee's choosing an academic research career.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72940/1/j.1553-2712.1999.tb00387.x.pd

Guidelines of the Brazilian Association of Studies on Alcohol and Other Drugs (ABEAD) for diagnoses and treatment of psychiatric comorbidity with alcohol and other drugs dependence

Recently, several studies have focused on comorbity psychiatric disorders with alcohol and other substance dependence. The Brazilian Association of Studies on Alcohol and Other Drugs proposed the Brazilian Guidelines project. This study review diagnostic and therapeutic criteria to the most prevalent psychiatric comorbidities. Randomized clinical trials, epidemiological, animal studies and other forms of research are reviewed. The main psychiatric comorbidities are studied based on guidelines adopted by other countries and the literature data resumed. Epidemiological aspects, diagnoses, integrated treatment and service organization, as well as specific psychotherapic and pharmacological treatment are discussed. The Brazilian Association of Studies on Alcohol and Other Drugs Guidelines reassures the importance of adequate diagnoses and treatment regarding alcoholic and drug dependent patients suffering of comorbid psychiatric disorders.O diagnóstico e tratamento de comorbidade psiquiátrica e dependência de álcool e outras substâncias tem sido objeto de inúmeros estudos nos últimos anos. A Associação Brasileira de Estudos do Álcool e Outras Drogas desenvolveu o projeto Diretrizes. Este trabalho visa o desenvolvimento de critérios diagnósticos e terapêuticos atualizados para as comorbidades psiquiátricas mais prevalentes. Ensaios clínicos randomizados, estudos epidemiológicos, com animais e outros estudos são revisados. As principais comorbidades psiquiátricas são estudadas e os dados de literatura resumidos, tendo como referência diretrizes adotadas em outros países. São abordados aspectos epidemiológicos, critérios diagnósticos, tratamento integrado e organização de serviço especializado, assim como especificidades do tratamento psicoterápico e farmacológico. As Diretrizes da Associação Brasileira de Estudos do Álcool e Outras Drogas reforçam a importância da abordagem adequada do dependente químico portador de comorbidade psiquiátrica.Universidade Federal de Santa Catarina Núcleo de PsiquiatriaInstituto de Psiquiatria de Santa CatarinaUniversidade Federal de São Paulo (UNIFESP) Unidade de Pesquisa em Álcool e DrogasSanta Casa de Misericórdia de São Paulo Unidade de Álcool e DrogasUniversidade de São Paulo Faculdade de Medicina Hospital das ClinicasCentro de Atendimento Médico e SocialHospital de Clínicas de Porto AlegreHospital Israelita Albert EinsteinSanta Casa do Rio de Janeiro Setor de Dependência QuímicaUniversidade Gama FilhoUNIFESP, Unidade de Pesquisa em Álcool e DrogasSciEL

Compulsive features in behavioural addictions: the case of pathological gambling

Aims To describe, in the context of DSM-V, how a focus on addiction and compulsion is emerging in the consideration of pathological gambling (PG). Methods A systematic literature review of evidence for the proposed re-classification of PG as an addiction. Results Findings include: (i) phenomenological models of addiction highlighting a motivational shift from impulsivity to compulsivity associated with a protracted withdrawal syndrome and blurring of the ego-syntonic/ego-dystonic dichotomy; (ii) common neurotransmitter (dopamine, serotonin) contributions to PG and substance use disorders (SUDs); (iii) neuroimaging support for shared neurocircuitries between behavioural and substance addictions and differences between obsessivecompulsive disorder (OCD), impulse control disorders (ICDs) and SUDs; (iv) genetic findings more closely related to endophenotypic constructs such as compulsivity and impulsivity than to psychiatric disorders; (v) psychological measures such as harm avoidance identifying a closer association between SUDs and PG than with OCD; (vi) community and pharmacotherapeutic trials data supporting a closer association between SUDs and PG than with OCD. Adapted behavioural therapies, such as exposure therapy, appear applicable to OCD, PG or SUDs, suggesting some commonalities across disorders. Conclusions PG shares more similarities with SUDs than with OCD. Similar to the investigation of impulsivity, studies of compulsivity hold promising insights concerning the course, differential diagnosis and treatment of PG, SUDs, and OCD.LundbeckLundbeckServierServierCristaliaCristaliaRocheRocheSandozSandozMohegan Sun CasinoMohegan Sun CasinoNational Center for Responsible GamingNational Center for Responsible GamingAlberta Gaming Research InstituteAlberta Gaming Research InstituteNIH [R01 DA019039, R01 DA020908, RL1 AA017539, RC1 DA028279, P20 DA027844]NI

Overview on the management of radioactive waste from fusion facilities: ITER, demonstration machines and power plants

In the absence of official standards and guidelines for nuclear fusion plants, fusion designers adopted, as far as possible, well-established standards for fission-based nuclear power plants (NPPs). This often implies interpretation and/or extrapolation, due to differences in structures, systems and components, materials, safety mitigation systems, risks, etc. This approach could result in the consideration of overconservative measures that might lead to an increase in cost and complexity with limited or negligible improvements. One important topic is the generation of radioactive waste in fusion power plants. Fusion waste is significantly different to fission NPP waste, i.e. the quantity of fusion waste is much larger. However, it mostly comprises low-level waste (LLW) and intermediate level waste (ILW). Notably, the waste does not contain many long-lived isotopes, mainly tritium and other activation isotopes but no-transuranic elements. An important benefit of fusion employing reduced-activation materials is the lower decay heat removal and rapid radioactivity decay overall. The dominant fusion wastes are primarily composed of structural materials, such as different types of steel, including reduced activation ferritic martensitic steels, such as EUROFER97 and F82H, AISI 316L, bainitic, and JK2LB. The relevant long-lived radioisotopes come from alloying elements, such as niobium, molybdenum, nickel, carbon, nitrogen, copper and aluminum and also from uncontrolled impurities (of the same elements, but also, e.g. of potassium and cobalt). After irradiation, these isotopes might preclude disposal in LLW repositories. Fusion power should be able to avoid creating high-level waste, while the volume of fusion ILW and LLW will be significant, both in terms of pure volume and volume per unit of electricity produced. Thus, efforts to recycle and clear are essential to support fusion deployment, reclaim resources (through less ore mining) and minimize the radwaste burden for future generations

Retrospective and prospectively assessed childhood adversity in association with major depression, alcohol consumption and painful conditions.

Background. Considerable evidence now links childhood adversity to a variety of adult health problems. Unfortunately, almost all of these studies have relied upon retrospective assessment of childhood events, creating a vulnerability to bias. In this study, we sought to examine three associations using data sources that allowed for both prospective and retrospective assessment of childhood events. Methods. Methods. A 1994 national survey of children between the ages of 0 and 11 collected data from a ‘person most knowledgeable’ (usually the mother) about a child. It was possible to link data for n = 1977 of these respondents to data collected from the same people in a subsequent adult study. The latter survey included retrospective reports of childhood adversity. We examined three adult health outcomes in relation to prospectively and retrospectively assessed childhood adversity: major depressive episodes, excessive alcohol consumption and painful conditions. Results. Results. A strong association between childhood adversities (as assessed by both retrospective and prospective methods) and major depression was identified although the association with retrospective assessment was stronger. Weaker associations were found for painful conditions, but these did not depend on the method of assessment. Associations were not found for excessive alcohol consumption irrespective of the method of assessment. Conclusions. These findings help to allay concerns that associations between childhood adversities and health outcomes during adulthood are merely artefacts of recall bias. In this study, retrospective and prospective assessment strategies produced similar results