Manipulating Heat Shock Factor-1 in Xenopus Tadpoles: Neuronal Tissues Are Refractory to Exogenous Expression

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Flow distribution in the accelerator-production-of-tritium target

Achieving nearly uniform flow distributions in the accelerator production of tritium (APT) target structures is an important design objective. Manifold effects tend to cause a nonuniform distribution in flow systems of this type, although nearly even distribution can be achieved. A program of hydraulic experiments is underway to provide a database for validation of calculational methodologies that may be used for analyzing this problem and to evaluate the approach with the most promise for achieving a nearly even flow distribution. Data from the initial three tests are compared to predictions made using four calculational methods. The data show that optimizing the ratio of the supply-to-return-manifold areas can produce an almost even flow distribution in the APT ladder assemblies. The calculations compare well with the data for ratios of the supply-to-return-manifold areas spanning the optimum value. Thus, the results to date show that a nearly uniform flow distribution can be achieved by carefully sizing the supply and return manifolds and that the calculational methods available are adequate for predicting the distributions through a range of conditions

Broadening the Berlin definition of ARDS to patients receiving high-flow nasal oxygen:an observational study in patients with acute hypoxemic respiratory failure due to COVID-19

BACKGROUND: High-flow nasal oxygen (HFNO) is increasingly used in patients with acute hypoxemic respiratory failure. It is uncertain whether a broadened Berlin definition of acute respiratory distress syndrome (ARDS), in which ARDS can be diagnosed in patients who are not receiving ventilation, results in similar groups of patients receiving HFNO as in patients receiving ventilation.METHODS: We applied a broadened definition of ARDS in a multicenter, observational study in adult critically ill patients with acute hypoxemic respiratory failure due to coronavirus disease 2019 (COVID-19), wherein the requirement for a minimal level of 5 cm H2O PEEP with ventilation is replaced by a minimal level of airflow rate with HFNO, and compared baseline characteristics and outcomes between patients receiving HFNO and patients receiving ventilation. The primary endpoint was ICU mortality. We also compared outcomes in risk for death groups using the PaO2/FiO2 cutoffs as used successfully in the original definition of ARDS. Secondary endpoints were hospital mortality; mortality on days 28 and 90; need for ventilation within 7 days in patients that started with HFNO; the number of days free from HFNO or ventilation; and ICU and hospital length of stay.RESULTS: Of 728 included patients, 229 patients started with HFNO and 499 patients with ventilation. All patients fulfilled the broadened Berlin definition of ARDS. Patients receiving HFNO had lower disease severity scores and lower PaO2/FiO2 than patients receiving ventilation. ICU mortality was lower in receiving HFNO (22.7 vs 35.6%; p = 0.001). Using PaO2/FiO2 cutoffs for mild, moderate and severe arterial hypoxemia created groups with an ICU mortality of 16.7%, 22.0%, and 23.5% (p = 0.906) versus 19.1%, 37.9% and 41.4% (p = 0.002), in patients receiving HFNO versus patients receiving ventilation, respectively.CONCLUSIONS: Using a broadened definition of ARDS may facilitate an earlier diagnosis of ARDS in patients receiving HFNO; however, ARDS patients receiving HFNO and ARDS patients receiving ventilation have distinct baseline characteristics and mortality rates.TRIAL REGISTRATION: The study is registered at ClinicalTrials.gov (identifier NCT04719182).</p

A Measurement of the Tau Hadronic Branching Ratios

The exclusive and semi-exclusive branching ratios of the tau lepton hadronic decay modes (h- v_t, h- pi0 v_t, h- pi0 pi0 v_t, h- \geq 2pi0 v_t, h- \geq 3pi0 v_t, 2h- h+ v_t, 2h- h+ pi0 v_t, 2h- h+ \geq 2pi0 v_t, 3h- 2h+ v_t and 3h- 2h+ \geq 1pi0 v_t) were measured with data from the DELPHI detector at LEP.Comment: 53 pages, 18 figures, Accepted by Eur. Phys. J.

Magnetic dating of the Holocene monogenetic Tkarsheti volcano in the Kazbeki region (Great Caucasus)

The radiocarbon technique is widely used to date Late Pleistocene and Holocene lava flows. The significant difference with palaeomagnetic methods is that the 14C dating is performed on the organic matter carbonized by the rock formation or the paleosols found within or below the lava flow. On the contrary, the archaeomagnetic dating allows to date the moment when the lava is cooling down below the Curie temperatures. In the present study, we use the paleomagnetic dating to constrain the age of the Tkarsheti monogenetic volcano located within the Kazbeki Volcanic Province (Great Caucasus). A series of rock-magnetic experiments including the measurement of hysteresis curves, isothermal remanence, back-field and continuous thermomagnetic curves were applied. These experiments indicated that Pseudo-Single-Domain Ti-poor titanomagnetite is responsible for remanence. A characteristic remanent magnetization was obtained for all twenty analyzed samples yielding a stable single magnetization component observed upon both thermal and alternating field treatments. Comparison of the mean directions obtained (Inc = 48.6º, Dec = 6.4º, A95 = 4.0° and K = 67) with the SCHA.DIF.14k model yielded two main time intervals (4740–4650 or 4427– 4188 BC) as the best age estimate of the Lesser Tkarsheti lava flow. These results suggest an earlier age (between approximately 200 and 700 years) for this monogenetic lava flow than expected from the estimated age provided by a former 14C dating obtained in 1973 on woody remains. This first attempt to use the archaeomagnetic technique in the Caucasus indicates that the SCHA.DIF.14k geomagnetic model may be successfully used for dating purposes in the region.Projects BU0066U16 and BU235P18 (Junta de Castilla y Leon, Spain) and the European Regional Development Fund (ERDF). AG is grateful for financial support of CONACyT 252149 and UNAM-PAPIIT project 101717. MC-R and AC acknowledge the financial support given by the Junta de Castilla y León (project BU235P18) and the European Regional Development Fund (ERD)

Epidemiology, ventilation management and outcomes of COVID–19 ARDS patients versus patients with ARDS due to pneumonia in the Pre–COVID era

Background: Ventilation management may differ between COVID–19 ARDS (COVID–ARDS) patients and patients with pre–COVID ARDS (CLASSIC–ARDS); it is uncertain whether associations of ventilation management with outcomes for CLASSIC–ARDS also exist in COVID–ARDS. Methods: Individual patient data analysis of COVID–ARDS and CLASSIC–ARDS patients in six observational studies of ventilation, four in the COVID–19 pandemic and two pre–pandemic. Descriptive statistics were used to compare epidemiology and ventilation characteristics. The primary endpoint were key ventilation parameters; other outcomes included mortality and ventilator–free days and alive (VFD–60) at day 60. Results: This analysis included 6702 COVID–ARDS patients and 1415 CLASSIC–ARDS patients. COVID–ARDS patients received lower median VT (6.6 [6.0 to 7.4] vs 7.3 [6.4 to 8.5] ml/kg PBW; p < 0.001) and higher median PEEP (12.0 [10.0 to 14.0] vs 8.0 [6.0 to 10.0] cm H2O; p < 0.001), at lower median ΔP (13.0 [10.0 to 15.0] vs 16.0 [IQR 12.0 to 20.0] cm H2O; p < 0.001) and higher median Crs (33.5 [26.6 to 42.1] vs 28.1 [21.6 to 38.4] mL/cm H2O; p < 0.001). Following multivariable adjustment, higher ΔP had an independent association with higher 60–day mortality and less VFD–60 in both groups. Higher PEEP had an association with less VFD–60, but only in COVID–ARDS patients. Conclusions: Our findings show important differences in key ventilation parameters and associations thereof with outcomes between COVID–ARDS and CLASSIC–ARDS. Trial registration: Clinicaltrials.gov (identifier NCT05650957), December 14, 2022

Pressure during decision making of continuous sedation in end-of-life situations in Dutch general practice

<p>Abstract</p> <p>Background</p> <p>Little is known about pressure from patients or relatives on physician’s decision making of continuous palliative sedation. We aim to describe experienced pressure by general practitioners (GPs) in cases of continuous sedation after the introduction of the Dutch practice guideline, using a questionnaire survey.</p> <p>Methods</p> <p>A sample of 918 Dutch GPs were invited to fill out a questionnaire about their last patient under continuous sedation. Cases in which GPs experienced pressure from the patient, relatives or other persons were compared to those without pressure.</p> <p>Results</p> <p>399 of 918 invite GPs (43%) returned the questionnaire and 250 provided detailed information about their most recent case of continuous sedation. Forty-one GPs (16%) indicated to have experienced pressure from the patient, relatives or colleagues. In GPs younger than 50, guideline knowledge was not related to experienced pressure, whereas in older GPs, 15% with and 36% without guideline knowledge reported pressure. GPs experienced pressure more often when patients had psychological symptoms (compared to physical symptoms only) and when patients had a longer estimated life expectancy. A euthanasia request of the patient coincided with a higher prevalence of pressure for GPs without, but not for GPs with previous experience with euthanasia. GPs who experienced pressure had consulted a palliative consultation team more often than GPs who did not experience pressure.</p> <p>Conclusion</p> <p>One in six GPs felt pressure from patients or relatives to start sedation. This pressure was related to guideline knowledge, especially in older GPs, longer life expectancy and the presence of a euthanasia request, especially for GPs without previous experience of euthanasia.</p

Global ecological predictors of the soil priming effect

Identifying the global drivers of soil priming is essential to understanding C cycling in terrestrial ecosystems. We conducted a survey of soils across 86 globally-distributed locations, spanning a wide range of climates, biotic communities, and soil conditions, and evaluated the apparent soil priming effect using 13C-glucose labeling. Here we show that the magnitude of the positive apparent priming effect (increase in CO2 release through accelerated microbial biomass turnover) was negatively associated with SOC content and microbial respiration rates. Our statistical modeling suggests that apparent priming effects tend to be negative in more mesic sites associated with higher SOC contents. In contrast, a single-input of labile C causes positive apparent priming effects in more arid locations with low SOC contents. Our results provide solid evidence that SOC content plays a critical role in regulating apparent priming effects, with important implications for the improvement of C cycling models under global change scenarios

Differential Affinity and Catalytic Activity of CheZ in E. coli Chemotaxis

Push–pull networks, in which two antagonistic enzymes control the activity of a messenger protein, are ubiquitous in signal transduction pathways. A classical example is the chemotaxis system of the bacterium Escherichia coli, in which the kinase CheA and the phosphatase CheZ regulate the phosphorylation level of the messenger protein CheY. Recent experiments suggest that both the kinase and the phosphatase are localized at the receptor cluster, and Vaknin and Berg recently demonstrated that the spatial distribution of the phosphatase can markedly affect the dose–response curves. We argue, using mathematical modeling, that the canonical model of the chemotaxis network cannot explain the experimental observations of Vaknin and Berg. We present a new model, in which a small fraction of the phosphatase is localized at the receptor cluster, while the remainder freely diffuses in the cytoplasm; moreover, the phosphatase at the cluster has a higher binding affinity for the messenger protein and a higher catalytic activity than the phosphatase in the cytoplasm. This model is consistent with a large body of experimental data and can explain many of the experimental observations of Vaknin and Berg. More generally, the combination of differential affinity and catalytic activity provides a generic mechanism for amplifying signals that could be exploited in other two-component signaling systems. If this model is correct, then a number of recent modeling studies, which aim to explain the chemotactic gain in terms of the activity of the receptor cluster, should be reconsidered