Poecilorhynchus perplexus n. g., n. sp. (Trypanorhyncha: Eutetrarhynchidae) from the brownbanded bambooshark, Chiloscyllium punctatum Müller & Henle, from Australia

A new genus of trypanorhynch cestodes is described from the brownbanded bambooshark, Chiloscyllium punctatum Müller & Henle (Hemiscylliidae) from off Nickol Bay, Western Australia. Poecilorhynchus perplexus n. g., n. sp. is placed in the Eutetrarhynchidae Guiart, 1927 because it is characterised by an elongate, acraspedote scolex with two oval bothria, the absence of bothrial pits, elongate bulbs, the presence of gland-cells within the bulbs and prebulbar organs, retractor muscles inserting at the base of each bulb and an acraspedote strobila. It can be distinguished from all other genera in this family by its possession of a poeciloacanthous typical armature, with a chainette composed of two longitudinal files of uncinate hooks on the external tentacular surface.     

Efficient probabilistic model personalization integrating uncertainty on data and parameters: Application to Eikonal-Diffusion models in cardiac electrophysiology

Biophysical models are increasingly used for medical applications at the organ scale. However, model predictions are rarely associated with a confidence measure although there are important sources of uncertainty in computational physiology methods. For instance, the sparsity and noise of the clinical data used to adjust the model parameters (personalization), and the difficulty in modeling accurately soft tissue physiology. The recent theoretical progresses in stochastic models make their use computationally tractable, but there is still a challenge in estimating patient-specific parameters with such models. In this work we propose an efficient Bayesian inference method for model personalization using polynomial chaos and compressed sensing. This method makes Bayesian inference feasible in real 3D modeling problems. We demonstrate our method on cardiac electrophysiology. We first present validation results on synthetic data, then we apply the proposed method to clinical data. We demonstrate how this can help in quantifying the impact of the data characteristics on the personalization (and thus prediction) results. Described method can be beneficial for the clinical use of personalized models as it explicitly takes into account the uncertainties on the data and the model parameters while still enabling simulations that can be used to optimize treatment. Such uncertainty handling can be pivotal for the proper use of modeling as a clinical tool, because there is a crucial requirement to know the confidence one can have in personalized models.     

Effectiveness of a quality-improvement program in improving management of primary care practices

Background:

The European Practice Assessment program provides feedback and outreach visits to primary care practices to facilitate quality improvement in five domains (infrastructure, people, information, finance, and quality and safety). We examined the effectiveness of this program in improving management in primary care practices in Germany, with a focus on the domain of quality and safety.

Methods:

In a before–after study, 102 primary care practices completed a practice assessment using the European Practice Assessment instrument at baseline and three years later (intervention group). A comparative group of 102 practices was included that completed their first assessment using this instrument at the time of the intervention group’s second assessment. Mean scores were based on the proportion of indicators for which a positive response was achieved by all of the practices, on a scale of 0 to 100.

Results:

We found significant improvements in all domains between the first and second assessments in the intervention group. In the domain of quality and safety, improvements in scores (mean scores were based on the proportion of indicators for which a positive response was achieved by all of the practices, on a scale of 0 to 100) were observed in the following dimensions: complaint management (from a mean score of 51.2 at first assessment to 80.7 at second assessment); analysis of critical incidents (from 79.1 to 89.6); and quality development, quality policy (from 40.7 to 55.6). Overall scores at the time of the second assessment were significantly higher in the intervention group than in the comparative group.

Interpretation:

Primary care practices that completed the European Practice Assessment instrument twice over a three-year period showed improvements in practice management. Our findings show the value of the quality-improvement cycle in the context of practice assessment and the use of established organizational standards for practice management with the Europeaen Practice Assessment.A variety of quality-improvement initiatives in health care management have been implemented in most health care systems.^1,2 Countries such as Australia, New Zealand, the United Kingdom and the United States have a long tradition in, and established standards for, quality management in primary care. In Canada, such initiatives in primary care are in their infancy, despite support by the federal Primary Health Care Transition Fund since 2000.³ In Ontario, a comprehensive book was recently issued that provides recommendations on practice management and clinical indicators for improving quality in primary care settings in the province.⁴ The indicators were adopted and refined from the Royal New Zealand College of General Practitioners, the Royal Australian College of General Practitioners’ National Expert Committee on Standards for General Practices, the TOPAS–Europe Association European Practice Assessment, the United Kingdom’s Quality and Outcomes Framework and the Canadian Institute for Health Information.In Germany, similar developments took place. In 2005, the German government stipulated that health care providers implement a system of annual assessment of quality management.⁵ One of the systems available to practices is the European Practice Assessment (www.epa-qm.de), a validated instrument based on quality indicators for assessing practice management.⁶ The five key domains of the European Practice Assessment instrument and their respective dimensions are described in Figure 1.Open in a separate windowFigure 1:The domains and dimensions (and number of indicators) of the European Practice Assessment instrument used to measure the quality of practice management in primary care practices. For an example of how the pentagon shape is used to provide feedback to individual practices, see Appendix 1 (available at www.cmaj.ca/lookup/suppl/doi:10.1503/cmaj.110412/-/DC1). GP = general practitioner.The European Practice Assessment is used to help general practices both assess and improve their quality of practice management set against predefined criteria with embedded quality indicators. The improvement process is ongoing (e.g., through plan–do–study–act cycles⁷): each step is reviewed and redesigned with a view to improving the quality of the end product, thereby fostering continuous improvement.⁸ The multifaceted strategy has three essential components: assessment and feedback using validated instruments based on quality indicators; external support through an outreach educational visit by a trained visitor (physician or nurse) to support the practice in improving areas of management identified by the practice;⁹ and formal accreditation by an external organization.Three requirements have to be fulfilled by practices to receive accreditation: achieve a positive response for more than 50% of the indicators; meet predefined safety indicators (e.g., the vaccination status of staff regarding hepatitis B vaccination is recorded and medical equipment is checked regularly according to national regulations); and highlight areas for continuous quality improvement.Accreditation is one method for assessing and benchmarking the performance of general practice care across a broad range of clinical and organizational domains. It describes a formal process of self-assessment and external and independent peer review to encourage best management practice and can result in recommendations for continuous improvement of safety and quality in the practice.⁸ Practice accreditation can be used for different purposes: quality control, regulation, quality improvement, providing data on performance, and marketing.⁸ In Germany, it is used for quality improvement, leading to a certificate.We conducted a study to determine whether improvements in practice management occurred in general practices that completed the European Practice Assessment twice over three years, compared with general practices that completed the European Practice Assessment once. We focused our analysis on the domain of quality and safety, expecting an association between practice organization and quality improvement.^10,11 We hypothesized that the initial use of the European Practice Assessment and reassessment with it three years later would result in improved scores in the dimensions and indicators within the domain of quality and safety.     

Towards a scientific concept of free will as a biological trait: spontaneous actions and decision-making in invertebrates

Until the advent of modern neuroscience, free will used to be a theological and a metaphysical concept, debated with little reference to brain function. Today, with ever increasing understanding of neurons, circuits and cognition, this concept has become outdated and any metaphysical account of free will is rightfully rejected. The consequence is not, however, that we become mindless automata responding predictably to external stimuli. On the contrary, accumulating evidence also from brains much smaller than ours points towards a general organization of brain function that incorporates flexible decision-making on the basis of complex computations negotiating internal and external processing. The adaptive value of such an organization consists of being unpredictable for competitors, prey or predators, as well as being able to explore the hidden resource deterministic automats would never find. At the same time, this organization allows all animals to respond efficiently with tried-and-tested behaviours to predictable and reliable stimuli. As has been the case so many times in the history of neuroscience, invertebrate model systems are spearheading these research efforts. This comparatively recent evidence indicates that one common ability of most if not all brains is to choose among different behavioural options even in the absence of differences in the environment and perform genuinely novel acts. Therefore, it seems a reasonable effort for any neurobiologist to join and support a rather illustrious list of scholars who are trying to wrestle the term 'free will' from its metaphysical ancestry. The goal is to arrive at a scientific concept of free will, starting from these recently discovered processes with a strong emphasis on the neurobiological mechanisms underlying them.     

Circular permuted proteins in the universe of protein folds

Finding and identifying circular permuted protein pairs (CPP) is one of the harder tasks for structure alignment programs, because of the different location of the break in the polypeptide chain connectivity. The protein structure alignment tool GANGSTA+ was used to search for CPPs in a database of nearly 10,000 protein structures. It also allows determination of the statistical significance of the occurrence of circular permutations in the protein universe. The number of detected CPPs was found to be higher than expected, raising questions about the evolutionary processes leading to CPPs. The GANGSTA+ protein structure alignment tool is available online via the web server at http://gangsta.chemie.fu‐berlin.de . On the same webpage the complete data base of similar protein structure pairs based on the ASTRAL40 set of protein domains is provided and one can select CPPs specifically. Proteins 2010. © 2009 Wiley‐Liss, Inc.     

Operant conditioning in invertebrates

Learning to anticipate future events on the basis of past experience with the consequences of one's own behavior (operant conditioning) is a simple form of learning that humans share with most other animals, including invertebrates. Three model organisms have recently made significant contributions towards a mechanistic model of operant conditioning, because of their special technical advantages. Research using the fruit fly Drosophila melanogaster implicated the ignorant gene in operant conditioning in the heat-box, research on the sea slug Aplysia californica contributed a cellular mechanism of behavior selection at a convergence point of operant behavior and reward, and research on the pond snail Lymnaea stagnalis elucidated the role of a behavior-initiating neuron in operant conditioning. These insights demonstrate the usefulness of a variety of invertebrate model systems to complement and stimulate research in vertebrates.     

A Model for Collaborative Curation, The IEDB and ChEBI Curation of Non-peptidic Epitopes

The Immune Epitope Database (IEDB) recently expanded and enhanced its non-peptidic epitope related data utilizing a collaboration with Chemical Entities of Biological Interest (ChEBI), resulting in the first resource that brings together published immunological data with the expertise of the ChEBI database. This procedure took advantage of the distinct expertise of the IEDB and ChEBI databases to improve content and enhance interoperability of both databases. This project has resulted in the comprehensive inventory and curation of immune epitope data related to non-peptidic structures and serves as a model for successful collaborative curation between established resources.     

Polyfunctional CD4(+) T Cell Responses to Immunodominant Epitopes Correlate with Disease Activity of Virulent Salmonella

Salmonella enterica serovars are intracellular bacteria capable of causing typhoid fever and gastroenteritis of significant morbidity and mortality worldwide. Current prophylactic and therapeutic treatment is hampered by the emergence of multidrug-resistant (MDR) strains of Salmonella, and vaccines provide only temporal and partial protection in vaccinees. To develop more effective Salmonella vaccines, it is important to understand the development of protective adaptive immunity to virulent Salmonella. Here we report the identification of novel CD4(+) T cell peptide epitopes, which are conserved among Salmonella serovars. Immunization of Salmonella-infected mice with these peptide epitopes reduces the burden of Salmonella disease. Furthermore, we show that distinct polyfunctional (interferon-γ(+), tumor necrosis factor(+), and interleukin-2(+)) Salmonella-specific CD4(+) T cell responses develop with respect to magnitude and kinetics. Moreover, we found that CD4(+) T cell responses against immunodominant epitopes are predictive for active Salmonella disease. Collectively, these data could contribute to improved diagnosis of Salmonella-related diseases and rational design of Salmonella vaccines.     

Identification of Biomarkers of Human Skin Ageing in Both Genders. Wnt Signalling - A Label of Skin Ageing?

The goal of our work has been to investigate the mechanisms of gender-independent human skin ageing and examine the hypothesis of skin being an adequate model of global ageing. For this purpose, whole genome gene profiling was employed in sun-protected skin obtained from European Caucasian young and elderly females (mean age 26.7±4 years [n1 = 7] and 70.75±3.3 years [n2 = 4], respectively) and males (mean age 25.8±5.2 years [n3 = 6] and 76±3.8 years [n4 = 7], respectively) using the Illumina array platform. Confirmation of gene regulation was performed by real-time RT-PCR and immunohistochemistry. 523 genes were significantly regulated in female skin and 401 genes in male skin for the chosen criteria. Of these, 183 genes exhibited increased and 340 decreased expression in females whereas 210 genes showed increased and 191 decreased expression in males with age. In total, 39 genes were common in the target lists of significant regulated genes in males and females. 35 of these genes showed increased (16) or decreased (19) expression independent of gender. Only 4 overlapping genes (OR52N2, F6FR1OP2, TUBAL3 and STK40) showed differential regulation with age. Interestingly, Wnt signalling pathway showed to be significantly downregulated in aged skin with decreased gene and protein expression for males and females, accordingly. In addition, several genes involved in central nervous system (CNS) ageing (f.i. APP, TAU) showed to be expressed in human skin and were significanlty regulated with age. In conclusion, our study provides biomarkers of endogenous human skin ageing in both genders and highlight the role of Wnt signalling in this process. Furthermore, our data give evidence that skin could be used as a good alternative to understand ageing of different tissues such as CNS.     

Pancrustacean phylogeny in the light of new phylogenomic data: support for Remipedia as the possible sister group of Hexapoda

Remipedes are a small and enigmatic group of crustaceans, first described only 30 years ago. Analyses of both morphological and molecular data have recently suggested a close relationship between Remipedia and Hexapoda. If true, the remipedes occupy an important position in pancrustacean evolution and may be pivotal for understanding the evolutionary history of crustaceans and hexapods. However, it is important to test this hypothesis using new data and new types of analytical approaches. Here, we assembled a phylogenomic data set of 131 taxa, incorporating newly generated 454 expressed sequence tag (EST) data from six species of crustaceans, representing five lineages (Remipedia, Laevicaudata, Spinicaudata, Ostracoda, and Malacostraca). This data set includes all crustacean species for which EST data are available (46 species), and our largest alignment encompasses 866,479 amino acid positions and 1,886 genes. A series of phylogenomic analyses was performed to evaluate pancrustacean relationships. We significantly improved the quality of our data for predicting putative orthologous genes and for generating data subsets by matrix reduction procedures, thereby improving the signal to noise ratio in the data. Eight different data sets were constructed, representing various combinations of orthologous genes, data subsets, and taxa. Our results demonstrate that the different ways to compile an initial data set of core orthologs and the selection of data subsets by matrix reduction can have marked effects on the reconstructed phylogenetic trees. Nonetheless, all eight data sets strongly support Pancrustacea with Remipedia as the sister group to Hexapoda. This is the first time that a sister group relationship of Remipedia and Hexapoda has been inferred using a comprehensive phylogenomic data set that is based on EST data. We also show that selecting data subsets with increased overall signal can help to identify and prevent artifacts in phylogenetic analyses.