The influence of transition metal solutes on dislocation core structure and values of Peierls stress and barrier in tungsten

Several transition metals were examined to evaluate their potential for improving the ductility of tungsten. The dislocation core structure and Peierls stress and barrier of $1/2$ screw dislocations in binary tungsten-transition metal alloys (W$_{1-x}$TM$_{x}$) were investigated using first principles electronic structure calculations. The periodic quadrupole approach was applied to model the structure of $1/2$ dislocation. Alloying with transition metals was modeled using the virtual crystal approximation and the applicability of this approach was assessed by calculating the equilibrium lattice parameter and elastic constants of the tungsten alloys. Reasonable agreement was obtained with experimental data and with results obtained from the conventional supercell approach. Increasing the concentration of a transition metal from the VIIIA group, i.e. the elements in columns headed by Fe, Co and Ni, leads to reduction of the $C^\prime$ elastic constant and increase of elastic anisotropy A=$C_{44}/C^\prime$. Alloying W with a group VIIIA transition metal changes the structure of the dislocation core from symmetric to asymmetric, similar to results obtained for W$_{1-x}$Re$_{x}$ alloys in the earlier work of Romaner {\it et al} (Phys. Rev. Lett. 104, 195503 (2010))\comments{\cite{WRECORE}}. In addition to a change in the core symmetry, the values of the Peierls stress and barrier are reduced. The latter effect could lead to increased ductility in a tungsten-based alloy\comments{\cite{WRECORE}}. Our results demonstrate that alloying with any of the transition metals from the VIIIA group should have similar effect as alloying with Re.Comment: 12 pages, 8 figures, 3 table

MicroRNA-135b Regulates Leucine Zipper Tumor Suppressor 1 in Cutaneous Squamous Cell Carcinoma

Cutaneous squamous cell carcinoma (cSCC) is the second most common skin malignancy and it presents a therapeutic challenge in organ transplant recipient patients. Despite the need, there are only a few targeted drug treatment options. Recent studies have revealed a pivotal role played by microRNAs (miRNAs) in multiple cancers, but only a few studies tested their function in cSCC. Here, we analyzed differential expression of 88 cancer related miRNAs in 43 study participants with cSCC; 32 immunocompetent, 11 OTR patients, and 15 non-lesional skin samples by microarray analysis. Of the examined miRNAs, miR-135b was the most upregulated (13.3-fold, 21.5-fold; p=0.0001) in both patient groups. Similarly, the miR-135b expression was also upregulated in three cSCC cell lines when evaluated by quantitative real-time PCR. In functional studies, inhibition of miR-135b by specific anti-miR oligonucleotides resulted in upregulation of its target gene LZTS1 mRNA and protein levels and led to decreased cell motility and invasion of both primary and metastatic cSCC cell lines. In contrast, miR-135b overexpression by synthetic miR-135b mimic induced further down-regulation of LZTS1 mRNA in vitro and increased cancer cell motility and invasiveness. Immunohistochemical evaluation of 67 cSCC tumor tissues demonstrated that miR-135b expression inversely correlated with LZTS1 staining intensity and the tumor grade. These results indicate that miR-135b functions as an oncogene in cSCC and provide new understanding into its pathological role in cSCC progression and invasiveness

Malnutrition as assessed by nutritional risk index is associated with worse outcome in patients admitted with acute decompensated heart failure: an ACAP-HF data analysis

Malnutrition is common at hospital admission and tends to worsen during hospitalization. This controlled population study aimed to determine if serum albumin or moderate and severe nutritional depletion by Nutritional Risk Index (NRI) at hospital admission are associated with increased length of hospital stay (LOS) in patients admitted with acute decompensated heart failure (ADHF). Serum albumin levels and lymphocyte counts were retrospectively determined at hospital admission in 1740 consecutive patients admitted with primary and secondary diagnosis of ADHF. The Nutrition Risk Score (NRI) developed originally in AIDS and cancer populations was derived from the serum albumin concentration and the ratio of actual to usual weight, as follows: NRI = (1.519 × serum albumin, g/dL) + {41.7 × present weight (kg)/ideal body weight(kg)}. Patients were classified into four groups as no, mild, moderate or severe risk by NRI. Multiple logistic regressions were used to determine the association between nutritional risk category and LOS

Study protocol: Cost-effectiveness of transmural nutritional support in malnourished elderly patients in comparison with usual care

BACKGROUND: Malnutrition is a common consequence of disease in older patients. Both in hospital setting and in community setting oral nutritional support has proven to be effective. However, cost-effectiveness studies are scarce. Therefore, the aim of our study is to investigate the effectiveness and cost-effectiveness of transmural nutritional support in malnourished elderly patients, starting at hospital admission until three months after discharge. METHODS: This study is a randomized controlled trial. Patients are included at hospital admission and followed until three months after discharge. Patients are eligible to be included when they are > or = 60 years old and malnourished according to the following objective standards: Body Mass Index (BMI in kg/m2) < 20 and/or > or = 5% unintentional weight loss in the previous month and/or > or = 10% unintentional weight loss in the previous six months. We will compare usual nutritional care with transmural nutritional support (energy and protein enriched diet, two additional servings of an oral nutritional supplement, vitamin D and calcium supplementation, and consultations by a dietitian). Each study arm will consist of 100 patients. The primary outcome parameters will be changes in activities of daily living (determined as functional limitations and physical activity) between intervention and control group. Secondary outcomes will be changes in body weight, body composition, quality of life, and muscle strength. An economic evaluation from a societal perspective will be conducted alongside the randomised trial to evaluate the cost-effectiveness of the intervention in comparison with usual care. CONCLUSION: In this randomized controlled trial we will evaluate the effect of transmural nutritional support in malnourished elderly patients after hospital discharge, compared to usual care. Primary endpoints of the study are changes in activities of daily living, body weight, body composition, quality of life, and muscle strength. An economic evaluation will be performed to evaluate the cost-effectiveness of the intervention in comparison with usual care. TRIAL REGISTRATION: Netherlands Trial Register (ISRCTN29617677, registered 14-Sep-2005)

Photochemistry Of Monochloro Complexes Of Copper(ii) In Methanol Probed By Ultrafast Transient Absorption Spectroscopy

Ultrafast transient absorption spectra in the deep to near UV range (212-384 nm) were measured for the [Cu-II(MeOH)(5)Cl](+) complexes in methanol following 255-nm excitation of the complex into the ligand-to-metal charge-transfer excited state. The electronically excited complex undergoes sub-200 fs radiationless decay, predominantly via back electron transfer, to the hot electronic ground state followed by fast vibrational relaxation on a 0.4-4 Ps time scale. A minor photochemical channel is Cu-Cl bond dissociation, leading to the reduction of copper(H) to copper(I) and the formation of MeOH center dot Cl charge-transfer complexes. The depletion of ground-state [Cu-II(MeOH)(5)Cl](+) perturbs the equilibrium between several forms of copper(II) complexes present in solution. Complete re-equilibration between [Cu-II(MeOH)(5)Cl](+) and [Cu-II(MeOH)(4)Cl-2] is established on a 10-500 ps time scale, slower than methanol diffusion, suggesting that the involved ligand exchange mechanism is dissociative

The clinical relevance of oliguria in the critically ill patient : Analysis of a large observational database

Funding Information: Marc Leone reports receiving consulting fees from Amomed and Aguettant; lecture fees from MSD, Pfizer, Octapharma, 3 M, Aspen, Orion; travel support from LFB; and grant support from PHRC IR and his institution. JLV is the Editor-in-Chief of Critical Care. The other authors declare that they have no relevant financial interests. Publisher Copyright: © 2020 The Author(s). Copyright: Copyright 2020 Elsevier B.V., All rights reserved.Background: Urine output is widely used as one of the criteria for the diagnosis and staging of acute renal failure, but few studies have specifically assessed the role of oliguria as a marker of acute renal failure or outcomes in general intensive care unit (ICU) patients. Using a large multinational database, we therefore evaluated the occurrence of oliguria (defined as a urine output 16 years) patients in the ICON audit who had a urine output measurement on the day of admission were included. To investigate the association between oliguria and mortality, we used a multilevel analysis. Results: Of the 8292 patients included, 2050 (24.7%) were oliguric during the first 24 h of admission. Patients with oliguria on admission who had at least one additional 24-h urine output recorded during their ICU stay (n = 1349) were divided into three groups: transient - oliguria resolved within 48 h after the admission day (n = 390 [28.9%]), prolonged - oliguria resolved > 48 h after the admission day (n = 141 [10.5%]), and permanent - oliguria persisting for the whole ICU stay or again present at the end of the ICU stay (n = 818 [60.6%]). ICU and hospital mortality rates were higher in patients with oliguria than in those without, except for patients with transient oliguria who had significantly lower mortality rates than non-oliguric patients. In multilevel analysis, the need for RRT was associated with a significantly higher risk of death (OR = 1.51 [95% CI 1.19-1.91], p = 0.001), but the presence of oliguria on admission was not (OR = 1.14 [95% CI 0.97-1.34], p = 0.103). Conclusions: Oliguria is common in ICU patients and may have a relatively benign nature if only transient. The duration of oliguria and need for RRT are associated with worse outcome.publishersversionPeer reviewe

Aberrant expression of the S1P regulating enzymes, SPHK1 and SGPL1, contributes to a migratory phenotype in OSCC mediated through S1PR2.

Oral squamous cell carcinoma (OSCC) is a lethal disease with a 5-year mortality rate of around 50%. Molecular targeted therapies are not in routine use and novel therapeutic targets are required. Our previous microarray data indicated sphingosine 1-phosphate (S1P) metabolism and signalling was deregulated in OSCC. In this study, we have investigated the contribution of S1P signalling to the pathogenesis of OSCC. We show that the expression of the two major enzymes that regulate S1P levels were altered in OSCC: SPHK1 was significantly upregulated in OSCC tissues compared to normal oral mucosa and low levels of SGPL1 mRNA correlated with a worse overall survival. In in vitro studies, S1P enhanced the migration/invasion of OSCC cells and attenuated cisplatin-induced death. We also demonstrate that S1P receptor expression is deregulated in primary OSCCs and that S1PR2 is over-expressed in a subset of tumours, which in part mediates S1P-induced migration of OSCC cells. Lastly, we demonstrate that FTY720 induced significantly more apoptosis in OSCC cells compared to non-malignant cells and that FTY720 acted synergistically with cisplatin to induce cell death. Taken together, our data show that S1P signalling promotes tumour aggressiveness in OSCC and identify S1P signalling as a potential therapeutic target.This article is freely available via Open Access. Click on the 'Additional Link' above to access the full-text via the publisher's site.Published (Open Access