Level-Set Mass-Conservative Front-Tracking Technique for Multistep Simulations of In-Flight Ice Accretion

This paper presents a novel level-set-based approach to model evolving boundary problems for in-flight ice accretion. No partial differential equations are solved as in the standard level-set formulation, but simple geometrical quantities are employed to provide an implicit discretization of the updated boundary. This method avoids mesh entanglements and grid intersections typical of algebraic and mesh deforming techniques, making it suitable for generating a body-fitted discretization of arbitrarily complex geometries as in-flight ice shapes, including the collision of separate ice fronts. Moreover, this paper presents a local ice thickness correction, which accounts for the body's curvature, to conserve the prescribed iced mass locally. The verification includes ice accretion over an ellipse and a manufactured example to show the proposed strategy's advantages and robustness compared to standard algebraic methods. Finally, the method is applied to ice accretion problems. A temporal and grid convergence study is presented for automatic multistep in-flight simulations over a NACA0012 airfoil in rime, glaze, and mixed ice conditions

Clinical relevance of thymidylate syntetase expression in the signet ring cell histotype component of colorectal carcinoma

Thymidylate Synthase (TS) is the key enzyme for DNA synthesis pathways and is inhibited by 5-fluorouracil (5FU). The aim of this work was to study TS expression and the proliferation rate in the different histological types of colorectal carcinoma (CRC). 50 patients with CRC were included in this study and evaluated immunohistochemically using the monoclonal antibodies, TS106 and Ki67. 20 tumours were of the intestinal type, 15 cases were signet ring cell carcinoma (SRCCs) and 15 cases were "mixed-type", with at least two different histological components. Intestinal and mucinous histotypes were positive for TS and Ki67, while "signet ring cell" samples were negative or showed only weak and focal positivity for both the TS and Ki67 antibodies. Our results show that signet ring cells (that are also often present in intestinal and mucinous carcinomas), are in the post-mitotic phase of the cell cycle and show a low proliferation index and TS expression. As TS is the key enzyme for DNA synthesis pathways and is inhibited by 5-fluorouracil (5FU), we can hypothesise that TS expression levels in the different histotypes of CRC could affect the potential responsiveness of these tumours to fluoropyrimidine chemotherapy, with a low efficacy being expected in signet ring cell areas

Dor versus Toupet fundoplication after Laparoscopic Heller Myotomy: Systematic review and Bayesian meta-analysis of randomized controlled trials

Laparoscopic Heller Myotomy (LHM) with partial fundoplication has become the treatment of choice for esophageal achalasia. However, the choice of the partial fundoplication is debated. The aim of this study was to compare outcomes for Dor and Toupet fundoplication after LHM. A systematic search of randomized controlled trials comparing Dor and Toupet fundoplication was performed using PubMed, EMBASE and Web of Science. Three studies met the inclusion criteria. Overall, 174 patients were included in the analysis. The postoperative abnormal acid reflux [pooled Risk Ratio 0.98 (95% HPD 0.54-1.80)] and dysphagia [pooled Risk Ratio 1.03 (95% HPD 0.51-2.05)] were similar comparing Dor and Toupet fundoplication. The % total time pH  64 4 [estimated pooled mean difference -0.08 (95% HPD -1.04-0.90)] and DeMeester score [estimated pooled mean difference 0.51 (95% HPD -0.90-1.94)] were comparable. Additionally, the operative time [estimated pooled mean difference 0.02 (95% HPD -0.53-0.52)] and iatrogenic esophageal perforation [pooled Risk Ratio 1.05 (95% HPD 0.52-2.10)] were similar in the two groups. Dor and Toupet fundoplication after laparoscopic Heller myotomy seem comparable in term of postoperative abnormal acid exposure and dysphagia. The choice of the partial fundoplication should be left to surgeon experience and tailored on each patient

Role of CBP and SATB-1 in Aging, Dietary Restriction, and Insulin-Like Signaling

Increased transcriptional complex activity, or pharmacological mimics of increased complex activity, predict lifespan in mice and mediate the protective effects of dietary restriction during aging

GREENPEG – exploration for pegmatite minerals to feed the energy transition: first steps towards the Green Stone Age

This is the final version. Available on open access from the Geological Society via the DOI in this recordData availability: All data generated or analysed during this study are included in this published article.The GREENPEG project, which is funded by the European Commission Horizon 2020 ‘Climate action, environment, resource efficiency and raw materials’ programme, aims to develop multimethod exploration toolsets for the identification of European, buried, small-scale (0.01–5 million m3) pegmatite ore deposits of the Nb–Y–F (NYF) and Li–Cs–Ta (LCT) chemical types. The project is being coordinated by the Natural History Museum of the University of Oslo and involves four exploration services/mining operators, one geological survey, one non-profit helix association of administration, industry and academia, two consulting companies and five academic institutions from eight European countries. The target raw materials are Li, high-purity quartz for silica and metallic Si, ceramic feldspar, rare earth elements, Ta, Be and Cs, which are naturally concentrated in granitic pegmatites. Silicon and Li are two of the most sought-after green technology metals as they are essential for photovoltaics and Li-ion batteries for electric cars, respectively. GREENPEG will change the focus of exploration strategies from large-volume towards small-volume, high-quality ores and overcome the lack of exploration technologies for pegmatite ore deposits by developing toolsets tailored to these ore types. This contribution focuses on the methods applied in the GREENPEG project and as such provides a potential pathway towards the ‘Green Stone Age’ from the perspective of pegmatite-sourced minerals.European Union Horizon 2020FCT – Fundação para a Ciência e a TecnologiaScience Foundation IrelandEuropean Regional Development Fund (ERDF)Society of the Friendly Sons of St. Patrick for the Relief of Emigrants from Irelan

Incidence of traumatic brain injuries in head‐injured children with seizures

Objective: Incidence and short‐term outcomes of clinically important traumatic brain injury (ciTBI) in head‐injured children presenting to ED with post‐traumatic seizure (PTS) is not described in current literature. Methods: Planned secondary analysis of a prospective observational study undertaken in 10 Australasian Paediatric Research in Emergency Department International Collaborative (PREDICT) network EDs between 2011 and 2014 of head‐injured children 24 h (9 [2.7%] AR 2.5 [95% CI 0.8–4.2]) and neurosurgery (8 [2.4%] AR 2.0 [95% CI 0.4–3.7]), were higher than those without PTS. Children with PTS and GCS 15 or 14 had no neurosurgery, intubations or death, with two deaths in children with PTS and GCS ≤13. Conclusions: PTS was uncommon in head‐injured children presenting to the ED but associated with an increased risk of ciTBI in those with reduced GCS on arrival

Optimized EGFR blockade strategies in <i>EGFR</i> addicted gastroesophageal adenocarcinomas

Purpose: Gastric and gastroesophageal adenocarcinomas represent the third leading cause of cancer mortality worldwide. Despite significant therapeutic improvement, the outcome of patients with advanced gastroesophageal adenocarcinoma is poor. Randomized clinical trials failed to show a significant survival benefit in molecularly unselected patients with advanced gastroesophageal adenocarcinoma treated with anti-EGFR agents.Experimental Design: We performed analyses on four cohorts: IRCC (570 patients), Foundation Medicine, Inc. (9,397 patients), COG (214 patients), and the Fondazione IRCCS Istituto Nazionale dei Tumori (206 patients). Preclinical trials were conducted in patient-derived xenografts (PDX).Results: The analysis of different gastroesophageal adenocarcinoma patient cohorts suggests that EGFR amplification drives aggressive behavior and poor prognosis. We also observed that EGFR inhibitors are active in patients with EGFR copy-number gain and that coamplification of other receptor tyrosine kinases or KRAS is associated with worse response. Preclinical trials performed on EGFR-amplified gastroesophageal adenocarcinoma PDX models revealed that the combination of an EGFR mAb and an EGFR tyrosine kinase inhibitor (TKI) was more effective than each monotherapy and resulted in a deeper and durable response. In a highly EGFR-amplified nonresponding PDX, where resistance to EGFR drugs was due to inactivation of the TSC2 tumor suppressor, cotreatment with the mTOR inhibitor everolimus restored sensitivity to EGFR inhibition.Conclusions: This study underscores EGFR as a potential therapeutic target in gastric cancer and identifies the combination of an EGFR TKI and a mAb as an effective therapeutic approach. Finally, it recognizes mTOR pathway activation as a novel mechanism of primary resistance that can be overcome by the combination of EGFR and mTOR inhibitors