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To make progress towards the development of a theory on the motion of inclusions in thin structured films and membranes, we here consider as an initial step a circular disk in a two-dimensional, uniaxially anisotropic fluid layer. We assume overdamped dynamics, incompressibility of the fluid, and global alignment of the axis of anisotropy. Motion within this layer is affected by additional linear friction with the environment, for instance, a supporting substrate. We investigate the induced flows in the fluid when the disk is translated parallel or perpendicular to the direction of anisotropy. Moreover, expressions for corresponding mobilities and resistance coefficients of the disk are derived. Our results are obtained within the framework of a perturbative expansion in the parameters that quantify the anisotropy of the fluid. Good agreement is found for moderate anisotropy when compared to associated results from finite-element simulations. At pronounced anisotropy, the induced flow fields are still predicted qualitatively correctly by the perturbative theory, although quantitative deviations arise. We hope to stimulate with our investigations corresponding experimental analyses, for example, concerning fluid flows in anisotropic thin films on uniaxially rubbed supporting substrates.
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The Radar for Europa Assessment and Sounding: Ocean to Near-surface (REASON) is a dual-frequency ice-penetrating radar (9 and 60 MHz) onboard the Europa Clipper mission. REASON is designed to probe Europa from exosphere to subsurface ocean, contributing the third dimension to observations of this enigmatic world. The hypotheses REASON will test are that (1) the ice shell of Europa hosts liquid water, (2) the ice shell overlies an ocean and is subject to tidal flexing, and (3) the exosphere, near-surface, ice shell, and ocean participate in material exchange essential to the habitability of this moon. REASON will investigate processes governing this material exchange by characterizing the distribution of putative non-ice material (e.g., brines, salts) in the subsurface, searching for an ice-ocean interface, characterizing the ice shell's global structure, and constraining the amplitude of Europa's radial tidal deformations. REASON will accomplish these science objectives using a combination of radar measurement techniques including altimetry, reflectometry, sounding, interferometry, plasma characterization, and ranging. Building on a rich heritage from Earth, the moon, and Mars, REASON will be the first ice-penetrating radar to explore the outer solar system. Because these radars are untested for the icy worlds in the outer solar system, a novel approach to measurement quality assessment was developed to represent uncertainties in key properties of Europa that affect REASON performance and ensure robustness across a range of plausible parameters suggested for the icy moon. REASON will shed light on a never-before-seen dimension of Europa and - in concert with other instruments on Europa Clipper - help to investigate whether Europa is a habitable world.
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ABSTRACTBorna disease virus 1 (BoDV-1) was just recently shown to cause predominantly fatal encephalitis in humans. Despite its rarity, bornavirus encephalitis (BVE) can be considered a model disease for encephalitic infections caused by neurotropic viruses and understanding its pathomechanism is of utmost relevance. Aim of this study was to compare the extent and distribution pattern of cerebral inflammation with the clinical course of disease, and individual therapeutic procedures. For this, autoptic brain material from seven patients with fatal BVE was included in this study. Tissue was stained immunohistochemically for pan-lymphocytic marker CD45, the nucleoprotein of BoDV-1, as well as glial marker GFAP and microglial marker Iba1. Sections were digitalized and counted for CD45-positive and BoDV-1-positive cells. For GFAP and Iba1, a semiquantitative score was determined. Furthermore, detailed information about the individual clinical course and therapy were retrieved and summarized in a standardized way. Analysis of the distribution of lymphocytes shows interindividual patterns. In contrast, when looking at the BoDV-1-positive glial cells and neurons, a massive viral involvement in the brain stem was noticeable. Three of the seven patients received early high-dose steroids, which led to a significantly lower lymphocytic infiltration of the central nervous tissue and a longer survival compared to the patients who were treated with steroids later in the course of disease. This study highlights the potential importance of early high-dose immunosuppressive therapy in BVE. Our findings hint at a promising treatment option which should be corroborated in future observational or prospective therapy studies.ABBREVIATIONS: BoDV-1: Borna disease virus 1; BVE: bornavirus encephalitis; Cb: cerebellum; CNS: central nervous system; FL: frontal lobe; GFAP: glial fibrillary acid protein; Hc: hippocampus; Iba1: ionized calcium-binding adapter molecule 1; Iba1act: general activation of microglial cells; Iba1nod: formation of microglial nodules; IL: insula; Me: mesencephalon; Mo: medulla oblongata; OL: occipital lobe; pASS: per average of 10 screenshots; patearly: patients treated with early high dose steroid shot; patlate: patients treated with late or none high dose steroid shot; Po: pons; So: stria olfactoria; Str: striatum.
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Encéfalo , Humanos , Masculino , Femenino , Encéfalo/virología , Encéfalo/inmunología , Enfermedad de Borna/tratamiento farmacológico , Enfermedad de Borna/virología , Linfocitos/inmunología , Proteínas de Microfilamentos/metabolismo , Antígenos Comunes de Leucocito/metabolismo , Proteína Ácida Fibrilar de la Glía/metabolismo , Proteínas de Unión al Calcio/metabolismo , Terapia de Inmunosupresión , Virus de la Enfermedad de Borna/fisiología , Encefalitis Viral/tratamiento farmacológico , Encefalitis Viral/virología , Encefalitis Viral/inmunología , Neuroglía/virología , Neuroglía/metabolismoRESUMEN
BACKGROUND: The incidence of inflammatory bowel disease (IBD) in children is on the increase worldwide. Growth disorders are common in pediatric patients with inflammatory bowel disease. The aim of this paper is to investigate anthropometric indicators, including height and weight in children with inflammatory bowel disease in Saxony, one of the German federal states, and to evaluate growth trends in patients by comparing their height and weight with that of healthy children in Germany. METHODS: In Saxony, all children and adolescents with IBD were registered in the Saxon Pediatric IBD Registry from 2000 to 2014. The data used are therefore based on a total area-wide survey over 15 years. For this study, 421 datasets of children and adolescents aged 0-14 years with Crohn's disease (CD) (n = 291) or ulcerative colitis (UC) (n = 130) were analyzed. Z-score and percentile calculations were used to compare differences between IBD patients and the general population. RESULTS: The children with CD or UC (both sexes) had a significant lower weight at diagnosis (the mean weight z-score had negative values) versus the general population. The weight values lay mostly below P50 (the 50th percentile, median), more precisely, mostly between P10 and P50 of the body weight child growth curve for corresponding sexes (KiGGS 2003-2006). The height values of both sexes at diagnosis lay also mostly below P50 (the 50th percentile, median) of the child body growth curve for corresponding sexes (KiGGS 2003-2006), i.e. the mean height z-score was negative. But only the children with CD had a significant lower height, more precisely, mostly between P25 and P50 versus the general population (KIGGS). For children with UC the difference was not significant. CONCLUSION: In pediatric patients with IBD the possibility of growth disturbance, mainly in the form of weight retardation, is very probable.
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Colitis Ulcerosa , Enfermedad de Crohn , Enfermedades Inflamatorias del Intestino , Femenino , Masculino , Humanos , Adolescente , Niño , Enfermedades Inflamatorias del Intestino/epidemiología , Colitis Ulcerosa/epidemiología , Enfermedad de Crohn/epidemiología , Investigación , Sistema de RegistrosRESUMEN
OBJECTIVE: In Saxony, the incidence of Crohn's disease (CD) in children and adolescents increased significantly from 3.3 per 100,000 person-years in 2000 to 5.1 in 2014. The aim of this study was to describe the initial characteristics and the clinical course of CD in children and adolescents and to identify drug treatment options associated with an advantage for a mild course or remission. METHODS: Clinical data were collected from patients who suffered from inflammatory bowel disease (IBD) and were recruited in the Saxon Pediatric IBD-Registry. All children newly diagnosed with CD in this registry in Saxony between 2000 and 2014 were included in this registry study. Characteristics such as age, disease location and extra-intestinal manifestations at diagnosis were accessed. The severity level of the disease at diagnosis as well as at follow-up were analysed by PCDAI index. Patients were divided into 3 groups according to length of follow-up: 1-3 years, 4-6 years and 7-9 years after diagnosis. A logistic regression model was conducted to examine which baseline parameters are associated with disease progression. RESULTS: There were 338 children and adolescents with CD included in this registry study. At diagnosis, the median age of patients was 12.0 (0.7-14.9), 61.5% (n = 208) of the patients were male. The most common disease location observed in pediatric CD patients was the L3 (55%, n = 176). Patients aged 10-14 years were significantly more likely to present an L2 than patients aged 0-4 years (80.3%, n = 53 vs. 19.7%, n = 13, p = 0.01). During the follow-up, data from 71.3% (n = 241) othe patients were available. Disease activity measured by PCDAI decreased in 47.7% (n = 115) of the patients, 40.7% (n = 98) of the patients were stable and increased in 11.6% (n = 28) of the patients. Patients with intermediate/severe disease at onset were more likely to have an active disease at the end of follow up, too (p = 0.00). Logistic regression analysis of the initial characteristics showed that the age at diagnosis, gender, initial location and initial extra-intestinal manifestation are not associated with the progression of the disease (p>0.05). Furthermore, drug treatment options could be identified from our data, which are associated with benefits for a milder course or remission. CONCLUSION: From 2000 to 2014, the health status of most pediatric patients with CD had improved or remained stable. Initial characteristics including age at diagnosis, initial localization and initial extra-intestinal manifestation are not associated with the progression of the disease, only the initial activity by PCDAI.
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Enfermedad de Crohn , Enfermedades Inflamatorias del Intestino , Humanos , Adolescente , Niño , Masculino , Femenino , Enfermedad de Crohn/diagnóstico , Enfermedad de Crohn/tratamiento farmacológico , Enfermedad de Crohn/epidemiología , Alemania/epidemiología , Sistema de Registros , Progresión de la EnfermedadRESUMEN
AIMS: An increasing number of children and adolescents worldwide suffer from inflammatory bowel disease (IBD) such as Crohn's disease (CD) and ulcerative colitis (UC). The present work aims to investigate the incidence, prevalence and future trends of IBD in children and adolescents in Saxony, Germany. METHODS: The Saxon Pediatric IBD Registry collected data on patients up to 15 years of age from all 31 pediatric hospitals and pediatric gastroenterologists in Saxony over a 15-year period (2000-2014). In 2019, an independent survey estimated a registry completeness of 95.7%. Age-standardized incidence rates (ASR) per 100,000 person-years (PY) and prevalence per 100,000 children and adolescents were calculated. Evaluation was also been performed in sex and age subgroups. Joinpoint and Poisson regression were used for trend analyses and projections. RESULTS: 532 patients with confirmed IBD during 2000-2014 were included in the epidemiological evaluation. 63.5% (n = 338) patients had CD, 33.1% (n = 176) had UC and 3.4% (n = 18) had unclassified IBD (IBD-U). The 15-year IBD prevalence was 111.8 [95%-CI: 102.3-121.3] per 100,000. The incidence ASR of IBD per 100,000 PY over the whole observation period was 7.5 [6.9-8.1]. ASR for the subtypes were 4.8 [4.3-5.3] for CD, 2.5 [2.1-2.9] for UC and 0.3 [0.1-0.4] for IBD-U. The trend analysis of ASR using the joinpoint regression confirmed a significant increase for incidence of IBD as well as CD. For IBD, the ASR per 100,000 PY increased from 4.6 [2.8-6.3] in 2000 to 8.2 [7.5-13.6] in 2014; projected incidence rates for IBD in Germany are 12.9 [6.5-25.5] in the year 2025 and 14.9 [6.7-32.8] in 2030, respectively. Thus, the number of new IBD diagnoses in Germany would more than triple (325%) in 2030 compared to 2000. The increase is expected to be faster in CD than UC, and be more in males than in females. The expected number of newly diagnosed children with IBD in Germany is projected to rise to about 1,584 [1,512-1,655] in 2025, and to about 1,918 [1,807-2,29] in 2030. CONCLUSION: The incidence of IBD in children and adolescents in Saxony increased at a similar rate as in other developed countries during the observation period. Given this trend, the health care system must provide adequate resources for the care of these young patients in the future.
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Colitis Ulcerosa , Enfermedad de Crohn , Enfermedades Inflamatorias del Intestino , Adolescente , Niño , Enfermedad Crónica , Colitis Ulcerosa/epidemiología , Enfermedad de Crohn/epidemiología , Femenino , Alemania/epidemiología , Humanos , Incidencia , Enfermedades Inflamatorias del Intestino/epidemiología , Masculino , Sistema de RegistrosRESUMEN
We demonstrate accurate estimation of generalized optical signal to noise ratio (GOSNR) for wavelength division multiplexed fiber communication systems using an experimentally trained multi-tasking convolutional neural network while simultaneously estimating linear and nonlinear noise contributions. Using dual-polarized 32-GBaud 16QAM DWDM links we extract learnable features from constellation density matrices and accurately estimate GOSNR while simultaneously estimating linear and nonlinear contributions. Estimation of the OSNRASE, OSNRNL and GOSNR are demonstrated with < 0.5 dB mean absolute error. We also assess the universality of our model within the regime of metro networks by cross-training with data from such links comprised of different fiber types. We demonstrate a path to a practical universal training method that includes additional link parameters. The methods do not require contiguous high-speed sampling, additional hardware nor transmission of special symbols or patterns and are readily implemented in deployed systems.
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While traditional image compression algorithms take a full three-component color representation of an image as input, capturing of such images is done in many applications with Bayer CFA pattern sensors that provide only a single color information per sensor element and position. In order to avoid additional complexity at the encoder side, such CFA pattern images can be compressed directly without prior conversion to a full color image. In this paper, we describe a recent activity of the JPEG committee (ISO SC 29 WG 1) to develop such a compression algorithm in the framework of JPEG XS. It turns out that it is important to understand the "development process" from CFA patterns to full color images in order to optimize the image quality of such a compression algorithm, which we will also describe shortly. We introduce (1) a novel decorrelation step upfront processing (the so-called Star-Tetrix transform), along with (2) a pre-emphasis function to improve the compression efficiency of the subsequent compression algorithm (here, JPEG XS). Our experiments clearly indicate a gain over a RGB compression workflow in terms of complexity and quality (between 1.5dB and more than 4dB depending on the target bitrate). A comparison is also made with other state-of-the-art CFA compression techniques.
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AIMS: In developed countries, the incidence of inflammatory bowel disease (IBD) such as Crohn's disease (CD) and ulcerative colitis (UC) is increasing. Therefore, we aimed to investigate the incidence rates and trends over time in the population of children and adolescents in one of the federal states of Germany, in Saxony. METHODS: Over the 10-year period 2000-2009 all 31 children's hospitals and pediatric gastroenterologists, respectively in Saxony reported all IBD patients up to 15 years of age to the Saxon Pediatric IBD Registry. The completeness of the registry was estimated as 96.7% by independent surveys in the years 2005-2009. Incidence rates were presented as age-standardized incidence rates (ASR) regarding New European Standard Population 1990 per 100,000 person-years (PY) with 95% confidence intervals [CI]. Joinpoint and linear regression was used for trend analyses. RESULTS: 344 patients with confirmed IBD between 2000-2009 were included in the epidemiological evaluation: 212 (61.6%) patients with CD, 122 (35.6%) with UC and 10 (2.9%) with unclassified IBD (IBD-U). The ASR per 100,000 PY over the whole observation period was 7.2 [6.4-7.9] for IBD, 4.4 [3.8-5.0] for CD, 2.6 [2.1-3.0] for UC and 0.2 [0.1-0.3] for IBD-U. For IBD, the ASR per 100,000 PY increased from 4.6 [2.8-6.3] in 2000 to 10.5 [7.5-13.6] in 2009. The incidence trend analysis of ASRs using the joinpoint regression confirmed a significant increase of IBD as well as UC. The mean age at first diagnosis decreased significantly during the observation period from 11.5 (11.0-13.4) in 2000 to 9.6 (5.1-13.5) years in 2009. The median of the diagnostic latency among IBD patients was 3 months. CONCLUSION: The incidence of IBD in children and adolescents in Saxony was slightly higher than the average of other countries in the same time period and followed the trend towards a general increase of IBD. The age at diagnosis was subject to a very unfavorable downward trend.
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Enfermedades Inflamatorias del Intestino/epidemiología , Adolescente , Edad de Inicio , Niño , Preescolar , Femenino , Alemania/epidemiología , Humanos , Incidencia , Lactante , Recién Nacido , MasculinoRESUMEN
Biotech nanocellulose (bacterial nanocellulose, BNC) is a high potential natural polymer. Moreover, it is the only cellulose type that can be produced biotechnologically using microorganisms resulting in hydrogels with high purity, high mechanical strength and an interconnecting micropore system. Recently, the subject of intensive research is to influence this biosynthesis to create function-determining properties. This review reports on the progress in product design and today's state of technical and medical applications. A novel, dynamic, template-based technology, called Mobile Matrix Reservoir Technology (MMR Tech), is highlighted. Thereby, shape, dimensions, surface properties, and nanonetwork structures can be designed in a process-controlled manner. The formed multilayer materials open up new applications in medicine and technology. Especially medical materials for cardiovascular and visceral surgery, and drug delivery systems are developed. The effective production of layer-structured composites and coatings are important for potential applications in the electronics, paper, food and packaging technologies.
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Técnicas Biosensibles/métodos , Biotecnología/métodos , Celulosa/química , Sistemas de Liberación de Medicamentos/métodos , Embalaje de Alimentos/métodos , Nanocompuestos/química , Prótesis e Implantes , Ingeniería de Tejidos/métodos , Acetobacteraceae/metabolismo , Gluconacetobacter xylinus/metabolismo , Hidrogeles/químicaRESUMEN
High-performance polymers such as polymethacrylimides have outstanding properties, for example, a unique strength-to-weight ratio and a high thermal stability, usually coupled to a high glass transition temperature. However, the requirement of high processing temperatures caused by these high glass-transition temperatures is often not desired for melt extrusion processes. Herein, a novel and straightforward imidization process of poly(methacrylic anhydrides) is presented with different ratios of ammonia and N-isopropylamine that is induced by thermal treatment. Therefore, polymethacrylimides with a varying degree of N-substitution, and thus a varying number of hydrogen-bond-donating moieties, are synthesized under facile reaction conditions. An in-depth investigation into the structures obtained with this new methodology is undertaken via a combination of nuclear magnetic resonance spectroscopy (NMR), Fourier-transform infrared spectroscopy (FT-IR), and high-resolution electrospray ionization mass spectrometry (ESI-MS). Additionally, thermal properties of the materials are investigated using thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC) analyses. These latter measurements highlight the key opportunity available with this novel synthesis to tailor the thermal properties of the polymer by providing a clear correlation between hydrogen bond formation, as observed by FT-IR, and the glass transition temperature.
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Polímeros , Rastreo Diferencial de Calorimetría , Enlace de Hidrógeno , Espectroscopía Infrarroja por Transformada de Fourier , TemperaturaRESUMEN
Chemical and mechanical pattern formation is fundamental during embryogenesis and tissue development. Yet, the underlying molecular and cellular mechanisms are still elusive in many cases. Most current theories assume that tissue development is driven by chemical processes: either as a sequence of chemical patterns each depending on the previous one, or by patterns spontaneously arising from specific chemical interactions (such as "Turing-patterns"). Within both theories, mechanical patterns are usually regarded as passive by-products of chemical pre-patters. However, several experiments question these theories, and an increasing number of studies shows that tissue mechanics can actively influence chemical patterns during development. In this study, we thus focus on the interplay between chemical and mechanical processes during tissue development. On one hand, based on recent experimental data, we develop new mechanochemical simulation models of evolving tissues, in which the full 3D representation of the tissue appears to be critical for obtaining a realistic mechanochemical behaviour. The presented modelling approach is flexible and numerically studied using state of the art finite element methods. Thus, it may serve as a basis to combine simulations with new experimental methods in tissue development. On the other hand, we apply the developed approach and demonstrate that even simple interactions between tissue mechanics and chemistry spontaneously lead to robust and complex mechanochemical patterns. Especially, we demonstrate that the main contradictions arising in the framework of purely chemical theories are naturally and automatically resolved using the mechanochemical patterning theory.
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Fenómenos Biomecánicos , Tipificación del Cuerpo , Simulación por Computador , Desarrollo Embrionario , Retroalimentación Fisiológica , Modelos Biológicos , Animales , Fenómenos QuímicosRESUMEN
BACKGROUND & AIMS: Celiac disease can be identified by a serologic test for IgA against tissue transglutaminase (IgA-TTG) in a large proportion of children. However, the increased concentrations of antibody rarely normalize within the months after children are placed on a gluten-free diet (GFD). Early serologic predictors of sufficient adherence to GFD are required for optimal treatment. METHODS: In a prospective study, we observed the response to a GFD in 345 pediatric patients (67% girls; mean age, 8.4 y) who underwent duodenal biopsy to confirm or refute celiac disease from October 2012 through December 2015. Baseline serum samples were tested centrally for IgA-TTG and IgG against deamidated gliadin. Follow-up serologic analyses of children on a GFD were performed about 3 months later. RESULTS: The geometric mean concentration of IgA-TTG decreased from 72.4-fold to 5.2-fold the upper limit of normal (ULN), or by a factor of 14.0 (95% CI, 12.0-16.4). A substantial response (defined as a larger change than the typical variation in patients not on a GFD) was observed in 80.6% of the children. Only 28.1% of patients had a substantial response in the concentration of IgG against deamidated gliadin. Concentration of IgA-TTG remained above 1-fold the ULN in 83.8% of patients, and above 10-fold the ULN in 26.6% of patients with a substantial response. CONCLUSIONS: Serum concentration of IgA-TTG decreases substantially in most children with celiac disease within 3 months after they are placed on a GFD, but does not normalize in most. This information on changes in antibody concentrations can be used to assess patient response to the diet at short-term follow-up evaluations. Patients with a substantial response to a GFD often still have high antibody levels after 3 months. German Clinical Trials Registry no. DRKS00003854.
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Autoanticuerpos/sangre , Enfermedad Celíaca/patología , Enfermedad Celíaca/terapia , Dieta Sin Gluten , Adolescente , Análisis Químico de la Sangre , Niño , Preescolar , Femenino , Estudios de Seguimiento , Humanos , Inmunoglobulina A/sangre , Lactante , Masculino , Estudios Prospectivos , Factores de TiempoAsunto(s)
Biomarcadores de Tumor/genética , Antígenos CD79/genética , Neoplasias Gastrointestinales/genética , Linfoma de Células B Grandes Difuso/genética , Mutación , Factor 88 de Diferenciación Mieloide/genética , Neoplasias Testiculares/genética , Anciano , Neoplasias Gastrointestinales/patología , Humanos , Linfoma de Células B Grandes Difuso/patología , Masculino , Tasa de Mutación , Pronóstico , Neoplasias Testiculares/patologíaRESUMEN
Due to their high resolution, dynamic medical 2D+t and 3D+t volumes from computed tomography (CT) and magnetic resonance tomography (MR) reach a size which makes them very unhandy for teleradiologic applications. A lossless scalable representation offers the advantage of a down-scaled version which can be used for orientation or previewing, while the remaining information for reconstructing the full resolution is transmitted on demand. The wavelet transform offers the desired scalability. A very high quality of the lowpass sub-band is crucial in order to use it as a down-scaled representation. We propose an approach based on compensated wavelet lifting for obtaining a scalable representation of dynamic CT and MR volumes with very high quality. The mesh compensation is feasible to model the displacement in dynamic volumes which is mainly given by expansion and contraction of tissue over time. To achieve this, we propose an optimized estimation of the mesh compensation parameters to optimally fit for dynamic volumes. Within the lifting structure, the inversion of the motion compensation is crucial in the update step. We propose to take this inversion directly into account during the estimation step and can improve the quality of the lowpass sub-band by 0.63 and 0.43 dB on average for our tested dynamic CT and MR volumes at the cost of an increase of the rate by 2.4% and 1.2% on average.
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BACKGROUND & AIMS: A diagnosis of celiac disease is made based on clinical, genetic, serologic, and duodenal morphology features. Recent pediatric guidelines, based largely on retrospective data, propose omitting biopsy analysis for patients with concentrations of IgA against tissue transglutaminase (IgA-TTG) >10-fold the upper limit of normal (ULN) and if further criteria are met. A retrospective study concluded that measurements of IgA-TTG and total IgA, or IgA-TTG and IgG against deamidated gliadin (IgG-DGL) could identify patients with and without celiac disease. Patients were assigned to categories of no celiac disease, celiac disease, or biopsy required, based entirely on antibody assays. We aimed to validate the positive and negative predictive values (PPV and NPV) of these diagnostic procedures. METHODS: We performed a prospective study of 898 children undergoing duodenal biopsy analysis to confirm or rule out celiac disease at 13 centers in Europe. We compared findings from serologic analysis with findings from biopsy analyses, follow-up data, and diagnoses made by the pediatric gastroenterologists (celiac disease, no celiac disease, or no final diagnosis). Assays to measure IgA-TTG, IgG-DGL, and endomysium antibodies were performed by blinded researchers, and tissue sections were analyzed by local and blinded reference pathologists. We validated 2 procedures for diagnosis: total-IgA and IgA-TTG (the TTG-IgA procedure), as well as IgG-DGL with IgA-TTG (TTG-DGL procedure). Patients were assigned to categories of no celiac disease if all assays found antibody concentrations <1-fold the ULN, or celiac disease if at least 1 assay measured antibody concentrations >10-fold the ULN. All other cases were considered to require biopsy analysis. ULN values were calculated using the cutoff levels suggested by the test kit manufacturers. HLA typing was performed for 449 participants. We used models that considered how specificity values change with prevalence to extrapolate the PPV and NPV to populations with lower prevalence of celiac disease. RESULTS: Of the participants, 592 were found to have celiac disease, 345 were found not to have celiac disease, and 24 had no final diagnosis. The TTG-IgA procedure identified patients with celiac disease with a PPV of 0.988 and an NPV of 0.934; the TTG-DGL procedure identified patients with celiac disease with a PPV of 0.988 and an NPV of 0.958. Based on our extrapolation model, we estimated that the PPV and NPV would remain >0.95 even at a disease prevalence as low as 4%. Tests for endomysium antibodies and HLA type did not increase the PPV of samples with levels of IgA-TTG ≥10-fold the ULN. Notably, 4.2% of pathologists disagreed in their analyses of duodenal morphology-a rate comparable to the error rate for serologic assays. CONCLUSIONS: In a prospective study, we validated the TTG-IgA procedure and the TTG-DGL procedure in identification of pediatric patients with or without celiac disease, without biopsy. German Clinical Trials Registry no.: DRKS00003854.
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Autoanticuerpos/sangre , Enfermedad Celíaca/diagnóstico , Proteínas de Unión al GTP/inmunología , Gliadina/inmunología , Inmunoglobulina A/sangre , Inmunoglobulina G/sangre , Transglutaminasas/inmunología , Autoanticuerpos/inmunología , Biopsia , Enfermedad Celíaca/inmunología , Enfermedad Celíaca/patología , Niño , Preescolar , Duodeno/patología , Europa (Continente) , Femenino , Humanos , Lactante , Masculino , Valor Predictivo de las Pruebas , Estudios Prospectivos , Proteína Glutamina Gamma Glutamiltransferasa 2 , Sensibilidad y Especificidad , Pruebas Serológicas/métodosRESUMEN
PURPOSE: To systematically study the number of U.S. resident deaths from all causes, including suicide. METHOD: The more than 9,900 programs accredited by the Accreditation Council for Graduate Medical Education (ACGME) annually report the status of residents. The authors aggregated ACGME data on 381,614 residents in training during years 2000 through 2014. Names of residents reported as deceased were submitted to the National Death Index to learn causes of death. Person-year calculations were used to establish resident death rates and compare them with those in the general population. RESULTS: Between 2000 and 2014, 324 individuals (220 men, 104 women) died while in residency. The leading cause of death was neoplastic disease, followed by suicide, accidents, and other diseases. For male residents the leading cause was suicide, and for female residents, malignancies. Resident death rates were lower than in the age- and gender-matched general population. Temporal patterns showed higher rates of death early in residency. Deaths by suicide were higher early in training, and during the first and third quarters of the academic year. There was no upward or downward trend in resident deaths over the 15 years of this study. CONCLUSIONS: Neoplastic disease and suicide were the leading causes of death in residents. Data for death by suicide suggest added risk early in residency and during certain months of the academic year. Providing trainees with a supportive environment and with medical and mental health services is integral to reducing preventable deaths and fostering a healthy physician workforce.
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Causas de Muerte/tendencias , Internado y Residencia/estadística & datos numéricos , Neoplasias/mortalidad , Médicos/estadística & datos numéricos , Estudiantes de Medicina/estadística & datos numéricos , Suicidio/estadística & datos numéricos , Adulto , Femenino , Predicción , Humanos , Masculino , Persona de Mediana Edad , Neoplasias/epidemiología , Estados Unidos/epidemiologíaRESUMEN
BACKGROUND: Immunofluorescence assays of antibodies against endomysium (EmA) on primate oesophagus sections represent the gold standard in serological testing for coeliac disease (CD). As alternative immunofluorescence technique, staining of primate liver tissue is in use. We compared performance and predictive power of IgA- and IgG-EmA on primate oesophagus and primate liver sections. METHODS: Sera of 298 paediatric biopsy-proven CD patients under gluten-containing diet and 574 disease controls were investigated. Samples were collected between 2004 and 2013 in six children's hospitals. The antibodies were assayed blinded to diagnoses and histological data. Sensitivity, specificity, and positive (PPV) and negative predictive values (NPV) were calculated for different assays. RESULTS: (Oesophagus vs liver): For IgA-EmA, sensitivity (0.953 vs 0.956) and specificity (0.981 vs 0.972) as well as PPV (0.963 vs 0.947) and NPV (0.976 vs 0.979) were comparable on both tissues. IgG-EmA on liver showed significantly higher sensitivity (0.520 vs 0.631; p=0.006) but significantly lower specificity (0.995 vs 0.963; p=0.002) and PPV (0.981 vs 0.899; p=0.0002) than on oesophagus. NPV on liver was higher than NPV on oesophagus, however, the difference was not statistically significant (0.799 vs 0.834; p=0.099). CONCLUSION: Primate liver can be used as alternative, equally well functioning substrate for IgA-EmA testing.
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Autoanticuerpos/análisis , Enfermedad Celíaca/diagnóstico , Tejido Conectivo/inmunología , Técnica del Anticuerpo Fluorescente Indirecta , Hígado/inmunología , Animales , Estudios de Casos y Controles , Niño , Preescolar , Esófago/inmunología , Humanos , Inmunoglobulina A , Inmunoglobulina G , Músculo Liso/inmunología , Primates , Sensibilidad y EspecificidadRESUMEN
BACKGROUND: During embryogenesis, chemical (morphogen) and mechanical patterns develop within tissues in a self-organized way. More than 60 years ago, Turing proposed his famous reaction-diffusion model for such processes, assuming chemical interactions as the main driving force in tissue patterning. However, experimental identification of corresponding molecular candidates is still incomplete. Recent results suggest that beside morphogens, also tissue mechanics play a significant role in these patterning processes. RESULTS: Combining continuous finite strain with discrete cellular tissue models, we present and numerically investigate mechanochemical processes, in which morphogen dynamics and tissue mechanics are coupled by feedback loops. We consider three different mechanical cues involved in such feedbacks: strain, stress, and compression. Based on experimental results, for each case, we present a feedback loop spontaneously creating robust mechanochemical patterns. In contrast to Turing-type models, simple mechanochemical interaction terms are sufficient to create de novo patterns. CONCLUSIONS: Our results emphasize mechanochemical processes as possible candidates controlling different steps of embryogenesis. To motivate further experimental research discovering related mechanisms in living tissues, we also present predictive in silicio experiments. REVIEWERS: Reviewer 1 - Marek Kimmel; Reviewer 2 - Konstantin Doubrovinski (nominated by Ned Wingreen); Reviewer 3 - Jun Allard (nominated by William Hlavacek).
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Tipificación del Cuerpo , Retroalimentación Fisiológica , Animales , Fenómenos Biomecánicos , Difusión , Modelos BiológicosRESUMEN
In this paper, a model is developed for the evolution of plaques in arteries, which is one of the main causes for the blockage of blood flow. Plaque rupture and spread of torn-off material may cause closures in the down-stream vessel system and lead to ischemic brain or myocardial infarctions. The model covers the flow of blood and its interaction with the vessel wall. It is based on the assumption that the penetration of monocytes from the blood flow into the vessel wall, and the accumulation of foam cells increasing the volume, are main factors for the growth of plaques. The dynamics of the vessel wall is governed by a deformation gradient, which is given as composition of a purely elastic tensor, and a tensor modeling the biologically caused volume growth. An equation for the evolution of the metric is derived quantifying the changing geometry of the vessel wall. To calculate numerically the solutions of the arising free boundary problem, the model system of partial differential equations is transformed to an ALE (Arbitrary Lagrangian-Eulerian) formulation, where all equations are given in fixed domains. The numerical calculations are using newly developed algorithms for ALE systems. The results of the simulations, obtained for realistic system parameters, are in good qualitative agreement with observations. They demonstrate that the basic modeling assumption can be justified. The increase of stresses in the vessel wall can be computed. Medical treatment tries to prevent critical stress values, which may cause plaque rupture and its consequences.