Thoracic Pressure Does Not Impact CSF Pressure via Compartment Compliance

Space acquired neuro-ocular syndrome (SANS) remains a difficult risk to characterize due to the complex multi-factorial etiology related to physiological responses to the spaceflight environment. Fluid shift and the resultant change on the Cardiovascular (CV) and cerebral spinal fluid systems (CSF) in the absence of gravity continue to be considered a contributing factor to the progression of SANS. In this study, we utilize a computational model of the CSF and CV interface to establish the sensitivity that intracranial pressure, and subsequently the optic nerve sheath pressure, exhibits due to variations in thoracic pressure, assuming the cranial perfusion pressure, i.e. mean arterial pressure (MAP) to central venous pressure (CVP), is known. Methods: The GRC Cross cutting computational modeling project created as model of the CSF and CV interaction within the cranial vault by extending the work of Stevens et al. [1] by modifying the representative anatomy to include a separate venous sinus, jugular veins, secondary veins and extra jugular pathways [2-3] to more adequately represent the vascular drainage pathways from the cranial vault (Figure 1). Assuming the MAP, CVP and thoracic pressure are known, we initiated this enhanced computational model assuming a supine positon and utilized a linear ramp to vary the thoracic pressure from the assumed supine state to the target pressure corresponding to set MAP and CVP values. The model generates the time based CSF pressure values (Figure2). Results and Conclusions: Following this analysis, CSF pressure shows significant independence from thoracic pressure changes (16 mmHg in thoracic pressure produces < 1mmHg change in CSF pressure), being mostly dependent on perfusion pressure. Similarly fluid redistribution is not predicted to be impacted over a level of 1mL. We note that this simulation represents an acute changes (order of 10's of minutes) and does not represent the long term effects

Glucocorticoid receptor expression in 20 solid tumor types using immunohistochemistry assay.

BackgroundGlucocorticoid receptor (GR) activity plays a role in many aspects of human physiology and may play a crucial role in chemotherapy resistance in a wide variety of solid tumors. A novel immunohistochemistry (IHC) based assay has been previously developed and validated in order to assess GR immunoreactivity in triple-negative breast cancer. The current study investigates the standardized use of this validated assay to assess GR expression in a broad range of solid tumor malignancies.MethodsArchived formalin-fixed paraffin-embedded tumor bank samples (n=236) from 20 different solid tumor types were analyzed immunohistochemically. Nuclear staining was reported based on the H-score method using differential intensity scores (0, 1+, 2+, or 3+) with the percent stained (out of at least 100 carcinoma cells) recorded at each intensity.ResultsGR was expressed in all tumor types that had been evaluated. Renal cell carcinoma, sarcoma, cervical cancer, and melanoma were those with the highest mean H-scores, indicating high levels of GR expression. Colon, endometrial, and gastric cancers had lower GR staining percentages and intensities, resulting in the lowest mean H-scores.ConclusionA validated IHC assay revealed GR immunoreactivity in all solid tumor types studied and allowed for standardized comparison of reactivity among the different malignancies.ImpactBaseline expression levels of GR may be a useful biomarker when pharmaceutically targeting GR in research or clinical setting

Self-consistent bounces in two dimensions

We compute bounce solutions describing false vacuum decay in a Phi**4 model in two dimensions in the Hartree approximation, thus going beyond the usual one-loop corrections to the decay rate. We use zero energy mode functions of the fluctuation operator for the numerical computation of the functional determinant and the Green's function. We thus avoid the necessity of discretizing the spectrum, as it is necessary when one uses numerical techniques based on eigenfunctions. Regularization is performed in analogy of standard perturbation theory; the renormalization of the Hartree approximation is based on the two-particle point-irreducible (2PPI) scheme. The iteration towards the self-consistent solution is found to converge for some range of the parameters. Within this range we find the corrections to the leading one-loop approximation to be relatively small, not exceeding one order of magnitude in the total transition rate.Comment: 30 pages, 12 figure

Monte Carlo simulation of SU(2) Yang-Mills theory with light gluinos

In a numerical Monte Carlo simulation of SU(2) Yang-Mills theory with light dynamical gluinos the low energy features of the dynamics as confinement and bound state mass spectrum are investigated. The motivation is supersymmetry at vanishing gluino mass. The performance of the applied two-step multi-bosonic dynamical fermion algorithm is discussed.Comment: latex, 48 pages, 16 figures with epsfi

Immunohistochemical Demonstration of IgG in Reed-Sternberg and Other Cells in Hodgkin\u27s Disease

Increased synthesis of IgG in vitro has been demonstrated in spleens from patients with Hodgkin\u27s disease, either with or without invasion of the organ by tumor (1). Interest in this laboratory has centered recently on cytochemical localization of immunoglobulins by means of an immunoglobulin-peroxidase bridge procedure (2) and a satisfactory method has been developed for selectively visualizing immunocytes with this technique. 1 As a means of assessing the basis for increased IgG biosynthesis in spleens of Hodgkin patients, this immunostaining procedure has been applied to localization of IgG-producing cells in specimens with Hodgkin\u27s disease

Wess-Zumino model with exact supersymmetry on the lattice

A lattice formulation of the four dimensional Wess-Zumino model that uses Ginsparg-Wilson fermions and keeps exact supersymmetry is presented. The supersymmetry transformation that leaves invariant the action at finite lattice spacing is determined by performing an iterative procedure in the coupling constant. The closure of the algebra, generated by this transformation is also showed.Comment: 13 pages. Few references added. New appendix on Ward identity added. Version to be published in JHE

Development and internal validation of prediction models for future hospital care utilization by patients with multimorbidity using electronic health record data

OBJECTIVE: To develop and internally validate prediction models for future hospital care utilization in patients with multiple chronic conditions. DESIGN: Retrospective cohort study. SETTING: A teaching hospital in the Netherlands (542 beds) PARTICIPANTS: All adult patients (n = 18.180) who received care at the outpatient clinic in 2017 for two chronic diagnoses or more (including oncological diagnoses) and who returned for hospital care or outpatient clinical care in 2018. Development and validation using a stratified random split-sample (n = 12.120 for development, n = 6.060 for internal validation). OUTCOMES: ≥2 emergency department visits in 2018, ≥1 hospitalization in 2018 and ≥12 outpatient visits in 2018. STATISTICAL ANALYSIS: Multivariable logistic regression with forward selection. RESULTS: Evaluation of the models’ performance showed c-statistics of 0.70 (95% CI 0.69–0.72) for the hospitalization model, 0.72 (95% CI 0.70–0.74) for the ED visits model and 0.76 (95% 0.74–0.77) for the outpatient visits model. With regard to calibration, there was agreement between lower predicted and observed probability for all models, but the models overestimated the probability for patients with higher predicted probabilities. CONCLUSIONS: These models showed promising results for further development of prediction models for future healthcare utilization using data from local electronic health records. This could be the first step in developing automated alert systems in electronic health records for identifying patients with multimorbidity with higher risk for high healthcare utilization, who might benefit from a more integrated care approach