Beyond the usual suspects: positive attitudes towards positive symptoms is associated with medication noncompliance in psychosis.

Antipsychotic medication represents the treatment of choice in psychosis according to clinical guidelines. Nevertheless, studies show that half to almost three-quarter of all patients discontinue medication with antipsychotics after some time, a fact which is traditionally ascribed to side-effects, mistrust against the clinician and poor illness insight. The present study investigated whether positive attitudes toward psychotic symptoms (ie, gain from illness) represent a further factor for medication noncompliance. An anonymous online survey was set up in order to prevent conservative response biases that likely emerge in a clinical setting. Following an iterative selection process, data from a total of 113 patients with a likely diagnosis of schizophrenia and a history of antipsychotic treatment were retained for the final analyses (80%). While side-effect profile and mistrust emerged as the most frequent reasons for drug discontinuation, 28% of the sample reported gain from illness (eg, missing voices, feeling of power) as a motive for noncompliance. At least every fourth patient reported the following reasons: stigma (31%), mistrust against the physician/therapist (31%), and rejection of medication in general (28%). Approximately every fifth patient had discontinued antipsychotic treatment because of forgetfulness. On average, patients provided 4 different explanations for noncompliance. Ambivalence toward symptoms and treatment should thoroughly be considered when planning treatment in psychosis. While antipsychotic medication represents the evidence-based cornerstone of the current treatment in schizophrenia, further research is needed on nonpharmacological interventions for noncompliant patients who are willing to undergo intervention but refuse pharmacotherapy.

Synchronization of EEG: bivariate and multivariate measures.

Synchronization behavior of electroencephalographic (EEG) signals is important for decoding information processing in the human brain. Modern multichannel EEG allows a transition from traditional measurements of synchronization in pairs of EEG signals to whole-brain synchronization maps. The latter can be based on bivariate measures (BM) via averaging over pair-wise values or, alternatively, on multivariate measures (MM), which directly ascribe a single value to the synchronization in a group. In order to compare BM versus MM, we applied nine different estimators to simulated multivariate time series with known parameters and to real EEGs.We found widespread correlations between BM and MM, which were almost frequency-independent for all the measures except coherence. The analysis of the behavior of synchronization measures in simulated settings with variable coupling strength, connection probability, and parameter mismatch showed that some of them, including S-estimator, S-Renyi, omega, and coherence, aremore sensitive to linear interdependences,while others, like mutual information and phase locking value, are more responsive to nonlinear effects. Onemust consider these properties together with the fact thatMM are computationally less expensive and, therefore, more efficient for the large-scale data sets than BM while choosing a synchronization measure for EEG analysis.

Aplicació INERCIPHER

El programa INERCIPHER és una aplicació per realitzar el xifrat i desxifrat dels arxius i per verificar la integritat dels documents. Com a base per desenvolupar aquestes funcionalitats han estat utilitzats dos tipus de xifrat de clau compartida: xifrat en flux i xifrat en bloc.

Effects of Trypanosoma brucei tryptophanyl-tRNA synthetases silencing by RNA interference

The kinetoplast genetic code deviates from the universal code in that 90% of mitochondrial tryptophans are specified by UGA instead of UGG codons. A single nucleus-encoded tRNA Trp(CCA) is used by both nuclear and mitochondria genes, since all kinetoplast tRNAs are imported into the mitochondria from the cytoplasm. To allow decoding of the mitochondrial UGA codons as tryptophan, the tRNA Trp(CCA) anticodon is changed to UCA by an editing event. Two tryptophanyl tRNA synthetases (TrpRSs) have been identified in Trypanosoma brucei: TbTrpRS1 and TbTrpRS2 which localize to the cytoplasm and mitochondria respectively. We used inducible RNA interference (RNAi) to assess the role of TbTrpRSs. Our data validates previous observations of TrpRS as potential drug design targets and investigates the RNAi effect on the mitochondria of the parasite.

Self-reported health needs and use of primary health care services by adolescents enrolled in post-mandatory schools or vocational training programmes in Switzerland.

BACKGROUND: The second Swiss Multicenter Adolescent Survey on Health (SMASH02) was conducted among a representative sample (n = 7428) of students and apprentices aged 16 to 20 from the three language areas of Switzerland during the year 2002. This paper reports on health needs expressed by adolescents and their use of health care services over the 12 months preceding the survey. METHODS: Nineteen cantons representing 80% of the resident population agreed to participate. A complex iterative random cluster sample of 600 classes was drawn with classes as primary sampling unit. The participation rate was 97.7% for the classes and 99.8% for the youths in attendance. The self-administered questionnaire included 565 items. The median rate of item non-response was 1.8%. Ethical and legal requirements applying to surveys of adolescent populations were respected. RESULTS: Overall more than 90% of adolescents felt in good to excellent health. Suffering often or very often from different physical complaints or pain was also reported such as headache (boys: 15.9%, girls: 37.4%), stomach-ache (boys: 9.7%, girls: 30.0%), joint pain (boys: 24.7%, girls: 29.5%) or back pain (boys: 24.3%, girls: 34.7%). Many adolescents reported a need for help on psychosocial and lifestyle issues, such as stress (boys: 28.5%, girls: 47.7%) or depression (boys: 18.9%, girls: 34.4%). Although about 75% of adolescents reported having consulted a general practitioner and about one-third having seen another specialist, reported reasons for visits do not correspond to the expressed needs. Less than 10% of adolescents had visited a psychiatrist, a family planning centre or a social worker. CONCLUSIONS: The reported rates of health services utilisation by adolescents does not match the substantial reported needs for help in various areas. This may indicate that the corresponding problems are not adequately detected and/or addressed by professionals from the health and social sectors.

The Value of Imperfection : the Wabi-Sabi Principle in Aesthetics and Learning

OER-based learning has the potential to overcome many shortcomings and problems of traditional education. It is not hampered by IP restrictions; can depend on collaborative, cumulative, iterative refinement of resources; and the digital form provides unprecedented flexibility with respect to configuration and delivery. The OER community is a progressive group of educators and learners with decades of learning research to draw from, who know that we must prepare learners for an evolving and diverse reality. Despite this OER tends to replicate the unsuccessful characteristics of traditional education. To remedy this we may need to remember the importance of imperfection, mistakes, problems, disagreement, and the incomplete for engaged learning, and relinquish our notions of perfection, acknowledging that learners learn differently and we need diverse learners. We must stretch our perceptions of quality and provide mechanisms for engaging the incredible pool of educators globally to fulfill the promise of inclusive education.

A survey addressing the fundamental matrix estimation problem

Epipolar geometry is a key point in computer vision and the fundamental matrix estimation is the only way to compute it. This article surveys several methods of fundamental matrix estimation which have been classified into linear methods, iterative methods and robust methods. All of these methods have been programmed and their accuracy analysed using real images. A summary, accompanied with experimental results, is given

KAM theory for conformally symplectic systems

We present a KAM theory for some dissipative systems (geometrically, these are conformally symplectic systems, i.e. systems that transform a symplectic form into a multiple of itself). For systems with n degrees of freedom depending on n parameters we show that it is possible to find solutions with n-dimensional (Diophantine) frequencies by adjusting the parameters. We do not assume that the system is close to integrable, but we use an a-posteriori format. Our unknowns are a parameterization of the solution and a parameter. We show that if there is a sufficiently approximate solution of the invariance equation, which also satisfies some explicit non–degeneracy conditions, then there is a true solution nearby. We present results both in Sobolev norms and in analytic norms. The a–posteriori format has several consequences: A) smooth dependence on the parameters, including the singular limit of zero dissipation; B) estimates on the measure of parameters covered by quasi–periodic solutions; C) convergence of perturbative expansions in analytic systems; D) bootstrap of regularity (i.e., that all tori which are smooth enough are analytic if the map is analytic); E) a numerically efficient criterion for the break–down of the quasi–periodic solutions. The proof is based on an iterative quadratically convergent method and on suitable estimates on the (analytical and Sobolev) norms of the approximate solution. The iterative step takes advantage of some geometric identities, which give a very useful coordinate system in the neighborhood of invariant (or approximately invariant) tori. This system of coordinates has several other uses: A) it shows that for dissipative conformally symplectic systems the quasi–periodic solutions are attractors, B) it leads to efficient algorithms, which have been implemented elsewhere. Details of the proof are given mainly for maps, but we also explain the slight modifications needed for flows and we devote the appendix to present explicit algorithms for flows.

Biochemical characterization of recombinant human telomerase

Résumé Les télomères sont les structures ADN-protéines des extrémités des chromosomes des eucaryotes. L'ADN télomérique est constitué de courtes séquences répétitives. L'intégrité des télomères est essentielle pour protéger les extrémités des chromosomes contre les systèmes de dégradations et pour les distinguer des cassures de l'ADN double brin. Parce que la machinerie de la réplication de l'ADN n'est pas capable de répliquer l'extrémité des chromosomes, les télomères raccourcissent au fur et à mesure des cycles de réplication. Dès que les télomères atteignent une longueur critique, leur structure protectrice est perdue. Cela induit un signal de dommage de l'ADN et l'arrêt du cycle cellulaire. Pour contrebalancer le raccourcissement des télomères, les cellules qui s'auto régénèrent, dont les cellules de la moelle osseuse, les lymphocytes activés et 80-90% des cellules cancéreuses, expriment la télomérase. C'est une ribonucléoprotéine qui a la capacité de synthétiser des séquences télomériques par transcription inverse d'une courte séquence contenue dans sa propre sous-unité ARN avec laquelle elle est associée. La télomérase humaine est une enzyme processive au niveau de l'addition des nucléotides et aussi des répétitions télomériques. La télomérase de levure et la télomérase humaine sont toutes deux dimériques et il a été montré que la télomérase humaine recombinante contient deux ARN qui coopèrent pour fonctionner ainsi que deux sous-unités catalytiques. Cependant, il n'a pas encore été montré quel est le rôle de la dimérisation dans l'activité de la télomérase. Afin d'élucider ce rôle, nous avons exprimé, reconstitué et purifié la télomérase humaine dimérique recombinante. Et pour étudier l'effet d'ARN mutants sur l'activité de la télomérase, nous avons développé une méthode pour reconstituer et enrichir en hétérodimères de télomérase. Les hétérodimères contiennent une sous-unité ARN sauvage et une sous-unité ARN mutée au niveau de la séquence de la matrice. Sur l'ARN muté nous avons introduit une étiquette aptamer ARN-S1 puis nous avons purifié la télomérase via l'etiquette Si. Nous avons montré que la dimérisation est essentielle pour l'activité de la télomérase. Nos données indiquent que chaque télomérase du dimère allonge leur substrat, l'ADN télomérique, indépendamment l'une de l'autre à chaque cycle d'élongation mais que l'addition itérative de répétitions télomériques nécessite une coopération entre les deux télomérases du dimère. Nous proposons donc un modèle dans lequel les deux télomérases du dimères se lient et allongent deux substrats télomères et que pendant l'élongation processive les deux enzymes subissent un changement de conformation de manière coordonnée, ce changement va permettre le repositionnement des substrats pour d'autres cycles d'additions de répétitions télomériques. Dyskeratosis congenita est une maladie mortelle due majoritairement au disfonctionnement de la moelle osseuse. Dans la forme autosomale de la maladie, l'ARN de la télomérase contient des mutations. En utilisant notre système de reconstitution, nous avons montré que ces ARN mutés, qui ont perdu leur activité enzymatique dans le cas d'un homodimère de mutants, sont dominant négatifs quand ils sont présents dans les hétérodimères sauvage/mutant. Cet effet trans-dominant négatif pourrait contribuer à la progression de la maladie. Abstract Telomeres are protein-DNA structures at the ends of linear eukaryotic chromosomes. The telomeric DNA consists of tandemly repeated sequences. Telomeric integrity is essential to protect chromosomal ends from nucleolytic degradation and to prevent their recognition as DNA double strand breaks. Due to the inability of the conventional DNA replication machinery to replicate terminal DNA stretches, telomeres shorten with continuous rounds of DNA replication. As soon as telomeres reach a critical length, their protective structure is lost and the deprotected telomeres will induce a DNA damage response leading to cell cycle arrest. To counteract telomere shortening, self-renewing cells, including bone marrow cells, activated lymphocytes and 80-90% of cancer cells express the cellular reverse transcriptase telomerase, which has the capacity to synthesize telomeric repeats by reverse transcription of a short template sequence encoded by its stably associated RNA subunit. Human telomerase is a processive enzyme for nucleotide as well as repeat addition. Both yeast and human telomerase are dimeric enzymes and recombinant human telomerase has been shown to contain two functionally cooperating RNAs and most probably also two protein subunits. However, it has remained unclear how dimerization may contribute to telomerase activity. To study the role of dimerization, we expressed, reconstituted and purified recombinant human telomerase. We also developed a new method to reconstitute and enrich for telomerase heterodimers containing wild-type (wt) and mutant telomerase RNA subunits. To this end we introduced an S1-RNA-aptamer tag into telomerase RNA and purified telomerase reconstituted with a mixture of untagged and tagged RNA via the S1-tag. Using this experimental system, we introduced template mutations in the tagged RNA subunit and examined the effect of mutant RNAs on wt telomerase activity in wt/mutant heterodimers. We obtained evidence that dimerization is essential for telomerase activity. Our data indicate that the two subunits elongate telomere substrates independently of each other during single rounds of elongation, but that iterative addition of telomeric repeats requires cooperation between the two subunits. We suggest a model, in which dimeric telomerases bind and elongate two telomere substrates and that the two subunits undergo coordinated conformational changes during processive elongation that enable repositioning the substrates for subsequent rounds of repeat addition. Dyskeratosis congenita is a multisystemic disease with bone marrow failure as the major cause of death. The autosomal form of this disease was found to harbor mutations in the telomerase RNA. Using our reconstitution system, we tested whether mutant dyskeratosis telomerase RNAs behaved in a dominant negative manner. We observed that dyskeratosis telomerase RNA mutants, which lacked enzymatic activity were dominant negative, when present in wt/ mutant heterodimers. The transdominant negative effect of these mutants may contribute to disease progression.

Identificació de paisatges funcionals mitjançant anàlisi cluster

El terme paisatge i les seves aplicacions són cada dia més utilitzats per les administracions i altres entitats com a eina de gestió del territori. Aprofitant la gran quantitat de dades en bases compatibles amb SIG (Sistemes d’Informació Geogràfica) existents a Catalunya s’ha desenvolupat una síntesi cartogràfica on s’identifiquen els Paisatges Funcionals (PF) de Catalunya, concepte que fa referència al comportament fisico-ecològic del terreny a partir de variables topogràfiques i climàtiques convenientment transformades i agregades. S’ha utilitzat un mètode semiautomàtic i iteratiu de classificació no supervisada (clustering) que permet la creació d’una llegenda jeràrquica o nivells de generalització. S’ha obtingut com a resultat el Mapa de Paisatges Funcionals de Catalunya (MPFC) amb una llegenda de 26 categories de paisatges i 5 nivells de generalització amb una resolució espacial de 180 m. Paral·lelament, s’han realitzat validacions indirectes sobre el mapa obtingut a partir dels coneixements naturalistes i la cartografia existent, així com també d’un mapa d’incertesa (aplicant lògica difusa) que aporten informació de la fiabilitat de la classificació realitzada. Els Paisatges Funcionals obtinguts permeten relacionar zones de condicions topo-climàtiques homogènies i dividir el territori en zones caracteritzades ambientalment i no políticament amb la intenció que sigui d’utilitat a l’hora de millorar la gestió dels recursos naturals i la planificació d’actuacions humanes.

The combination of social and personal contexts affects dominance hierarchy development in shore crabs, Carcinus maenas

Many animals that live in groups maintain competitive relationships, yet avoid continual fighting, by forming dominance hierarchies. We compare predictions of stochastic, individual-based models with empirical experimental evidence using shore crabs to test competing hypotheses regarding hierarchy development. The models test (1) what information individuals use when deciding to fight or retreat, (2) how past experience affects current resource-holding potential, and (3) how individuals deal with changes to the social environment. First, we conclude that crabs assess only their own state and not their opponent's when deciding to fight or retreat. Second, willingness to enter, and performance in, aggressive contests are influenced by previous contest outcomes. Winning increases the likelihood of both fighting and winning future interactions, while losing has the opposite effect. Third, when groups with established dominance hierarchies dissolve and new groups form, individuals reassess their ranks, showing no memory of previous rank or group affiliation. With every change in group composition, individuals fight for their new ranks. This iterative process carries over as groups dissolve and form, which has important implications for the relationship between ability and hierarchy rank. We conclude that dominance hierarchies emerge through an interaction of individual and social factors, and discuss these findings in terms of an underlying mechanism. Overall, our results are consistent with crabs using a cumulative assessment strategy iterated across changes in group composition, in which aggression is constrained by an absolute threshold in energy spent and damage received while fighting.

Spinal cord stimulation treatment for angina pectoris: more than a placebo?

BACKGROUND: The effects of thoracolumbal spinal cord stimulation (SCS) are confined to restricted microcirculatory areas. This limitation is generally attributed to a predominantly segmental mode of action on the autonomic nervous system. The goal of this study was to determine whether SCS applied close to supraspinal autonomic centers would induce generalized hemodynamic changes that could explain its alleged antianginal properties. METHODS: Invasive hemodynamic tests were performed in 15 anesthetized Göttingen minipigs submitted to iterative cervical SCS of various duration and intensity. RESULTS: Hemodynamic changes exceeding 10% were observed in 59 of 68 SCS sessions (87%). Their extent and time to peak varied with SCS intensity. At 2, 5, and 10 V, significant (t test p < 0.05) peak changes occurred in cardiac output (+34%, +29%, and +28%, respectively), stroke volume (+19%, +16%, +15%), mean pressure (+9%, +27%, +40%), heart rate (+14%, +23%, +14%), systemic (-17%, NS, NS), and pulmonary vascular (25%, NS, NS) resistances. Strikingly, at 2 V, the increase in cardiac output (+34%) was higher than the synchronous rise in rate pressure product (+22%), indicating efficient cardiac work. At 10 V, however, the cardiac work was inefficient (rate pressure product + 53%/cardiac output + 28%). CONCLUSIONS: Low-voltage cervical neuromodulation reduces the postcharge and improves cardiac work efficiency. The resulting reduction in oxygen myocardial demand may account for decreased anginal pain.

Let's talk: public evaluation of large projects: variational inequialities, bilevel programming and complementarity. a survey

Large projects evaluation rises well known difficulties because -by definition- they modify the current price system; their public evaluation presents additional difficulties because they modify too existing shadow prices without the project. This paper analyzes -first- the basic methodologies applied until late 80s., based on the integration of projects in optimization models or, alternatively, based on iterative procedures with information exchange between two organizational levels. New methodologies applied afterwards are based on variational inequalities, bilevel programming and linear or nonlinear complementarity. Their foundations and different applications related with project evaluation are explored. As a matter of fact, these new tools are closely related among them and can treat more complex cases involving -for example- the reaction of agents to policies or the existence of multiple agents in an environment characterized by common functions representing demands or constraints on polluting emissions.

Franklin D. Roosevelt i Frank Capra: missatges per a un país en crisi

En el context de la crisi econòmica i social que vivien els Estats Units a començament dels anys trenta, diversos actors polítics i socials van elaborar missatges que provaven d’acarar els ciutadans amb la realitat, però sobretot de restituir-los la confiança en ells mateixos i en el país. Aquest article analitza els discursos i les aportacions ideològiques de dues de les personalitats més destacades que participaren en aquest procés de reconstrucció emocional: el president Franklin D. Roosevelt i el cineasta Frank Capra. El text cerca d’establir les connexions entre aquests dos discursos, descobrir-ne les coincidències i, també, les diferències, i plantejar una aproximació al cinema com un mitjà de comunicació que va més enllà del simple entreteniment, per a convertir-se, en diverses ocasions, en un eficaç document amb el qual apropar-se a una època, desxifrar-ne els aspectes més significatius

Untangling the evolution of Rab G proteins: implications of a comprehensive genomic analysis.

BACKGROUND: Membrane-bound organelles are a defining feature of eukaryotic cells, and play a central role in most of their fundamental processes. The Rab G proteins are the single largest family of proteins that participate in the traffic between organelles, with 66 Rabs encoded in the human genome. Rabs direct the organelle-specific recruitment of vesicle tethering factors, motor proteins, and regulators of membrane traffic. Each organelle or vesicle class is typically associated with one or more Rab, with the Rabs present in a particular cell reflecting that cell's complement of organelles and trafficking routes. RESULTS: Through iterative use of hidden Markov models and tree building, we classified Rabs across the eukaryotic kingdom to provide the most comprehensive view of Rab evolution obtained to date. A strikingly large repertoire of at least 20 Rabs appears to have been present in the last eukaryotic common ancestor (LECA), consistent with the 'complexity early' view of eukaryotic evolution. We were able to place these Rabs into six supergroups, giving a deep view into eukaryotic prehistory. CONCLUSIONS: Tracing the fate of the LECA Rabs revealed extensive losses with many extant eukaryotes having fewer Rabs, and none having the full complement. We found that other Rabs have expanded and diversified, including a large expansion at the dawn of metazoans, which could be followed to provide an account of the evolutionary history of all human Rabs. Some Rab changes could be correlated with differences in cellular organization, and the relative lack of variation in other families of membrane-traffic proteins suggests that it is the changes in Rabs that primarily underlies the variation in organelles between species and cell types.