The area under the receiver operating characteristic (ROC) curve (AUC) is commonly used for assessing the discriminative ability of prediction models even though the measure is criticized for being ...clinically irrelevant and lacking an intuitive interpretation. Every tutorial explains how the coordinates of the ROC curve are obtained from the risk distributions of diseased and non-diseased individuals, but it has not become common sense that therewith the ROC plot is just another way of presenting these risk distributions. We show how the ROC curve is an alternative way to present risk distributions of diseased and non-diseased individuals and how the shape of the ROC curve informs about the overlap of the risk distributions. For example, ROC curves are rounded when the prediction model included variables with similar effect on disease risk and have an angle when, for example, one binary risk factor has a stronger effect; and ROC curves are stepped rather than smooth when the sample size or incidence is low, when the prediction model is based on a relatively small set of categorical predictors. This alternative perspective on the ROC plot invalidates most purported limitations of the AUC and attributes others to the underlying risk distributions. AUC is a measure of the discriminative ability of prediction models. The assessment of prediction models should be supplemented with other metrics to assess their clinical utility.
Highlights • Anxiety is greater in PD patients who experience FOG compared to those who do not. • Anxiety may contribute to set-shifting deficits often seen in PD patients with FOG. • Anxiety may be ...a useful biomarker to identify those at risk for developing FOG.
Relationships between traits of organisms and the structure of their metacommunities have so far mainly been explored with meta‐analyses. We compared metacommunities of a wide variety of aquatic ...organism groups (12 groups, ranging from bacteria to fish) in the same set of 99 ponds to minimise biases inherent to meta‐analyses. In the category of passive dispersers, large‐bodied groups showed stronger spatial patterning than small‐bodied groups suggesting an increasing impact of dispersal limitation with increasing body size. Metacommunities of organisms with the ability to fly (i.e. insect groups) showed a weaker imprint of dispersal limitation than passive dispersers with similar body size. In contrast, dispersal movements of vertebrate groups (fish and amphibians) seemed to be mainly confined to local connectivity patterns. Our results reveal that body size and dispersal mode are important drivers of metacommunity structure and these traits should therefore be considered when developing a predictive framework for metacommunity dynamics.
Probiotics are live microorganisms that, when administered in adequate amounts, confer health benefit on the host. The therapeutic effects of probiotics have been mostly studied in the ...gastrointestinal tract, but recent evidence points toward the potential of these bacteria to prevent and/or treat chronic airway diseases. In this review, possible mechanisms of action of probiotics in the airways are described, with a particular focus on their capacity to modulate the epithelial barrier function and their mode of interaction with the immune system. Indeed, probiotic bacteria, mostly lactobacilli, can promote the expression and regulation of tight junctions and adherence junctions, resulting in the restoration of a defective epithelial barrier. These bacteria interact with the epithelial barrier and immune cells through pattern recognition receptors, such as Toll‐like receptors, which upon activation can stimulate or suppress various immune responses. Finally, the clinical potential of probiotics to treat inflammatory diseases of the upper and lower respiratory tract, and the difference between their mode of application (eg, oral or nasal) are discussed here.
The clinical potential of probiotics has gained interest as a novel oral and/or nasal treatment option for chronic airway diseases. Probiotics interact, via their microorganism‐associated molecular patterns (MAMPs), with pattern recognition receptors (PRRs) on epithelial cells. This interaction can modulate tight junctions (TJs) and adherence junctions (AJs), which results in the restoration of a defective epithelial barrier. Probiotics are able to modulate host immune responses via interactions with dendritic cells (DCs.), which on their turn promote regulatory T cells (Tregs) and reduce T helper 1 (Th1) and T helper 2 (Th2) cells.
We present a summary of the results included in the different treatments in this volume. The diversity and distribution of vertebrates, insects, crustaceans, molluscs and a suite of minor phyla is ...compared and commented upon. Whereas the available data on vertebrates and some emblematic invertebrate groups such as Odonata (dragonflies and damselflies) allow for a credible assessment, data are deficient for many other groups. This is owing to knowledge gaps, both in geographical coverage of available data and/or lack of taxonomic information. These gaps need to be addressed urgently, either by liberating date from inaccessible repositories or by fostering taxonomic research. A similar effort is required to compile environmental and ecological information in order to enable cross-linking and analysis of these complementary data sets. Only in this way will it be possible to analyse information on freshwater biodiversity for sustainable management and conservation of the world's freshwater resources.
Highlights • PD-FOG demonstrated both visuospatial and self-motion perceptual impairments beyond that of PD-nonFOG (experiment 1). • PD-FOG had a mismatch between actual and imagined movement that ...was amplified over greater distances (experiment 2). • Imagery error predicted distance estimation errors while walking. • This relationship suggests that self-motion deficits are independent of visuospatial impairments in PD-FOG.
In this paper, we exploit an analogy of the run-and-tumble process for bacterial motility with the Lorentz model of electron conduction in order to obtain analytical results for the intermediate ...scattering function. This allows to obtain an analytical result for the van Hove function in real space for two-dimensional systems. We furthermore consider the 2D circling motion of bacteria close to solid boundaries with tumbling, and show that the analogy to electron conduction in a magnetic field allows to predict the effective diffusion coefficient of the bacteria. The latter is shown to be reduced by the circling motion of the bacteria.
The fluoropyrimidines (FP) (5-Fluorouracil, capecitabine, and tegafur) are commonly used anti-cancer drugs, but lead to moderate to severe toxicity in about 10-40% of patients. DPD testing either the ...enzyme activity of dihydropyrimidine dehydrogenase (DPD) or the
genotype identifies patients at higher risk for toxicity who may be treated more safely with a lower drug dose. The Netherland's National guideline for colon carcinoma was updated in 2017 to recommend
genotyping before treatment with FP. Pretreatment
genotyping identifies approximately 50% of the patients that will develop severe FP toxicity. The aim of the study was to assess the uptake of DPD testing in the Amsterdam University Medical Centers over time and to evaluate stakeholder experiences to indicate barriers and facilitators of implementation in routine clinical care.
We used a mixed-method approach involving electronic patient records of 753 unique patients and pharmacy information systems analyses and fifteen semi-structured interviews with oncologists, pharmacists, and patients. The constellation perspective was used to identify barriers and facilitators at the level of practice, culture and structure. The proportion of FP users who were DPD tested pretreatment showed an increase from 1% (1/86) in Q2-2017 up to 87% (73/84) in Q4-2018. Unlike a landmark paper published in 2015, the National guideline for colorectal carcinoma followed by meetings to achieve local consensus led to this steep increase in the proportion of patients tested.
Facilitating factors for stakeholders to implement testing included the existence of clear protocols, (anecdotal) evidence of the utility, being aware that peers are adhering to standard practice and clear and simple procedures for ordering and reporting. Main barriers included the lack of clear divisions of responsibilities, the lack of consensus on a test approach, long turn-around times and non-user-friendly IT-infrastructures. More professional education on the utility and limitations of pharmacogenetic testing was desired by most stakeholders.
While the evidence for DPD testing was sufficient, only after the update of a National guideline and local consensus meetings the proportion of FP users that were DPD tested pretreatment rose to 87%. The implementation of personalized medicine requires stakeholders involved to attune practice, culture and structure.
A search for dark matter using an underground single-phase liquid xenon detector was conducted at the Kamioka Observatory in Japan, particularly for Weakly Interacting Massive Particles (WIMPs). We ...have used 705.9 live days of data in a fiducial volume containing 97kg of liquid xenon at the center of the detector. The event rate in the fiducial volume after the data reduction was (4.2±0.2)×10−3day−1kg−1keVee−1 at 5keVee, with a signal efficiency of 20%. All the remaining events are consistent with our background evaluation, mostly of the “mis-reconstructed events” originated from 210Pb in the copper plates lining the detector's inner surface. The obtained upper limit on a spin-independent WIMP-nucleon cross section was 2.2×10−44cm2 for a WIMP mass of 60GeV/c2 at the 90% confidence level, which was the most stringent limit among results from single-phase liquid xenon detectors.
Hidden photons and axion-like particles are candidates for cold dark matter if they were produced non-thermally in the early universe. We conducted a search for both of these bosons using 800 ...live-days of data from the XMASS detector with 327 kg of liquid xenon in the fiducial volume. No significant signal was observed, and thus we set constraints on the α′/α parameter related to kinetic mixing of hidden photons and the coupling constant gAe of axion-like particles in the mass range from 40 to 120 keV/c2, resulting in α′/α<6×10−26 and gAe<4×10−13. These limits are the most stringent over this mass range derived from both direct and indirect searches to date.
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