ELASTIC AND KINEMATIC HARDENING PLASTIC BLAST INDUCED DEFORMATIONS OF UNDERGROUND TUNNELS B)I THE FINITE ELEMENT METHOD

This research deals with the stress analysis of typical underground tunnels using isoparametric finite elements. Enhanced soflware is used for predicting and analyzing this behavior by using a single phase formulation. This software was developed from an original Computer code namea MXOYN The finite element method is used to solve the dynamic equiiibrium equation with step-by-step tirre integration schemes. A selected type of dynamic load was chosen which is blast loading. Frictional and paniculate materials, i.e., concrete and soil, are considered. The soil and concrele structures arc analyzed where a dynamic elastic model for concrete and a linear elastic one for soil are used. The soil is further analyzed by a bounding surface plasticity model. Tlie stress wavcs havel and the reflection effects especially in the no tension materials, i.e., soil are investigated. The effects of blast loading are then analyzed hypothetically placing the explosion at the grourd surface. The stresses and displacements are computed at different sections. The nonlinear analysis utilizing the bounding surface plasticity characterization gave better predictions over the linear elastic model. The linear elastic model is proposed to be used as a first prediction of the problems encountered, but it is incapable of realizing the actual behavior under dynamic loads

The Association of Intensive Blood Pressure Treatment and Non-Fatal Cardiovascular or Serious Adverse Events in Older Adults With Mortality: Mediation Analysis in Sprint

AIMS: Randomized clinical trials of hypertension treatment intensity evaluate the effects on incident major adverse cardiovascular events (MACEs) and serious adverse events (SAEs). Occurrences after a non-fatal index event have not been rigorously evaluated. The aim of this study was to evaluate the association of intensive (\u3c120 \u3emmHg) to standard (\u3c140 \u3emmHg) blood pressure (BP) treatment with mortality mediated through a non-fatal MACE or non-fatal SAE in 9361 participants in the Systolic Blood Pressure Intervention Trial. METHODS AND RESULTS: Logistic regression and causal mediation modelling to obtain direct and mediated effects of intensive BP treatment. Primary outcome was all-cause mortality (ACM). Secondary outcomes were cardiovascular (CVM) and non-CV mortality (non-CVM). The direct effect of intensive treatment was a lowering of ACM [odds ratio (OR) 0.75, 95% confidence interval (CI): 0.60-0.94]. The MACE-mediated effect substantially attenuated (OR 0.96, 95% CI: 0.92-0.99) ACM, while the SAE-mediated effect was associated with increased (OR 1.03, 95% CI: 1.01-1.05) ACM. Similar patterns were noted for intensive BP treatment on CVM and non-CVM. We also noted that SAE incidence was 3.9-fold higher than MACE incidence (13.7 vs. 3.5%), and there were a total of 365 (3.9%) ACM cases, with non-CVM being 2.6-fold higher than CVM [2.81% (263/9361) vs. 1.09% (102/9361)]. The SAE to MACE and non-CVM to CVM preponderance was found across all age groups, with the ≥80-year age group having the highest differences. CONCLUSION: The current analytic techniques demonstrated that intensive BP treatment was associated with an attenuated mortality benefit when it was MACE-mediated and possibly harmful when it was SAE-mediated. Current cardiovascular trial reporting of treatment effects does not allow expansion of the lens to focus on important occurrences after the index event

Uncoupling of ATP-Mediated Calcium Signaling and Dysregulated Interleukin-6 Secretion in Dendritic Cells by Nanomolar Thimerosal

Dendritic cells (DCs), a rare cell type widely distributed in the soma, are potent antigen-presenting cells that initiate primary immune responses. DCs rely on intracellular redox state and calcium (Ca(2+)) signals for proper development and function, but the relationship between these two signaling systems is unclear. Thimerosal (THI) is a mercurial used to preserve vaccines and consumer products, and is used experimentally to induce Ca(2+) release from microsomal stores. We tested adenosine triphosphate (ATP)-mediated Ca(2+) responses of DCs transiently exposed to nanomolar THI. Transcriptional and immunocytochemical analyses show that murine myeloid immature DCs (IDCs) and mature DCs (MDCs) express inositol 1,4,5-trisphosphate receptor (IP(3)R) and ryanodine receptor (RyR) Ca(2+) channels, known targets of THI. IDCs express the RyR1 isoform in a punctate distribution that is densest near plasma membranes and within dendritic processes, whereas IP(3)Rs are more generally distributed. RyR1 positively and negatively regulates purinergic signaling because ryanodine (Ry) blockade a) recruited 80% more ATP responders, b) shortened ATP-mediated Ca(2+) transients > 2-fold, and c) produced a delayed and persistent rise (≥ 2-fold) in baseline Ca(2+). THI (100 nM, 5 min) recruited more ATP responders, shortened the ATP-mediated Ca(2+) transient (≥ 1.4-fold), and produced a delayed rise (≥ 3-fold) in the Ca(2+) baseline, mimicking Ry. THI and Ry, in combination, produced additive effects leading to uncoupling of IP(3)R and RyR1 signals. THI altered ATP-mediated interleukin-6 secretion, initially enhancing the rate of cytokine secretion but suppressing cytokine secretion overall in DCs. DCs are exquisitely sensitive to THI, with one mechanism involving the uncoupling of positive and negative regulation of Ca(2+) signals contributed by RyR1

TAVR in Older Adults: Moving Toward a Comprehensive Geriatric Assessment and Away From Chronological Age

Calcific aortic stenosis can be considered a model for geriatric cardiovascular conditions due to a confluence of factors. The remarkable technological development of transcatheter aortic valve replacement was studied initially on older adult populations with prohibitive or high-risk for surgical valve replacement. Through these trials, the cardiovascular community has recognized that stratification of these chronologically older adults can be improved incrementally by invoking the concept of frailty and other geriatric risks. Given the complexity of the aging process, stratification by chronological age should only be the initial step but is no longer sufficient to optimally quantify cardiovascular and noncardiovascular risk. In this review, we employ a geriatric cardiology lens to focus on the diagnosis and the comprehensive management of aortic stenosis in older adults to enhance shared decision-making with patients and their families and optimize patient-centered outcomes. Finally, we highlight knowledge gaps that are critical for future areas of study

Building WF16: construction of a PPNA pisé structure in Southern Jordan

The Pre-Pottery Neolithic A (PPNA) period in Southwest Asia is essential for our understanding of the transition to sedentary, agricultural communities. Developments in architecture are key to understanding this transition, but many aspects of PPNA architecture remain elusive, such as construction techniques, the selection of building materials, and the functional use of space. The primary aim of the research described within this contribution was to build a PPNA-like structure in order to answer questions about PPNA architecture in general, while specifically addressing issues raised by the excavation of structures at the site of WF16, Southern Jordan. The second aim was to display a ‘PPNA’ building to visitors in Wadi Faynan to enhance their understanding of the period. The experimental construction based on one of the WF16 structures showed that 1) required materials can be acquired locally; 2) a construction technique using mud layers as described in this paper was likely used; 3) flat, or very slightly dome-shaped, roofs are functional and can also be used as a solid working platform; 4) the WF16 small semi-subterranean buildings appear inappropriate for housing a nuclear family unit

Early mobilization in the critical care unit: A review of adult and pediatric literature.

Early mobilization of critically ill patients is beneficial, suggesting that it should be incorporated into daily clinical practice. Early passive, active, and combined progressive mobilizations can be safely initiated in intensive care units (ICUs). Adult patients receiving early mobilization have fewer ventilator-dependent days, shorter ICU and hospital stays, and better functional outcomes. Pediatric ICU data are limited, but recent studies also suggest that early mobilization is achievable without increasing patient risk. In this review, we provide a current and comprehensive appraisal of ICU mobilization techniques in both adult and pediatric critically ill patients. Contraindications and perceived barriers to early mobilization, including cost and health care provider views, are identified. Methods of overcoming barriers to early mobilization and enhancing sustainability of mobilization programs are discussed. Optimization of patient outcomes will require further studies on mobilization timing and intensity, particularly within specific ICU populations

Novel Echocardiographic Biomarkers in the Management of Atrial Fibrillation

Purpose of Review: Atrial fibrillation (AF) is the most common arrhythmia in adults. The number of patients with AF is anticipated to increase annually, mainly due to the aging population alongside improved arrhythmia detection. AF is associated with a significantly elevated risk of hospitalization, stroke, thromboembolism, heart failure, and all-cause mortality. Echocardiography is one of the key components of routine assessment and management of AF. Therefore, the aim of this review is to briefly summarize current knowledge on “novel” echocardiographic parameters that may be of value in the management of AF patients. Recent Findings: Novel echocardiographic biomarkers and their clinical application related to the management of AF have been taken into consideration. Both standard parameters such as atrial size and volume but also novels like atrial strain and tissue Doppler techniques have been analyzed. Summary: A number of novel echocardiographic parameters have been proven to enable early detection of left atrial dysfunction along with increased diagnosis accuracy. This concerns particularly experienced echocardiographers. Hence, these techniques might improve the prediction of stroke and thromboembolic events among AF patients and need to be further developed and disseminated. Nonetheless, even the standard imaging parameters could be of significant value and should not be discontinued in everyday clinical practice. © 2019, The Author(s)

The cellular composition of the human immune system is shaped by age and cohabitation.

Detailed population-level description of the human immune system has recently become achievable. We used a 'systems-level' approach to establish a resource of cellular immune profiles of 670 healthy individuals. We report a high level of interindividual variation, with low longitudinal variation, at the level of cellular subset composition of the immune system. Despite the profound effects of antigen exposure on individual antigen-specific clones, the cellular subset structure proved highly elastic, with transient vaccination-induced changes followed by a return to the individual's unique baseline. Notably, the largest influence on immunological variation identified was cohabitation, with 50% less immunological variation between individuals who share an environment (as parents) than between people in the wider population. These results identify local environmental conditions as a key factor in shaping the human immune system