208 research outputs found

    Eliciting health state utilities for Dupuytren's contracture using a discrete choice experiment

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    Background and purpose An internet-based discrete choice experiment (DCE) was conducted to elicit preferences for a wide range of Dupuytren’s contracture (DC)-related health states. An algorithm was subsequently developed to convert these preferences into health state utilities that can be used to assess DC’s impact on quality of life and the value of its treatments. Methods Health state preferences for varying levels of DC hand severity were elicited via an internet survey from a sample of the UK adult population. Severity levels were deined using a combination of contractures (0, 45, or 90 degrees) in 8 proximal interphalangeal and metacarpophalangeal joints of the index, middle, ring, and little ingers. Right-handed, left-handed, and ambidextrous respondents indicated which hand was preferable in each of the 10 randomly-selected hand-pairings comparing different DC severity levels. For consistency across comparisons, anatomically precise digital hand drawings were used. To anchor preferences onto the traditional 0–1 utility scale used in health economic evaluations, unaffected hands were assigned a utility of 1.0 whereas the utility for a maximally affected hand (i.e., all 8 joints set at 90 degrees of contracture) was derived by asking respondents to indicate what combination of attributes and levels of the EQ-5D-5L proile most accurately relects the impact of living with such hand. Conditional logistic models were used to estimate indirect utilities, then rescaled to the anchor points on the EQ-5D-5L. Results Estimated utilities based on the responses of 1,745 qualiied respondents were 0.49, 0.57, and 0.63 for completely affected dominant hands, non-dominant hands, or ambidextrous hands, respectively. Utility for a dominant hand with 90-degree contracture in t h e metacarpophalangeal joints of the ring and little ingers was estimated to be 0.89. Separately, reducing the contracture of metacarpophalangeal joint for a little inger from 50 to 12 degrees would improve utility by 0.02. Interpretation DC is associated with substantial utility decrements. The algorithms presented herein provide a robust and lexible framework to assess utility for varying degrees of DC severity

    DDX5 plays essential transcriptional and post-transcriptional roles in the maintenance and function of spermatogonia

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    Mammalian spermatogenesis is sustained by mitotic germ cells with self-renewal potential known as undifferentiated spermatogonia. Maintenance of undifferentiated spermatogonia and spermatogenesis is dependent on tightly co-ordinated transcriptional and post-transcriptional mechanisms. The RNA helicase DDX5 is expressed by spermatogonia but roles in spermatogenesis are unexplored. Using an inducible knockout mouse model, we characterise an essential role for DDX5 in spermatogonial maintenance and show that Ddx5 is indispensable for male fertility. We demonstrate that DDX5 regulates appropriate splicing of key genes necessary for spermatogenesis. Moreover, DDX5 regulates expression of cell cycle genes in undifferentiated spermatogonia post-transcriptionally and is required for cell proliferation and survival. DDX5 can also act as a transcriptional co-activator and we demonstrate that DDX5 interacts with PLZF, a transcription factor required for germline maintenance, to co-regulate select target genes. Combined, our data reveal a critical multifunctional role for DDX5 in regulating gene expression programmes and activity of undifferentiated spermatogonia

    E(2)-Equivariant Features in Machine Learning for Morphological Classification of Radio Galaxies

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    With the growth of data from new radio telescope facilities, machine-learning approaches to the morphological classification of radio galaxies are increasingly being utilised. However, while widely employed deep-learning models using convolutional neural networks (CNNs) are equivariant to translations within images, neither CNNs nor most other machine-learning approaches are equivariant to additional isometries of the Euclidean plane, such as rotations and reflections. Recent work has attempted to address this by using G-steerable CNNs, designed to be equivariant to a specified subset of 2-dimensional Euclidean, E(2), transformations. Although this approach improved model performance, the computational costs were a recognised drawback. Here we consider the use of directly extracted E(2)-equivariant features for the classification of radio galaxies. Specifically, we investigate the use of Minkowski functionals (MFs), Haralick features (HFs) and elliptical Fourier descriptors (EFDs). We show that, while these features do not perform equivalently well to CNNs in terms of accuracy, they are able to inform the classification of radio galaxies, requiring ~50 times less computational runtime. We demonstrate that MFs are the most informative, EFDs the least informative, and show that combinations of all three result in only incrementally improved performance, which we suggest is due to information overlap between feature sets.Comment: accepted Royal Astronomical Society Techniques & Instruments (RASTI

    Modelos en ecología

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    Los modelos suelen estar rodeados por un “halo de misterio “ que restringe su uso. Nuestro objetivo es desmitificarlos, a fin de promover su difusión en la solución de los variados problemas que afrontan quienes deben manejar ecosistemas. Los puntos centrales de este artículo son los conceptos de modelo como simplificación de un sistema y de sistema como todo conjunto cost dos o más partes interrelacionadas. Del análisis de esos conceptos se deduce que los problemas básicos, tanto para construir como para usar modelos, son la definición del sistema y la identificación de sus partes y de las interacciones entre ellas. No existe un único tipo de modelos ni un único método para construirlos: la estructura, el desarrollo y los alcances de cada modelo dependen estrechamente del problema que se quiere resolver con él. A modo de ejemplo se detallan las diferentes etapas que se siguieron para la construcción de un modelo, utilizado confines didácticos, que simula la dinámica de la biomasa de los pastos en la estepa del Sudoeste de Chubut y su variabilidad en respuesta a diferentes condiciones ambientales. Se discute la necesidad de reformular supuestos básicos del modelo afín de que sus resultados resulten más acordes con el conocimiento actual del sistema estudiado.Models are usually surrounded by an atmospliere of mistery that limits their use. Our aire is to end this myth in order to promote the diffusion of models as tools to solve the problems faced by ecosystem managers. The retain points of this article are the concepts of a model as a simplification of a system, and system as a whole that contains at least two interrelated parts. The three basic problems of constructing and using models, which can be deduced from the analysis of those concepts, are the definition of the system, their parts, and the interactions among them. There is not ti single kind of model or method to construct it: the structure, the construction, and the achievements of each model closely depend on the problem to be solved with it. As an example, this paper details the different steps followed to construct a model, used with educational purposes, which predicts the biomass dynamics of the steppe of SW Chubut, Argentina, and its variability in response to environmental conditions. We discuss some discrepaticies between the results of the model and our knowledge of the system, and show how some of the basic assumptions must be reformulated

    Valoración de las aguas residuales mediante procedimientos analíticos y biológicos

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    Some procedures, based on analytical and biological methods, are useful tools for risk assessment of treatment plant wastewater. In fact, urban effluents, called “complex mixtures” due to their nature, origin and toxicologic and environmental variability, need a more realistic evaluation. In this study, 11 municipal wastewater effluents were studied. Chemical analysis (GC/MS) and biological methods (acute and chronic toxicity bioassays and estrogenicity, mutagenity and teratogeny tests) were carried out to identify the most frequent organic compounds and toxic effluents. Results showed 7 effluents with acute toxicity, 3 with chronic toxicity and 4, with estrogenic effects. When toxicity and analytical results were compared, it was observed that in effluents with estrogenic effects, at least 3 estrogenic substances were identified. Attending all these results, the inclusion of combined methodologies must be considered to get more realistic information about these situations.Ciertos procedimientos, basados en aproximaciones analíticas y biológicas, están demostrando ser útiles en la valoración del riesgo de las aguas residuales urbanas procedentes de las Plantas de Tratamiento. Estos efluentes, considerados “mezclas complejas”, compuestos por sustancias de muy diferente naturaleza, origen y características toxicológicas y medio ambientales, requieren una valoración realista. Con el fin de colaborar al conocimiento de una parte de la realidad de nuestro país, presentamos un estudio sobre once depuradoras urbanas en las que se ha realizado un perfil de compuestos orgánicos y una valoración toxicológica mediante tests de toxicidad agudos, crónicos, de estrogenicidad, mutagenicidad y teratogenia. Los resultados muestran que 7 efluentes presentan toxicidad aguda, 3 toxicidad crónica y 4 estrogenicidad. Destacamos el hecho de que los 4 efluentes que presentan estrogenicidad, poseen al menos 3 de las sustancias estrogénicas detectadas mediante el perfil cromatográfico. Este tipo de consideraciones nos hace reflexionar sobre la necesidad de incorporar este tipo de metodologías para disponer de un conocimiento más realista de estas situaciones

    Potential Future Impact of a Partially Effective HIV Vaccine in a Southern African Setting.

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    It is important for public health and within the HIV vaccine development field to understand the potential population level impact of an HIV vaccine of partial efficacy-both in preventing infection and in reducing viral load in vaccinated individuals who become infected-in the context of a realistic future implementation scenario in resource limited settings

    Antisense oligonucleotides and all-trans retinoic acid have a synergistic anti-tumor effect on oral squamous cell carcinoma

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    <p>Abstract</p> <p>Background</p> <p>Antisense oligonucleotides against hTR (As-ODN-hTR) have shown promising results as treatment strategies for various human malignancies. All-trans retinoic acid (ATRA) is a signalling molecule with important roles in differentiation and apoptosis. Biological responses to ATRA are currently used therapeutically in various human cancers. The aim of this study was to evaluate the anti-tumor effects of As-ODN-hTR combined with ATRA in vivo.</p> <p>Methods</p> <p>In situ human oral squamous cell carcinoma (OSCC) models were established by subcutaneous injection of Tca8113 cells. Mice were treated with sense oligonucleotides against hTR(S-ODN-hTR) alone, As-ODN-hTR alone, ATRA alone, As-ODN-hTR plus ATRA, or S-ODN-hTR plus ATRA. Tumor size and weight were assessed in the mice. Telomerase activity was detected by a TRAP assay, apoptotic cells were evaluated with a Tunel assay, the expression of apoptosis-related proteins (Bcl-2 and Bax) was evaluated by immunohistochemistry and ultrastructural morphological changes in the tumor specimen were examined.</p> <p>Results</p> <p>Both As-ODN-hTR and ATRA can significantly inhibit tumor growth in this OSCC xenograft solid-tumor model, and the combination of the two agents had a synergistic anti-tumorogenic effect. We also demonstrated that this anti-tumor effect correlated with inhibition of telomerase activity. Furthermore, significant increases in the number of apoptotic cells, typical apoptotic morphology and a downregulation of the anti-apoptotic protein, bcl-2 were observed in the treated tissues.</p> <p>Conclusion</p> <p>The combination of As-ODN-hTR and ATRA has a synergistic anti-tumor effect. This anti-tumor effect can be mainly attributed to apoptosis induced by a decrease in telomerase activity. Bcl-2 plays an important role in this process. Therefore, combining As-ODN-hTR and ATRA may be an approach for the treatment of human oral squamous cell carcinoma.</p

    First search for dark photon dark matter with a MADMAX prototype

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    We report the first result from a dark photon dark matter search in the mass range from 78.62{78.62} to 83.95 μeV/c283.95~\mathrm{\mu eV}/c^2 with a dielectric haloscope prototype for MADMAX (Magnetized Disc and Mirror Axion eXperiment). Putative dark photons would convert to observable photons within a stack consisting of three sapphire disks and a mirror. The emitted power of this system is received by an antenna and successively digitized using a low-noise receiver. No dark photon signal has been observed. Assuming unpolarized dark photon dark matter with a local density of ρχ=0.3 GeV/cm3\rho_{\chi}=0.3~\mathrm{GeV/cm^3} we exclude a dark photon to photon mixing parameter χ>3.0×1012\chi > 3.0 \times 10^{-12} over the full mass range and χ>1.2×1013\chi > 1.2 \times 10^{-13} at a mass of 80.57 μeV/c280.57~\mathrm{\mu eV}/c^2 with a 95\% confidence level. This is the first physics result from a MADMAX prototype and exceeds previous constraints on χ\chi in this mass range by up to almost three orders of magnitude.Comment: v
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