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Necessary Step (necessary + step)
Selected AbstractsThe First-Episode Psychosis Outcome Study: premorbid and baseline characteristics of an epidemiological cohort of 661 first-episode psychosis patientsEARLY INTERVENTION IN PSYCHIATRY, Issue 2 2007Philippe Conus Abstract Aims:, Studies conducted in first-episode psychosis (FEP) samples avoid many biases. However, very few studies are based on epidemiological cohorts treated in specialized FEP services. The aim of this file audit study was to examine premorbid and baseline characteristics of a large epidemiological sample of FEP. Methods:, File audit study of all patients admitted to the Early Psychosis Prevention and Intervention Centre between 1998 and 2000 using a specialized questionnaire. Results:, There were 661 patient files included in the study. Premorbid evaluation revealed high rates of substance use disorder (74.1%), history of psychiatric disorder (47.5%), past traumatic events (82.7%) suicide attempts (14.3%) and family history of psychiatric illness (55.6%). Baseline characteristics revealed high intensity of illness (mean CGI 5.5), high prevalence of lack of insight (62%) and high rate of comorbidity (70%). Conclusion:, High rates of traumatic events or episodes of mental illness before treatment for FEP must be considered when designing treatment approaches because a too narrow focus on positive psychotic symptoms will inevitably lead to incomplete treatment. Additionally, early intervention programmes need sufficient range of resources to address the multiple challenges presented by FEP patients such as high severity of illness, comorbidities and functional impairment. Finally, observation of an important degree of functional impairment despite short duration of untreated psychosis suggests that while early detection of FEP is a necessary step in early intervention, it may not be sufficient to improve functional recovery in psychosis and that efforts aimed at identifying people during the prodromal phase of psychotic disorders should be pursued. [source] Spatial metrics and methods for riverscapes: quantifying variability in riverine fish habitat patternsENVIRONMETRICS, Issue 5 2009Céline Le Pichon Abstract Defining the optimal configuration of all habitats required during a life cycle, called vital habitat, is a necessary step for effective management of riverine fishes and restoration of river habitats. Landscape ecology provides many metrics and methods to study the composition and configuration of habitats, but they need to be adapted for fishes in river environments or riverscapes. For example, hydrographic distance seems more appropriate than Euclidean distance for measuring distances between vital habitats in riverscapes. We adapted some metrics to assess habitats patterns of a threatened cyprinid species (Barbus barbus) for natural and artificial riverscapes of the Seine river, France. Composition metrics provided essential quantification of the relative abundance of the vital habitats, whereas configuration metrics were relevant to quantify their spatial arrangement and spatial relationships. Nearest-neighbor hydrographic distance was useful to evaluate the influence of flow variability in the natural riverscape, but was not relevant to discriminate the artificial riverscape from the natural one. Conversely, a proximity index revealed high fragmentation in the artificial riverscape. Spatial habitat relationships between feeding and resting habitats, evaluated with a moving window analysis, provided a map of daily activity patches and emphasized the gaps in the biological continuity of the riverscape. The spatial metrics and methods we adapted to the particularities of the Seine river allowed us to detect natural and artificial variability in fish habitat patterns. They should help in evaluating impacts of habitat alteration and isolation and prioritize preservation and restoration policies in human-impacted rivers. Copyright © 2008 John Wiley & Sons, Ltd. [source] Distribution and signaling of TREM2/DAP12, the receptor system mutated in human polycystic lipomembraneous osteodysplasia with sclerosing leukoencephalopathy dementiaEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 10 2004Giuseppina Sessa Abstract Together with its adaptor protein, the adaptor protein of 12 kDa also known as KARAP and TYROBP (DAP12), triggering r (TREM2) is a stimulatory membrane receptor of the immunoglobulin/lectin-like superfamily, well known in myeloid cells. In humans, however, loss-of-function mutations of TREM2/DAP12 leave myeloid cells unaffected but induce an autosomal recessive disease characterized, together with bone cysts, by a spectrum of pathological lesions in the cortex, thalamus and basal ganglia with clinical symptoms of progressive dementia (polycystic lipomembraneous osteodysplasia with sclerosing leukoencephalopathy). Nothing was known about the role of TREM2/DAP12 in brain cell biology and physiology. By confocal immunocytochemistry we demonstrate that, in both human and mouse cerebral cortex, TREM2/DAP12, strongly expressed by microglia, is also present in a fraction of neurons but not in astrocytes and oligodendrocytes. In contrast, in the hippocampal cortex TREM2-expressing neurons are rare. Both in neurons and microglia the receptor appears to be located mostly intracellularly in a discrete compartment(s) partially coinciding with (or adjacent to) the Golgi complex/trans-Golgi network. Four nerve cell lines were identified as expressing the intracellular receptor system. In living human microglia CHME-5 and glioblastoma T98G cells, activation of TREM2 by its specific antibody induced [Ca2+]i responses, documenting its surface expression and functioning. Surface expression of TREM2, low in resting CHME-5 and T98G cells, increases significantly and transiently (60 min) when cells are stimulated by ionomycin, as revealed by both surface biotinylation and surface immunolabeling. Our results provide the first information about the expression, distribution (mostly intracellular) and functioning of TREM2/DAP12 system in nerve cells, a necessary step in the understanding of the cellular mechanisms affected in polycystic lipomembraneous osteodysplasia with sclerosing leukoencephalopathy. [source] THE EFFECTS OF GENOTYPE, AGE, AND SOCIAL ENVIRONMENT ON MALE ORNAMENTATION, MATING BEHAVIOR, AND ATTRACTIVENESSEVOLUTION, Issue 11 2005Lisa K. Miller Abstract The traits thought to advertise genetic quality are often highly susceptible to environmental variation and prone to change with age. These factors may either undermine or reinforce the potential for advertisement traits to signal quality depending on the magnitude of age-dependent expression, environmental variation, and genotype-age and genotype-environment interaction. Measurements of the magnitude of these effects are thus a necessary step toward assessing the implications of age dependence and environmental variability for the evolution of signals of quality. We conducted a longitudinal study of male guppies (Poecilia reticulata) from 22 full-sibling families. Each fish was assigned at maturity to one of three treatments in order to manipulate his allocation of resources to reproduction: a control in which the male was kept alone, a courtship-only treatment in which he could see and court a female across a clear partition, and a mating treatment in which he interacted freely with a female. We measured each male's size, ornamental color patterns, courtship, attractiveness to females, and mating success at three ages. Size was influenced by treatment and age-treatment interactions, indicating that courtship and mating may impose costs on growth. Tail size and color patterns were influenced by age but not by treatment, suggesting fixed age-dependent trajectories in these advertisement traits. By contrast, display rate and attempted sneak copulation rate differed among treatments but not among ages, suggesting greater plasticity of these behavioral traits. As a result of the different patterns of variation in ornamentation and behavior, male attractiveness and mating success responded to male age, treatment, and the interaction between age and treatment. Neither age nor treatment obscured the presence of genetic variation, and the genetic relationship between male ornamentation and attractiveness remained the same among treatments. Our findings suggest that neither age-dependent variation nor environmentally induced variation in reproductive effort is likely to undermine the reliability of male signaling. [source] The Xhosa Cattle-Killing Movement in History and LiteratureHISTORY COMPASS (ELECTRONIC), Issue 6 2009Andrew Offenburger In South Africa's Eastern Cape frontier zone, a millenarian movement known as the Xhosa Cattle-Killing (1856,1857) devastated local populations and stunned observers. How could the messages of its prophetess, Nongqawuse, and the exhortations of her uncle, Mhlakaza, lead to the slaughter of hundreds of thousands of cattle, to the death of tens of thousands of people, and to the subjugation of the Xhosa? Historians and authors of literary works have attempted to answer this question, and their explanations have followed the contours of South African history through three general phases. The first (1857,1947) characterized the movement as a failed revolt against British expansion and a necessary step in social and religious Darwinism. The second period (1948,1988) saw the continuation of these interpretations, and, with National Party rule and the rise of the Black Consciousness Movement, an increasingly radical group of historians brought about politicized and alternative interpretations embedded in Xhosa oral history. The third phase (1989,) began with the publication of Jeff Peires'The Dead Will Arise, which renewed interest in the history and has inspired a new wave of historical critique. [source] Towards an isotopic ecology of herbivory in the Puna ecosystem: new results and patterns on Lama glamaINTERNATIONAL JOURNAL OF OSTEOARCHAEOLOGY, Issue 2 2009H. D. Yacobaccio Abstract We present stable isotopic data obtained in order to elucidate the diet of current domestic camelids and their feeding areas, as a necessary step for the interpretation of archaelogical assemblages, and to answer questions regarding past diet, herd structure, foraging zones and interaction with human populations. Seventeen new ,13C collagen isotope values from Lama glama bones were measured in order to start a systematic study of the isotopic ecology of herbivory in the Puna ecosystem of Jujuy province, Argentina. These values were compared with those previously available, and a reliable correlation between altitude and variation in isotopic values was found: of the order of ,2, depletion for each 500,m increase in altitude. These results were interpreted as related to variation in vegetal assemblage due to altitude. We consider that the outcomes of this research exceed the scope of our study area, being important to the Argentine Puna as a whole, and will also contribute to the development of current animal population ecological models applied to the interpretation of archaeological remains. Copyright © 2009 John Wiley & Sons, Ltd. [source] Reducing risk of shortages due to drought in water supply systems using genetic algorithms,IRRIGATION AND DRAINAGE, Issue 2 2009V. Nicolosi évaluation des risques; gestion de l'eau; sécheresse; éléments déclenchant pour les plans sécheresse Abstract The evaluation of risk of shortages due to drought in water supply systems is a necessary step both in the planning and in the operation stage. A methodology for unconditional (planning) and conditional (operation) risk evaluation is presented in this study. The risk evaluation is carried out by means of an optimisation model based on genetic algorithms aimed to define thresholds for the implementation of mitigation measures tested through Monte Carlo simulation that makes use of a stochastic generation of streamflows. The GA enables the optimisation of reservoir storages which identify monthly thresholds for shifting three states of the system (normal, alert and alarm) to which correspond different mitigation measures such as water demand rationing, additional supplies from alternative sources or reduction of release for ecological use. For unconditional risk evaluation a long time horizon has been considered (40 years), while the conditional risk evaluation is performed on a short time horizon (2,3 months). Results of simulations have been studied by means of consolidated indices of performance and frequency analysis of shortages of a given entity corresponding to different planning/management policies. A multi-use water system has been used as a case study including competing irrigation and industrial demands. Copyright © 2008 John Wiley & Sons, Ltd. L'évaluation du risque de manques d'eau dus à la sécheresse dans les systèmes d'approvisionnement en eau est une étape nécessaire à la fois pour la planification et l'exploitation. Une méthodologie pour l'évaluation du risque inconditionnel (planification) et conditionnel (exploitation) est présentée dans cette étude. L'évaluation du risque est effectuée au moyen d'un modèle d'optimisation basé sur des algorithmes génétiques visant à définir des seuils pour la mise en ,uvre des mesures d'atténuation testés par une méthode de Monte Carlo générant les débits des rivières. L'algorithme génétique permet d'optimiser les stockages de réservoir avec des seuils mensuels pour identifier trois états du système (normal, alerte et alarme) auxquels correspondent différentes mesures d'atténuation telles que rationnement de la demande en eau, approvisionnements complémentaires par des sources alternatives ou réduction des lâchures pour l'usage écologique. Pour l'évaluation des risques inconditionnels un horizon à long terme a été considéré (40 ans) tandis que l'évaluation conditionnelle est faite sur un horizon à court terme (2 ou 3 mois). Les résultats des simulations ont été étudiés au moyen d'indices de performance consolidés et de l'analyse de la fréquence des manques d'eau pour une entité donnée correspondant à différentes politiques de planification et gestion. L'étude de cas porte sur un système multi-usage comportant une demande d'irrigation en concurrence avec les demandes industrielles. Copyright © 2008 John Wiley & Sons, Ltd. [source] An overview of the mathematical modelling of liquid membrane separation processes in hollow fibre contactorsJOURNAL OF CHEMICAL TECHNOLOGY & BIOTECHNOLOGY, Issue 11 2009E Bringas Abstract Liquid membranes have traditionally been employed for liquid/liquid mass transfer and have found applications in industrial, biomedical and analytical fields as well as in hydrometallurgical processes, wastewater treatment and remediation of polluted groundwater. However, in spite of the known advantages of liquid membranes, there are few examples of industrial application. The development of reliable mathematical models and design parameters (mass transport coefficients and equilibrium or kinetic parameters associated with the interfacial reactions) is a necessary step for design, cost estimation, process optimisation and scale-up. This work reports an overview of the different approaches that have been proposed in the literature to the mathematical modelling of liquid membrane separation processes in hollow fibre contactors providing, at the same time, a useful guideline to characterise the mass transport phenomena and a tool for the optimal design and intensification of separation processes. Copyright © 2009 Society of Chemical Industry [source] Publication of clinical trials: accountability and accessibilityJOURNAL OF INTERNAL MEDICINE, Issue 4 2004M. B. Tumber Abstract. Publication of findings from clinical trials is a necessary step in the research continuum, to provide a record of the work done, convey information to the community, and support translation of research into clinical practice. Systematic reviews of randomized controlled trials are now widely regarded as the highest level of evidence in determining the effect of an intervention on an outcome. They largely depend on internationally accessible, published reports of all trials undertaken. Investigators and their institutions or organizations have responsibility for reporting their clinical trials accurately and completely, including disclosure of potential conflicts of interest. To ensure evidence-based health care, issues relating to accessibility and accountability of clinical trial results require immediate action. [source] Implementing Evidence-Based Substance Use Prevention Curricula in North Carolina Public School DistrictsJOURNAL OF SCHOOL HEALTH, Issue 9 2004Melinda M. Pankratz ABSTRACT: The Safe and Drug-Free Schools and Communities Act (SDFSCA) provides funding for prevention education to nearly every school district in the nation. Recent federal policy requires SDFSCA recipients to implement evidence-based prevention programs. This paper reports the extent to which North Carolina public school districts implement evidence-based substance use prevention curricula. Results showed that while the majority of school districts use evidence-based prevention curricula, they are rarely the most commonly used curricula. Evidence-based curricula are much more likely to be used at the middle school level than at the elementary or high school levels. Urbanicity, coordinator time, and coordinator experience correlated with extensive use of evidence-based curricula in the bivariate analysis, but only time spent on prevention by the Safe and Drug-Free Schools (SDFS) coordinator significantly predicted extensive use in the multivariate analysis. Increasing district SDFSCA coordinator time is a necessary step for diffusing evidence-based curricula. (J Sch Health. 2004;74(9):353,358) [source] The Canyon Diablo impact event: Projectile motion through the atmosphereMETEORITICS & PLANETARY SCIENCE, Issue 1 2009Natalia ARTEMIEVA Its location in arid northern Arizona has been ideal for the preservation of the structure and the surviving meteoric material. The recovery of a large amount of meteoritic material in and around the crater has allowed a rough reconstruction of the impact event: an iron object 50 m in diameter impacted the Earth's surface after breaking up in the atmosphere. The details of the disruption, however, are still debated. The final crater morphology (deep, bowl-shaped crater) rules out the formation of the crater by an open or dispersed swarm of fragments, in which the ratio of swarm radius to initial projectile radius Cd is larger than 3 (the final crater results from the sum of the craters formed by individual fragments). On the other hand, the lack of significant impact melt in the crater has been used to suggest that the impactor was slowed down to 12 km/s by the atmosphere, implying significant fragmentation and fragments' separation up to 4 initial radii. This paper focuses on the problem of entry and motion through the atmosphere for a possible Canyon Diablo impactor as a first but necessary step for constraining the initial conditions of the impact event which created Meteor Crater. After evaluating typical models used to investigate meteoroid disruption, such as the pancake and separated fragment models, we have carried out a series of hydrodynamic simulations using the 3D code SOVA to model the impactor flight through the atmosphere, both as a continuum object and a disrupted swarm. Our results indicate that the most probable pre-atmospheric mass of the Meteor Crater projectile was in the range of 4.108to 1.2.109kg (equivalent to a sphere 46,66 m in diameter). During the entry process the projectile lost probably 30% to 70% of its mass, mainly because of mechanical ablation and gross fragmentation. Even in the case of a tight swarm of particles (Cd < 3), small fragments can separate from the crater-forming swarm and land on the plains (tens of km away from the crater) as individual meteorites. Starting from an impactor pre-atmospheric velocity of ,18 km/s, which represents an average value for Earth-crossing asteroids, we find that after disruption, the most probable impact velocity at the Earth's surface for a tight swarm is around 15 km/s or higher. A highly dispersed swarm would result in a much stronger deceleration of the fragments but would produce a final crater much shallower than observed at Meteor Crater. [source] Defining reproductively isolated units in a cryptic and syntopic species complex using mitochondrial and nuclear markers: the brooding brittle star, Amphipholis squamata (Ophiuroidea)MOLECULAR ECOLOGY, Issue 7 2008E. BOISSIN Abstract At a time when biodiversity is threatened, we are still discovering new species, and particularly in the marine realm. Delimiting species boundaries is the first step to get a precise idea of diversity. For sympatric species which are morphologically undistinguishable, using a combination of independent molecular markers is a necessary step to define separate species. Amphipholis squamata, a cosmopolitan brittle star, includes several very divergent mitochondrial lineages. These lineages appear totally intermixed in the field and studies on morphology and colour polymorphism failed to find any diagnostic character. Therefore, these mitochondrial lineages may be totally interbreeding presently. To test this hypothesis, we characterized the genetic structure of the complex in the French Mediterranean coast using sequences of mitochondrial DNA (16S) and for the first time, several nuclear DNA markers (introns and microsatellites). The data revealed six phylogenetic lineages corresponding to at least four biological species. These sibling species seem to live in syntopy. However, they seem to display contrasted levels of genetic diversity, suggesting they have distinct demographic histories and/or life-history traits. Genetic differentiation and isolation-by-distance within the French Mediterranean coasts are revealed in three lineages, as expected for a species without a free larval phase. Finally, although recombinant nuclear genotypes are common within mitochondrial lineages, the data set displays a total lack of heterozygotes, suggesting a very high selfing rate, a feature likely to have favoured the formation of the species complex. [source] The role of lipopolysaccharides in induction of plant defence responsesMOLECULAR PLANT PATHOLOGY, Issue 5 2003Gitte Erbs SUMMARY Lipopolysaccharides (LPS) are ubiquitous, indispensable components of the cell surface of Gram-negative bacteria that apparently have diverse roles in bacterial pathogenesis of plants. As an outer membrane component, LPS may contribute to the exclusion of plant-derived antimicrobial compounds promoting the ability of a bacterial plant pathogen to infect plants. In contrast, LPS can be recognized by plants to directly trigger some plant defence-related responses. LPS also sensitize plant tissue to respond more rapidly or to a greater extent to subsequently inoculated phytopathogenic bacteria. Sensitization is manifested by an accelerated synthesis of antimicrobial hydroxycinnamoyl-tyramine conjugates, in the expression patterns of genes coding for some pathogenesis-related (PR) proteins, and prevention of the hypersensitive reaction caused by avirulent bacteria. The description at the molecular level of the various effects of LPS on plants is a necessary step towards an understanding of the signal transduction mechanisms through which LPS triggers these responses. A definition of these signal transduction pathways should allow an assessment of the contribution that LPS signalling makes to plant disease resistance in both natural infections and biocontrol. [source] Fluorescence Detection of the Ornamental Fish Cardinal Tetra (Paracheirodon axelrodi)PHOTOCHEMISTRY & PHOTOBIOLOGY, Issue 1 2009Richard P. Brinn The fluorescence spectra of the tropical fish, Cardinal Tetra (Paracheirodon axelrodi), originating in the Amazon region of Brazil, were determined. These spectra were then treated using factor analysis, generating two contributing spectra and separating out the noise. Time-resolved fluorescence results indicated that the fluorescent system in the epidermis undergoes excited state reaction. Excited state proton transfer is suggested as being present. Both intentionally stressed and nonstressed individuals were used and some small differences were noted in the contributions of the two calculated contributing spectra to the experimental spectra, presumably as a function of stress. The results are compared with those obtained by the standard determination of cortisol level using the whole body extraction method and it is suggested that the method could be tested as an improved, nondestructive way to determine stress in this species, which is a necessary step in the development of "best management practices" of methods for storage and transport of the fish. [source] The promise of geometric morphometricsAMERICAN JOURNAL OF PHYSICAL ANTHROPOLOGY, Issue S35 2002Joan T. Richtsmeier Abstract Nontraditional or geometric morphometric methods have found wide application in the biological sciences, especially in anthropology, a field with a strong history of measurement of biological form. Controversy has arisen over which method is the "best" for quantifying the morphological difference between forms and for making proper statistical statements about the detected differences. This paper explains that many of these arguments are superfluous to the real issues that need to be understood by those wishing to apply morphometric methods to biological data. Validity, the ability of a method to find the correct answer, is rarely discussed and often ignored. We explain why demonstration of validity is a necessary step in the evaluation of methods used in morphometrics. Focusing specifically on landmark data, we discuss the concepts of size and shape, and reiterate that since no unique definition of size exists, shape can only be recognized with reference to a chosen surrogate for size. We explain why only a limited class of information related to the morphology of an object can be known when landmark data are used. This observation has genuine consequences, as certain morphometric methods are based on models that require specific assumptions, some of which exceed what can be known from landmark data. We show that orientation of an object with reference to other objects in a sample can never be known, because this information is not included in landmark data. Consequently, a descriptor of form difference that contains information on orientation is flawed because that information does not arise from evidence within the data, but instead is a product of a chosen orientation scheme. To illustrate these points, we apply superimposition, deformation, and linear distance-based morphometric methods to the analysis of a simulated data set for which the true differences are known. This analysis demonstrates the relative efficacy of various methods to reveal the true difference between forms. Our discussion is intended to be fair, but it will be obvious to the reader that we favor a particular approach. Our bias comes from the realization that morphometric methods should operate with a definition of form and form difference consistent with the limited class of information that can be known from landmark data. Answers based on information that can be known from the data are of more use to biological inquiry than those based on unjustifiable assumptions. Yrbk Phys Anthropol 45:63,91, 2002. © 2002 Wiley-Liss, Inc. [source] Neurobiological Processes in Adolescent Addictive DisordersTHE AMERICAN JOURNAL ON ADDICTIONS, Issue 1 2008Ty S. Schepis PhD The purpose of this review is to summarize the neurobiological factors involved in the etiology of adolescent addiction and present evidence implicating various mechanisms in its development. Adolescents are at heightened risk for experimentation with substances, and early experimentation is associated with higher rates of SUD in adulthood. Both normative (e.g., immature frontal-limbic connections, immature frontal lobe development) and non-normative (e.g., lowered serotonergic function, abnormal hypothalamic-pituitary-adrenal axis function) neurobiological developmental factors can predispose adolescents to a heightened risk for SUD. In addition, a normative imbalance in the adolescent neurobiological motivational system may be caused by the relative underdevelopment of suppressive mechanisms when compared to stimulatory systems. These neurobiological liabilities may correspond to neurobehavioral impairments in decision-making, affiliation with deviant peers and externalizing behavior; these and other cognitive and behavioral traits converge with neurobiological factors to increase SUD risk. The progression to SUD acts as an amplifying feedback loop, where the development of SUD results in reciprocal impairments in neurobehavioral and neurobiological processes. A clearer understanding of adolescent neurobiology is a necessary step in the development of prevention and treatment interventions for adolescent SUD. [source] Protein kinase C mediates up-regulation of tetrodotoxin-resistant, persistent Na+ current in rat and mouse sensory neuronesTHE JOURNAL OF PHYSIOLOGY, Issue 3 2005Mark D. Baker The tetrodotoxin-resistant (TTX-r) persistent Na+ current, attributed to NaV1.9, was recorded in small (< 25 ,m apparent diameter) dorsal root ganglion (DRG) neurones cultured from P21 rats and from adult wild-type and NaV1.8 null mice. In conventional whole-cell recordings intracellular GTP-,-S caused current up-regulation, an effect inhibited by the PKC pseudosubstrate inhibitor, PKC19,36. The current amplitude was also up-regulated by 25 ,m intracellular 1-oleoyl-2-acetyl-sn-glycerol (OAG) consistent with PKC involvement. In perforated-patch recordings, phorbol 12-myristate 13-acetate (PMA) up-regulated the current, whereas membrane-permeant activators of protein kinase A (PKA) were without effect. PGE2 did not acutely up-regulate the current. Conversely, both PGE2 and PKA activation up-regulated the major TTX-r Na+ current, NaV1.8. Extracellular ATP up-regulated the persistent current with an average apparent Kd near 13 ,m, possibly consistent with P2Y receptor activation. Numerical simulation of the up-regulation qualitatively reproduced changes in sensory neurone firing properties. The activation of PKC appears to be a necessary step in the GTP-dependent up-regulation of persistent Na+ current. [source] Parentage assignment in Haliotis midae L.: a precursor to future genetic enhancement programmes for South African abaloneAQUACULTURE RESEARCH, Issue 9 2010Nicol-Candice Van Den Bergb Abstract The establishment and evaluation of family lines using pedigree information provides an advanced understanding of the variability that exists for complex, economically valuable traits and is a necessary step in the execution of an effective breeding programme. The aim of this study was to assign parentage to mass-spawned Haliotis midae juveniles using species-specific microsatellite markers. Screening of wild abalone individuals revealed that the nine loci selected complied with the minimum requirements for parentage analyses: a null allele frequency <5% as well as a high number and frequency of alleles per locus. A total of 598 individuals were genotyped (198 breeding individuals and 400 F1 progeny) from two farms, with parentage results yielding 91% and 90% successful assignment for Farms A and B respectively. This study, therefore, provided the necessary pedigree information required for controlled breeding of individual adult abalone and indicated the usefulness of the panel of microsatellite markers selected for parentage assignment. [source] What can we learn by computing 13C, chemical shifts for X-ray protein models?ACTA CRYSTALLOGRAPHICA SECTION D, Issue 7 2009Yelena A. Arnautova The room-temperature X-ray structures of ubiquitin (PDB code 1ubq) and of the RNA-binding domain of nonstructural protein 1 of influenza A virus (PDB code 1ail) solved at 1.8 and 1.9,Å resolution, respectively, were used to investigate whether a set of conformations rather than a single X-ray structure provides better agreement with both the X-ray data and the observed 13C, chemical shifts in solution. For this purpose, a set of new conformations for each of these proteins was generated by fitting them to the experimental X-ray data deposited in the PDB. For each of the generated structures, which show R and Rfree factors similar to those of the deposited X-ray structure, the 13C, chemical shifts of all residues in the sequence were computed at the DFT level of theory. The sets of conformations were then evaluated by their ability to reproduce the observed 13C, chemical shifts by using the conformational average root-mean-square-deviation (ca-r.m.s.d.). For ubiquitin, the computed set of conformations is a better representation of the observed 13C, chemical shifts in terms of the ca-r.m.s.d. than a single X-ray-derived structure. However, for the RNA-binding domain of nonstructural protein 1 of influenza A virus, consideration of an ensemble of conformations does not improve the agreement with the observed 13C, chemical shifts. Whether an ensemble of conformations rather than any single structure is a more accurate representation of a protein structure in the crystal as well as of the observed 13C, chemical shifts is determined by the dispersion of coordinates, in terms of the all-atom r.m.s.d. among the generated models; these generated models satisfy the experimental X-ray data with accuracy as good as the PDB structure. Therefore, generation of an ensemble is a necessary step to determine whether or not a single structure is sufficient for an accurate representation of both experimental X-ray data and observed 13C, chemical shifts in solution. [source] Committing to regional cooperation: ASEAN, globalisation and the Shin Corporation , Temasek Holdings dealASIA PACIFIC VIEWPOINT, Issue 3 2009Sajid Anwar Abstract This paper investigates the relationship between regional and national identities in the age of globalisation, with particular reference to the Association of Southeast Asian Nations (ASEAN). For members of ASEAN, economic integration is seen as a necessary step forward in order to (i) reduce reliance on Western countries during times of economic crisis and (ii) speed up the recovery process in the aftermath of a crisis. The concept of an ASEAN Economic Community represents a step towards achieving this goal. However, by means of a case study, this paper demonstrates that the idea of an ASEAN Economic Community does not yet have sufficiently solid foundations. Cracks appear when member states act in response to national interest. Given the frequency of friction between member nations, and the fact that ASEAN members are quite diverse in both economic and cultural respects, there is still much more to be done to realise the objective of forming an effective and credible regional economic group. In this paper some suggestions are offered that might assist with the achievement of this goal. [source] Model Selection in Estimating EquationsBIOMETRICS, Issue 2 2001Wei Pan Summary. Model selection is a necessary step in many practical regression analyses. But for methods based on estimating equations, such as the quasi-likelihood and generalized estimating equation (GEE) approaches, there seem to be few well-studied model selection techniques. In this article, we propose a new model selection criterion that minimizes the expected predictive bias (EPB) of estimating equations. A bootstrap smoothed cross-validation (BCV) estimate of EPB is presented and its performance is assessed via simulation for overdispersed generalized linear models. For illustration, the method is applied to a real data set taken from a study of the development of ewe embryos. [source] Local lung responses following local lung challenge with recombinant lungworm antigen in systemically sensitized sheepCLINICAL & EXPERIMENTAL ALLERGY, Issue 10 2001D. D. S. Collie Background Chronic mast cell-mediated inflammation may contribute significantly towards the extensive tissue remodelling that is a feature of lungworm infection in ruminants. Understanding the factors that control tissue remodelling is a necessary step toward effective management and treatment of conditions that feature such pathology. Objective We sought to define in a novel ovine model system, the cellular, immune and mast cell phenotypic events that occur following local lung challenge with a recombinant protein antigen, DvA-1, derived from the ruminant lungworm nematode, Dictyocaulus viviparus. Methods Two spatially disparate lung segments in systemically sensitized sheep were challenged on three occasions with DvA-1 (3xDVA) and two further segments were challenged with saline (3xSAL). Two months after the third challenge, one of the two segments previously repeatedly challenged with DvA-1 was challenged again with DvA-1 (3xDVA:DVA) whilst the other was challenged with saline (3xDVA:SAL). A similar protocol was followed with the saline challenged segments (3xSAL:SAL and 3xSAL:DVA). Bronchoalveolar lavage fluid (BALF) (n = 16) and tissue (n = 3) were collected after the last challenge. Results Cellular changes 24 h after the fourth challenge were characterized by an increase in the absolute numbers of neutrophils and eosinophils in BALF from 3xDVA:DVA and 3xSAL:DVA segments. Local antibody production was implied through increased levels of antibody in both 3xDVA:DVA and 3xDVA:SAL segments, with the latter being unaffected by inflammation. Levels of active transforming growth factor beta-1 (TGF-,1) were significantly increased in 3xDVA:SAL segments and a trend towards an increase was apparent in 3xDVA:DVA segments. Total TGF-,1 levels were significantly correlated with eosinophil counts in all except the 3xDVA:SAL segments. Such changes in the bronchoalveolar space were complemented by increased ratios of sheep mast cell proteinase-1 expressing cells and tryptase expressing cells, to toluidine blue positive cells in airways from 3xDVA:DVA segments. Conclusion Mast cell phenotypic events occurring as a consequence of antigen challenge were limited to segments in which changes in BALF were characterized by neutrophil influx and increased local antibody production. [source] Pharmacodynamics of H1-antihistamines: from concept to realityCLINICAL & EXPERIMENTAL ALLERGY REVIEWS, Issue 3 2003N. Frossard Summary Pharmacodynamics are designed to give objective criteria to the understanding and assessment of the potency and consistency of activity of antihistamines. They allow a determination of the onset of action in the skin, and of their duration of action, which is particularly important for defining a once- or twice-a-day dosing, for instance. They also predict the antihistaminic potency in the skin, studying the cutaneous reactivity to histamine at specific time-points, or over a 24-h period. These pre-clinical studies assess drug characteristics, which is helpful in understanding their clinical efficacy. Pharmacodynamics are thus a necessary step in clinical studies, and important in the assessment of the clinical efficacy of a drug in the allergic patient. [source] Translating knowledge into practice in the "post-genome" era,ACTA PAEDIATRICA, Issue 3 2004CR Scriver The Human Genome Project is "completed", but it is only a beginning in the understanding of genomic structure and function. A "human phenome project" is waiting in the wings. The complexity involving a phenotype can be glimpsed, for example, if one enquires into the relationships between mutant phenylalanine hydroxylase (PAH) genotypes and the clinical disorders called PKU /Hyperphenylalaninemia,so called lessons from PKU genotypes and phenotypes. Since genomes speak biochemistry, not phenotype (said RHA Plasterk), for genomics to penetrate medicine, biochemistry and biology must be allies. The ideal translators and ambassadors of the knowledge that must cross the gap between laboratory and bedside are the clinician scientists; restoration of that attenuated community of colleagues is a necessary step in the implementation of genomic medicine. [source] Heroin-assisted treatment in Switzerland: a case study in policy changeADDICTION, Issue 1 2010Ambros Uchtenhagen ABSTRACT Background Switzerland introduced a pragmatic national drug policy when the former conservative abstinence-orientated politics proved unable to cope with an escalating number of users and related negative consequences for public health and public order. The high visibility of ,needle parks' and the size of the acquired immune deficiency disorder (AIDS) epidemic called for a new approach and for national leadership. Aims To describe the intentions, the process and the results of setting up the new treatment approach of prescribing heroin to treatment resistant heroin addicts, as an example of drug policy change. Materials and Methods A systematic collection of relevant documents is analysed and used as evidence for describing the process of policy change. Results Measures to reduce the negative consequences of continued use and to prevent the spread of AIDS were started mainly by private initiatives and soon taken up officially in the ,four-pillar' drug policy (including harm reduction, prevention, treatment and law enforcement). Medical prescription of heroin to chronic, treatment-resistant heroin addicts was one of the innovations, based on extensive scientific and political preparation. Detailed documentation and evaluation, ample communication of results, adaptations made on the basis of results and extensive public debate helped to consolidate the new policy and heroin-assisted treatment, in spite of its limitations as an observational cohort study. All necessary steps were taken to proceed from a scientific experiment to a routine procedure. Discussion Comparable policy changes have been observed in a few other countries, such as The Netherlands and Germany, based on the Swiss experience, with equally positive results of heroin-assisted treatment. These experiments were designed as randomised controlled trials, comparing intravenous heroin against oral methadone, thereby demonstrating the specific value of pharmaceutical diamorphine for maintenance treatment in opiate dependence. The positive impact of policy change and the positive outcomes of heroin-assisted treatment were acknowledged increasingly nationally and internationally, but made it difficult to continue the process of adapting policy to new challenges, due to the low visibility of present drug problems and to changing political priorities. Conclusion A major change in drug policy was effectively realised under typical conditions of a federalist country with a longstanding tradition of democratic consensus building. Facilitating factors were the size and visibility of the heroin problem, the rise of the Aids epidemic, and a pragmatic attitude of tolerating private initiatives opening the way to official policy change. [source] Tyrosine phosphorylation of the GluR2 subunit is required for long-term depression of synaptic efficacy in young animals in vivoHIPPOCAMPUS, Issue 8 2007Christopher J. Fox Abstract The study of the intracellular mechanics that underlay changes in synaptic efficacy is a rapidly evolving field of research. It is currently believed that NMDA receptors play a significant role in the induction of synaptic plasticity, whereas AMPA receptors play a significant role in its expression. For AMPA receptors, it has been shown that tyrosine phosphorylation of the GluR2 carboxyl termini is required for the expression of long-term depression of synaptic efficacy (LTD) in vitro (Ahmadian et al. (2004) EMBO J 23:1040,1050). In the present study, we sought to determine whether similar mechanisms are involved in vivo, where different stimulation parameters are required for the induction of LTD. We initially used a paired-burst (PB) paradigm that reliably induces LTD in vivo. In these animals we were able to prevent the induction and expression of PB-LTD by administering a peptide (GluR-3Y) that acted as a competitive inhibitor of tyrosine phosphorylation. In a separate set of animals, we exposed animals to brief periods of stress (S) before using low-frequency stimuli to induce LTD (S-LTD). Again, GluR2,3Y blocked both the induction and expression of S-LTD. In contrast, an inert version of the peptide, with alanine replacing the three tyrosine residues, did not inhibit LTD induction. In addition, we demonstrated that GluR2,3Y did not affect the induction of long-term potentiation in vivo. These findings support the hypothesis that tyrosine phosphorylation and AMPA receptor endocytosis are necessary steps for the induction and maintenance of two forms of LTD in the CA1 region. © 2007 Wiley-Liss, Inc. [source] Adaptive remeshing in large plastic strain with damageINTERNATIONAL JOURNAL FOR NUMERICAL METHODS IN ENGINEERING, Issue 1 2005H. Borouchaki Abstract The analysis of mechanical structures using the finite element method in the framework of large elasto-plastic strain, needs frequent remeshing of the deformed domain during the computation. Indeed, the remeshing is due to the large geometrical distortion of finite elements and the adaptation to the physical behaviour of the solution as the plastic strain or the damage fields. This paper gives the necessary steps to remesh a mechanical structure during large elasto-plastic deformations with damage. An important part of this process concerns the geometrical and physical error estimates. The proposed method is integrated in a computational environment using the ABAQUS/Explicit solver and the BL2D-V2 adaptive mesher. After recalling the formulation of the elasto-plastic problem with damage, four types of applications using the proposed adaptive remeshing are given: orthogonal cutting, side-pressing of an infinite cylinder, blanking and backward extrusion with drilling. Copyright © 2005 John Wiley & Sons, Ltd. [source] Panbiogeographical study of hagfishes: an anachronistic analysisJOURNAL OF BIOGEOGRAPHY, Issue 3 2009J. C. Briggs Abstract In a recent paper by M. J. Cavalcanti and V. Gallo, ,Panbiogeographical analysis of distribution patterns in hagfishes (Craniata: Myxinidae)' (Journal of Biogeography, 2008, 35, 1258,1268), the authors studied the biogeography of an ancient fish family (Myxinidae) in the hope that the contemporary distributions of the species would reveal their past history and that of the ocean basins where they reside. In order to accomplish this task, there are several criteria that should have been met: (1) the ages of the taxa utilized (species) would have to be old enough to reflect the history of the areas where they are found, (2) the identification of the species as listed in the databases would have to be accurate, (3) the geographical locations indicated on the figures would have to be consistent with the statements in the text, and (4) the significance of the vicariant patterns would have to depend on evidence pertaining to the ages of such patterns. Unfortunately, it appears that none of these conditions has been met. It seems apparent that faith in an antiquated method of analysis led to neglect of the necessary steps in the analysis. This leaves little justification for publication of the paper, except to show that hagfishes are very widely distributed. [source] Unified QSAR & network-based computational chemistry approach to antimicrobials.JOURNAL OF COMPUTATIONAL CHEMISTRY, Issue 1 2010Abstract In the previous work, we reported a multitarget Quantitative Structure-Activity Relationship (mt-QSAR) model to predict drug activity against different fungal species. This mt-QSAR allowed us to construct a drug,drug multispecies Complex Network (msCN) to investigate drug,drug similarity (González-Díaz and Prado-Prado, J Comput Chem 2008, 29, 656). However, important methodological points remained unclear, such as follows: (1) the accuracy of the methods when applied to other problems; (2) the effect of the distance type used to construct the msCN; (3) how to perform the inverse procedure to study species,species similarity with multidrug resistance CNs (mdrCN); and (4) the implications and necessary steps to perform a substructural Triadic Census Analysis (TCA) of the msCN. To continue the present series with other important problem, we developed here a mt-QSAR model for more than 700 drugs tested in the literature against different parasites (predicting antiparasitic drugs). The data were processed by Linear Discriminate Analysis (LDA) and the model classifies correctly 93.62% (1160 out of 1239 cases) in training. The model validation was carried out by means of external predicting series; the model classified 573 out of 607, that is, 94.4% of cases. Next, we carried out the first comparative study of the topology of six different drug,drug msCNs based on six different distances such as Euclidean, Chebychev, Manhattan, etc. Furthermore, we compared the selected drug,drug msCN and species,species mdsCN with random networks. We also introduced here the inverse methodology to construct species,species msCN based on a mt-QSAR model. Last, we reported the first substructural analysis of drug,drug msCN using Triadic Census Analysis (TCA) algorithm. © 2009 Wiley Periodicals, Inc. J Comput Chem 2010 [source] Who's afraid of the big bad wolf?AUSTRALIAN OCCUPATIONAL THERAPY JOURNAL, Issue 4 2007Making sense of results from randomised controlled trials Background:, Reading and interpreting results from research can be challenging. Many therapists read the abstract and discussion but confess to bypassing the results section of journal articles. Methods:, This paper discusses necessary steps to reading the results section of a published randomised controlled trial. Recent clinical trials are used as examples. Results:, An ability to read and interpret the results section of a paper requires the therapist to consider whether the tests conducted are appropriate, the results reported are accurate and the conclusions drawn by the authors are appropriate. Estimates of treatment effect sizes can be calculated by the therapist and used to determine if the effect of treatment is likely to be large enough to be "clinically worthwhile". Conclusions:, The ability to extract meaningful statistical information from clinical trials is a fundamental skill that will enhance therapists' knowledge and understanding of evidence-based practice. [source] | ||||||||||||||||||||||||||||