A Study of Alcohol Problems and Marriage from a Treatment Perspective

This thesis is concerned with alcohol problems and marital relationships. It is particularly interested in these dynamics from a treatment perspective. The study addresses theory, research and clinical practice in the field of alcohol problems. It specifically considers these areas as they relate to enhancing understanding of the dynamics between alcohol problems and marriage. The study examines three theoretical paradigms, the disease concept of addiction, behavioural/cognitive behavioural and systems based approaches to understanding alcohol addiction. This provides a multiple theory base from which research in the field and the clinical data collected in the current research is analysed and interpreted. The study reviews research findings that have contributed to the recognition of marital treatment interventions as significant in the alcohol field. It highlights the discrepancies between such research findings and developments in actual clinical practice. In doing so, the study illustrates the gap between theory, research and clinical practice. The need for a more effective framework of information exchange across these areas of activity is identified and a model for better exchange is presented and discussed. This model highlights the importance of including clients' experiences to influence policy, practice, theory and research. In the research, specific attention is focused on the experiences of couples in alcohol treatment. Clinical data is collected from a series of alcohol treatment couples group therapy sessions. The research analysis of the clinical data identifies and extracts concerns as expressed by couples in treatment. Interpretation of these identified concerns or themes is conducted by employing the theoretical constructs of the three selected theoretical paradigms in conjunction with group work theory. On the basis of the findings in this thesis a model for a maritally sensitive assessment framework is developed. The model identifies a number of factors that should be considered in order to enhance appreciation of the interaction between alcohol problems and marital dynamics. This has particular significance for treatment interventions.This resource was contributed by The National Documentation Centre on Drug Use.

Intervenció psicopedagògica a Primària per millorar l'aprenentatge del càlcul mental a Cicle Mitjà

Es tracta d'un programa d'assessorament i intervenció psicopedagògica en una escola per a treballar el càlcul mental a primària, concretament al cicle mitjà, però també extensible a altres cicles, a partir de l'adaptació de diferents jocs de taula mitjançant la creació de tallers de matemàtiques i amb una pràctica basada en el constructivisme.

Does 'altitude training' increase exercise performance in elite athletes?

The general practice of altitude training is widely accepted as a means to enhance sport performance despite a lack of rigorous scientific studies. For example, the scientific gold-standard design of a double-blind, placebo-controlled, cross-over trial has never been conducted on altitude training. Given that few studies have utilised appropriate controls, there should be more scepticism concerning the effects of altitude training methodologies. In this brief review we aim to point out weaknesses in theories and methodologies of the various altitude training paradigms and to highlight the few well-designed studies to give athletes, coaches and sports medicine professionals the current scientific state of knowledge on common forms of altitude training. Another aim is to encourage investigators to design well-controlled studies that will enhance our understanding of the mechanisms and potential benefits of altitude training.

Environnement et capacités cognitives chez le rat : compétition entre les facteurs qui influencent les stratégies spatiales

RESUME Ce travail se propose de discuter des résultats comportementaux observés chez des rats obtenus dans trois paradigmes expérimentaux différents : le bassin de Morris (Morris Water Maze, Morris, 1984) ; la table à trous (Homing Board, Schenk, 1989) et le labyrinthe radial (Radial Arm Maze, Olton et Samuelson, 1976). Les deux premières tâches sont spatiales et permettent un apprentissage de place en environnements contrôlés, et la troisième est une tâche comportementale qui différencie deux habiletés particulières, celle d'élimination (basée sur la mémoire de travail) et celle de sélection (basée sur la mémoire de référence). La discussion des résultats porte sur les stratégies de navigation utilisées par les animaux pour résoudre les tâches et plus précisément sur les facteurs qui peuvent influencer le choix de ces stratégies. Le facteur environnemental (environnement contrôlé) et le facteur cognitif (vieillissement) représentent les variables étudiées ici. C'est ainsi que certaines hypothèses communément acceptées ont été malmenées par nos résultats. Or si l'espace est habituellement supposé homogène (toutes les positions spatiales présentent le même degré de difficulté lors d'un apprentissage en champ ouvert), ce travail établit qu'une position associée -sans contiguïté - à l'un des trois indices visuels situés dans la périphérie de l'environnement est plus difficile à apprendre qu'une position située entre deux des trois indices. Deuxièmement, alors qu'il est admis que l'apprentissage d'une place dans un environnement riche requiert le même type d'information. dans la bassin de Morris (tâche nagée) que sur la table à trous (tâche marchée), nous avons montré que la discrimination spatiale en bassin ne peut être assurée par les trois indices visuels périphériques et nécessite la présence d'au moins un élément supplémentaire. Enfin, l'étude du vieillissement a souvent montré que l'âge réduit les capacités cognitives nécessaires à la navigation spatiale, conduisant à un déficit général des performances d'un animal sénescent, alors que dans notre travail, nous avons trouvé les animaux âgés plus performants et plus efficaces que les adultes dans une tâche particulière de collecte de nourriture. Ces expériences s'inscrivent dans une étude générale qui met à l'épreuve le modèle théorique proposé pax Schenk et Jacobs (2003), selon lequel l'encodage de la carte cognitive (Tolman, 1948 ; O'Keefe et Nadel, 1978) se ferait dans l'hippocampe par l'activité de deux modules complémentaires :d'une part le CA3 - Gyrus Denté pour le traitement d'une trame spatiale basée sur des éléments directionnels et Jou distribués en gradient (bearing map) et d'autre part le CAl - Subiculum pour le traitement des représentations locales basées sur les positions relatives des éléments fixes de l'environnement (sketch map). SUMMARY This work proposes to talk about behavioural results observed in three different experimental paradigms with rats: the Morris Water Maze (Morris, 1984); the Homing Board (Schenk, 1989) and the Radial Arm Maze (Olton and Samuelson, 1976). The two first tasks are spatial ones and allow place learning in controlled environments. The third one is a behavioural task which contrasts two particular skills, the elimination (based on working memory) and the selection one (based on reference memory). The topic of the discussion will be the navigation strategies used by animals to solve the different tasks, and more precisely the factors which can bias this strategies' choice. The environmental (controlled) and the cognitive (aging) factors are the variables studied here. Thus, some hypotheses usually accepted were manhandled by our results. Indeed, if space is habitually homogenously considered (all spatial positions present the same degree of difficulty in an open field learning), this work establishes that an associated position -without being adjacent - to one of the three visual cues localised in the environmental periphery is more difficult to learn than a configurationnel position (situated between two of the three cues). Secondly, if it is received that place learning in a rich environment requires the same information in the Morris water maze (swimming task) that on the Homing board (walking task), we showed that spatial discrimination in the water maze can't be provided by the three peripheral cue cards and needs the presence of a supplementary cue. At last, aging studies often showed that oldness decreases cognitive skills in spatial navigation, leading to a general deficit in performances. But, in our work, we found that senescent rats were more efficient than adult ones in a special food collecting task. These experiments come within the scope of a general study which tests the theoretical model proposed by Jacobs and Schenk (2003), according to which the cognitive map's encoding (Tolman, 1948, O'Keefe and Nadel, 1978) should take place in the hippocampus by two complementary modules, first the DG-CA3 should encode directional and/or gradients references (the bearing map), and secondly the Subiculum-CAl should process locale elements (the sketch map).

Analysis of GPCR properties of Frizzled receptors and establishment of the "in vitro" platform for screening of Frizzled agonists/antagonists as potential therapeutic agents

Morphogens of the Wnt protein family are the secreted lipoglycoprotein ligands which initiate several pathways heavily involved in the coordination of various developmental stages of organisms in the majority of animal species. Deregulation of these pathways in the adult leads to formation and sustaining of multiple types of cancer. The latter notion is reinforced by the fact that the very discovery of the first Wnt ligand was due to its role as the causative factor of carcinogenic transformation (Nusse and Varmus, 1982). Nowadays our knowledge on Wnt signaling has "moved with the times" and these pathways were identified to be often crucial for tumor formation, its interactions with the microenvironment, and promotion of the metastases (Huang and Du, 2008; Zerlin et al., 2008; Jessen, 2009). Thus the relevance of the pathway as the target for drug development has further increased in the light of modern paradigms of the complex cancer treatments which target also spreading and growth- promoting factors of tumors by specific and highly efficient substances (Pavet et al., 2010). Presently the field of the Wnt-targeting drug research is almost solely dominated by assays based on transcriptional activation induced by the signaling. This approach resulted in development of a number of promising substances (Lee et al., 2011). Despite its effectiveness, the method nevertheless suffers from several drawbacks. Among the major ones is the fact that this approach is prone to identify compounds targeting rather downstream effectors of the pathway, which are indiscriminately used by all the subtypes of the Wnt signaling. Additionally, proteins which are involved in several signaling cascades and not just the Wnt pathway turn out as targets of the new compounds. These issues increase risks of side effects due to off-target interactions and blockade of the pathway in healthy cells. In the present work we put forward a novel biochemical approach for drug development on the Wnt pathway. It targets Frizzleds (Fzs) - a family of 7-transmbembrane proteins which serve as receptors for Wnt ligands. They offer unique properties for the development of highly specific and effective drugs as they control all branches of the Wnt signaling. Recent advances in the understanding of the roles of heterotrimeric G proteins downstream from Fzs (Katanaev et al., 2005; Liu et al., 2005; Jernigan et al., 2010) suggest application of enzymatic properties of these effectors to monitor the receptor-mediated events. We have applied this knowledge in practice and established a specific and efficient method based on utilization of a novel high-throughput format of the GTP-binding assay to follow the activation of Fzs. This type of assay is a robust and well-established technology for the research and screenings on the GPCRs (Harrison and Traynor, 2003). The conventional method of detection involves the radioactively labeled non-hydrolysable GTP analog [35S]GTPyS. Its application in the large-scale screenings is however problematic which promoted development of the novel non-radioactive GTP analog GTP-Eu. The new molecule employs phenomenon of the time-resolved fluorescence to provide sensitivity comparable to the conventional radioactive substance. Initially GTP-Eu was tested only in one of many possible types of GTP-binding assays (Frang et al., 2003). In the present work we expand these limits by demonstrating the general comparability of the novel label with the radioactive method in various types of assays. We provide a biochemical characterization of GTP-Eu interactions with heterotrimeric and small GTPases and a comparative analysis of the behavior of the new label in the assays involving heterotrimeric G protein effectors. These developments in the GTP-binding assay were then applied to monitor G protein activation by the Fz receptors. The data obtained in mammalian cultured cell lines provides for the first time an unambiguous biochemical proof for direct coupling of Fzs with G proteins. The specificity of this interaction has been confirmed by the experiments with the antagonists of Fz and by the pertussis toxin-mediated deactivation. Additionally we have identified the specificity of Wnt3a towards several members of the Fz family and analyzed the properties of human Fz-1 which was found to be the receptor coupled to the Gi/o family of G proteins. Another process playing significant role in the functioning of every GPCR is endocytosis. This phenomenon can also be employed for drug screenings on GPCRs (Bickle, 2010). In the present work we have demonstrated that Drosophila Fz receptors are involved in an unusual for many GPCRs manifestation of the receptor-mediated internalization. Through combination of biochemical approaches and studies on Drosophila as the model organism we have shown that direct interactions of the Fzs and the α-subunit of the heterotrimeric G protein Go with the small GTPase Rab5 regulate internalization of the receptor in early endosomes. We provide data uncovering the decisive role of this self-promoted endocytosis in formation of a proper signaling output in the canonical as well as planar cell polarity (PCP) pathways regulated by Fz. The results of this work thus establish a platform for the high-throughput screening to identify substances active in the cancer-related Wnt pathways. This methodology has been adjusted and applied to provide the important insights in Fz functioning and will be instrumental for further investigations on the Wnt-mediated pathways.

A Thematic Comparison of Eight Frameworks of Quality Criteria in Qualitative Health Research

Background: Despite the increasing incidences of the publication of assessment frameworks intending to establish the "standards" of the quality of qualitative research, the research conducted using such empirical methods are still facing difficulties in being published or recognised by funding agencies. Methods: We conducted a thematic content analysis of eight frameworks from psychology/psychiatry and general medicine. The frameworks and their criteria are then compared against each other. Findings: The results illustrated the difficulties in reaching consensus on the definition of quality criteria. This showed the differences between the frameworks from the point of views of the underlying epistemology and the criteria suggested. Discussion: The aforementioned differences reflect the diversity of paradigms implicitly referred to by the authors of the frameworks, although rarely explicitly mentioned in text. We conclude that the increase in qualitative research and publications has failed to overcome the difficulties in establishing shared criteria and the great heterogeneity of concepts raises methodological and epistemological problems.

Simultaneous EEG-fMRI at ultra-high field: Artifact prevention and safety assessment.

The simultaneous recording of scalp electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) can provide unique insights into the dynamics of human brain function, and the increased functional sensitivity offered by ultra-high field fMRI opens exciting perspectives for the future of this multimodal approach. However, simultaneous recordings are susceptible to various types of artifacts, many of which scale with magnetic field strength and can seriously compromise both EEG and fMRI data quality in recordings above 3T. The aim of the present study was to implement and characterize an optimized setup for simultaneous EEG-fMRI in humans at 7T. The effects of EEG cable length and geometry for signal transmission between the cap and amplifiers were assessed in a phantom model, with specific attention to noise contributions from the MR scanner coldheads. Cable shortening (down to 12cm from cap to amplifiers) and bundling effectively reduced environment noise by up to 84% in average power and 91% in inter-channel power variability. Subject safety was assessed and confirmed via numerical simulations of RF power distribution and temperature measurements on a phantom model, building on the limited existing literature at ultra-high field. MRI data degradation effects due to the EEG system were characterized via B0 and B1(+) field mapping on a human volunteer, demonstrating important, although not prohibitive, B1 disruption effects. With the optimized setup, simultaneous EEG-fMRI acquisitions were performed on 5 healthy volunteers undergoing two visual paradigms: an eyes-open/eyes-closed task, and a visual evoked potential (VEP) paradigm using reversing-checkerboard stimulation. EEG data exhibited clear occipital alpha modulation and average VEPs, respectively, with concomitant BOLD signal changes. On a single-trial level, alpha power variations could be observed with relative confidence on all trials; VEP detection was more limited, although statistically significant responses could be detected in more than 50% of trials for every subject. Overall, we conclude that the proposed setup is well suited for simultaneous EEG-fMRI at 7T.

El Treball per Projectes a secundària: estudi d'un cas a l'Institut de Sils

La metodologia del Treball per Projectes té cada cop més implantació en les nostres aules catalanes. No obstant, el cert es que aquest tipus de treball es realitza, majoritàriament, als centres de primària. El treball que es presenta a continuació pretén cercar, a un institut públic les causes d’aquest desequilibri però també analitzar els punts forts i febles d’aquesta metodologia, a partir de les vivències i els coneixements de tots els agents implicats

Progression of auditory discrimination based on neural decoding predicts awakening from coma.

Auditory evoked potentials are informative of intact cortical functions of comatose patients. The integrity of auditory functions evaluated using mismatch negativity paradigms has been associated with their chances of survival. However, because auditory discrimination is assessed at various delays after coma onset, it is still unclear whether this impairment depends on the time of the recording. We hypothesized that impairment in auditory discrimination capabilities is indicative of coma progression, rather than of the comatose state itself and that rudimentary auditory discrimination remains intact during acute stages of coma. We studied 30 post-anoxic comatose patients resuscitated from cardiac arrest and five healthy, age-matched controls. Using a mismatch negativity paradigm, we performed two electroencephalography recordings with a standard 19-channel clinical montage: the first within 24 h after coma onset and under mild therapeutic hypothermia, and the second after 1 day and under normothermic conditions. We analysed electroencephalography responses based on a multivariate decoding algorithm that automatically quantifies neural discrimination at the single patient level. Results showed high average decoding accuracy in discriminating sounds both for control subjects and comatose patients. Importantly, accurate decoding was largely independent of patients' chance of survival. However, the progression of auditory discrimination between the first and second recordings was informative of a patient's chance of survival. A deterioration of auditory discrimination was observed in all non-survivors (equivalent to 100% positive predictive value for survivors). We show, for the first time, evidence of intact auditory processing even in comatose patients who do not survive and that progression of sound discrimination over time is informative of a patient's chance of survival. Tracking auditory discrimination in comatose patients could provide new insight to the chance of awakening in a quantitative and automatic fashion during early stages of coma.

The role of hypocretin in driving arousal and goal-oriented behaviors.

The hypocretins (Hcrts), also called orexins, are two neuropeptides secreted by a few thousand neurons restricted to the lateral hypothalamus. The Hcrt peptides bind to two receptors located in nuclei associated with diverse cognitive and physiological functions. Experimental evidence has demonstrated that the physiological roles of hypocretins extend far beyond its initial role in food consumption and has emerged as a key system in the fields of sleep disorders and drug addiction. Here, we discuss recent evidence demonstrating a key role of hypocretin in the motivation for reward seeking in general, and drug taking in particular, and we delineate a physiological framework for this peptidergic system in orchestrating the appropriate levels of alertness required for the elaboration and the execution of goal-oriented behaviors. We propose a general role for hypocretins in mediating arousal, especially when an organism must respond to unexpected stressors and environmental challenges, which serve to shape survival behaviors. We also discuss the limit of the current experimental paradigms to address the question of how a system normally involved in the regulation of vigilance states and hyperarousal may promote a pathological state that elicits compulsive craving and relapse to drug seeking.

Protein-protein interactions at the adrenergic receptors.

The adrenergic receptors are among the best characterized G protein-coupled receptors (GPCRs) and knowledge on this receptor family has provided several important paradigms about GPCR function and regulation. One of the most recent paradigms initially supported by studies on adrenergic receptors is that both βarrestins and G proteincoupled receptors themselves can act as scaffolds binding a variety of proteins and this can result in growing complexity of the receptor-mediated cellular effects. In this review we will briefly summarize the main features of βarrestin binding to the adrenergic receptor subtypes and we will review more in detail the main proteins found to selectively interact with distinct AR subtype. At the end, we will review the main findings on oligomerization of the AR subtypes.

Interchange of callosal and association projections in the developing visual cortex.

Neurons projecting transitorily into the corpus callosum from area 17 of the cat were retrogradely labeled by the fluorescent tracer Fast Blue (FB) injected into contralateral areas 17 and 18 on postnatal days 1-5. During the second postnatal month these neurons were still labeled by the early injection, although they had eliminated their callosal axon. At this time, 15-20% of these neurons could be retrogradely relabeled by injections of Diamidino Yellow (DY) into ipsilateral areas 17 and 18, but few or none by similar injections in the other areas that receive from area 17 (19, 21a, PMLS, 20a, 20b, DLS). Similarly, area 17 neurons projecting transitorily to contralateral area PMLS during the first postnatal week could be relabeled by DY injections in ipsilateral areas 17 and 18 but not in PMLS. Already around birth, many transitorily callosal neurons in area 17 send bifurcating axons both to contralateral areas 17 and 18 and ipsilateral area 18. It is probable that during postnatal development some of these neurons selectively eliminate their callosal axon collaterals and maintain the projection to ipsilateral area 18. In fact, some transitorily callosal neurons in area 17 can be double-labeled by simultaneous perinatal injections of FB in contralateral areas 17 and 18 and of a new long-lasting retrograde tracer, rhodamine-conjugated latex microspheres, in ipsilateral area 18. The same neurons can then be relabeled by reinjecting ipsilateral area 18 with DY during the second postnatal month. This finding, however, does not exclude the possibility that some transitorily callosal neurons send an axon to ipsilateral area 18 after eliminating their callosal axon. In conclusion, area 17 neurons that project transitorily through the corpus callosum later participate, probably permanently, in ipsilateral corticocortical projections but selectively to areas 17-18. The mechanism responsible for this selectivity is unknown, but it may be related to the differential radial distribution (i.e., to birth date) of area 17 neurons engaged in the various corticocortical projections. The problems raised by the use of long-lasting retrograde fluorescent tracers in neurodevelopmental studies and by the quantification of results of double- and triple-labeling paradigms are also discussed.

An electronic voting platform with elliptic curve cryptography

The future of elections seems to be electronic voting systems du to its advantatges over the traditional voting. Nowadays, there are some different paradigms to ensure the security and reliability of e-voting. This document is part of a wider project which presents an e-Voting platform based on elliptic curve cryptography. It uses an hybrid combination of two of the main e-Voting paradigms to guarantee privacy and security in the counting phase, these are precisely, the mixnets and the homomorphic protocols. This document is focused in the description of the system and the maths and programming needed to solve the homomorphic part of it. In later chapters, there is a comparison between a simple mixing system and our system proposal.

Tree-based message diffusion for managing replicated data in unreliable and resource-constrained peer-to-peer environment

Abstract This thesis proposes a set of adaptive broadcast solutions and an adaptive data replication solution to support the deployment of P2P applications. P2P applications are an emerging type of distributed applications that are running on top of P2P networks. Typical P2P applications are video streaming, file sharing, etc. While interesting because they are fully distributed, P2P applications suffer from several deployment problems, due to the nature of the environment on which they perform. Indeed, defining an application on top of a P2P network often means defining an application where peers contribute resources in exchange for their ability to use the P2P application. For example, in P2P file sharing application, while the user is downloading some file, the P2P application is in parallel serving that file to other users. Such peers could have limited hardware resources, e.g., CPU, bandwidth and memory or the end-user could decide to limit the resources it dedicates to the P2P application a priori. In addition, a P2P network is typically emerged into an unreliable environment, where communication links and processes are subject to message losses and crashes, respectively. To support P2P applications, this thesis proposes a set of services that address some underlying constraints related to the nature of P2P networks. The proposed services include a set of adaptive broadcast solutions and an adaptive data replication solution that can be used as the basis of several P2P applications. Our data replication solution permits to increase availability and to reduce the communication overhead. The broadcast solutions aim, at providing a communication substrate encapsulating one of the key communication paradigms used by P2P applications: broadcast. Our broadcast solutions typically aim at offering reliability and scalability to some upper layer, be it an end-to-end P2P application or another system-level layer, such as a data replication layer. Our contributions are organized in a protocol stack made of three layers. In each layer, we propose a set of adaptive protocols that address specific constraints imposed by the environment. Each protocol is evaluated through a set of simulations. The adaptiveness aspect of our solutions relies on the fact that they take into account the constraints of the underlying system in a proactive manner. To model these constraints, we define an environment approximation algorithm allowing us to obtain an approximated view about the system or part of it. This approximated view includes the topology and the components reliability expressed in probabilistic terms. To adapt to the underlying system constraints, the proposed broadcast solutions route messages through tree overlays permitting to maximize the broadcast reliability. Here, the broadcast reliability is expressed as a function of the selected paths reliability and of the use of available resources. These resources are modeled in terms of quotas of messages translating the receiving and sending capacities at each node. To allow a deployment in a large-scale system, we take into account the available memory at processes by limiting the view they have to maintain about the system. Using this partial view, we propose three scalable broadcast algorithms, which are based on a propagation overlay that tends to the global tree overlay and adapts to some constraints of the underlying system. At a higher level, this thesis also proposes a data replication solution that is adaptive both in terms of replica placement and in terms of request routing. At the routing level, this solution takes the unreliability of the environment into account, in order to maximize reliable delivery of requests. At the replica placement level, the dynamically changing origin and frequency of read/write requests are analyzed, in order to define a set of replica that minimizes communication cost.

An Analysis of black-box optimization problems in reinsurance: evolutionary-based approaches

Black-box optimization problems (BBOP) are de ned as those optimization problems in which the objective function does not have an algebraic expression, but it is the output of a system (usually a computer program). This paper is focussed on BBOPs that arise in the eld of insurance, and more speci cally in reinsurance problems. In this area, the complexity of the models and assumptions considered to de ne the reinsurance rules and conditions produces hard black-box optimization problems, that must be solved in order to obtain the optimal output of the reinsurance. The application of traditional optimization approaches is not possible in BBOP, so new computational paradigms must be applied to solve these problems. In this paper we show the performance of two evolutionary-based techniques (Evolutionary Programming and Particle Swarm Optimization). We provide an analysis in three BBOP in reinsurance, where the evolutionary-based approaches exhibit an excellent behaviour, nding the optimal solution within a fraction of the computational cost used by inspection or enumeration methods.