Understanding how a geosynthetic-reinforced soil deforms in response to the formation of an underlying void is crucial to provide appropriate designs of these systems. Centrifuge models employing a ...trapdoor to simulate the void formation below a geosynthetic-reinforced sand were conducted to investigate the behaviour in a controlled environment at realistic stress levels. The plane-strain models allowed visual observations of the deformation mechanisms using Particle Image Velocimetry (PIV). These observations were used to validate assumptions about the geosynthetic behaviour made in current design recommendations, and address limitations related to the fill behaviour. Soil expansion was observed to be confined to a parabolic zone above the void related to the soil dilatancy, rather than with a single, unique coefficient of expansion. The zone of subsidence was characterised by an initial vertical prism with a funnel to the surface, with the surface settlement profile better described by a Gaussian distribution rather than the parabolic profile used historically. Detailed interpretation of the centrifuge tests has given new insight into the soil and geosynthetic behaviour relevant to how these systems deform in practice. This paves the way for more efficient design recommendations and consequently will facilitate better predictions of geosynthetic-reinforced soil behaviour above voids.
The assumption with the biggest impact on the design of geosynthetic-reinforced soils above voids is the presence and degree of soil arching, which affects the predicted applied stress on the ...geosynthetic. A series of centrifuge tests were conducted to investigate the soil arching in geosynthetic-reinforced soils with measurements of the soil stresses and observation of soil and geosynthetic deformation used to infer the arching behaviour. Detailed analysis of the results showed that arching significantly reduces the stress at the base of the soil when a void forms; this mechanism is due to stress redistributions and not the formation of a physical arch as suggested in some models. A new method to reliably predict this reduction is proposed by calculating the coefficient of lateral stress on vertical failure planes based on the observations of a continuous convex arc of major principal strains above the void, and the assumption that this is indicative of the stress behaviour.
Introduction
Patients undergoing transsphenoidal pituitary surgery (TSS) are at risk for several serious complications, including the syndrome of inappropriate antidiuretic hormone and subsequent ...hyponatremia.
Objective
In this study, we examined the effect of 1 week of post-discharge fluid restriction to 1.0 L daily on rates of post-operative readmission for hyponatremia.
Methods
We retrospectively analyzed all patients undergoing TSS from 2008 to 2014 and prospectively recorded patient data from 2015 to 2017. Patients were divided into a control cohort (2008–2014), who were discharged with instructions to drink to thirst; and an intervention cohort (2015–2017) who were instructed to drink less than 1.0 L daily for 1 week post-operatively.
Results
This study included 788 patients; 585 (74.2%) in the control cohort and 203 (25.8%) in the intervention cohort. Overall, 436 (55.3%) were women, the median age was 47 (range 15–89), and average BMI was 29.4 kg/m
2
(range 17.7–101.7). Patients were relatively well matched. Of patients in the intervention group, none was readmitted for hyponatremia (0/203), compared to 3.41% (20/585) in the control group (p = 0.003). Patients in the intervention group also had significantly higher post-operative week one sodium levels (140.1 vs 137.5 mEq/L; p = 0.002). No fluid balance complications occurred in patients who followed this protocol.
Conclusion
Hyponatremia can be a life-threatening complication of TSS, and prevention of readmission for hyponatremia can help improve patient safety and decrease costs. Mandatory post-discharge fluid restriction is a simple and inexpensive intervention associated with decreased rates of readmission for hyponatremia and normal post-operative sodium levels.
This paper applies the technology acceptance model to explore the digital divide and transformational government (t-government) in the United States. Successful t-government is predicated on citizen ...adoption and usage of e-government services. The contribution of this research is to enhance our understanding of the factors associated with the usage of e-government services among members of a community on the unfortunate side of the divide. A questionnaire was administered to members, of a techno-disadvantaged public housing community and neighboring households, who partook in training or used the community computer lab. The results indicate that perceived access barriers and perceived ease of use (PEOU) are significantly associated with usage, while perceived usefulness (PU) is not. Among the demographic characteristics, educational level, employment status, and household income all have a significant impact on access barriers and employment is significantly associated with PEOU. Finally, PEOU is significantly related to PU. Overall, the results emphasize that t-government cannot cross the digital divide without accompanying employment programs and programs that enhance citizens’ ease in using such services.
Stereotypical expression in laboratory-housed rodents can be explained by different motivational, coping, and motor dysfunction theories. Here, we aimed to explore the neurocognitive underpinnings of ...high stereotypical (HS) expression in deer mice
, previously proposed as a model system of compulsive-like behavioral persistence. Specifically, we aimed to establish whether HS behavior is related to an underlying escape-related trigger.
One-hundred and sixteen deer mice were classified as either non-stereotypical (NS) or HS. Mice of each cohort were further subdivided and exposed to either sub-acute (3-day) or chronic (25-day) behavioral restriction (R), and high-dose escitalopram (ESC), lorazepam (LOR), alone and in combination with R (ESC+R and LOR+R, respectively). Mice were reassessed for stereotypical behavior at both time points.
Our results indicate that HS behavior is likely not temporally and functionally related to an anxiogenic trigger, i.e., R, but rather that HS is associated with parallel changes in anxiogenic feedback processing. We also show that chronic R alone significantly decreased the time spent in expressing HS behavior in animals of the HS, but not NS phenotype.
This points to the possibility that HS-expressing mice represent a subgroup of
in which unique interactions between neurobiology and processes of gradual behavioral organization, may contribute to the expression of the typical behaviors observed in this cohort. Collectively, our findings highlight the value of the deer mouse model system to investigate the potential neurocognitive mechanisms that may underlie the development of persistent phenotypes that can likely not be explained entirely by current theories.
KRAS, NRAS and BRAF mutations are among the most important oncogenic drivers in many major cancer types, such as melanoma, lung, colorectal and pancreatic cancer. There is currently no effective ...therapy for the treatment of RAS mutant cancers. LY3009120, a pan-RAF and RAF dimer inhibitor advanced to clinical study has been shown to inhibit both RAS and BRAF mutant cell proliferation in vitro and xenograft tumor growth in vivo. Abemaciclib, a CDK4/6-selective inhibitor, is currently in phase III studies for ER-positive breast cancer and KRAS mutant lung cancer. In this study, we found that combinatory treatment with LY3009120 and abemaciclib synergistically inhibited proliferation of tumor cells in vitro and led to tumor growth regression in xenograft models with a KRAS, NRAS or BRAF mutation at the doses of two drugs that were well tolerated in combination. Further in vitro screen in 328 tumor cell lines revealed that tumor cells with KRAS, NRAS or BRAF mutation, or cyclin D activation are more sensitive, whereas tumor cells with PTEN, PIK3CA, PIK3R1 or retinoblastoma (Rb) mutation are more resistant to this combination treatment. Molecular analysis revealed that abemaciclib alone inhibited Rb phosphorylation partially and caused an increase of cyclin D1. The combinatory treatment cooperatively demonstrated more complete inhibition of Rb phosphorylation, and LY3009120 suppressed the cyclin D1 upregulation mediated by abemaciclib. These results were further verified by CDK4/6 siRNA knockdown. Importantly, the more complete phospho-Rb inhibition and cyclin D1 suppression by LY3009120 and abemaciclib combination led to more significant cell cycle G
/G
arrest of tumor cells. These preclinical findings suggest that combined inhibition of RAF and d-cyclin-dependent kinases might provide an effective approach to treat patients with tumors harboring mutations in RAS or RAF genes.
A minute fraction of atmospheric particles exert a disproportionate effect on the phase of mixed-phase clouds by acting as ice-nucleating particles (INPs). To understand the effects of these ...particles on weather and climate, both now and into the future, we must first develop a quantitative understanding of the major INP sources worldwide. Previous work has demonstrated that aerosols such as desert dusts are globally important INPs, but the role of biogenic INPs is unclear, with conflicting evidence for their importance. Here, we show that at a temperate site all INPs active above -18 °C at concentrations >0.1 L
are destroyed on heating, consistent with these INPs being of biological origin. Furthermore, we show that a global model of desert dust INPs dramatically underestimates the measured INP concentrations, but is consistent with the thermally-stable component. Notably, the heat sensitive INPs are active at temperatures where shallow cloud layers in Northern Europe are frequently observed to glaciate. Hence, we suggest that biogenic material is important for primary ice production in this region. The prevalence of heat sensitive, most likely biogenic, INPs in this region highlights that, as a community, we need to quantify the sources and transport of these particles as well as determine their atmospheric abundance across the globe and at cloud altitudes.
Quaking aspen (Populus tremuloides Michx.), a widespread and keystone tree species in North America, experienced heat and drought stress in the years 2002 and 2003 in the southwestern United States. ...This led to widespread aspen mortality that has altered the composition of forests, and is expected to occur again if climate change continues. Understanding interactions between aspen and its environments is essential to understanding future mortality risk in forests. Polyploidy, which is common in aspen, can modify plant structure and function and therefore plant-environment interactions, but the influence of polyploidy on aspen physiology is still not well understood. Furthermore, the ploidy types of aspen have different biogeographies, with triploids being most frequent at lower latitudes in generally warmer and drier climates, while the northerly populations are virtually 100% diploid. This suggests that ploidy-environment interactions differ, and could mean that the ploidy types have different vulnerabilities to environmental stress. In this study, to understand aspen ploidy-environment interactions, we measured 38 different traits important to carbon uptake, water loss and water-use efficiency in diploid and triploid aspen in Colorado. We found that triploid aspen had lower stand density, and greater leaf area, leaf mass, leaf mass per area, percent nitrogen content, chlorophyll content and stomatal size. These differences corresponded to greater potential net carbon assimilation (A, measured using A/Ci curves, and chlorophyll fluorescence) and stomatal conductance (gs) in triploids than diploids. While triploid aspen had higher intrinsic water-use efficiency (iWUE, calculated from measurements of δ13C in leaf tissue), they also had greater potential water loss from higher measured gs and lower stomatal sensitivity to increasing vapor pressure deficit. Therefore, despite greater iWUE, triploids may have lower resilience to climate-induced stress. We conclude that ploidy type strongly influences physiological traits and function, and mediates drought stress responses in quaking aspen.
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