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This paper presents the investigation of high-frequency thermoacoustic oscillations and associated flame dynamics in an experimental gas turbine reheat combustor at atmospheric pressure. Examination of dynamic pressure measurements reveals bursts of high-frequency periodic oscillations which appear randomly amidst stochastic fluctuations in the reheat combustor. Analysis of the flame dynamics during these bursts of periodic behaviour reveals that increased heat release in the reactive shear layers of the reheat flame is associated with greater thermoacoustic driving potential. This redistribution of heat release is likely due to the stochastic nature of auto-ignition kernel formation. To determine the underlying flame-acoustic coupling mechanism behind the driving potential, phase-resolved flame dynamics over the acoustic cycle are investigated which reveal the presence of an oscillatory heat release pattern associated with the first transverse eigenmode. An in-phase interaction between the acoustic field and these heat release oscillations in the shear layer regions indicates that this phenomenon likely constitutes a thermoacoustic driving mechanism. This is an important step towards the development of models for high-frequency thermoacoustic driving mechanisms relevant to reheat combustion systems, which will allow accurate prediction and mitigation of thermoacoustic instabilities in future designs.

The environmental conditions that marine populations experience are being altered because of climate change. In particular, changes in temperature and increased variability can cause shifts in spatial distribution, leading to changes in local physiological rates and recruitment success. Yet, management of fish stocks rarely accounts for variable spatial dynamics or changes in movement rates when estimating management quantities such as stock abundance or maximum sustainable yield. To address this concern, a management strategy evaluation (MSE) was developed to evaluate the robustness of the international management system for Pacific hake, an economically important migratory stock, by incorporating spatio-temporal population dynamics. Alternative hypotheses about climate-induced changes in age-specific movement rates, in combination with three different harvest control rules (HCR), were evaluated using a set of simulations that coupled single-area estimation models with alternative operating models representing spatial stock complexity. Movement rates intensified by climate change caused a median decline in catches, increased annual catch variability, and lower average spawning biomass. Impacts varied by area and HCR, underscoring the importance of spatial management. Incorporating spatial dynamics and climate change effects into management procedures for fish stocks with spatial complexity is warranted to mitigate risk and uncertainty for exploited marine populations.

Little is known about metabolic and nutrition characteristics of patients with coronavirus disease 2019 (COVID-19) and persistent critical illness. We aimed to compare those characteristics in patients with PCI and COVID-19 and patients without COVID-19 infection (non-CO)-primarily, their energy balance. This is a prospective observational study including two consecutive cohorts, defined as needing intubation for >10 days. We collected demographic data, severity scores, nutrition variables, length of stay, and mortality. Altogether, 104 patients (52 per group) were included (59 ± 14 years old [mean ± SD], 75% men) between July 2019 and May 2020. SAPSII, Nutrition Risk Screening (NRS) score, proportion of obese patients, duration of intubation (18.2 ± 11.7 days), and mortality rates were similar. Patients with COVID-19 (vs non-CO) had lower SOFA scores (P = 0.013) and more frequently needed prone position (P < 0.0001) and neuromuscular blockade (P < 0.0001): lengths of ICU (P = 0.03) and hospital stays were shorter (P < 0.0001). Prescribed energy targets were below those of the ICU protocol. The energy balance of patients with COVID-19 was significantly more negative after day 10. Enteral nutrition (EN) started earlier (P < 0.0001). During the first 10 days, COVID-19 patients received more lipid (propofol sedation) and less protein. Higher admission C-reactive protein (P = 0.002) decreased faster (P < 0.001). Whereas intestinal function was characterized by constipation in both groups during the first 10 days, diarrhea was less common in patients with COVID-19 thereafter. Compared with non-CO patients, COVID-19 patients were not more obese, had lower SOFA scores, and were fed more rapidly with EN, because of a more normal gastrointestinal function possibly due to fewer non-respiratory organ failures: their energy balances were more negative after the first 10 days. Propofol sedation reduced protein delivery.

Introduction: Coagulation disorders occur during the first 48 h after major burn injury, affecting mainly PT/INR and aPTT. Some authors consider them burn specific. The aim was to assess the magnitude of coagulation disorders during the first 10 days after severe burn injury and its eventual association with fluid intakes. Methods: Retrospective study of prospectively collected data including patients with burns ≥ 20%BSA (body surface area) who stayed ≥ 24 h at the burn-intensive care unit (ICU). Predetermined data for the analysis of fluid and blood products administration and laboratory values were extracted from the computerized information system. Descriptive statistics, data as median. Results: 167 patients included. The volumes of fluid resuscitation decreased over the first 10 days (median 6815 ml on day 1 decreasing to 4190 ml by day 10, p

The indications and contraindications of parenteral nutrition (PN) are discussed in view of recent clinical findings. For decades, PN has been restricted to patients unable to tolerate enteral nutrition (EN) intake owing to the perceived risk of severe side-effects. The evolution of the PN substrate composition and delivery of nutrition via all-in-one bags has dramatically improved the application prospects of PN. Recent studies show similar complication rates of nutrition therapy administered through enteral and intravenous routes. Therefore, indications of PN have, based on evidence, extended beyond complete gastrointestinal (GI) failure to include conditions such as insufficient EN generating persistent negative energy balance and insufficient protein intakes, malabsorption, or specific needs that are impossible to cover with EN feeds.

Triarylboranes have been known for more than 100 years and have found potential applications in various fields such as anion sensors and optoelectronics, for example in organic light emitting diodes (OLEDs), field effect transistors (OFETs), and organic photovoltaic devices. However, biological applications, such as bioimaging agents and biomolecule sensors have evolved much more recently. This review summarises progress in this relatively young field and highlights the potential of triarylboranes in biological applications.

Inhibitors targeting the epidermal growth factor receptor (EGFR) are an effective therapy for patients with non-small cell lung cancer harboring drug-sensitive activating mutations in the EGFR kinase domain. Drug resistance due to treatment-acquired mutations has motivated the development of successive generations of inhibitors that bind in the ATP site. The third-generation agent osimertinib is now a first-line treatment for this disease. Recently, allosteric inhibitors have been developed to overcome drug-resistant mutations that confer a resistance to osimertinib. Here, we present the structure-guided design and synthesis of a mutant-selective lead compound, which consists of a pyridinyl imidazole-fused benzylisoindolinedione scaffold that simultaneously occupies the orthosteric and allosteric sites. The compound potently inhibits enzymatic activity in L858R/T790M/C797S mutant EGFR (4.9 nM), with a significantly lower activity for wild-type EGFR (47 nM). Additionally, this compound achieves modest cetuximab-independent and mutant-selective cellular efficacies on the L858R (1.2 μM) and L858R/T790M (4.4 μM) variants.

The opioid crisis is a national health emergency with immense morbidity, mortality, and socioeconomic cost. Emergency department (ED) pain management is tightly linked to the issue of opioid use disorder (OUD), because opioid exposure is necessary for development of OUD. Emergency nurses are on the frontlines of this complex problem, yet little, if any, attention has been paid to the role they play in the prevention and management of either pain or OUD in this unique and important setting. A framework that conceptualizes and optimizes emergency nurses as change agents in the opioid epidemic is urgently needed. While ED pain management and OUD prevention is dependent on the entire care team, this innovative study qualitatively characterizes emergency nurse perceptions of pain management, OUD prevention, and their potential role in each. Content analysis produced 14 categories that were clustered into two themes, “nurses influence ED pain management” and “adjustments in ED pain management”, and an overarching message that “pain management depends on the care team.” By generating a more comprehensive and nuanced understanding of the role played by emergency nurses, our findings provide essential insights into potential interventions and frameworks.

BackgroundGalectin-9 is a member of the family of lectin proteins and crucially regulates human immune responses, particularly because of its ability to suppress the anticancer activities of T lymphocytes and natural killer cells. Recent evidence demonstrated that galectin-9 is highly expressed in a wide range of human malignancies including the most aggressive tumors, such as high-grade glioblastomas and pancreatic ductal adenocarcinomas, as well as common malignancies such as breast, lung and colorectal cancers. However, solid tumor cells at rest are known to secrete either very low amounts of galectin-9 or, in most of the cases, do not secrete it at all. Our aims were to elucidate whether T cells can induce galectin-9 secretion in human cancer cells derived from solid malignant tumors and whether this soluble form displays higher systemic immunosuppressive activity compared with the cell surface-based protein.MethodsA wide range of human cancer cell lines derived from solid tumours, keratinocytes and primary embryonic cells were employed, together with helper and cytotoxic T cell lines and human as well as mouse primary T cells. Western blot analysis, ELISA, quantitative reverse transcriptase-PCR, on-cell Western and other measurement techniques were used to conduct the study. Results were validated using in vivo mouse model.ResultsWe discovered that T lymphocytes induce galectin-9 secretion in various types of human cancer cells derived from solid malignant tumors. This was demonstrated to occurviatwo differential mechanisms: first by translocation of galectin-9 onto the cell surface followed by its proteolytic shedding and second due to autophagy followed by lysosomal secretion. For both mechanisms a protein carrier/trafficker was required, since galectin-9 lacks a secretion sequence. Secreted galectin-9 pre-opsonised T cells and, following interaction with other immune checkpoint proteins, their activity was completely attenuated. As an example, we studied the cooperation of galectin-9 and V-domain Ig-containing suppressor of T cell activation (VISTA) proteins in human cancer cells.ConclusionOur results underline a crucial role of galectin-9 in anticancer immune evasion. As such, galectin-9 and regulatory pathways controlling its production should be considered as key targets for immunotherapy in a large number of cancers.

To examine glycemic variability within one month and one year following surgery and throughout adjuvant chemotherapy among patients with stage II-III colon cancer, with and without type 2 diabetes (T2D).58 patients with stage II-III colon cancer treated with surgery and chemotherapy.A retrospective analysis of electronic health record data over one year showed glycemic variability, measured as standard deviation and coefficient of variation. Chi-square, Fisher's exact, and Mann-Whitney U tests and Spearman's correlation coefficient were calculated.Patients with T2D had higher glycemic variability throughout chemotherapy and within one year following surgery. A significant increase in glycemic variability throughout chemotherapy was observed in patients without T2D. Significant associations between glycemic variability and demographic and clinical characteristics differed by T2D status, standard deviation, and coefficient of variation.Nurses need to assess serial blood glucose levels in patients with and without T2D. Teaching patients how to maintain glycemic control during treatment is a priority. Research should include predictive models to identify risk factors for higher glycemic variability and cancer-related symptoms and outcomes.

Larger processing equipment to produce minced meat could affect its structure due to intensive processing and a high energy intake in the meat mass. To assess if this would result in alterations in the minced meat quality, finely chopped meat (FCM) was added in different concentrations (15, 30, 45, 60, 75, 90, and 100%) to minced meat and quality parameters were analyzed. FCM was used to simulate different intensity of an unintended destruction of meat cells due to various processes. The amount of non-intact cells (ANIC) was determined histologically and furthermore, soluble protein content, water holding capacity, mechanical and sensory texture, and scanning electron and confocal laser scanning microscopy was applied to analyze the meat structure and quality. ANIC indicated that even adding 15% FCM was statistically (p < 0.05) distinguishable from 100% minced meat and 30% FCM had already 50 Vol.-% ANIC. In contrast, the addition of 15% or 30% FCM did not result in significant differences in drip loss of raw and cooked meat as well as mechanical and sensory texture analysis. This study showed that intensive processing might be detectable via ANIC, but that the minced meat quality was not affected.

Data supporting the clinical utility of multi-target stool DNA (mt-sDNA) at the guideline-recommended 3-year interval have not been reported. Between April 2015 and July 2016, candidates for colorectal cancer screening whose providers prescribed the mt-sDNA test were enrolled. Participants with a positive baseline test were recommended for colonoscopy and completed the study. Those with a negative baseline test were followed annually for 3 years. In year 3, the mt-sDNA test was repeated and colonoscopy was recommended independent of results. Data were analyzed using the Predictive Summary Index (PSI), a measure of the gain in certainty for dichotomous diagnostic tests (where a positive value indicates a net gain), and by comparing observed versus expected colorectal cancers and advanced precancerous lesions. Of 2,404 enrolled subjects, 2,044 (85%) had a valid baseline mt-sDNA result [284 (13.9%) positive and 1,760 (86.1%) negative]. Following participant attrition, the year 3 intention to screen cohort included 591 of 1,760 (33.6%) subjects with valid mt-sDNA and colonoscopy results, with no colorectal cancers and 63 advanced precancerous lesions [22 (34.9%) detected by mt-sDNA] and respective PSI values of 0% (P = 1) and 9.3% (P = 0.01). The observed 3-year colorectal cancer yield was lower than expected (one-sided P = 0.09), while that for advanced precancerous lesions was higher than expected (two-sided P = 0.009). Repeat mt-sDNA screening at a 3-year interval resulted in a statistically significant gain in detection of advanced precancerous lesions. Due to absence of year 3 colorectal cancers, the PSI estimate for colorectal cancer was underpowered and could not be reliably quantified. Larger studies are required to assess the colorectal cancer study findings. Prevention Relevance: Understanding the 3-year yield of mt-sDNA for colorectal cancer and advanced precancerous polyps is required to ensure the clinical appropriateness of the 3-year interval and to optimize mt-sDNA's screening effectiveness.

Background QRS complex prolongation is an established prognostic marker in patients with heart failure, (HF) and identifies patients for whom standard treatment includes cardiac resynchronization therapy (CRT). In contrast, the role of QRS width progression over time on clinical status and whether it can be predicted has been incompletely explored. Purpose To provide pilot data that could help to identify features associated with QRS progression and deteriorating clinical status. Methods The present retrospective analysis relates to 100 consecutive attendees to our HF clinic between April and August 2021. Each patient with a least one past visit including an ECG was included and a maximum of 4 past visits were assessed per patient. Results In total 240 datasets were generated from at least two consecutive visits and included clinical status, electrocardiographic (ECG), laboratory and echocardiographic data. Mean age and left ventricular ejection fraction were 58±13 years and 36±10%. The mean time between visits was 227 days. Datasets were stratified into tertiles based on change in QRS duration (mm/month). These were labelled as “QRS width regression” (>−0.34 ms/month), “QRS stability” (−0.33 to 0.49 ms/month and “QRS width progression” (>0.50 ms/month). The incidence of the combined endpoint of worsening symptomatic HF (deterioration in NYHA class by at least one grade) and HF hospitalisation was significantly higher in the QRS progression group compared with the stable group (Log Rank test: progression v stability p=0.013). In addition, patients with QRS progression had a higher baseline plasma NT-pro-BNP levels (p=0.008) and higher baseline heart rate (p=0.007). To explore whether patients at higher risk of QRS progression could be identified at baseline, we built a prediction model based upon baseline NTproBNP levels and baseline heart rate. We determined that an NT-pro-BNP >837 pg/ml and a heart rate >83/bpm were reliable thresholds for greater risk of QRS progression (Figure 1A & B). Both of these variables were independent of guideline-directed medical HF therapy (including beta-antagonist use and dose). An interaction analysis revealed that combining these two risk factors was associated with a 14-fold increased risk of QRS progression compared with neither or either alone, suggesting synergism between these variables (HR: 14.2 [95% 6.9–53.6]; p Conclusion In the current pilot study, we demonstrate that QRS progression is associated with future risk of clinical deterioration of HF. In addition, we show that higher baseline NTproBNP plasma levels combined with higher baseline heart rate indicate a group at markedly increased risk of progression of QRS width, independently of HF therapy. These parameters might therefore identify people potentially benefitting from intensified follow up, optimisation of GDMT and could also help coordinate the application of a more personalised approach to device therapy Funding Acknowledgement Type of funding sources: None.

Introduction Cytokines might play a key role in the pathophysiology of major depressive disorder (MDD). The speed of onset of depressive episodes has been discussed as an important clinical parameter in MDD. The aim of this study was to investigate a potential influence of the speed of onset of the depressive episode on cytokine serum levels. Method Serum level of the cytokines interleukin (IL)-2, IL-4, IL-6, IL-8, IL-10, tumor necrosis factor alpha (TNF-α), interferon-gamma (IFN-γ) granulocyte and monocyte colony stimulating factor (GM-CSF) were measured in a total of 92 patients with MDD that did not respond to at least one previous antidepressant treatment. Patients were retrospectively divided in two groups: Faster (≤4 weeks) and slower (>4 weeks) onset of the depressive episode defined as the time passing from the first depressive symptoms to a full-blown depressive episode by using information from a clinical interview. Results We found significantly lower serum levels of IL-2, IL-4, IL-6, IL-10, TNF-α and IFN-γ in patients with a faster onset compared to patients with a slower onset of the depressive episodes. Furthermore, lower cytokine serum levels of IL-2, IL-8, IL-10 and IFN-γ were found in patients with a shorter duration (less than 6 months) compared to a longer duration (6–24 months) of the current depressive episode. This effect on cytokines was independent from the effect of the speed of onset of the depressive episode. Conclusions Patients with faster onset of the depressive episode might represent a biological subtype of MDD with lower serum levels of IL-2, IL-4, IL-6, IL-10, TNF-α and IFN-γ.

The synthesis, photophysical, and electrochemical properties of selectively mono-, bis- and tris-dimethylamino- and trimethylammonium-substituted bis-triarylborane bithiophene chromophores are presented along with the water solubility and singlet oxygen sensitizing efficiency of the cationic compounds Cat1+ , Cat2+ , Cat(i)2+ , and Cat3+ . Comparison with the mono-triarylboranes reveals the large influence of the bridging unit on the properties of the bis-triarylboranes, especially those of the cationic compounds. Based on these preliminary investigations, the interactions of Cat1+ , Cat2+ , Cat(i)2+ , and Cat3+ with DNA, RNA, and DNApore were investigated in buffered solutions. The same compounds were investigated for their ability to enter and localize within organelles of human lung carcinoma (A549) and normal lung (WI38) cells showing that not only the number of charges but also their distribution over the chromophore influences interactions and staining properties.

Silver diamine fluoride (SDF) is a dental biomaterial used to arrest dental caries. To better understand SDF’s mechanism of action, we examined the localization of silver within the tissues of SDF-treated teeth. Carious primary teeth fixed within 2 min of SDF application (SDF-minutes, n = 3), at 3 wk after SDF application in vivo (SDF-weeks, n = 4), and at 2 y after multiple SDF applications in vivo (SDF-multiple, n = 1) were investigated in this study. Carious primary teeth without SDF application (no-SDF, n = 3) served as controls. Mineral density and structural analyses were performed via micro–X-ray computed tomography and scanning electron microscopy. Elemental analyses were performed through X-ray fluorescence microprobe and energy-dispersive X-ray spectroscopic techniques. SDF-treated teeth revealed higher X-ray–attenuated surface and subsurface regions within carious lesions, and similar regions were not present in no-SDF teeth. Regions of higher mineral density correlated with regions of silver abundance in SDF-treated teeth. The SDF penetration depth was approximated to 0.5 ± 0.02 mm and 0.6 ± 0.05 mm (mean ± SD) for SDF-minutes and SDF-weeks specimens, respectively. A higher percentage of dentin tubular occlusion by silver or calcium phosphate particles was observed in primary teeth treated with SDF-weeks as compared with SDF-minutes. Elemental analysis also revealed zinc abundance in carious lesions and around the pulp chamber. SDF-weeks teeth had significantly increased tertiary dentin than SDF-minutes and no-SDF teeth. These results suggest that SDF treatment on primary teeth affected by caries promotes pathologic biomineralization by altering their physicochemical properties, occluding dentin tubules, and increasing tertiary dentin volume. These seemingly serendipitous effects collectively contribute to the cariostatic activity of SDF.

Exercise interventions may influence adverse effects experienced during hospitalization for hematopoietic stem cell transplantation (HSCT). Adherence to exercise interventions is challenging. This review aimed to synthesize the literature to identify exercise interventions implemented during hospitalization for HSCT, including intervention characteristics, adherence, barriers and facilitators, and behavior change techniques using the behavior change technique taxonomy. A review of PubMed, CINAHL, PsycINFO, and Embase was completed. The sample included 19 studies. Exercise interventions demonstrated heterogeneity in prescription components, definitions, measures, and reporting of adherence. Barriers and facilitators of adherence to exercise were reported infrequently. Behavior change techniques most frequently used in studies reporting adherence rates of ≥75% included instruction on how to perform the behavior, graded tasks, and adding objects to the environment. The heterogeneity in definitions and measures of adherence limit forming conclusions to identify barriers and facilitators and determine which behavior change techniques increase adherence to exercise during HSCT.