5,067 research outputs found
Avoidable flaws in observational analyses: an application to statins and cancer
The increasing availability of large healthcare databases is fueling an intense debate on whether real-world data should play a role in the assessment of the benefit–risk of medical treatments. In many observational studies, for example, statin users were found to have a substantially lower risk of cancer than in meta-analyses of randomized trials. Although such discrepancies are often attributed to a lack of randomization in the observational studies, they might be explained by flaws that can be avoided by explicitly emulating a target trial (the randomized trial that would answer the question of interest). Using the electronic health records of 733,804 UK adults, we emulated a target trial of statins and cancer and compared our estimates with those obtained using previously applied analytic approaches. Over the 10-yr follow-up, 28,408 individuals developed cancer. Under the target trial approach, estimated observational analogs of intention-to-treat and per-protocol 10-yr cancer-free survival differences were −0.5% (95% confidence interval (CI) −1.0%, 0.0%) and −0.3% (95% CI −1.5%, 0.5%), respectively. By contrast, previous analytic approaches yielded estimates that appeared to be strongly protective. Our findings highlight the importance of explicitly emulating a target trial to reduce bias in the effect estimates derived from observational analyses
Tuning of Human Modulation Filters Is Carrier-Frequency Dependent
Licensed under the Creative Commons Attribution License
Diagnostic Accuracy of Adenosine Deaminase and Lymphocyte Proportion in Pleural Fluid for Tuberculous Pleurisy in Different Prevalence Scenarios
BACKGROUND: Tuberculous pleural effusion (TPE) is a paucibacillary manifestation of tuberculosis, so isolation of Mycobacterium tuberculosis is difficult, biomarkers being an alternative for diagnosis. Adenosine deaminase (ADA) is the most cost-effective pleural fluid marker and is routinely used in high prevalence settings, whereas its value is questioned in areas with low prevalence. The lymphocyte proportion (LP) is known to increase the specificity of ADA for this diagnosis. We analyse the diagnostic usefulness of ADA alone and the combination of ADA ≥ 40 U/l (ADA(40)) and LP ≥ 50% (LP(50)) in three different prevalence scenarios over 11 years in our area. MATERIALS AND METHODS: Biochemistry, cytology and microbiology studies from 472 consecutive pleural fluid samples were retrospectively analyzed. ADA and differential cell count were determined in all samples. We established three different prevalence periods, based on percentage of pleural effusion cases diagnosed as tuberculosis: 1998-2000 (31.3%), 2001-2004 (11.8%), and 2005-2008 (7.4%). ROC curves, dispersion diagrams and pre/post-test probability graphs were produced. TPE accounted for 73 episodes (mean prevalence: 15.5%). The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for ADA(40) were 89%, 92.7%, 69.2% and 97.9%, respectively. For ADA(40)+LP(50) the specificity and PPV increased (98.3% and 90%) with hardly any decrease in the sensitivity or NPV (86.3% and 97.5%). No relevant differences were observed between the three study periods. CONCLUSIONS/SIGNIFICANCE: ADA remains useful for the diagnosis of TPE even in low-to-intermediate prevalence scenarios when combined with the lymphocyte proportion
Effects of intermediate scales on renormalization group running of fermion observables in an SO(10) model
In the context of non-supersymmetric SO(10) models, we analyze the
renormalization group equations for the fermions (including neutrinos) from the
GUT energy scale down to the electroweak energy scale, explicitly taking into
account the effects of an intermediate energy scale induced by a Pati--Salam
gauge group. To determine the renormalization group running, we use a numerical
minimization procedure based on a nested sampling algorithm that randomly
generates the values of 19 model parameters at the GUT scale, evolves them, and
finally constructs the values of the physical observables and compares them to
the existing experimental data at the electroweak scale. We show that the
evolved fermion masses and mixings present sizable deviations from the values
obtained without including the effects of the intermediate scale.Comment: Comments: 20 pages, 3 figures. Final version published in JHE
Interaction imaging with amplitude-dependence force spectroscopy
Knowledge of surface forces is the key to understanding a large number of
processes in fields ranging from physics to material science and biology. The
most common method to study surfaces is dynamic atomic force microscopy (AFM).
Dynamic AFM has been enormously successful in imaging surface topography, even
to atomic resolution, but the force between the AFM tip and the surface remains
unknown during imaging. Here, we present a new approach that combines high
accuracy force measurements and high resolution scanning. The method, called
amplitude-dependence force spectroscopy (ADFS) is based on the
amplitude-dependence of the cantilever's response near resonance and allows for
separate determination of both conservative and dissipative tip-surface
interactions. We use ADFS to quantitatively study and map the nano-mechanical
interaction between the AFM tip and heterogeneous polymer surfaces. ADFS is
compatible with commercial atomic force microscopes and we anticipate its
wide-spread use in taking AFM toward quantitative microscopy
Evaluation of the diagnostic accuracy of prototype rapid tests for human African trypanosomiasis
Peer reviewedPublisher PD
Complete larval development of the hermit crabs Clibanarius aequabilis and Clibanarius erythropus (Decapoda : Anomura : Diogenidae), under laboratory conditions, with a revision of the larval features of genus Clibanarius
The complete larval development (four zoeae and one megalopa) of Clibanarius aequabilis and C. erythropus, reared under laboratory conditions, is described and illustrated. The larval stages of the two northeastern Atlantic Clibanarius species cannot be easily differentiated. Their morphological characters are compared with those of other known Clibanarius larvae. The genus Clibanarius is very homogeneous with respect to larval characters. All Clibanarius zoeae display a broad and blunt rostrum, smooth abdominal segments and an antennal scale without a terminal spine. Beyond the second zoeal stage, the fourth telson process is present as a fused spine, and the uropods are biramous. In the fourth larval stage all species display a mandibular palp. The Clibanarius megalopa presents weakly developed or no ocular scales, symmetrical chelipeds, apically curved corneous dactylus in the second and third pereiopods, and 5-11 setae on the posterior margin of the telson. Apart from the number of zoeal stages, Clibanarius species may be separated, beyond the second zoeal stage, by the telson formula and the morphology of the fourth telson process.info:eu-repo/semantics/publishedVersio
Serial optical coherence microscopy for label-free volumetric histopathology
The observation of histopathology using optical microscope is an essential procedure for examination of tissue biopsies or surgically excised specimens in biological and clinical laboratories. However, slide-based microscopic pathology is not suitable for visualizing the large-scale tissue and native 3D organ structure due to its sampling limitation and shallow imaging depth. Here, we demonstrate serial optical coherence microscopy (SOCM) technique that offers label-free, high-throughput, and large-volume imaging of ex vivo mouse organs. A 3D histopathology of whole mouse brain and kidney including blood vessel structure is reconstructed by deep tissue optical imaging in serial sectioning techniques. Our results demonstrate that SOCM has unique advantages as it can visualize both native 3D structures and quantitative regional volume without introduction of any contrast agents
The Evolution of a Capacity to Build Supra-Cellular Ropes Enabled Filamentous Cyanobacteria to Colonize Highly Erodible Substrates
Several motile, filamentous cyanobacteria display the ability to self-assemble into tightly woven or twisted groups of filaments that form macroscopic yarns or ropes, and that are often centimeters long and 50-200 microm in diameter. Traditionally, this trait has been the basis for taxonomic definition of several genera, notably Microcoleus and Hydrocoleum, but the trait has not been associated with any plausible function.Through the use of phylogenetic reconstruction, we demonstrate that pedigreed, rope-building cyanobacteria from various habitats do not form a monophyletic group. This is consistent with the hypothesis that rope-building ability was fixed independently in several discrete clades, likely through processes of convergent evolution or lateral transfer. Because rope-building cyanobacteria share the ability to colonize geologically unstable sedimentary substrates, such as subtidal and intertidal marine sediments and non-vegetated soils, it is also likely that this supracellular differentiation capacity imparts a particular fitness advantage in such habitats. The physics of sediment and soil erosion in fact predict that threads in the 50-200 microm size range will attain optimal characteristics to stabilize such substrates on contact.Rope building is a supracellular morphological adaptation in filamentous cyanobacteria that allows them to colonize physically unstable sedimentary environments, and to act as successful pioneers in the biostabilization process
Searches for Long Lived Neutral Particles
An intriguing possibility for TeV scale physics is the existence of neutral
long lived particles (LOLIPs) that subsequently decay into SM states. Such
particles are many cases indistinguishable from missing transverse energy (MET)
at colliders. We propose new methods to search for these particles using
neutrino telescopes. We study their detection prospects, assuming production
either at the LHC or through dark matter (DM) annihilations in the Sun and the
Earth. We find that the sensitivity for LOLIPs produced at the LHC is limited
by luminosity and detection energy thresholds. On the other hand, in the case
of DM annihilation into LOLIPs, the sensitivity of neutrino telescopes is
promising and may extend beyond the reach of upcoming direct detection
experiments. In the context of low scale hidden sectors weakly coupled to the
SM, such indirect searches allow to probe couplings as small as 10^-15.Comment: 22 pages, 6 figure
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