Outcome of implantable loop recorder evaluation

Background: The aim of this study was to evaluate implantable loop recorders (ILRs) in an unselected cohort in order to determine diagnostic yield, time to pacemaker/implantable cardioverter-defibrillator (ICD) implantation, predictors thereof, safety issues, and syncope management including usage of preceding diagnostic tools. Methods: Patients who underwent ILR evaluation in any of three centers in Region Gävleborg, Swe­den, between April 2007 and April 2013 were included and their medical records retrieved. Logistic regression was used to evaluate predictors of pacemaker/ICD outcome expressed as odds ratios (ORs) and Kaplan-Meier estimates for time-dependent analysis. Results: A total of 173 patients (52.6% females) with a mean age of 56.2 years received an ILR dur­ing a mean follow-up of 605 days. In the 146 patients evaluated for syncope/presyncope, 28.1% received a pacemaker (n = 39) or ICD (n = 2). The cumulative incidence at 6, 12, and 18 months were 8.8%, 21.3%, and 26.7%, respectively. Age > 75 years was the only significant predictor for outcome (p = 0.010) and the following variables showed a tendency toward significance: abnormal elevation of the biomarker B-type natriuretic peptide (OR 2.05, p = 0.100), a history of trauma (OR 1.71, p = 0.179), and patho­logic electrocardiogram (OR 1.68, p = 0.231). A computerized tomography of the skull was performed in 52.1% of the syncope cases. Conclusions: In syncope evaluation in an unselected cohort, 28.1% were diagnosed with an arrhyth­mia necessitating a pacemaker/ICD. The only significant predictor was advanced age. Time to diag­nosis is unpredictable and prolonged ILR monitoring is warranted in addition to optimal use of other diagnostic tools

Vaccination with recombinant neuraminidase protects against influenza virus infection in mice

While the efficacy of most influenza virus vaccines is measured by the ability to induce antibodies against the hemagglutinin (HA), antibodies against the viral neuraminidase (NA) are also correlated with less severe disease in humans and animal models. Yet, neither the amount nor the enzymatic activity of NA is standardized in current seasonal vaccines, and the breadth of NA-based protection is unknown. In the present study, different subtypes of recombinant NA were expressed in a baculovirus system and used to vaccinate mice prior to homologous, heterologous, or heterosubtypic virus challenge. Additionally, pre- and post-vaccination human serum samples from vaccinees that received TIV were studied to compare induction of antibodies against the HA and NA. Finally, the amounts of NA in 4 different vaccine formulations from 2013-2014 were quantified using ELISA. Mice immunized with N2 were 100% protected from morbidity and mortality in a homologous challenge and displayed significantly reduced viral lung titers. Heterologous challenge with a drifted strain resulted in morbidity but no mortality. Mice immunized with B/Yamagata/16/88 NA were 100% protected from morbidity and mortality when lethally challenged with a recent Victoria lineage strain. In our human cohorts, the increase in endpoint titers against N1 NA post-vaccination was less robust than that against HA and, as our quantification data suggests, the N1 NA amounts in seasonal vaccine formulations is quite variable. To confirm the broad protective effects of anti-influenza B NA antibodies on a monoclonal level, a panel of mouse monoclonal antibodies was generated against influenza B virus NA; several of these displayed broad reactivity in ELISA to whole virus and recombinant NA and protected against lethal influenza B virus challenge in mice when delivered at a dose of 5 mg/kg prophylactically, or therapeutically, 48 hours post-infection. Analysis of the protective epitopes is currently in progress. The demonstrated protective capacity of anti-NA antibodies suggests that targeting the NA through vaccination may offer increased protection against influenza virus infection

A cross-linguistic data bank for oral picture naming in Dutch, English, German, French, Italian, Russian, Spanish, and Swedish (PEDOI)

The well established effect of word frequency on adult's picture naming performance is now called into question. This is particularly true for variables which are correlated with frequency, as is the case of age of word acquisition. Since the work of there is growing agreement among researchers to confer an important role in lexical access to this variable. Indeed, it has been shown () that for normal English-speaking adults only the variables 'age-of-acquisition' and 'name agreement' are independent predictors of naming success among the various variables considered. However, when brain-damaged subjects with and without degenerative pathologies are studied, word frequency and word length as well as concept familiarity all give significant effects (; ; ). Finally, it has been suggested that the production of specific error types may be related to such variables. According to the production of semantic errors is specifically affected by 'imageability' and in the recent study by 'age of acquisition' predicts (frank) word finding difficulties

Ethnic Variation in Inflammatory Profile in Tuberculosis

PMCID: PMC3701709This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Realising local government visions for developing district heating: experiences from a learning country

District heating (DH) has an important role to play in enabling cities to transition to low-carbon heating. Although schemes are commonplace in some countries, in ‘learning countries’ where building-level technologies make up the majority of heating systems there are numerous barriers to introducing DH. Local governments are seen as key actors in helping to create a ‘shared vision’ for DH amongst stakeholders. This study uses interviews with stakeholders from a range of sectors in the UK (an example of a learning country) to examine the visions of local actors for developing DH and the types of national policy that would support local implementation of these visions. The analysis shows that in engaging with DH development local governments seek multiple types of value. Realising this value will most likely happen by taking a long-term, planned approach to development. In contrast, national government policy is geared towards techno-economic criteria and may lead to only a minority of potential sites being developed, without realisation of wider social or environmental benefits aligned to local visions. The work highlights the importance of local strategic planning, enabled by aligned national policy, in realising the full economic, environmental and social benefits of DH

Randomized clinical trial comparing percutaneous closure of patent foramen ovale (PFO) using the Amplatzer PFO Occluder with medical treatment in patients with cryptogenic embolism (PC-Trial): rationale and design

<p>Abstract</p> <p>Background</p> <p>Several studies have shown an association of cryptogenic stroke and embolism with patent foramen ovale (PFO), but the question how to prevent further events in such patients is unresolved. Options include antithrombotic treatment with warfarin or antiplatelet agents or surgical or endovascular closure of the PFO. The PC-Trial was set up to compare endovascular closure and best medical treatment for prevention of recurrent events.</p> <p>Methods</p> <p>The PC-Trial is a randomized clinical trial comparing the efficacy of percutaneous closure of the PFO using the Amplatzer PFO occluder with best medical treatment in patients with cryptogenic embolism, i.e. mostly cryptogenic stroke. Warfarin for 6 months followed by antiplatelet agents is recommended as medical treatment. Randomization is stratified according to patients age (<45 versus ≥45 years), presence of atrial septal aneurysm (ASA yes or no) and number of embolic events before randomization (one versus more than one event). Primary endpoints are death, nonfatal stroke and peripheral embolism.</p> <p>Discussion</p> <p>patients were randomized in 29 centers of Europe, Canada, and Australia. Randomization started February 2000. Enrollment of 414 patients was completed in February 2009. All patients will be followed-up longitudinally. Follow-up is maintained until the last enrolled patient is beyond 2.5 years of follow-up (expected in 2011).</p> <p>Trial Registration</p> <p>Trial listed in ClinicalTrials.gov as <a href="http://www.clinicaltrials.gov/ct2/show/NCT00166257">NCT00166257</a> and sponsored by AGA Medical, Plymouth, MN, USA</p

Proteinortho: Detection of (Co-)orthologs in large-scale analysis

<p>Abstract</p> <p>Background</p> <p>Orthology analysis is an important part of data analysis in many areas of bioinformatics such as comparative genomics and molecular phylogenetics. The ever-increasing flood of sequence data, and hence the rapidly increasing number of genomes that can be compared simultaneously, calls for efficient software tools as brute-force approaches with quadratic memory requirements become infeasible in practise. The rapid pace at which new data become available, furthermore, makes it desirable to compute genome-wide orthology relations for a given dataset rather than relying on relations listed in databases.</p> <p>Results</p> <p>The program <monospace>Proteinortho</monospace> described here is a stand-alone tool that is geared towards large datasets and makes use of distributed computing techniques when run on multi-core hardware. It implements an extended version of the reciprocal best alignment heuristic. We apply <monospace>Proteinortho</monospace> to compute orthologous proteins in the complete set of all 717 eubacterial genomes available at NCBI at the beginning of 2009. We identified thirty proteins present in 99% of all bacterial proteomes.</p> <p>Conclusions</p> <p><monospace>Proteinortho</monospace> significantly reduces the required amount of memory for orthology analysis compared to existing tools, allowing such computations to be performed on off-the-shelf hardware.</p

Defining the Boundaries of Normal Thrombin Generation: Investigations into Hemostasis

In terms of its soluble precursors, the coagulation proteome varies quantitatively among apparently healthy individuals. The significance of this variability remains obscure, in part because it is the backdrop against which the hemostatic consequences of more dramatic composition differences are studied. In this study we have defined the consequences of normal range variation of components of the coagulation proteome by using a mechanism-based computational approach that translates coagulation factor concentration data into a representation of an individual's thrombin generation potential. A novel graphical method is used to integrate standard measures that characterize thrombin generation in both empirical and computational models (e.g max rate, max level, total thrombin, time to 2 nM thrombin (“clot time”)) to visualize how normal range variation in coagulation factors results in unique thrombin generation phenotypes. Unique ensembles of the 8 coagulation factors encompassing the limits of normal range variation were used as initial conditions for the computational modeling, each ensemble representing “an individual” in a theoretical healthy population. These “individuals” with unremarkable proteome composition was then compared to actual normal and “abnormal” individuals, i.e. factor ensembles measured in apparently healthy individuals, actual coagulopathic individuals or artificially constructed factor ensembles representing individuals with specific factor deficiencies. A sensitivity analysis was performed to rank either individual factors or all possible pairs of factors in terms of their contribution to the overall distribution of thrombin generation phenotypes. Key findings of these analyses include: normal range variation of coagulation factors yields thrombin generation phenotypes indistinguishable from individuals with some, but not all, coagulopathies examined; coordinate variation of certain pairs of factors within their normal ranges disproportionately results in extreme thrombin generation phenotypes, implying that measurement of a smaller set of factors may be sufficient to identify individuals with aberrant thrombin generation potential despite normal coagulation proteome composition

Macro-level Modeling of the Response of C. elegans Reproduction to Chronic Heat Stress

A major goal of systems biology is to understand how organism-level behavior arises from a myriad of molecular interactions. Often this involves complex sets of rules describing interactions among a large number of components. As an alternative, we have developed a simple, macro-level model to describe how chronic temperature stress affects reproduction in C. elegans. Our approach uses fundamental engineering principles, together with a limited set of experimentally derived facts, and provides quantitatively accurate predictions of performance under a range of physiologically relevant conditions. We generated detailed time-resolved experimental data to evaluate the ability of our model to describe the dynamics of C. elegans reproduction. We find considerable heterogeneity in responses of individual animals to heat stress, which can be understood as modulation of a few processes and may represent a strategy for coping with the ever-changing environment. Our experimental results and model provide quantitative insight into the breakdown of a robust biological system under stress and suggest, surprisingly, that the behavior of complex biological systems may be determined by a small number of key components