Diffusion coefficient of an inclusion in a liquid membrane supported by a solvent of arbitrary thickness

The diffusion coefficient of a circular shaped inclusion in a liquid membrane is investigated by taking into account the interaction between membranes and bulk solvents of arbitrary thickness. As illustrative examples, the diffusion coefficients of two types of inclusions - a circular domain composed of fluid with the same viscosity as the host membrane and that of a polymer chain embedded in the membrane are studied.The diffusion coefficients are expressed in terms of the hydrodynamic screening lengths which vary according to the solvent thickness. When the membrane fluid is dragged by the solvent of finite thickness, via stick boundary conditions, multiple hydrodynamic screening lengths together with the weight factors to the diffusion coefficients are obtained from the dispersion relation. The condition for which the diffusion coefficients can be approximated by the expression including only a single hydrodynamic screening length are also shown.Comment: 6 figures; Physical Review E 201

Identification of jet lubrication oil as a major component of aircraft exhaust nanoparticles

Jet engine aircraft are ubiquitous and significant sources of atmospheric nanoparticles. Using size-resolved particulate samples collected near a runway of the Narita International Airport, Japan, we clearly demonstrate that organic compounds in the ambient nanoparticles (diameters: &lt;&thinsp;30&thinsp;nm) were dominated by nearly intact forms of jet engine lubrication oil. This finding provides direct evidence for the importance of unburned lubrication oil as a source of aircraft exhaust nanoparticles and also has an implication for their environmental impacts near airports and in the upper troposphere.</p

Differences in code status practice patterns among emergency clinicians working in Japan and the United States

ObjectiveThis study aimed to examine self-reported code-status practice patterns among emergency clinicians from Japan and the U.S.MethodsA cross-sectional questionnaire was distributed to emergency clinicians from one academic medical center and four general hospitals in Japan and two academic medical centers in the U.S. The questionnaire was based on a hypothetical case involving a critically ill patient with end-stage lung cancer. The questionnaire items assessed whether respondent clinicians would be likely to pose questions to patients about their preferences for medical procedures and their values and goals.ResultsA total of 176 emergency clinicians from Japan and the U.S participated. After adjusting for participants' backgrounds, emergency clinicians in Japan were less likely to pose procedure-based questions than those in the U.S. Conversely, emergency clinicians in Japan showed a statistically higher likelihood of asking 10 out of 12 value-based questions.ConclusionSignificant differences were found between emergency clinicians in Japan and the U.S. in their reported practices on posing procedure-based and patient value-based questions.Practice implicationsSerious illness communication training based in the U.S. must be adapted to the Japanese context, considering the cultural characteristics and practical responsibilities of Japanese emergency clinicians

TEAD and YAP regulate the enhancer network of human embryonic pancreatic progenitors.

The genomic regulatory programmes that underlie human organogenesis are poorly understood. Pancreas development, in particular, has pivotal implications for pancreatic regeneration, cancer and diabetes. We have now characterized the regulatory landscape of embryonic multipotent progenitor cells that give rise to all pancreatic epithelial lineages. Using human embryonic pancreas and embryonic-stem-cell-derived progenitors we identify stage-specific transcripts and associated enhancers, many of which are co-occupied by transcription factors that are essential for pancreas development. We further show that TEAD1, a Hippo signalling effector, is an integral component of the transcription factor combinatorial code of pancreatic progenitor enhancers. TEAD and its coactivator YAP activate key pancreatic signalling mediators and transcription factors, and regulate the expansion of pancreatic progenitors. This work therefore uncovers a central role for TEAD and YAP as signal-responsive regulators of multipotent pancreatic progenitors, and provides a resource for the study of embryonic development of the human pancreas

p73 Regulates Neurodegeneration and Phospho-Tau Accumulation during Aging and Alzheimer's Disease

SummaryThe genetic mechanisms that regulate neurodegeneration are only poorly understood. We show that the loss of one allele of the p53 family member, p73, makes mice susceptible to neurodegeneration as a consequence of aging or Alzheimer's disease (AD). Behavioral analyses demonstrated that old, but not young, p73+/− mice displayed reduced motor and cognitive function, CNS atrophy, and neuronal degeneration. Unexpectedly, brains of aged p73+/− mice demonstrated dramatic accumulations of phospho-tau (P-tau)-positive filaments. Moreover, when crossed to a mouse model of AD expressing a mutant amyloid precursor protein, brains of these mice showed neuronal degeneration and early and robust formation of tangle-like structures containing P-tau. The increase in P-tau was likely mediated by JNK; in p73+/− neurons, the activity of the p73 target JNK was enhanced, and JNK regulated P-tau levels. Thus, p73 is essential for preventing neurodegeneration, and haploinsufficiency for p73 may be a susceptibility factor for AD and other neurodegenerative disorders

Net ultrafiltration prescription and practice among critically ill patients receiving renal replacement therapy : a multinational survey of critical care practitioners

Objectives: To assess the attitudes of practitioners with respect to net ultrafiltration prescription and practice among critically ill patients with acute kidney injury treated with renal replacement therapy. Design: Multinational internet-assisted survey. Setting: Critical care practitioners involved with 14 societies in 80 countries. Subjects: Intensivists, nephrologists, advanced practice providers, ICU and dialysis nurses. Intervention: A cross-sectional survey. Measurement and Main Results: Of 2,567 practitioners who initiated the survey, 1,569 (61.1%) completed the survey. Most practitioners were intensivists (72.7%) with a median duration of 13.2 years of practice (interquartile range, 7.2-22.0 yr). Two third of practitioners (71.0%; regional range, 55.0-95.5%) reported using continuous renal replacement therapy with a net ultrafiltration rate prescription of median 80.0 mL/hr (interquartile range, 49.0-111.0 mL/hr) for hemodynamically unstable and a maximal rate of 299.0 mL/hr (interquartile range, 200.0-365.0 mL/hr) for hemodynamically stable patients, with regional variation. Only a third of practitioners (31.5%; range, 13.7-47.8%) assessed hourly net fluid balance during continuous renal replacement therapy. Hemodynamic instability was reported in 20% (range, 20-38%) of patients and practitioners decreased the rate of fluid removal (70.3%); started or increased the dose of a vasopressor (51.5%); completely stopped fluid removal (35.8%); and administered a fluid bolus (31.6%), with significant regional variation. Compared with physicians, nurses were most likely to report patient intolerance to net ultrafiltration (73.4% vs 81.3%; p = 0.002), frequent interruptions (40.4% vs 54.5%; p < 0.001), and unavailability of trained staff (11.9% vs 15.6%; p = 0.04), whereas physicians reported unavailability of dialysis machines (14.3% vs 6.1%; p < 0.001) and costs associated with treatment as barriers (12.1% vs 3.0%; p < 0.001) with significant regional variation. Conclusions: Our study provides new knowledge about the presence and extent of international practice variation in net ultrafiltration. We also identified barriers and specific targets for quality improvement initiatives. Our data reflect the need for evidence-based practice guidelines for net ultrafiltration

Efficacy and Safety of Trifluridine/Tipiracil Treatment in Patients With Metastatic Gastric Cancer Who Had Undergone Gastrectomy: Subgroup Analyses of a Randomized Clinical Trial

Importance Trifluridine/tipiracil (FTD/TPI) treatment has shown clinical benefit in patients with pretreated metastatic gastric cancer or gastroesophageal junction cancer (mGC/GEJC). Patients who have undergone gastrectomy constitute a significant proportion of patients with mGC/GEJC. Objective To assess the efficacy and safety of FTD/TPI among patients with previously treated mGC/GEJC who had or had not undergone gastrectomy. Design, Setting, and Participants This preplanned subgroup analysis of TAGS (TAS-102 Gastric Study), a phase 3, randomized, placebo-controlled, clinical trial included patients with mGC/GEJC who had received at least 2 previous chemotherapy regimens, and was conducted at 110 academic hospitals in 17 countries in Europe, Asia, and North America, with enrollment between February 24, 2016, and January 5, 2018; the data cutoff was March 31, 2018. Interventions Patients were randomized 2:1 to receive oral FTD/TPI 35 mg/m2 twice daily or placebo twice daily with best supportive care on days 1 through 5 and days 8 through 12 of each 28-day treatment cycle. Main Outcomes and Measures The primary end point was overall survival. This subgroup analysis was conducted to examine potential trends and was not powered for statistical significance. Efficacy and safety end points were evaluated in the subgroups. Results Of 507 randomized patients (369 [72.8%] male; mean [SD] age, 62.5 [10.5] years), 221 (43.6%) had undergone gastrectomy (147 randomized to FTD/TPI and 74 to placebo) and 286 (56.4%) had not undergone gastrectomy (190 randomized to FTD/TPI and 96 to placebo). In the gastrectomy subgroup, the overall survival hazard ratio (HR) in the FTD/TPI group vs placebo group was 0.57 (95% CI, 0.41-0.79), and the progression-free survival HR was 0.48 (95% CI, 0.35-0.65). In the no gastrectomy subgroup, the overall survival HR in the FTD/TPI group vs placebo group was 0.80 (95% CI, 0.60-1.06), and the progression-free survival HR was 0.65 (95% CI, 0.49-0.85). Among FTD/TPI-treated patients, grade 3 or higher adverse events of any cause occurred in 122 of 145 patients (84.1%) in the gastrectomy subgroup and 145 of 190 (76.3%) in the no gastrectomy subgroup: 64 (44.1%) in the gastrectomy subgroup and 50 (26.3%) in the no gastrectomy subgroup had grade 3 or higher neutropenia, 31 (21.4%) in the gastrectomy subgroup and 33 (17.4%) in the no gastrectomy subgroup had grade 3 or higher anemia, and 21 (14.5%) in the gastrectomy subgroup and 10 (5.3%) in the no gastrectomy subgroup hD grade 3 or higher leukopenia. In the gastrectomy subgroup, 94 (64.8%) had dosing modifications because of adverse events vs 101 (53.2%) in the no gastrectomy subgroup; 15 (10.3%) in the gastrectomy group and 28 (14.7%) in the no gastrectomy group discontinued treatment because of adverse events. Treatment exposure was similar between groups. Conclusions and Relevance The FTD/TPI treatment was tolerable and provided efficacy benefits among patients with pretreated mGC/GEJC regardless of previous gastrectomy

Renal failure and leukocytosis are predictors of a complicated course of clostridium difficile infection if measured on day of diagnosis

Nonsevere Clostridium difficile infection (CDI) and severe CDI, which carries a higher risk than nonsevere CDI for treatment failure and CDI recurrence, are difficult to distinguish at the time of diagnosis. To investigate the prognostic value of 3 markers of severe CDI suggested by recent guidelines (fever, leukocytosis, and renal failure), we used the database of 2 randomized controlled trials, which contained information for 1105 patients with CDI. Leukocytosis (risk ratio [RR], 2.29; 95% confidence interval [CI], 1.63–3.21) and renal failure (RR, 2.52; 95% CI, 1.82–3.50) were associated with treatment failure. Fever, although associated with treatment failure (RR, 2.45; 95% CI, 1.07–5.61), was rare. Renal failure was the only significant predictor of recurrence (RR, 1.45; 95% CI, 1.05–2.02). Different timing of measurements of leukocyte count and serum creatinine level around the CDI diagnosis led to a different severity classification in many cases. In conclusion, both leukocytosis and renal failure are useful predictors, although timing of measurement is important