The effects of Gilles de la Tourette syndrome and other chronic tic disorders on quality of life across the lifespan:a systematic review

Gilles de la Tourette syndrome (GTS) and other chronic tic disorders are neurodevelopmental conditions characterized by the presence of tics and associated behavioral problems. Whilst converging evidence indicates that these conditions can affect patients' quality of life (QoL), the extent of this impairment across the lifespan is not well understood. We conducted a systematic literature review of published QoL studies in GTS and other chronic tic disorders to comprehensively assess the effects of these conditions on QoL in different age groups. We found that QoL can be perceived differently by child and adult patients, especially with regard to the reciprocal contributions of tics and behavioral problems to the different domains of QoL. Specifically, QoL profiles in children often reflect the impact of co-morbid attention-deficit and hyperactivity symptoms, which tend to improve with age, whereas adults' perception of QoL seems to be more strongly affected by the presence of depression and anxiety. Management strategies should take into account differences in age-related QoL needs between children and adults with GTS or other chronic tic disorders

A habituation account of change detection in same/different judgments

We investigated the basis of change detection in a short-term priming task. In two experiments, participants were asked to indicate whether or not a target word was the same as a previously presented cue. Data from an experiment measuring magnetoencephalography failed to find different patterns for “same” and “different” responses, consistent with the claim that both arise from a common neural source, with response magnitude defining the difference between immediate novelty versus familiarity. In a behavioral experiment, we tested and confirmed the predictions of a habituation account of these judgments by comparing conditions in which the target, the cue, or neither was primed by its presentation in the previous trial. As predicted, cue-primed trials had faster response times, and target-primed trials had slower response times relative to the neither-primed baseline. These results were obtained irrespective of response repetition and stimulus–response contingencies. The behavioral and brain activity data support the view that detection of change drives performance in these tasks and that the underlying mechanism is neuronal habituation

International Veterinary Epilepsy Task Force Consensus Proposal: Outcome of therapeutic interventions in canine and feline epilepsy

Common criteria for the diagnosis of drug resistance and the assessment of outcome are needed urgently as a prerequisite for standardized evaluation and reporting of individual therapeutic responses in canine epilepsy. Thus, we provide a proposal for the definition of drug resistance and partial therapeutic success in canine patients with epilepsy. This consensus statement also suggests a list of factors and aspects of outcome, which should be considered in addition to the impact on seizures. Moreover, these expert recommendations discuss criteria which determine the validity and informative value of a therapeutic trial in an individual patient and also suggest the application of individual outcome criteria. Agreement on common guidelines does not only render a basis for future optimization of individual patient management, but is also a presupposition for the design and implementation of clinical studies with highly standardized inclusion and exclusion criteria. Respective standardization will improve the comparability of findings from different studies and renders an improved basis for multicenter studies. Therefore, this proposal provides an in-depth discussion of the implications of outcome criteria for clinical studies. In particular ethical aspects and the different options for study design and application of individual patient-centered outcome criteria are considered

Systematic search for putative new domain families in Mycoplasma gallisepticum genome

<p>Abstract</p> <p>Background</p> <p>Protein domains are the fundamental units of protein structure, function and evolution. The delineation of different domains in proteins is important for classification, understanding of structure, function and evolution. The delineation of protein domains within a polypeptide chain, namely at the genome scale, can be achieved in several ways but may remain problematic in many instances. Difficulties in identifying the domain content of a given sequence arise when the query sequence has no homologues with experimentally determined structure and searching against sequence domain databases also results in insignificant matches. Identification of domains under low sequence identity conditions and lack of structural homologues acquire a crucial importance especially at the genomic scale.</p> <p>Findings</p> <p>We have developed a new method for the identification of domains in unassigned regions through indirect connections and scaled up its application to the analysis of 434 unassigned regions in 726 protein sequences of <it>Mycoplasma gallisepticum </it>genome. We could establish 71 new domain relationships and probable 63 putative new domain families through intermediate sequences in the unassigned regions, which importantly represent an overall 10% increase in PfamA domain annotation over the direct assignment in this genome.</p> <p>Conclusions</p> <p>The systematic analysis of the unassigned regions in the <it>Mycoplasma gallisepticum </it>genome has provided some insight into the possible new domain relationships and putative new domain families. Further investigation of these predicted new domains may prove beneficial in improving the existing domain prediction algorithms.</p

DAKOTA, a multilevel parallel object-oriented framework for design optimization, parameter estimation, uncertainty quantification, and sensitivity analysis:version 4.0 reference manual

The DAKOTA (Design Analysis Kit for Optimization and Terascale Applications) toolkit provides a flexible and extensible interface between simulation codes and iterative analysis methods. DAKOTA contains algorithms for optimization with gradient and nongradient-based methods; uncertainty quantification with sampling, reliability, and stochastic finite element methods; parameter estimation with nonlinear least squares methods; and sensitivity/variance analysis with design of experiments and parameter study methods. These capabilities may be used on their own or as components within advanced strategies such as surrogate-based optimization, mixed integer nonlinear programming, or optimization under uncertainty. By employing object-oriented design to implement abstractions of the key components required for iterative systems analyses, the DAKOTA toolkit provides a flexible and extensible problem-solving environment for design and performance analysis of computational models on high performance computers. This report serves as a reference manual for the commands specification for the DAKOTA software, providing input overviews, option descriptions, and example specifications

Dakota, a multilevel parallel object-oriented framework for design optimization, parameter estimation, uncertainty quantification, and sensitivity analysis:version 4.0 developers manual.

The DAKOTA (Design Analysis Kit for Optimization and Terascale Applications) toolkit provides a flexible and extensible interface between simulation codes and iterative analysis methods. DAKOTA contains algorithms for optimization with gradient and nongradient-based methods; uncertainty quantification with sampling, reliability, and stochastic finite element methods; parameter estimation with nonlinear least squares methods; and sensitivity/variance analysis with design of experiments and parameter study methods. These capabilities may be used on their own or as components within advanced strategies such as surrogate-based optimization, mixed integer nonlinear programming, or optimization under uncertainty. By employing object-oriented design to implement abstractions of the key components required for iterative systems analyses, the DAKOTA toolkit provides a flexible and extensible problem-solving environment for design and performance analysis of computational models on high performance computers. This report serves as a developers manual for the DAKOTA software and describes the DAKOTA class hierarchies and their interrelationships. It derives directly from annotation of the actual source code and provides detailed class documentation, including all member functions and attributes

Phamerator: a bioinformatic tool for comparative bacteriophage genomics

Background: Bacteriophage genomes have mosaic architectures and are replete with small open reading frames of unknown function, presenting challenges in their annotation, comparative analysis, and representation.Results: We describe here a bioinformatic tool, Phamerator, that assorts protein-coding genes into phamilies of related sequences using pairwise comparisons to generate a database of gene relationships. This database is used to generate genome maps of multiple phages that incorporate nucleotide and amino acid sequence relationships, as well as genes containing conserved domains. Phamerator also generates phamily circle representations of gene phamilies, facilitating analysis of the different evolutionary histories of individual genes that migrate through phage populations by horizontal genetic exchange.Conclusions: Phamerator represents a useful tool for comparative genomic analysis and comparative representations of bacteriophage genomes. © 2011 Cresawn et al; licensee BioMed Central Ltd

Combining evidence and values in priority setting: testing the balance sheet method in a low-income country

<p>Abstract</p> <p>Background</p> <p>Procedures for priority setting need to incorporate both scientific evidence and public values. The aim of this study was to test out a model for priority setting which incorporates both scientific evidence and public values, and to explore use of evidence by a selection of stakeholders and to study reasons for the relative ranking of health care interventions in a setting of extreme resource scarcity.</p> <p>Methods</p> <p>Systematic search for and assessment of relevant evidence for priority setting in a low-income country. Development of a balance sheet according to Eddy's explicit method. Eight group interviews (n-85), using a modified nominal group technique for eliciting individual and group rankings of a given set of health interventions.</p> <p>Results</p> <p>The study procedure made it possible to compare the groups' ranking before and after all the evidence was provided to participants. A rank deviation is significant if the rank order of the same intervention differed by two or more points on the ordinal scale. A comparison between the initial rank and the final rank (before deliberation) showed a rank deviation of 67%. The difference between the initial rank and the final rank after discussion and voting gave a rank deviation of 78%.</p> <p>Conclusion</p> <p>Evidence-based and deliberative decision-making does change priorities significantly in an experimental setting. Our use of the balance sheet method was meant as a demonstration project, but could if properly developed be feasible for health planners, experts and health workers, although more work is needed before it can be used for laypersons.</p

Outcomes research in the development and evaluation of practice guidelines

BACKGROUND: Practice guidelines have been developed in response to the observation that variations exist in clinical medicine that are not related to variations in the clinical presentation and severity of the disease. Despite their widespread use, however, practice guideline evaluation lacks a rigorous scientific methodology to support its development and application. DISCUSSION: Firstly, we review the major epidemiological foundations of practice guideline development. Secondly, we propose a chronic disease epidemiological model in which practice patterns are viewed as the exposure and outcomes of interest such as quality or cost are viewed as the disease. Sources of selection, information, confounding and temporal trend bias are identified and discussed. SUMMARY: The proposed methodological framework for outcomes research to evaluate practice guidelines reflects the selection, information and confounding biases inherent in its observational nature which must be accounted for in both the design and the analysis phases of any outcomes research study

The context influences doctors' support of shared decision-making in cancer care

Most cancer patients in westernised countries now want all information about their situation, good or bad, and many wish to be involved in decision-making. The attitudes to and use of shared decision-making (SDM) by cancer doctors is not well known. Australian cancer clinicians treating breast, colorectal, gynaecological, haematological, or urological cancer were surveyed to identify their usual approach to decision-making and their comfort with different decision-making styles when discussing treatment with patients. A response rate of 59% resulted in 624 complete surveys, which explored usual practice in discussing participation in decision-making, providing information, and perception of the role patients want to play. Univariate and multivariate analyses were performed to identify predictors of use of SDM. Most cancer doctors (62.4%) reported using SDM and being most comfortable with this approach. Differences were apparent between reported high comfort with SDM and less frequent usual practice. Multivariate analysis showed that specialisation in breast or urological cancers compared to other cancers (AOR 3.02), high caseload of new patients per month (AOR 2.81) and female gender (AOR 1.87) were each independently associated with increased likelihood of use of SDM. Barriers exist to the application of SDM by doctors according to clinical situation and clinician characteristics