Vacuum inversion and securing of distal colonic pseudodiverticula with novel spiked O-rings

Diverticular disease is increasingly prevalent in Western societies and is associated with significant morbidity. OBJECTIVE: Two-stage endoscopic device development for inversion and secured ligation of colonic diverticula; first, human cadaver studies were performed to measure forces required for diverticular inversion; second, a novel set of devices (elastic spiked O-ring with delivery system) was tested in animals. DESIGN: Prospective, observational study of human cadavers and prospective, interventional study of a porcine model. SETTING: University hospital pathology laboratory and animal facility. INTERVENTION: Full-thickness inversion of the colonic wall with a pipelike delivery instrument to produce an inverted pseudodiverticulum that was secured with a spiked O-ring. MAIN OUTCOME MEASUREMENTS: The forces required for diverticular inversion, the secured closure of inverted pseudodiverticula, and the time until necrotic tissue falls off. RESULTS: A total of 248 of 248 of cadaveric sigmoid diverticula could be inverted by means of vacuum or forceps. The forces required for inversion ranged from 0.28 to 0.47 N (median, 0.37 N). Twenty-four spiked O-rings were delivered in 6 living pigs to produce 24 inverted pseudodiverticula. One animal died the day after the procedure of a pulmonary thromboembolism. In the remaining 5 pigs, all delivered spiked O-rings remained in place for 7 to 22 days. At necropsy, none of the inverted sites showed signs of perforation but rather full-thickness reparative scarring with ingrowth of connective tissue. LIMITATIONS: Animal model, stiff pipelike delivery instrument, variations in diverticular location, diameter, and size. CONCLUSIONS: Endoluminal inversion and securing of colonic diverticula induces tissue necrosis, diverticular sloughing, and full-thickness scarring

Static and vibration analysis of functionally graded beams using refined shear deformation theory

Static and vibration analysis of functionally graded beams using refined shear deformation theory is presented. The developed theory, which does not require shear correction factor, accounts for shear deformation effect and coupling coming from the material anisotropy. Governing equations of motion are derived from the Hamilton's principle. The resulting coupling is referred to as triply coupled axial-flexural response. A two-noded Hermite-cubic element with five degree-of-freedom per node is developed to solve the problem. Numerical results are obtained for functionally graded beams with simply-supported, cantilever-free and clamped-clamped boundary conditions to investigate effects of the power-law exponent and modulus ratio on the displacements, natural frequencies and corresponding mode shapes

Novel inhibitors of the calcineurin/NFATc hub - alternatives to CsA and FK506?

The drugs cyclosporine A (CsA) and tacrolimus (FK506) revolutionized organ transplantation. Both compounds are still widely used in the clinic as well as for basic research, even though they have dramatic side effects and modulate other pathways than calcineurin-NFATc, too. To answer the major open question - whether the adverse side effects are secondary to the actions of the drugs on the calcineurin-NFATc pathway - alternative inhibitors were developed. Ideal inhibitors should discriminate between the inhibition of (i) calcineurin and peptidyl-prolyl cis-trans isomerases (PPIases; the matchmaker proteins of CsA and FK506), (ii) calcineurin and the other Ser/Thr protein phosphatases, and (iii) NFATc and other transcription factors. In this review we summarize the current knowledge about novel inhibitors, synthesized or identified in the last decades, and focus on their mode of action, specificity, and biological effects

Sustainable Groundwater Management in the Arid Southwestern US: Coachella Valley, California

Sustainable groundwater management requires approaches to assess the influence of climate and management actions on the evolution of groundwater systems. Traditional approaches that apply continuity to assess groundwater sustainability fail to capture the spatial variability of aquifer responses. To address this gap, our study evaluates groundwater elevation data from the Coachella Valley, California, within a groundwater sustainability framework given the adoption of integrative management strategies in the valley. Our study details an innovative approach employing traditional statistical methods to improve understanding of aquifer responses. In this analysis, we evaluate trends at individual groundwater observation wells and regional groundwater behaviors using field significance. Regional elevation trends identified no significant trends during periods of intense groundwater replenishment, active since 1973, despite spatial variability in individual well trends. Our results illustrate the spatially limited effects of groundwater replenishment occur against a setting of long-term groundwater depletion, raising concerns over the definition of sustainable groundwater management in aquifer systems employing integrative management strategies

Deformation analysis of functionally graded beams by the direct approach

In this paper we employ the direct approach to the theory of rods and beams, which is based on the deformable curve model with a triad of rotating directors attached to each point. We show that this model (also called directed curve) is an efficient approach for analyzing the deformation of elastic beams with a complex material structure. Thus, we consider non-homogeneous, composite and functionally graded beams made of isotropic or orthotropic materials and we determine the effective stiffness properties in terms of the three-dimensional elasticity constants. We present general analytical expressions of the effective stiffness coefficients, valid for beams of arbitrary cross-section shape. Finally, we apply this method for FGM beams made of metal foams and compare our analytical results with the numerical results obtained by a finite element analysis