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Showing papers by "University College Dublin published in 2013"


Journal ArticleDOI
TL;DR: The ACR/EULAR classification criteria for SSc performed better than the 1980 ACR criteria and should allow for more patients to be classified correctly as having the disease.
Abstract: OBJECTIVE: The 1980 American College of Rheumatology (ACR) classification criteria for systemic sclerosis (SSc) lack sensitivity for early SSc and limited cutaneous SSc. The present work, by a joint committee of the ACR and the European League Against Rheumatism (EULAR), was undertaken for the purpose of developing new classification criteria for SSc. METHODS: Using consensus methods, 23 candidate items were arranged in a multicriteria additive point system with a threshold to classify cases as SSc. The classification system was reduced by clustering items and simplifying weights. The system was tested by 1) determining specificity and sensitivity in SSc cases and controls with scleroderma-like disorders, and 2) validating against the combined view of a group of experts on a set of cases with or without SSc. RESULTS: It was determined that skin thickening of the fingers extending proximal to the metacarpophalangeal joints is sufficient for the patient to be classified as having SSc; if that is not present, 7 additive items apply, with varying weights for each: skin thickening of the fingers, fingertip lesions, telangiectasia, abnormal nailfold capillaries, interstitial lung disease or pulmonary arterial hypertension, Raynaud's phenomenon, and SSc-related autoantibodies. Sensitivity and specificity in the validation sample were, respectively, 0.91 and 0.92 for the new classification criteria and 0.75 and 0.72 for the 1980 ACR classification criteria. All selected cases were classified in accordance with consensus-based expert opinion. All cases classified as SSc according to the 1980 ACR criteria were classified as SSc with the new criteria, and several additional cases were now considered to be SSc. CONCLUSION: The ACR/EULAR classification criteria for SSc performed better than the 1980 ACR criteria for SSc and should allow for more patients to be classified correctly as having the disease.

2,743 citations


Journal ArticleDOI
11 Apr 2013-Nature
TL;DR: The authors showed that inhibition of glycolysis with 2-deoxyglucose suppresses lipopolysaccharide-induced interleukin-1β but not tumour-necrosis factor-α in mouse macrophages.
Abstract: Macrophages activated by the Gram-negative bacterial product lipopolysaccharide switch their core metabolism from oxidative phosphorylation to glycolysis. Here we show that inhibition of glycolysis with 2-deoxyglucose suppresses lipopolysaccharide-induced interleukin-1β but not tumour-necrosis factor-α in mouse macrophages. A comprehensive metabolic map of lipopolysaccharide-activated macrophages shows upregulation of glycolytic and downregulation of mitochondrial genes, which correlates directly with the expression profiles of altered metabolites. Lipopolysaccharide strongly increases the levels of the tricarboxylic-acid cycle intermediate succinate. Glutamine-dependent anerplerosis is the principal source of succinate, although the 'GABA (γ-aminobutyric acid) shunt' pathway also has a role. Lipopolysaccharide-induced succinate stabilizes hypoxia-inducible factor-1α, an effect that is inhibited by 2-deoxyglucose, with interleukin-1β as an important target. Lipopolysaccharide also increases succinylation of several proteins. We therefore identify succinate as a metabolite in innate immune signalling, which enhances interleukin-1β production during inflammation.

2,504 citations


Journal ArticleDOI
TL;DR: The ACR/EULAR classification criteria for SSc performed better than the 1980 ACR criteria and should allow for more patients to be classified correctly as having the disease.
Abstract: Objective The 1980 American College of Rheumatology (ACR) classification criteria for systemic sclerosis (SSc) lack sensitivity for early SSc and limited cutaneous SSc. The present work, by a joint committee of the ACR and the European League Against Rheumatism (EULAR), was undertaken for the purpose of developing new classification criteria for SSc. Methods Using consensus methods, 23 candidate items were arranged in a multicriteria additive point system with a threshold to classify cases as SSc. The classification system was reduced by clustering items and simplifying weights. The system was tested by (1) determining specificity and sensitivity in SSc cases and controls with scleroderma-like disorders, and (2) validating against the combined view of a group of experts on a set of cases with or without SSc. Results It was determined that skin thickening of the fingers extending proximal to the metacarpophalangeal joints is sufficient for the patient to be classified as having SSc; if that is not present, seven additive items apply, with varying weights for each: skin thickening of the fingers, fingertip lesions, telangiectasia, abnormal nailfold capillaries, interstitial lung disease or pulmonary arterial hypertension, Raynaud9s phenomenon, and SSc-related autoantibodies. Sensitivity and specificity in the validation sample were, respectively, 0.91 and 0.92 for the new classification criteria and 0.75 and 0.72 for the 1980 ACR classification criteria. All selected cases were classified in accordance with consensus-based expert opinion. All cases classified as SSc according to the 1980 ACR criteria were classified as SSc with the new criteria, and several additional cases were now considered to be SSc. Conclusions The ACR/EULAR classification criteria for SSc performed better than the 1980 ACR criteria for SSc and should allow for more patients to be classified correctly as having the disease.

1,899 citations


Journal ArticleDOI
TL;DR: The metabolic responses and molecular mechanisms that underpin the adaptatation of skeletal muscle to acute exercise and exercise training are reviewed.

1,505 citations


Journal ArticleDOI
TL;DR: It is shown that when nanoparticles are placed in a complex biological environment, interaction with other proteins in the medium and the formation of a protein corona can 'screen' the targeting molecules on the surface of nanoparticles and cause loss of specificity in targeting.
Abstract: Nanoparticles have been proposed as carriers for drugs, genes and therapies to treat various diseases. Many strategies have been developed to target nanomaterials to specific or over-expressed receptors in diseased cells, and these typically involve functionalizing the surface of nanoparticles with proteins, antibodies or other biomolecules. Here, we show that the targeting ability of such functionalized nanoparticles may disappear when they are placed in a biological environment. Using transferrin-conjugated nanoparticles, we found that proteins in the media can shield transferrin from binding to both its targeted receptors on cells and soluble transferrin receptors. Although nanoparticles continue to enter cells, the targeting specificity of transferrin is lost. Our results suggest that when nanoparticles are placed in a complex biological environment, interaction with other proteins in the medium and the formation of a protein corona can 'screen' the targeting molecules on the surface of nanoparticles and cause loss of specificity in targeting.

1,484 citations


Journal ArticleDOI
TL;DR: The historical background, the advantages and limitations of ABPM, the threshold levels for practice, and the cost-effectiveness of the technique are considered, while the role ofABPM in research circumstances, such as pharmacological trials and in the prediction of outcome in epidemiological studies is examined.
Abstract: Ambulatory blood pressure monitoring (ABPM) is being used increasingly in both clinical practice and hypertension research. Although there are many guidelines that emphasize the indications for ABPM, there is no comprehensive guideline dealing with all aspects of the technique. It was agreed at a consensus meeting on ABPM in Milan in 2011 that the 34 attendees should prepare a comprehensive position paper on the scientific evidence for ABPM.This position paper considers the historical background, the advantages and limitations of ABPM, the threshold levels for practice, and the cost-effectiveness of the technique. It examines the need for selecting an appropriate device, the accuracy of devices, the additional information and indices that ABPM devices may provide, and the software requirements.At a practical level, the paper details the requirements for using ABPM in clinical practice, editing considerations, the number of measurements required, and the circumstances, such as obesity and arrhythmias, when particular care needs to be taken when using ABPM.The clinical indications for ABPM, among which white-coat phenomena, masked hypertension, and nocturnal hypertension appear to be prominent, are outlined in detail along with special considerations that apply in certain clinical circumstances, such as childhood, the elderly and pregnancy, and in cardiovascular illness, examples being stroke and chronic renal disease, and the place of home measurement of blood pressure in relation to ABPM is appraised.The role of ABPM in research circumstances, such as pharmacological trials and in the prediction of outcome in epidemiological studies is examined and finally the implementation of ABPM in practice is considered in relation to the issue of reimbursement in different countries, the provision of the technique by primary care practices, hospital clinics and pharmacies, and the growing role of registries of ABPM in many countries.

1,183 citations


Journal ArticleDOI
TL;DR: In this paper, the authors conducted a quantitative review of the literature and found that there is indeed support for the value of entrepreneurship education and training (EET) in the context of human capital theory and found a significant relationship between EET and entrepreneurship-related human capital assets.

1,043 citations


Journal ArticleDOI
TL;DR: A critical assessment of the current understanding of silver nanoparticle toxicity is provided and a set of pointers and guidelines for experimental design of future studies to assess the environmental and biological impacts of nanosilver are provided.
Abstract: Nanosilver, due to its small particle size and enormous specific surface area, facilitates more rapid dissolution of ions than the equivalent bulk material; potentially leading to increased toxicity of nanosilver. This, coupled with their capacity to adsorb biomolecules and interact with biological receptors can mean that nanoparticles can reach sub-cellular locations leading to potentially higher localized concentrations of ions once those particles start to dissolve or degrade in situ. Further complicating the story is the capacity for nanoparticles to generate reactive oxygen species, and to interact with, and potentially disturb the functioning of biomolecules such as proteins, enzymes and DNA. The fact that the nanoparticle size, shape, surface coating and a host of other factors contribute to these interactions, and that the particles themselves are evolving or ageing leads to further complications in terms of elucidating mechanisms of interaction and modes of action for silver nanoparticles, in contrast to dissolved silver species. This review aims to provide a critical assessment of the current understanding of silver nanoparticle toxicity, as well as to provide a set of pointers and guidelines for experimental design of future studies to assess the environmental and biological impacts of silver nanoparticles. In particular; in future we require a detailed description of the nanoparticles; their synthesis route and stabilisation mechanisms; their coating; and evolution and ageing under the exposure conditions of the assay. This would allow for comparison of data from different particles; different environmental or biological systems; and structure-activity or structure-property relationships to emerge as the basis for predictive toxicology. On the basis of currently available data; such comparisons or predictions are difficult; as the characterisation and time-resolved data is not available; and a full understanding of silver nanoparticle dissolution and ageing under different conditions is observed. Clear concerns are emerging regarding the overuse of nanosilver and the potential for bacterial resistance to develop. A significant conclusion includes the need for a risk-benefit analysis for all applications and eventually restrictions of the uses where a clear benefit cannot be demonstrated.

865 citations


Journal ArticleDOI
TL;DR: A range of bio-based polymers are presented, focusing on general methods of production, properties, and commercial applications, and the major industry players who are bringing these materials to the market are discussed.
Abstract: This article reviews the recent trends, developments, and future applications of bio-based polymers produced from renewable resources. Bio-based polymers are attracting increased attention due to environmental concerns and the realization that global petroleum resources are finite. Bio-based polymers not only replace existing polymers in a number of applications but also provide new combinations of properties for new applications. A range of bio-based polymers are presented in this review, focusing on general methods of production, properties, and commercial applications. The review examines the technological and future challenges discussed in bringing these materials to a wide range of applications, together with potential solutions, as well as discusses the major industry players who are bringing these materials to the market.

797 citations


Journal ArticleDOI
TL;DR: These findings show how targeting TAMs can effectively overcome therapeutic resistance mediated by TICs and improve chemotherapeutic efficacy, inhibits metastasis, and increases antitumor T-cell responses.
Abstract: Tumor-infiltrating immune cells can promote chemoresistance and metastatic spread in aggressive tumors. Consequently, the type and quality of immune responses present in the neoplastic stroma are highly predictive of patient outcome in several cancer types. In addition to host immune responses, intrinsic tumor cell activities that mimic stem cell properties have been linked to chemoresistance, metastatic dissemination, and the induction of immune suppression. Cancer stem cells are far from a static cell population; rather, their presence seems to be controlled by highly dynamic processes that are dependent on cues from the tumor stroma. However, the impact immune responses have on tumor stem cell differentiation or expansion is not well understood. In this study, we show that targeting tumor-infiltrating macrophages (TAM) and inflammatory monocytes by inhibiting either the myeloid cell receptors colony-stimulating factor-1 receptor (CSF1R) or chemokine (C-C motif) receptor 2 (CCR2) decreases the number of tumor-initiating cells (TIC) in pancreatic tumors. Targeting CCR2 or CSF1R improves chemotherapeutic efficacy, inhibits metastasis, and increases antitumor T-cell responses. Tumor-educated macrophages also directly enhanced the tumor-initiating capacity of pancreatic tumor cells by activating the transcription factor STAT3, thereby facilitating macrophage-mediated suppression of CD8(+) T lymphocytes. Together, our findings show how targeting TAMs can effectively overcome therapeutic resistance mediated by TICs.

780 citations


Journal ArticleDOI
B. S. Acharya1, Marcos Daniel Actis2, T. Aghajani3, G. Agnetta4  +979 moreInstitutions (122)
TL;DR: The Cherenkov Telescope Array (CTA) as discussed by the authors is a very high-energy (VHE) gamma ray observatory with an international collaboration with more than 1000 members from 27 countries in Europe, Asia, Africa and North and South America.

Journal ArticleDOI
S. Schael1, R. Barate2, R. Brunelière2, D. Buskulic2  +1672 moreInstitutions (143)
TL;DR: In this paper, the results of the four LEP experiments were combined to determine fundamental properties of the W boson and the electroweak theory, including the branching fraction of W and the trilinear gauge-boson self-couplings.

Journal ArticleDOI
TL;DR: It is concluded that the adsorption of proteins on the nanoparticle surface strongly reduces nanoparticle adhesion in comparison to what is observed for the bare material, and it is suggested that future nanoparticle-cell studies include an evaluation of the adhesion properties of the material to relevant membranes.
Abstract: The interactions between nanosized particles and living systems are commonly mediated by what adsorbs to the nanoparticle in the biological environment, its biomolecular corona, rather than the pristine surface. Here, we characterize the adhesion toward the cell membrane of nanoparticles of different material and size and study how this is modulated by the presence or absence of a corona on the nanoparticle surface. The results are corroborated with adsorption to simple model supported lipid bilayers using a quartz crystal microbalance. We conclude that the adsorption of proteins on the nanoparticle surface strongly reduces nanoparticle adhesion in comparison to what is observed for the bare material. Nanoparticle uptake is described as a two-step process, where the nanoparticles initially adhere to the cell membrane and subsequently are internalized by the cells via energy-dependent pathways. The lowered adhesion in the presence of proteins thereby causes a concomitant decrease in nanoparticle uptake eff...

Journal ArticleDOI
TL;DR: In this article, a detailed description of the analysis used by the CMS Collaboration in the search for the standard model Higgs boson in pp collisions at the LHC, which led to the observation of a new boson.
Abstract: A detailed description is reported of the analysis used by the CMS Collaboration in the search for the standard model Higgs boson in pp collisions at the LHC, which led to the observation of a new boson. The data sample corresponds to integrated luminosities up to 5.1 inverse femtobarns at sqrt(s) = 7 TeV, and up to 5.3 inverse femtobarns at sqrt(s) = 8 TeV. The results for five Higgs boson decay modes gamma gamma, ZZ, WW, tau tau, and bb, which show a combined local significance of 5 standard deviations near 125 GeV, are reviewed. A fit to the invariant mass of the two high resolution channels, gamma gamma and ZZ to 4 ell, gives a mass estimate of 125.3 +/- 0.4 (stat) +/- 0.5 (syst) GeV. The measurements are interpreted in the context of the standard model Lagrangian for the scalar Higgs field interacting with fermions and vector bosons. The measured values of the corresponding couplings are compared to the standard model predictions. The hypothesis of custodial symmetry is tested through the measurement of the ratio of the couplings to the W and Z bosons. All the results are consistent, within their uncertainties, with the expectations for a standard model Higgs boson.

Journal ArticleDOI
Roel Aaij1, Bernardo Adeva2, Marco Adinolfi3, C. Adrover4  +653 moreInstitutions (44)
TL;DR: A measurement of form-factor-independent angular observables in the decay B(0)→K*(892)(0)μ(+)μ(-) is presented, based on a data sample collected by the LHCb experiment in pp collisions at a center-of-mass energy of 7 TeV.
Abstract: We present a measurement of form-factor-independent angular observables in the decay B-0 -> K*(892)(0)mu(+)mu(-). The analysis is based on a data sample corresponding to an integrated luminosity of 1.0 fb(-1), collected by the LHCb experiment in pp collisions at a center-of-mass energy of 7 TeV. Four observables are measured in six bins of the dimuon invariant mass squared q(2) in the range 0.1 < q(2) < 19.0 GeV2/c(4). Agreement with recent theoretical predictions of the standard model is found for 23 of the 24 measurements. A local discrepancy, corresponding to 3.7 Gaussian standard deviations is observed in one q(2) bin for one of the observables. Considering the 24 measurements as independent, the probability to observe such a discrepancy, or larger, in one is 0.5%.

Journal ArticleDOI
TL;DR: The design and development of the European Health Literacy Survey Questionnaire (HLS-EU-Q), an innovative, comprehensive tool to measure health literacy in populations, is described to provide a deeper understanding of its purpose, its capability and its limitations for others using the tool.
Abstract: Several measurement tools have been developed to measure health literacy. The tools vary in their approach and design, but few have focused on comprehensive health literacy in populations. This paper describes the design and development of the European Health Literacy Survey Questionnaire (HLS-EU-Q), an innovative, comprehensive tool to measure health literacy in populations. Based on a conceptual model and definition, the process involved item development, pre-testing, field-testing, external consultation, plain language check, and translation from English to Bulgarian, Dutch, German, Greek, Polish, and Spanish. The development process resulted in the HLS-EU-Q, which entailed two sections, a core health literacy section and a section on determinants and outcomes associated to health literacy. The health literacy section included 47 items addressing self-reported difficulties in accessing, understanding, appraising and applying information in tasks concerning decisions making in healthcare, disease prevention, and health promotion. The second section included items related to, health behaviour, health status, health service use, community participation, socio-demographic and socio-economic factors. By illuminating the detailed steps in the design and development process of the HLS-EU-Q, it is the aim to provide a deeper understanding of its purpose, its capability and its limitations for others using the tool. By stimulating a wide application it is the vision that HLS-EU-Q will be validated in more countries to enhance the understanding of health literacy in different populations.

Posted Content
TL;DR: In this paper, the authors argue that while the increase in acceptance and activity is welcome and has lead to a greater understanding of sustainability, our present knowledge is not sufficient to create truly sustainable supply chains.
Abstract: In the last two decades the topic of sustainability has moved from the fringes of supply chain management research to the mainstream and is now an area of significant research activity. In this paper we argue that while this increase in acceptance and activity is welcome and has lead to a greater understanding of sustainability, our present knowledge is not sufficient to create truly sustainable supply chains. We build on this insight to identify five main issues that future research needs to address. We argue that when it comes to the theory of sustainable supply chain management, previous research has focused on the synergistic and familiar while overlooking trade-offs and radical innovation. These theoretical issues are compounded by measures that do not truly capture a supply chain’s impacts and methods that are better at looking backwards than forwards. The paper concludes by proposing a series of recommendations that address these issues to help in the development of truly sustainable supply chains.

Journal ArticleDOI
TL;DR: There is a need to provide standards for patient/participant selection criteria in research focused on CAI, with justifications using the best available evidence.
Abstract: While research on chronic ankle instability (CAI) and awareness of its impact on society and health care systems has grown substantially in the last 2 decades, the inconsistency in participant/patient selection criteria across studies presents a potential obstacle to addressing the problem properly. This major gap within the literature limits the ability to generalise this evidence to the target patient population. Therefore, there is a need to provide standards for patient/participant selection criteria in research focused on CAI with justifications using the best available evidence. The International Ankle Consortium provides this position paper to present and discuss an endorsed set of selection criteria for patients with CAI based on the best available evidence to be used in future research and study designs. These recommendations will enhance the validity of research conducted in this clinical population with the end goal of bringing the research evidence to the clinician and patient.

Journal ArticleDOI
TL;DR: This work experimentally demonstrates a new nematic order, formed by achiral molecules, in which the director follows an oblique helicoid, maintaining a constant oblique angle with the helix axis and experiencing twist and bend.
Abstract: A state of matter in which molecules show a long-range orientational order and no positional order is called a nematic liquid crystal. The best known and most widely used (for example, in modern displays) is the uniaxial nematic, with the rod-like molecules aligned along a single axis, called the director. When the molecules are chiral, the director twists in space, drawing a right-angle helicoid and remaining perpendicular to the helix axis; the structure is called a chiral nematic. Here using transmission electron and optical microscopy, we experimentally demonstrate a new nematic order, formed by achiral molecules, in which the director follows an oblique helicoid, maintaining a constant oblique angle with the helix axis and experiencing twist and bend. The oblique helicoids have a nanoscale pitch. The new twist-bend nematic represents a structural link between the uniaxial nematic (no tilt) and a chiral nematic (helicoids with right-angle tilt).

Journal ArticleDOI
TL;DR: This paper proposes a compositional mixture of the food sources corrected for various metabolic factors based on the isometric log‐ratio transform, which can apply a range of time series and non‐parametric smoothing relationships.
Abstract: In this paper, we review recent advances in stable isotope mixing models (SIMMs) and place them into an overarching Bayesian statistical framework, which allows for several useful extensions. SIMMs are used to quantify the proportional contributions of various sources to a mixture. The most widely used application is quantifying the diet of organisms based on the food sources they have been observed to consume. At the centre of the multivariate statistical model we propose is a compositional mixture of the food sources corrected for various metabolic factors. The compositional component of our model is based on the isometric log-ratio transform. Through this transform, we can apply a range of time series and non-parametric smoothing relationships. We illustrate our models with three case studies based on real animal dietary behaviour.

Journal ArticleDOI
TL;DR: The SL2013sv model as discussed by the authors is constrained by an unprecedentedly large set of waveform fits (∼3/4 of a million broad-band seismograms), computed in seismogram-dependent frequency bands, up to a maximum period range of 11-450 s. The model is parametrized on a triangular grid with a ∼280 km spacing.
Abstract: S U M M A R Y The rapid expansion of broad-band seismic networks over the last decade has paved the way for a new generation of global tomographic models. Significantly improved resolution of global upper-mantle and crustal structure can now be achieved, provided that structural information is extracted effectively from both surface and body waves and that the effects of errors in the data are controlled and minimized. Here, we present a new global, vertically polarized shear speed model that yields considerable improvements in resolution, compared to previous ones, for a variety of features in the upper mantle and crust. The model, SL2013sv, is constrained by an unprecedentedly large set of waveform fits (∼3/4 of a million broad-band seismograms), computed in seismogram-dependent frequency bands, up to a maximum period range of 11– 450 s. Automated multimode inversion of surface and S-wave forms was used to extract a set of linear equations with uncorrelated uncertainties from each seismogram. The equations described perturbations in elastic structure within approximate sensitivity volumes between sources and receivers. Going beyond ray theory, we calculated the phase of every mode at every frequency and its derivative with respect to Sand P-velocity perturbations by integration over a sensitivity area in a 3-D reference model; the (normally small) perturbations of the 3-D model required to fit the waveforms were then linearized using these accurate derivatives. The equations yielded by the waveform inversion of all the seismograms were simultaneously inverted for a 3-D model of shear and compressional speeds and azimuthal anisotropy within the crust and upper mantle. Elaborate outlier analysis was used to control the propagation of errors in the data (source parameters, timing at the stations, etc.). The selection of only the most mutually consistent equations exploited the data redundancy provided by our data set and strongly reduced the effect of the errors, increasing the resolution of the imaging. Our new shear speed model is parametrized on a triangular grid with a ∼280 km spacing. In well-sampled continental domains, lateral resolution approaches or exceeds that of regionalscale studies. The close match of known surface expressions of deep structure with the distribution of anomalies in the model provides a useful benchmark. In oceanic regions, spreading ridges are very well resolved, with narrow anomalies in the shallow mantle closely confined near the ridge axis, and those deeper, down to 100–120 km, showing variability in their width and location with respect to the ridge. Major subduction zones worldwide are well captured, extending from shallow depths down to the transition zone. The large size of our waveform fit data set also provides a strong statistical foundation to re-examine the validity field of the JWKB approximation and surface wave ray theory. Our analysis shows that the approximations are likely to be valid within certain time–frequency portions of most seismograms with high signal-to-noise ratios, and these portions can be identified using a set of consistent criteria that we apply in the course of waveform fitting.

Journal ArticleDOI
TL;DR: By interfering with pathogen adhesion, such glycocompounds including glycopolymers, glycoclusters, glycodendrimers and glyconanoparticles have the potential to improve or replace antibiotic treatments that are now subverted by resistance.
Abstract: Multivalency plays a major role in biological processes and particularly in the relationship between pathogenic microorganisms and their host that involves protein-glycan recognition. These interactions occur during the first steps of infection, for specific recognition between host and bacteria, but also at different stages of the immune response. The search for high-affinity ligands for studying such interactions involves the combination of carbohydrate head groups with different scaffolds and linkers generating multivalent glycocompounds with controlled spatial and topology parameters. By interfering with pathogen adhesion, such glycocompounds including glycopolymers, glycoclusters, glycodendrimers and glyconanoparticles have the potential to improve or replace antibiotic treatments that are now subverted by resistance. Multivalent glycoconjugates have also been used for stimulating the innate and adaptive immune systems, for example with carbohydrate-based vaccines. Bacteria present on their surfaces natural multivalent glycoconjugates such as lipopolysaccharides and S-layers that can also be exploited or targeted in anti-infectious strategies.

Journal ArticleDOI
TL;DR: A brief overview of deep learning methods is presented and in particular how recursive neural network approaches can be applied to the problem of predicting molecular properties, by considering an ensemble of recursive neural networks associated with all possible vertex-centered acyclic orientations of the molecular graph.
Abstract: Shallow machine learning methods have been applied to chemoinformatics problems with some success. As more data becomes available and more complex problems are tackled, deep machine learning methods may also become useful. Here, we present a brief overview of deep learning methods and show in particular how recursive neural network approaches can be applied to the problem of predicting molecular properties. However, molecules are typically described by undirected cyclic graphs, while recursive approaches typically use directed acyclic graphs. Thus, we develop methods to address this discrepancy, essentially by considering an ensemble of recursive neural networks associated with all possible vertex-centered acyclic orientations of the molecular graph. One advantage of this approach is that it relies only minimally on the identification of suitable molecular descriptors because suitable representations are learned automatically from the data. Several variants of this approach are applied to the problem of p...

Journal ArticleDOI
03 Jul 2013-JAMA
TL;DR: Among patients at risk of heart failure, BNP-based screening and collaborative care reduced the combined rates of LV systolic dysfunction, diastolic dysfunction and heart failure.
Abstract: Importance Prevention strategies for heart failure are needed. Objective To determine the efficacy of a screening program using brain-type natriuretic peptide (BNP) and collaborative care in an at-risk population in reducing newly diagnosed heart failure and prevalence of significant left ventricular (LV) systolic and/or diastolic dysfunction. Design, Setting, and Participants The St Vincent’s Screening to Prevent Heart Failure Study, a parallel-group randomized trial involving 1374 participants with cardiovascular risk factors (mean age, 64.8 [SD, 10.2] years) recruited from 39 primary care practices in Ireland between January 2005 and December 2009 and followed up until December 2011 (mean follow-up, 4.2 [SD, 1.2] years). Intervention Patients were randomly assigned to receive usual primary care (control condition; n=677) or screening with BNP testing (n=697). Intervention-group participants with BNP levels of 50 pg/mL or higher underwent echocardiography and collaborative care between their primary care physician and specialist cardiovascular service. Main Outcomes and Measures The primary end point was prevalence of asymptomatic LV dysfunction with or without newly diagnosed heart failure. Secondary end points included emergency hospitalization for arrhythmia, transient ischemic attack, stroke, myocardial infarction, peripheral or pulmonary thrombosis/embolus, or heart failure. Results A total of 263 patients (41.6%) in the intervention group had at least 1 BNP reading of 50 pg/mL or higher. The intervention group underwent more cardiovascular investigations (control, 496 per 1000 patient-years vs intervention, 850 per 1000 patient-years; incidence rate ratio, 1.71; 95% CI, 1.61-1.83; P P =.01). The primary end point of LV dysfunction with or without heart failure was met in 59 (8.7%) of 677 in the control group and 37 (5.3%) of 697 in the intervention group (odds ratio [OR], 0.55; 95% CI, 0.37-0.82; P = .003). Asymptomatic LV dysfunction was found in 45 (6.6%) of 677 control-group patients and 30 (4.3%) of 697 intervention-group patients (OR, 0.57; 95% CI, 0.37-0.88; P = .01). Heart failure occurred in 14 (2.1%) of 677 control-group patients and 7 (1.0%) of 697 intervention-group patients (OR, 0.48; 95% CI, 0.20-1.20; P = .12). The incidence rates of emergency hospitalization for major cardiovascular events were 40.4 per 1000 patient-years in the control group vs 22.3 per 1000 patient-years in the intervention group (incidence rate ratio, 0.60; 95% CI, 0.45-0.81; P = .002). Conclusion and Relevance Among patients at risk of heart failure, BNP-based screening and collaborative care reduced the combined rates of LV systolic dysfunction, diastolic dysfunction, and heart failure. Trial Registration clinicaltrials.gov Identifier:NCT00921960

Journal ArticleDOI
TL;DR: VR and exergaming technology have been primarily investigated in post-CVA rehabilitation, however, more recent work has shown this type of biofeedback to be effective in improving exercise technique in musculoskeletal populations.
Abstract: This paper reviews the literature relating to the biofeedback used in physical rehabilitation. The biofeedback methods used in rehabilitation are based on biomechanical measurements and measurements of the physiological systems of the body. The physiological systems of the body which can be measured to provide biofeedback are the neuromuscular system, the respiratory system and the cardiovascular system. Neuromuscular biofeedback methods include electromyography (EMG) biofeedback and real-time ultrasound imaging (RTUS) biofeedback. EMG biofeedback is the most widely investigated method of biofeedback and appears to be effective in the treatment of many musculoskeletal conditions and in post cardiovascular accident (CVA) rehabilitation. RTUS biofeedback has been demonstrated effective in the treatment of low back pain (LBP) and pelvic floor muscle dysfunction. Cardiovascular biofeedback methods have been shown to be effective in the treatment of a number of health conditions such as hypertension, heart failure, asthma, fibromyalgia and even psychological disorders however a systematic review in this field has yet to be conducted. Similarly, the number of large scale studies examining the use of respiratory biofeedback in rehabilitation is limited. Measurements of movement, postural control and force output can be made using a number of different devices and used to deliver biomechanical biofeedback. Inertial based sensing biofeedback is the most widely researched biomechanical biofeedback method, with a number of studies showing it to be effective in improving measures of balance in a number of populations. Other types of biomechanical biofeedback include force plate systems, electrogoniometry, pressure biofeedback and camera based systems however the evidence for these is limited. Biofeedback is generally delivered using visual displays, acoustic or haptic signals, however more recently virtual reality (VR) or exergaming technology have been used as biofeedback signals. VR and exergaming technology have been primarily investigated in post-CVA rehabilitation, however, more recent work has shown this type of biofeedback to be effective in improving exercise technique in musculoskeletal populations. While a number of studies in this area have been conducted, further large scale studies and reviews investigating different biofeedback applications in different clinical populations are required.

Journal ArticleDOI
TL;DR: In this paper, measurements of two-and four-particle angular correlations for charged particles emitted in pPb collisions are presented over a wide range in pseudorapidity and full azimuth.

Journal ArticleDOI
TL;DR: This review will investigate obese AT biology, initiation of the inflammatory, and insulin resistant environment; and the mechanisms through which dietary anti-inflammatory components/functional nutrients may be beneficial.
Abstract: Obesity and associated chronic inflammation initiate a state of insulin resistance (IR). The secretion of chemoattractants such as MCP-1 and MIF and of cytokines IL-6, TNF-α, and IL-1β, draw immune cells including dendritic cells, T cells, and macrophages into adipose tissue (AT). Dysfunctional AT lipid metabolism leads to increased circulating free fatty acids, initiating inflammatory signaling cascades in the population of infiltrating cells. A feedback loop of pro-inflammatory cytokines exacerbates this pathological state, driving further immune cell infiltration and cytokine secretion and disrupts the insulin signaling cascade. Disruption of normal AT function is causative of defects in hepatic and skeletal muscle glucose homeostasis, resulting in systemic IR and ultimately the development of type 2 diabetes. Pharmaceutical strategies that target the inflammatory milieu may have some potential; however there are a number of safety concerns surrounding such pharmaceutical approaches. Nutritional anti-inflammatory interventions could offer a more suitable long-term alternative; whilst they may be less potent than some pharmaceutical anti-inflammatory agents, this may be advantageous for long-term therapy. This review will investigate obese AT biology, initiation of the inflammatory, and insulin resistant environment; and the mechanisms through which dietary anti-inflammatory components/functional nutrients may be beneficial.

Journal ArticleDOI
TL;DR: In this article, the authors explored the relationship between energy balance closure and landscape heterogeneity using MODIS products and GLOBEstat elevation data and found that landscape-level heterogeneity in vegetation and topography cannot be ignored as a contributor to incomplete energy balance closures at the surface-atmosphere exchange measurements.

Journal ArticleDOI
01 Mar 2013
TL;DR: A new model of irony detection that is assessed along two dimensions: representativeness and relevance is constructed, and initial results are largely positive, and provide valuable insights into the figurative issues facing tasks such as sentiment analysis, assessment of online reputations, or decision making.
Abstract: Irony is a pervasive aspect of many online texts, one made all the more difficult by the absence of face-to-face contact and vocal intonation. As our media increasingly become more social, the problem of irony detection will become even more pressing. We describe here a set of textual features for recognizing irony at a linguistic level, especially in short texts created via social media such as Twitter postings or "tweets". Our experiments concern four freely available data sets that were retrieved from Twitter using content words (e.g. "Toyota") and user-generated tags (e.g. "#irony"). We construct a new model of irony detection that is assessed along two dimensions: representativeness and relevance. Initial results are largely positive, and provide valuable insights into the figurative issues facing tasks such as sentiment analysis, assessment of online reputations, or decision making.

Journal ArticleDOI
Suzanne A. Eccles1, Eric O. Aboagye2, Simak Ali2, Annie S. Anderson3, Jo Armes4, Fedor Berditchevski5, Jeremy P. Blaydes6, Keith Brennan7, Nicola J. Brown8, Helen E. Bryant8, Nigel J Bundred7, Joy Burchell4, Anna Campbell3, Jason S. Carroll9, Robert Clarke7, Charlotte E. Coles10, Gary Cook4, Angela Cox8, Nicola J. Curtin11, Lodewijk V. Dekker12, Isabel dos Santos Silva13, Stephen W. Duffy14, Douglas F. Easton9, Diana Eccles6, Dylan R. Edwards15, Joanne Edwards16, D. G. R. Evans7, Deborah Fenlon6, James M. Flanagan2, Claire Foster6, William M. Gallagher17, Montserrat Garcia-Closas1, Julia Margaret Wendy Gee18, Andy J. Gescher19, Vicky Goh4, Ashley M. Groves20, Amanda J. Harvey21, Michelle Harvie7, Bryan T. Hennessy22, Stephen Edward Hiscox18, Ingunn Holen8, Sacha J Howell7, Anthony Howell7, Gill Hubbard23, Nicholas J. Hulbert-Williams24, Myra S. Hunter4, Bharat Jasani18, Louise J. Jones14, Timothy J. Key25, Cliona C. Kirwan7, Anthony Kong25, Ian Kunkler26, Simon P. Langdon26, Martin O. Leach1, David J. Mann2, John Marshall14, Lesley Ann Martin1, Stewart G. Martin12, Jennifer E. Macdougall27, David Miles4, William R. Miller26, Joanna R. Morris5, Sue Moss14, Paul B. Mullan28, Rachel Natrajan1, James P B O'Connor7, Rosemary O'Connor29, Carlo Palmieri30, Paul D.P. Pharoah9, Emad A. Rakha12, Elizabeth Reed, Simon P. Robinson1, Erik Sahai31, John M. Saxton15, Peter Schmid32, Matthew J. Smalley18, Valerie Speirs33, Robert Stein20, John Stingl9, Charles H. Streuli, Andrew Tutt4, Galina Velikova33, Rosemary A. Walker19, Christine J. Watson9, Kaye J. Williams7, Leonie S. Young22, Alastair M. Thompson3 
TL;DR: With resources to conduct further high-quality targeted research focusing on the gaps identified, increased knowledge translating into improved clinical care should be achievable within five years.
Abstract: Introduction: Breast cancer remains a significant scientific, clinical and societal challenge. This gap analysis has reviewed and critically assessed enduring issues and new challenges emerging from recent research, and proposes strategies for translating solutions into practice. Methods: More than 100 internationally recognised specialist breast cancer scientists, clinicians and healthcare professionals collaborated to address nine thematic areas: genetics, epigenetics and epidemiology; molecular pathology and cell biology; hormonal influences and endocrine therapy; imaging, detection and screening; current/ novel therapies and biomarkers; drug resistance; metastasis, angiogenesis, circulating tumour cells, cancer ‘stem’ cells; risk and prevention; living with and managing breast cancer and its treatment. The groups developed summary papers through an iterative process which, following further appraisal from experts and patients, were melded into this summary account. (Continued on next page)