LICAVAL: combination therapy in acute and maintenance treatment of bipolar disorder

Background: The challenge of Bipolar Disorder (BD) treatment is due to the complexity of the disease. Current guidelines represent an effort to help clinicians in their everyday practice but still have limitations, specially concerning to long term treatment. LICAVAL (efficacy and tolerability of the combination of LIthium and CArbamazepine compared to lithium and VALproic acid in the treatment of young bipolar patients) study aim to evaluate acute and maintenance phase of BD treatment with two combined drugs. Methods: LICAVAL is a single site, parallel group, randomized, outcome assessor blinded trial. BD I patients according to the DSM-IV-TR, in depressive, manic,/hypomanic or mixed episode, aged 18 to 35 years are eligible. After the diagnostic assessments, the patients are allocated for one of the groups of treatment (lithium + valproic acid or lithium + carbamazepine). Patients will be followed up for 8 weeks in phase I (acute treatment), 6 months in phase II (continuation treatment) and 12 months in phase III (maintenance treatment). Outcome assessors are blind to the treatment. The main outcome is the evaluation of changes in mean scores on CGI-BP-M between baseline and endpoint at the end of each phase of the study. Results: LICAVAL is currently in progress, with patients in phase I, II or III. It will extended until august 2012. Conclusions: Trials comparing specific treatments efficacy in BD (head to head) can show relevant information in clinical practice. Long term treatment is an issue of great important and should be evaluated carefully in more studies as long as BD is a chronic disease.

Anaphylactic reaction induced by a polysulfone/polyvinylpyrrolidone membrane in the 10th session of hemodialysis with the same dialyzer

The majority of severe hypersensitivity reactions in hemodialysis patients have occurred due to sensitization to ethylene oxide or to nonbiocompatible membrane dialyzers. The use of polysulfone dialyzers rarely causes hypersensitivity reactions. In the present study, we describe a case of severe life-threatening reactions induced by polysulfone dialyzers (from different manufacturers subjected to a variety of sterilization methods), which occurred after 9 sessions of hemodialysis with the same prescription, exemplifying the complexity of such reactions.

Puzzling challenges in contemporary neuroscience: Insights from complexity and emergence in epileptogenic circuits

The brain is a complex system that, in the normal condition, has emergent properties like those associated with activity-dependent plasticity in learning and memory, and in pathological situations, manifests abnormal long-term phenomena like the epilepsies. Data from our laboratory and from the literature were classified qualitatively as sources of complexity and emergent properties from behavior to electrophysiological, cellular, molecular, and computational levels. We used such models as brainstem-dependent acute audiogenic seizures and forebrain-dependent kindled audiogenic seizures. Additionally we used chemical OF electrical experimental models of temporal lobe epilepsy that induce status epilepticus with behavioral, anatomical, and molecular sequelae such as spontaneous recurrent seizures and long-term plastic changes. Current Computational neuroscience tools will help the interpretation. storage, and sharing of the exponential growth of information derived from those studies. These strategies are considered solutions to deal with the complexity of brain pathologies such as the epilepsies. (C) 2008 Elsevier Inc. All rights reserved.

The visual ecology of avian photoreceptors

The spectral sensitivities of avian retinal photoreceptors are examined with respect to microspectrophotometric measurements of single cells, spectrophotometric measurements of extracted or in vitro regenerated visual pigments, and molecular genetic analyses of visual pigment opsin protein sequences. Bird species from diverse orders are compared in relation to their evolution, their habitats and the multiplicity of visual tasks they must perform. Birds have five different types of visual pigment and seven different types of photo receptor-rods, double (uneven twin) cones and four types of single cone. The spectral locations of the wavelengths of maximum absorbance (lambda (max)) of the different visual pigments, and the spectral transmittance characteristics of the intraocular spectral filters (cone oil droplets) that also determine photoreceptor spectral sensitivity, vary according to both habitat and phylogenetic relatedness. The primary influence on avian retinal design appears to be the range of wavelengths available for vision, regardless of whether that range is determined by the spectral distribution of the natural illumination or the spectral transmittance of the ocular media (cornea, aqueous humour, lens, vitreous humour). Nevertheless, other variations in spectral sensitivity exist that reflect the variability and complexity of avian visual ecology. (C) 2001 Elsevier Science Ltd. All rights reserved.

Attachment style and coping resources as predictors of coping strategies in the transition to parenthood

The relations among adult attachment style, coping resources, appraised strain, and coping strategies were examined in a prospective study of married couples having their first child (N = 92). Attachment and coping resources were measured during the second trimester of pregnancy, and parenting strain and coping strategies were assessed when the babies were about 6 weeks old. Results supported a theoretical model proposing that attachment is predictive of coping resources and appraised strain, and that attachment, resources, and strain are predictive of coping strategies. Results also highlighted the complexity of associations among attachment, stress, and coping: Gender differences in mean scores and predictive associations were obtained, and some interactions were found between resources and strain in predicting coping strategies. The findings support the utility of integrating theories of attachment and coping in explaining couples' adjustment to important developmental transitions.

Proactive interference and complexity

C. L. Isaac and A. R. Mayes (1999a, 1999b) compared forgetting rates in amnesic patients and normal participants across a range of memory tasks. Although the results are complex, many of them appear to be replicable and there are several commendable features to the design and analysis. Nevertheless, the authors largely ignored 2 relevant literatures: the traditional literature on proactive inhibition/interference and the formal analyses of the complexity of the bindings (associations) required for memory tasks. It is shown how the empirical results and conceptual analyses in these literatures are needed to guide the choice of task, the design of experiments, and the interpretation of results for amnesic patients and normal participants.

Initiation of cell locomotility is a morphogenetic checkpoint in thyroid epithelial cells regulated by ERK and PI3-kinase signals

Epithelial locomotility is a fundamental determinant of tissue patterning that is subject to strict physiological regulation. The current, study sought to identify cellular signals that initiate cell migration in cultured thyroid epithelial cells. Porcine thyroid cells cultured as 3-dimensional follicles convert to 2-dimensional monolayers when deprived of agents that stimulate cAMP/PKA signaling. This morphogenetic event is driven by the activation of cell-on-substrate locomotility, providing a convenient assay for events that regulate the initiation of locomotion. In this system, the extracellular signal regulated kinase (ERK) pathway became activated as follicles converted to monolayer, as demonstrated by immunoblotting for activation-specific phosphorylation and nuclear accumulation of ERK. Inhibition of ERK activation using the drug PD98059 effectively prevented cells from beginning to migrate. PD98059 inhibited cell spreading, actin filament reorganization and the assembly of focal adhesions, cellular events that mediate the initiation of thyroid cell locomotility. Akt (PKB) signaling was also activated during follicle-to-monolayer conversion and the phosphoinositide 3-kinase (PI3-kinase) inhibitor, wortmannin, also blocked the initiation of cell movement. Wortmannin did not, however, block activation of ERK signaling. These findings, therefore, identify the ERK and PI3-kinase signaling pathways as important stimulators of thyroid cell locomotility. These findings are incorporated into a model where the initiation of thyroid cell motility constitutes a morphogenetic checkpoint regulated by coordinated changes in stimulatory (ERK, PI3-kinase) and tonic inhibitory (cAMP/PKA) signaling pathways. Cell Motil. Cytoskeleton 49:93-103, 2001. (C) 2001 Wiley-Liss, Inc.

Phenotypic characterization of five dendritic cell subsets in human tonsils

Heterogeneous expression of several antigens on the three currently defined tonsil dendritic cell (DC) subsets encouraged us to re-examine tonsil DCs using a new method that minimized DC differentiation and activation during their preparation. Three-color flow cytometry and dual-color immunohistology was used in conjunction with an extensive panel of antibodies to relevant DC-related antigens to analyze lin(-) HLA-DR+ tonsil DCs. Here we identify, quantify, and locate five tonsil DC subsets based on their relative expression of the HLA-DR, CD11c, CD13, and CD123 antigens. In situ localization identified four of these DC subsets as distinct interdigitating DC populations. These included three new interdigitating DC subsets defined as HLA-DRhi CD11c(+) DCs, HLA-DRmod CD11c+ CD13(+) DCs, and HLA-DRmod CD11c(-) CD123(-) DCs, as well as the plasmacytoid DCs (HLA-DRmod CD11c- CD123(+)). These subsets differed in their expression of DC-associated differentiation/activation antigens and co-stimulator molecules including CD83, CMRF-44, CMRF-56, 2-7, CD86, and 4-1BB ligand. The fifth HLA-DRmod CD11c(+) DC subset was identified as germinal center DCs, but contrary to previous reports they are redefined as lacking the CD13 antigen. The definition and extensive phenotypic analysis of these five DC subsets In human tonsil extends our understanding of the complexity of DC biology.

Environmental regulation of land use and public compensation: principles, and Swiss and Australian examples

The authors discuss the regulation of rural land use and compensation for property-rights restrictions, both of which appear to have become more commonplace in recent years but also more contested. The implications of contemporary theories in relation to this matter are examined, including: the applicability of new welfare economics; the relevance of the neoclassical theory of politics; and the implications of contemporary theories of social conflict resolution and communication. Examination of examples of Swiss and Australian regulation of the use of rural properties, and the ensuing conflicts, reveals that many decisions reflect a mixture of these elements. Rarely, if ever, are social decisions in this area made solely on the basis of welfare economics, for instance social cost-benefit analysis. Only some aspects of such decisions can be explained by the neoclassical theory of politics. Theories of social conflict resolution suggest why, and in what way, approaches of discourse and participation may resolve conflicts regarding regulation and compensation. These theories and their practical application seem to gain in importance as opposition to government decisions increases. The high degree of complexity of most conflicts concerning regulation and compensation cannot be tackled with narrow economic theories. Moreover, the Swiss and Australian examples show that approaches involving conflict resolution may favour environmental standards.

Adaptive multiscale principal components analysis for online monitoring of wastewater treatment

Fault detection and isolation (FDI) are important steps in the monitoring and supervision of industrial processes. Biological wastewater treatment (WWT) plants are difficult to model, and hence to monitor, because of the complexity of the biological reactions and because plant influent and disturbances are highly variable and/or unmeasured. Multivariate statistical models have been developed for a wide variety of situations over the past few decades, proving successful in many applications. In this paper we develop a new monitoring algorithm based on Principal Components Analysis (PCA). It can be seen equivalently as making Multiscale PCA (MSPCA) adaptive, or as a multiscale decomposition of adaptive PCA. Adaptive Multiscale PCA (AdMSPCA) exploits the changing multivariate relationships between variables at different time-scales. Adaptation of scale PCA models over time permits them to follow the evolution of the process, inputs or disturbances. Performance of AdMSPCA and adaptive PCA on a real WWT data set is compared and contrasted. The most significant difference observed was the ability of AdMSPCA to adapt to a much wider range of changes. This was mainly due to the flexibility afforded by allowing each scale model to adapt whenever it did not signal an abnormal event at that scale. Relative detection speeds were examined only summarily, but seemed to depend on the characteristics of the faults/disturbances. The results of the algorithms were similar for sudden changes, but AdMSPCA appeared more sensitive to slower changes.

Optical barcoding of colloidal suspensions: applications in genomics, proteomics and drug discovery

The enormous amount of information generated through sequencing of the human genome has increased demands for more economical and flexible alternatives in genomics, proteomics and drug discovery. Many companies and institutions have recognised the potential of increasing the size and complexity of chemical libraries by producing large chemical libraries on colloidal support beads. Since colloid-based compounds in a suspension are randomly located, an encoding system such as optical barcoding is required to permit rapid elucidation of the compound structures. We describe in this article innovative methods for optical barcoding of colloids for use as support beads in both combinatorial and non-combinatorial libraries. We focus in particular on the difficult problem of barcoding extremely large libraries, which if solved, will transform the manner in which genomics, proteomics and drug discovery research is currently performed.

Alterations in Plasmodium falciparum genotypes during sequential infections suggest the presence of strain specific immunity

Many of the asexual stage Plasmodium falciparum proteins that are the targets of host protective responses are markedly polymorphic. The full repertoire of diversity is not defined for any antigen. Most studies have focused on the genes encoding merozoite surface proteins 1 and 2 (MSP1, MSP2). We explored the extent of diversity of some of the less studied merozoite surface antigens and analyzed the degree of complexity of malaria field isolates by deriving nucleotide sequences of several antigens. We have determined the genotype of apical membrane antigen 1 (AMA1) in a group of 30 field samples, collected over 29 months, from individuals living in an area of intense malaria transmission in Irian Jaya, identifying 14 different alleles. AMA1 genotyping was combined with previously determined MSP2 typing. AMA1 had the greatest power in distinguishing between isolates but methodological problems, especially when mixed infections are present, suggest it is not an ideal typing target. MSP1, MSP3, and glutamate-rich protein genotypes were also determined from a smaller group of samples, and all results were combined to derive an extended antigenic haplotype. Within this subset of 10 patients, nine different genotypes could be discerned; however, five patients were all infected with the same strain. This strain was present in individuals from two separate villages and was still present 12 months later. This strain was predominant at the first time point but had disappeared at the fourth time point. This significant change in malaria genotypes could be due to strain-specific immunity developing in this population.

Cash, customers, and care: The experience and meaning of differential payment for high care places in aged care facilities

The introduction of new asset/income tested charges for high care residents was the 1997-98 Commonwealth government policy response to concerns about financing residential aged care. This in-depth study of residents, families, staff and managers in three aged care facilities explores issues of equity, access and empowerment arising when some residents pay more for the same level of care and amenity. The study reports little evidence of financial contributions affecting access to high care places and the delivery of care, the potential for differential access to amenities such as single rooms linked to the extra payments, and no evidence of a sense of empowerment linked to payment of the new charges. The complexity of current financial arrangements, access to appropriate financial advice at the time of entry, and the potential for an informal two tier system in relation to the allocation Of amenities are identified as developing policy issues.

The impact of genotyping error on haplotype reconstruction and frequency estimation

The choice of genotyping families vs unrelated individuals is a critical factor in any large-scale linkage disequilibrium (LD) study. The use of unrelated individuals for such studies is promising, but in contrast to family designs, unrelated samples do not facilitate detection of genotyping errors, which have been shown to be of great importance for LD and linkage studies and may be even more important in genotyping collaborations across laboratories. Here we employ some of the most commonly-used analysis methods to examine the relative accuracy of haplotype estimation using families vs unrelateds in the presence of genotyping error. The results suggest that even slight amounts of genotyping error can significantly decrease haplotype frequency and reconstruction accuracy, that the ability to detect such errors in large families is essential when the number/complexity of haplotypes is high (low LD/common alleles). In contrast, in situations of low haplotype complexity (high LD and/or many rare alleles) unrelated individuals offer such a high degree of accuracy that there is little reason for less efficient family designs. Moreover, parent-child trios, which comprise the most popular family design and the most efficient in terms of the number of founder chromosomes per genotype but which contain little information for error detection, offer little or no gain over unrelated samples in nearly all cases, and thus do not seem a useful sampling compromise between unrelated individuals and large families. The implications of these results are discussed in the context of large-scale LD mapping projects such as the proposed genome-wide haplotype map.

Global job satisfaction and facet description: The moderating role of facet importance

Recent research support sLocke's (1976) model of facet satisfaction in which the range of affect of objectively defined facet descriptions is moderated by subjective evaluations of facet importance (McFarlin & Rice, 1992). This study examined the utility of Locke's moderated model of face t satisfaction for the prediction of organizationally important global measures of job satisfaction. A large dataset of two groups of workers allowed testing over different time periods and across a broad range of satisfaction measures. The hypothesis derived from Locke's model, that global satisfaction would represent a linear function of facet satisfaction (i.e., facet description x facet importance), was not supported. Instead, a simple (have-want) discrepancy model (operationalized as facet description) provided the most consistent set of predictors. The results suggests that workers, when providing global measures of job satisfaction, may use cognitive heuristics to reduce the complexity of facet description x importance calculations. The implications of these data for Locke's model and directions for future research are outlined.