Prognostic model to predict postoperative acute kidney injury in patients undergoing major gastrointestinal surgery based on a national prospective observational cohort study.

Background: Acute illness, existing co-morbidities and surgical stress response can all contribute to postoperative acute kidney injury (AKI) in patients undergoing major gastrointestinal surgery. The aim of this study was prospectively to develop a pragmatic prognostic model to stratify patients according to risk of developing AKI after major gastrointestinal surgery. Methods: This prospective multicentre cohort study included consecutive adults undergoing elective or emergency gastrointestinal resection, liver resection or stoma reversal in 2-week blocks over a continuous 3-month period. The primary outcome was the rate of AKI within 7 days of surgery. Bootstrap stability was used to select clinically plausible risk factors into the model. Internal model validation was carried out by bootstrap validation. Results: A total of 4544 patients were included across 173 centres in the UK and Ireland. The overall rate of AKI was 14·2 per cent (646 of 4544) and the 30-day mortality rate was 1·8 per cent (84 of 4544). Stage 1 AKI was significantly associated with 30-day mortality (unadjusted odds ratio 7·61, 95 per cent c.i. 4·49 to 12·90; P < 0·001), with increasing odds of death with each AKI stage. Six variables were selected for inclusion in the prognostic model: age, sex, ASA grade, preoperative estimated glomerular filtration rate, planned open surgery and preoperative use of either an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker. Internal validation demonstrated good model discrimination (c-statistic 0·65). Discussion: Following major gastrointestinal surgery, AKI occurred in one in seven patients. This preoperative prognostic model identified patients at high risk of postoperative AKI. Validation in an independent data set is required to ensure generalizability

Magnitude of latent heat in thermally loaded clays

International audienceTemperature changes are known to induce specific couplings in clay, in particular, an anomalously high thermal pressurization in undrained conditions, or a thermal compaction in drained conditions, both of which are potential threats for the mechan- ical stability and sealing capacity of the geomaterials. Thermodynamical analysis of those peculiar thermo-mechanical couplings points to a potentially important latent energy which in turn could limit the temperature change upon heating or cooling. The direct measurement of latent energy developed during a laboratory geomechanical test is challenging. Instead, proper identification of thermal hardening in conven- tional experiments with temperature changes provides an alternative route to estimate latent energy. In this work, existing laboratory thermomechanical tests of clays are analyzed with a rigorous thermodynamic framework to quantify the magnitude of latent energy in thermo-mechanically loaded clays. A thermodynamically consistent constitutive model for fully saturated clays that combines two key features: i) the temperature dependence of the blocked energy and ii) the framework of bounding plasticity, is proposed. The performance of the model is validated by reproducing results obtained in laboratory tests for Boom and Opalinus clays. The thermomechan- ical loads considered to validate the model performance, were then used to estimate the percentage ofwork that remains latent in the clayey material during plastic yield- ing. We find that the magnitude of latent energy is quite significant, typically a few tens of percent of the total dissipated energy, and increases significantly with temper- ature. Accordingly, it is expected to play an important role in the thermo-mechanical response of clays

The double-stranded RNA-binding protein, PACT, is required for postnatal anterior pituitary proliferation

PACT is a double-stranded RNA-binding protein that also binds and activates the latent protein kinase, PKR, which plays a major role in cellular antiviral defense in mammals. For evaluating PACT's contribution to the innate immune system, Pact−/− mice have been generated; these mice exhibit notable developmental abnormalities including microtia, with craniofacial, ear, and hearing defects. Here we report that, in addition, Pact−/− mice had smaller body size and fertility defects, both of which were caused by defective pituitary functions. Pact−/− mice exhibited anterior pituitary lobe (AL) hypoplasia, which developed postnatally, when the second phase of pituitary expansion occurs. Among the 5 cell types in AL, the numbers of corticotrophs, gonadotrophs, and somatotrophs were equally decreased in Pact−/− mice with a greater impact on lactotrophs and a lesser impact on thyrotrophs. PACT mRNA and protein were highly expressed in the pituitary of wild-type (Wt) mice during the postnatal wave of AL proliferation, the same period in which the hypoplasia developed in Pact−/− mice. During this time, the pituitaries of Pact−/− mice did not exhibit significantly increased apoptosis compared with Wt mice but showed a decrease in cell proliferation. The inhibition of cell proliferation observed in vivo could be recapitulated in vitro in GH3 somato/lactotroph and LβT2 gonadotroph cell lines; knockdown of PACT expression with siRNA diminished the rate of proliferation of these cells. Our study revealed a physiologically significant role for PACT in cell proliferation and an essential role of a dsRNA-binding protein in mammalian pituitary expansion

Research Challenges Involving Coupled Flows in Geotechnical Engineering

Coupled fluid, chemical, heat, and electrical flows are common phenomena that arc relevant to a wide variety of applications in Geotechnical Engineering, including the use of engineered clay barriers for waste containment, electro-osmosis for soil consolidation, highly compacted bentonite buffers for high-level radioactive nuclear waste disposal, and electrokinetics for soil contaminant removal. among others. For all of these applications, a fundamental understanding of coupled flow phenomena is required, including the basis of the various phenomena. the potential effect of the phenomena on fundamental soil behavior, and the applicability of the phenomena in both natural and built environments. This chapter highlights some of the advances over the past approximate three decades, including the effects of osmotic phenomena (chemico-osmosis, electro-osmosis, and thermo-osmosis) on the mechanical behavior of clays, the formulations and measurement of coupled flow phenomena, the distinction between phenomenological and microscopic (physical-based) formalisms, and considerations with respect to both saturated and unsaturated soil conditions. Based on the description of these advances, research challenges pertaining lo the study of coupled flow phenomena for Geotechnical Engineering applications are identified