Endoscopic ultrasound—guided fine needle aspiration in the diagnosis of mediastinal masses of unknown origin

The ability of endosonography to diagnose a variety of gastrointestinal pathology has been significantly advanced with the introduction of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) biopsy. EUS-FNA technology can also be applied to the evaluation of non-GI disorders. The role of EUS-FNA to establish the diagnosis of unexplained mediastinal masses has not been previously described. The aim of this study was to determine the diagnostic accuracy, impact on subsequent workup, and role of EUS-FNA in treating mediastinal masses of unknown cause. METHODS : A total of 26 patients (15 men and 11 women, mean age 61 yr, range 39–77 yr) underwent EUS-FNA in patients presenting with unexplained mediastinal masses at four tertiary referral centers. Presenting symptoms included: chest pain (10 patients), dysphagia (eight), cough (seven), fever (six), night sweats (three), and no symptoms/abnormal x-ray (five patients). Five of 26 patients had prior history of cancer (three lung, one tracheal, and one esophageal). RESULTS : Final diagnosis using EUS-FNA, surgery, autopsy, other diagnostic study, or long-term follow-up was available in all patients. EUS-FNA results were classified under three disease categories: 1) infectious, 2) benign/inflammatory, and 3) malignant. Final diagnosis included infectious in five patents, benign/inflammatory in nine, and malignant in 12. EUS-FNA was successful in 21 of 26 patients (81%) for all disease categories (infectious 60%, benign/inflammatory 78%, and malignant 92%). EUS-FNA was successful in directing subsequent workup in 77% (20 of 26) and therapy in 73% (19 of 26). Mean EUS-FNA passes for adequate tissue sampling was lower of nonmalignant disease categories (3.0 and 3.4) versus malignant disease (4.4). No complications were seen during the course of this study. CONCLUSIONS : EUS-FNA in patients presenting with idiopathic mediastinal masses establishes the diagnosis in the vast majority of cases, particularly for those with malignant disease. The emergence of transesophageal EUS-FNA of the mediastinum provides the ability to alter subsequent workup and therapy, obviating the need for more invasive diagnostic studies such as thoracotomy.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72588/1/j.1572-0241.2002.06023.x.pd

Infinite volume limit of the Abelian sandpile model in dimensions d >= 3

We study the Abelian sandpile model on Z^d. In dimensions at least 3 we prove existence of the infinite volume addition operator, almost surely with respect to the infinite volume limit mu of the uniform measures on recurrent configurations. We prove the existence of a Markov process with stationary measure mu, and study ergodic properties of this process. The main techniques we use are a connection between the statistics of waves and uniform two-component spanning trees and results on the uniform spanning tree measure on Z^d.Comment: First version: LaTeX; 29 pages. Revised version: LaTeX; 29 pages. The main result of the paper has been extended to all dimensions at least 3, with a new and simplyfied proof of finiteness of the two-component spanning tree. Second revision: LaTeX; 32 page

Embodied Discourses of Literacy in the Lives of Two Preservice Teachers

This study examines the emerging teacher literacy identities of Ian and A.J., two preservice teachers in a graduate teacher education program in the United States. Using a poststructural feminisms theoretical framework, the study illustrates the embodiment of literacy pedagogy discourses in relation to the literacy courses’ discourse of comprehensive literacy and the literacy biographical discourses of Ian and A.J. The results of this study indicate the need to deconstruct how the discourse of comprehensive literacy limits how we, as literacy teacher educators, position, hear and respond to our preservice teachers and suggests the need for differentiation in our teacher education literacy courses

Factors affecting individual foraging specialization and temporal diet stability across the range of a large “generalist” apex predator

Individual niche specialization (INS) is increasingly recognized as an important component of ecological and evolutionary dynamics. However, most studies that have investigated INS have focused on the effects of niche width and inter- and intraspecific competition on INS in small-bodied species for short time periods, with less attention paid to INS in large-bodied reptilian predators and the effects of available prey types on INS. We investigated the prevalence, causes, and consequences of INS in foraging behaviors across different populations of American alligators (Alligator mississippiensis), the dominant aquatic apex predator across the southeast US, using stomach contents and stable isotopes. Gut contents revealed that, over the short term, although alligator populations occupied wide ranges of the INS spectrum, general patterns were apparent. Alligator populations inhabiting lakes exhibited lower INS than coastal populations, likely driven by variation in habitat type and available prey types. Stable isotopes revealed that over longer time spans alligators exhibited remarkably consistent use of variable mixtures of carbon pools (e.g., marine and freshwater food webs). We conclude that INS in large-bodied reptilian predator populations is likely affected by variation in available prey types and habitat heterogeneity, and that INS should be incorporated into management strategies to efficiently meet intended goals. Also, ecological models, which typically do not consider behavioral variability, should include INS to increase model realism and applicability

Consumption paths under prospect utility in an optimal growth model

This paper studies the Cass-Koopmans-Ramsey model of optimal economic growth in the presence of loss aversion and habit formation. The representative agent’s preferences for consumption can be gradually varied between the standard constant intertemporal elasticity of substitution (CIES) case and Kahneman and Tversky’s prospect utility. We find that the transitional dynamics of optimal consumption paths differ distinctly from the standard model, in particular consumption smoothing is more pronounced. We also show that prospect utility can cause the economy to remain in a steady state with low consumption and low capital

PEtab -- interoperable specification of parameter estimation problems in systems biology

Reproducibility and reusability of the results of data-based modeling studies are essential. Yet, there has been -- so far -- no broadly supported format for the specification of parameter estimation problems in systems biology. Here, we introduce PEtab, a format which facilitates the specification of parameter estimation problems using Systems Biology Markup Language (SBML) models and a set of tab-separated value files describing the observation model and experimental data as well as parameters to be estimated. We already implemented PEtab support into eight well-established model simulation and parameter estimation toolboxes with hundreds of users in total. We provide a Python library for validation and modification of a PEtab problem and currently 20 example parameter estimation problems based on recent studies. Specifications of PEtab, the PEtab Python library, as well as links to examples, and all supporting software tools are available at https://github.com/PEtab-dev/PEtab, a snapshot is available at https://doi.org/10.5281/zenodo.3732958. All original content is available under permissive licenses

Huntington's disease: a clinical review

Huntington's disease (HD) is a fully penetrant neurodegenerative disease caused by a dominantly inherited CAG trinucleotide repeat expansion in the huntingtin gene on chromosome 4. In Western populations HD has a prevalence of 10.6-13.7 individuals per 100,000. It is characterised by cognitive, motor and psychiatric disturbance. At the cellular level mutant huntingtin results in neuronal dysfunction and death through a number of mechanisms, including disruption of proteostasis, transcription and mitochondrial function and direct toxicity of the mutant protein. Early macroscopic changes are seen in the striatum with involvement of the cortex as the disease progresses. There are currently no disease modifying treatments therefore supportive and symptomatic management is the mainstay of treatment. In recent years there have been significant advances in understanding both the cellular pathology and the macroscopic structural brain changes that occur as the disease progresses. In the last decade there has been a large growth in potential therapeutic targets and clinical trials. Perhaps the most promising of these are the emerging therapies aimed at lowering levels of mutant huntingtin. Antisense oligonucleotide therapy is one such approach with clinical trials currently underway. This may bring us one step closer to treating and potentially preventing this devastating condition

The ANTENATAL multicentre study to predict postnatal renal outcome in fetuses with posterior urethral valves: objectives and design

Abstract Background Posterior urethral valves (PUV) account for 17% of paediatric end-stage renal disease. A major issue in the management of PUV is prenatal prediction of postnatal renal function. Fetal ultrasound and fetal urine biochemistry are currently employed for this prediction, but clearly lack precision. We previously developed a fetal urine peptide signature that predicted in utero with high precision postnatal renal function in fetuses with PUV. We describe here the objectives and design of the prospective international multicentre ANTENATAL (multicentre validation of a fetal urine peptidome-based classifier to predict postnatal renal function in posterior urethral valves) study, set up to validate this fetal urine peptide signature. Methods Participants will be PUV pregnancies enrolled from 2017 to 2021 and followed up until 2023 in >30 European centres endorsed and supported by European reference networks for rare urological disorders (ERN eUROGEN) and rare kidney diseases (ERN ERKNet). The endpoint will be renal/patient survival at 2 years postnatally. Assuming α = 0.05, 1–β = 0.8 and a mean prevalence of severe renal outcome in PUV individuals of 0.35, 400 patients need to be enrolled to validate the previously reported sensitivity and specificity of the peptide signature. Results In this largest multicentre study of antenatally detected PUV, we anticipate bringing a novel tool to the clinic. Based on urinary peptides and potentially amended in the future with additional omics traits, this tool will be able to precisely quantify postnatal renal survival in PUV pregnancies. The main limitation of the employed approach is the need for specialized equipment. Conclusions Accurate risk assessment in the prenatal period should strongly improve the management of fetuses with PUV

Modeling complex metabolic reactions, ecological systems, and financial and legal networks with MIANN models based on Markov-Wiener node descriptors

[Abstract] The use of numerical parameters in Complex Network analysis is expanding to new fields of application. At a molecular level, we can use them to describe the molecular structure of chemical entities, protein interactions, or metabolic networks. However, the applications are not restricted to the world of molecules and can be extended to the study of macroscopic nonliving systems, organisms, or even legal or social networks. On the other hand, the development of the field of Artificial Intelligence has led to the formulation of computational algorithms whose design is based on the structure and functioning of networks of biological neurons. These algorithms, called Artificial Neural Networks (ANNs), can be useful for the study of complex networks, since the numerical parameters that encode information of the network (for example centralities/node descriptors) can be used as inputs for the ANNs. The Wiener index (W) is a graph invariant widely used in chemoinformatics to quantify the molecular structure of drugs and to study complex networks. In this work, we explore for the first time the possibility of using Markov chains to calculate analogues of node distance numbers/W to describe complex networks from the point of view of their nodes. These parameters are called Markov-Wiener node descriptors of order kth (Wk). Please, note that these descriptors are not related to Markov-Wiener stochastic processes. Here, we calculated the Wk(i) values for a very high number of nodes (>100,000) in more than 100 different complex networks using the software MI-NODES. These networks were grouped according to the field of application. Molecular networks include the Metabolic Reaction Networks (MRNs) of 40 different organisms. In addition, we analyzed other biological and legal and social networks. These include the Interaction Web Database Biological Networks (IWDBNs), with 75 food webs or ecological systems and the Spanish Financial Law Network (SFLN). The calculated Wk(i) values were used as inputs for different ANNs in order to discriminate correct node connectivity patterns from incorrect random patterns. The MIANN models obtained present good values of Sensitivity/Specificity (%): MRNs (78/78), IWDBNs (90/88), and SFLN (86/84). These preliminary results are very promising from the point of view of a first exploratory study and suggest that the use of these models could be extended to the high-throughput re-evaluation of connectivity in known complex networks (collation)