Tumor-associated macrophages (TAMs) frequently help to sustain tumor growth and mediate immune suppression in the tumor microenvironment (TME). Here, we identified a subset of iron-loaded, ...pro-inflammatory TAMs localized in hemorrhagic areas of the TME. The occurrence of iron-loaded TAMs (iTAMs) correlated with reduced tumor size in patients with non-small cell lung cancer.
experiments established that TAMs exposed to hemolytic red blood cells (RBCs) were converted into pro-inflammatory macrophages capable of directly killing tumor cells. This anti-tumor effect could also be elicited
iron oxide nanoparticles. When tested
, tumors injected with such iron oxide nanoparticles led to significantly smaller tumor sizes compared to controls. These results identify hemolytic RBCs and iron as novel players in the TME that repolarize TAMs to exert direct anti-tumor effector function. Thus, the delivery of iron to TAMs emerges as a simple adjuvant therapeutic strategy to promote anti-cancer immune responses.
Many work-related stresses are experienced by oncologists. Ukraine is currently undergoing numerous crises, including the SARS-CoV-2 pandemic and military conflicts, which represent stressful ...situations. The aim of this study was to explore the personal resources that Ukrainian oncologists use to cope with work demands in a situation featuring manifold crises. This study identified the ways in which people deal with stressful situations and the roles that they play in shaping the challenging situations that they encounter (work-related behavior) as well as how they cope with stress (stress management).
Forty oncologists (18 men and 22 women) working in a clinic in Kharkiv (Ukraine) with an average age of 46.3 ± 13.37 years (ranging from 26 to 74 years) participated in this study. The occupational psychological survey consisted of the Work-Related Behavior and Experience Patterns (German: Arbeitsbezogenes Verhaltens- und Erlebensmuster, AVEM) questionnaire, which was developed by Schaarschmidt and Fischer, and the Differential Stress Inventory (DSI), which was developed by Léfevre and Kubinger.
65% of oncologists exhibited AVEM risk pattern A or B. No gender differences were observed with regard to the distribution of AVEM patterns. Women obtained significantly higher scores than did men on only one dimension: experience of social support (4.86 vs. 3.44; p = 0.045). When the DSI categories were differentiated by gender, no significant differences were observed. Spearman's correlation analysis revealed a medium-sized correlation between perfection striving and palliative coping (ρ = 0.404).
Few gender-based differences in work-related behaviors, experiences, and stress management strategies are evident among oncologists. AVEM risk patterns are more prevalent among Ukrainian oncologists than among comparable occupational groups, and interventions in the context of health management are recommended.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Fluid flow on different scales is of interest for several Earth science disciplines like petrophysics, hydrogeology and volcanology. To parameterize fluid flow in large-scale numerical simulations ...(e.g. groundwater and volcanic systems), flow properties on the microscale need to be considered. For this purpose experimental and numerical investigations of flow through porous media over a wide range of porosities are necessary. In the present study we sinter glass bead media with various porosities and measure the permeability experimentally. The microstructure, namely effective porosity and effective specific surface, is investigated using image processing. We determine flow properties like tortuosity and permeability using numerical simulations. We test different parameterizations for isotropic low-porosity media on their potential to predict permeability by comparing their estimations to computed and experimentally measured values.
As a contribution to the Large-Scale Biosphere-Atmosphere Experiment in Amazonia – Cooperative LBA Airborne Regional Experiment (LBA-CLAIRE-2001) field campaign in the heart of the Amazon Basin, we ...analyzed the temporal and spatial dynamics of the urban plume of Manaus City during the wet-to-dry season transition period in July 2001. During the flights, we performed vertical stacks of crosswind transects in the urban outflow downwind of Manaus City, measuring a comprehensive set of trace constituents including O3, NO, NO2, CO, VOC, CO2, and H2O. Aerosol loads were characterized by concentrations of total aerosol number (CN) and cloud condensation nuclei (CCN), and by light scattering properties. Measurements over pristine rainforest areas during the campaign showed low levels of pollution from biomass burning or industrial emissions, representative of wet season background conditions. The urban plume of Manaus City was found to be joined by plumes from power plants south of the city, all showing evidence of very strong photochemical ozone formation. One episode is discussed in detail, where a threefold increase in ozone mixing ratios within the atmospheric boundary layer occurred within a 100 km travel distance downwind of Manaus. Observation-based estimates of the ozone production rates in the plume reached 15 ppb h−1. Within the plume core, aerosol concentrations were strongly enhanced, with ΔCN/ΔCO ratios about one order of magnitude higher than observed in Amazon biomass burning plumes. ΔCN/ΔCO ratios tended to decrease with increasing transport time, indicative of a significant reduction in particle number by coagulation, and without substantial new particle nucleation occurring within the time/space observed. While in the background atmosphere a large fraction of the total particle number served as CCN (about 60–80% at 0.6% supersaturation), the CCN/CN ratios within the plume indicated that only a small fraction (16±12%) of the plume particles were CCN. The fresh plume aerosols showed relatively weak light scattering efficiency. The CO-normalized CCN concentrations and light scattering coefficients increased with plume age in most cases, suggesting particle growth by condensation of soluble organic or inorganic species. We used a Single Column Chemistry and Transport Model (SCM) to infer the urban pollution emission fluxes of Manaus City, implying observed mixing ratios of CO, NOx and VOC. The model can reproduce the temporal/spatial distribution of ozone enhancements in the Manaus plume, both with and without accounting for the distinct (high NOx) contribution by the power plants; this way examining the sensitivity of ozone production to changes in the emission rates of NOx. The VOC reactivity in the Manaus region was dominated by a high burden of biogenic isoprene from the background rainforest atmosphere, and therefore NOx control is assumed to be the most effective ozone abatement strategy. Both observations and models show that the agglomeration of NOx emission sources, like power plants, in a well-arranged area can decrease the ozone production efficiency in the near field of the urban populated cores. But on the other hand remote areas downwind of the city then bear the brunt, being exposed to increased ozone production and N-deposition. The simulated maximum stomatal ozone uptake fluxes were 4 nmol m−2 s−1 close to Manaus, and decreased only to about 2 nmol m−2 s−1 within a travel distance >1500 km downwind from Manaus, clearly exceeding the critical threshold level for broadleaf trees. Likewise, the simulated N deposition close to Manaus was ~70 kg N ha−1 a−1 decreasing only to about 30 kg N ha−1 a−1 after three days of simulation.
Conjunctival melanoma is a rare type of ocular melanoma, which is prone to local recurrence and metastasis and can lead to patient death. Novel therapeutic strategies have revolutionized cutaneous ...melanoma management. The efficacy of these therapies in conjunctival melanoma, however, has not been evaluated in larger patient cohorts.
In this multi-center retrospective cohort study with additional screening of the ADOREG database, data were collected from 34 patients with metastatic conjunctival melanoma who received targeted therapy (TT) (BRAF ± MEK inhibitors) or immune checkpoint inhibitors (ICI) (anti-PD-1 ± anti-CTLA4). In 15 cases, tissue was available for targeted next-generation-sequencing (611 genes) and RNA sequencing. Driver mutations, tumor mutational burden, copy number variations and inflammatory/IFNγ gene expression signatures were determined.
Genetic characterization identified frequent BRAF (46.7%, 7/15), NRAS (26.7%, 4/15), NF1 (20%, 3/15), and TERT promoter (46.7%, 7/15) mutations. UV associated C>T and CC>TT mutations were common. Median follow-up time after start of first TT or ICI therapy was 13.2 months. In 26 patients receiving first-line ICI, estimated one-year progression-free survival (PFS) rate was 42.0%, PFS and overall survival (OS) 6.2 and 18.0 months, respectively. First-line TT was given to 8 patients, estimated one-year PFS rate was 54.7%, median PFS and OS 12.6 and 29.1 months, respectively.
Our findings support the role of UV irradiation in conjunctival melanoma and the genetic similarity with cutaneous melanoma. Conjunctival melanoma patients with advanced disease benefit from both targeted therapies (BRAF ± MEK inhibitors) and immune checkpoint inhibitors.
•Our findings support the role of UV irradiation in conjunctival melanoma.•Oncogene mutation patterns are similar to cutaneous melanoma.•In contrast to uveal melanoma, lymph node metastasis is common.•Response to immune checkpoint inhibition (ICI) is better than in uveal melanoma.•Targeted therapy (TT) should be considered in BRAF mutated conjunctival melanoma.
Haemophilus influenzae (Hi) serotype b (Hib) conjugate vaccine was incorporated into the infant immunisation schedule in Brazil in 1999, where Hib was one of the major etiologic sources of ...community-acquired bacterial meningitis.
The purpose of this study is to describe the molecular epidemiology of invasive Hi disease in Rio de Janeiro state, Brazil, before and after vaccine introduction.
Surveillance data from 1986 to 2014 were analysed. Hi isolates recovered from cerebrospinal fluid (CSF) or blood from 1993 to 2014 were serotyped by slide agglutination, genotyped by multilocus sequence typing (MLST), and the capsule type evaluation, differentiation of serologically non-typeable isolates, and characterisation of the capsule (cap) locus was done by polymerase chain reaction. Antimicrobial susceptibility testing was performed using E-test.
From 1986 to 1999 and from 2000 to 2014, 2580 and 197 (42% without serotype information) confirmed cases were reported, respectively. The case fatality rate was 17% and did not correlate with the strain. Hib and b- variant isolates belonged to ST-6, whereas serotype a isolates belonged to the ST-23 clonal complex. Serotype a appeared to emerge during the 2000s. Non-encapsulated isolates were non-clonal and distinct from the encapsulated isolates. Ampicillin-resistant isolates were either of serotype b or were non-encapsulated, and all of them were β-lactamase-positive but amoxicillin-clavulanic acid susceptible.
Although Hi meningitis became a relatively rare disease in Rio de Janeiro after the introduction of the Hib conjugate vaccine, the isolates recovered from patients have become more diverse. These results indicate the need to implement an enhanced surveillance system to continue monitoring the impact of the Hib conjugate vaccine.
The flow of fluids through porous media such as groundwater flow or magma migration is a key process in geological sciences. Flow is controlled by the permeability of the rock; thus, an accurate ...determination and prediction of its value is of crucial importance. For this reason, permeability has been measured across different scales. As laboratory measurements exhibit a range of limitations, the numerical prediction of permeability at conditions where laboratory experiments struggle has become an important method to complement laboratory approaches. At high resolutions, this prediction becomes computationally very expensive, which makes it crucial to develop methods that maximize accuracy. In recent years, the flow of non-Newtonian fluids through porous media has gained additional importance due to, e.g., the use of nanofluids for enhanced oil recovery. Numerical methods to predict fluid flow in these cases are therefore required.
Zusammenfassung
Hintergrund
Onkologen unterliegen hohen – allgemein im ärztlichen Tätigkeitsfeld und typisch in der Onkologie zutreffenden – psychischen Arbeitsbelastungen, die eine mehr oder weniger ...starke Beanspruchung bedeuten können. Krisenzeiten verstärken das Gefühl der negativen Beanspruchung. Viele Studien bestätigen den Zusammenhang zwischen Effort-Reward-Imbalance bzw. beruflichen Gratifikationskrisen im normalen Arbeitsalltag und verschiedenen Erkrankungen. Aufgrund fehlender Studiendaten war das Ziel dieser Pilotstudie, die subjektive psychische und physische Gesundheit ukrainischer Onkologen während der Krisensituationen zu ermitteln. Es soll der Frage nachgegangen werden, inwiefern Assoziationen zwischen Verausgabung, Belohnung sowie Overcommitment und der Gesundheit der Ärzteschaft gelten.
Methodik
An dieser Pilotstudie nahmen 23 Onkologen (12 Männer und 11 Frauen) im Alter zwischen 26 und 72 Jahren (im Mittel 47,4 ± 12,74 Jahre) freiwillig teil. Die durchschnittliche Dauer der Berufstätigkeit lag bei 19,0 ± 11,92 Jahren. Es wurden Daten mittels des Fragebogens Effort-Reward-Imbalance (ERI) mit Fragen zum Overcommitment (OC) und des Beschwerdefragebogens (BFB) erhoben. Es erfolgte eine Einteilung zwischen Befragten mit einem normalen ERI-Ratio (≤ 1) oder hohen ERI-Ratio (> 1) für die Gruppenvergleiche der gesundheitlichen Beschwerden. Zudem erfolgte eine Korrelationsanalyse zwischen den ERI-Subskalen, OC und den BFB-Skalen.
Ergebnisse
Die Verteilung von Alter und Berufsjahren war über die ERI-Gruppen identisch. Bei einer Spannweite von 0,20 bis 1,76 Punkten wiesen einige Onkologen (39,1 %) eine hohe Effort-Reward-Imbalance auf. Die Gesamtstichprobe bot eine durchschnittliche Ausprägung des ERI (0,93 ± 0,40 Punkte). Bei 26,1 % (
n
= 6) der Gesamtstichprobe fand sich ein erhöhtes OC (> 16 Punkte), wobei 1 Proband davon auch ein ERI > 1 aufwies. Alle 6 Onkologen boten zwar mehr psychische, physische und gesamte Symptomatik im BFB an, was jedoch im Vergleich zu der Gruppe mit einem normalen ERI statistisch nicht signifikant war. Bei 39,1 % (
n
= 9) der Gesamtstichprobe konnten neurotische Werte im BFB nachgewiesen werden (4 Probanden mit ERI > 1). BFB-Skalen korrelierten nicht mit den ERI-Subskalen und OC.
Diskussion
Die Daten zeigen eine hohe Beschwerdeprävalenz (39,1 %) sowohl in der Gruppe mit normaler Effort-Reward-Imbalance (35,7 %) als auch in der Gruppe mit hoher ERI-Ratio (44,4 %). Hohen Beanspruchungen kann unterschiedlich lang entgegengewirkt werden. Daher bedarf es betrieblicher Maßnahmen zum Gesundheitserhalt, gerade auch in Krisensituationen. Hier könnte die Arbeitsmedizin in der Ukraine von einem Erfahrungsaustausch zur ganzheitlichen arbeitsmedizinischen Vorsorge mit Arbeitsmedizinern in Deutschland profitieren.
We estimated the isoprene and monoterpene source strengths of a pristine tropical forest north of Manaus in the central Amazon Basin using three different micrometeorological flux measurement ...approaches. During the early dry season campaign of the Cooperative LBA Airborne Regional Experiment (LBA-CLAIRE-2001), a tower-based surface layer gradient (SLG) technique was applied simultaneously with a relaxed eddy accumulation (REA) system. Airborne measurements of vertical profiles within and above the convective boundary layer (CBL) were used to estimate fluxes on a landscape scale by application of the mixed layer gradient (MLG) technique. The mean daytime fluxes of organic carbon measured by REA were 2.1 mg C m−2 h−1 for isoprene, 0.20 mg C m−2 h−1 for α-pinene, and 0.39 mg C m−2 h−1 for the sum of monoterpenes. These values are in reasonable agreement with fluxes determined with the SLG approach, which exhibited a higher scatter, as expected for the complex terrain investigated. The observed VOC fluxes are in good agreement with simulations using a single-column chemistry and climate model (SCM). In contrast, the model-derived mixing ratios of VOCs were by far higher than observed, indicating that chemical processes may not be adequately represented in the model. The observed vertical gradients of isoprene and its primary degradation products methyl vinyl ketone (MVK) and methacrolein (MACR) suggest that the oxidation capacity in the tropical CBL is much higher than previously assumed. A simple chemical kinetics model was used to infer OH radical concentrations from the vertical gradients of (MVK+MACR)/isoprene. The estimated range of OH concentrations during the daytime was 3–8×106 molecules cm−3, i.e., an order of magnitude higher than is estimated for the tropical CBL by current state-of-the-art atmospheric chemistry and transport models. The remarkably high OH concentrations were also supported by results of a simple budget analysis, based on the flux-to-lifetime relationship of isoprene within the CBL. Furthermore, VOC fluxes determined with the airborne MLG approach were only in reasonable agreement with those of the tower-based REA and SLG approaches after correction for chemical decay by OH radicals, applying a best estimate OH concentration of 5.5×106 molecules cm−3. The SCM model calculations support relatively high OH concentration estimates after specifically being constrained by the mixing ratios of chemical constituents observed during the campaign. The relevance of the VOC fluxes for the local carbon budget of the tropical rainforest site during the measurements campaign was assessed by comparison with the concurrent CO2 fluxes, estimated by three different methods (eddy correlation, Lagrangian dispersion, and mass budget approach). Depending on the CO2 flux estimate, 1–6% or more of the carbon gained by net ecosystem productivity appeared to be re-emitted through VOC emissions.
OBJECTIVES
Transapical (TA) aortic valve implantation (AVI) has evolved as an alternative procedure for high-risk patients. We evaluated the second-generation SAPIEN XT™ prosthesis in a prospective ...multicentre clinical trial.
METHODS
A total of 150 patients (age: 81.6 ± 5.8 years; 40.7% female) were included. Prosthetic valves (diameter: 23 mm (n = 36), 26 mm (n = 57) and 29 mm (n = 57)) were implanted. The ASCENDRA-II™ modified delivery system was used in the smaller sizes. Mean logistic EuroSCORE was 24.3 ± 7.0%, and mean STS score 7.5 ± 4.4%. All patients gave written informed consent.
RESULTS
Off-pump AVI was performed using femoral arterial and venous access wires as a safety net. All but two patients received TA-AVI, as planned. The 29-mm valve showed similar function as the values of two other diameters did. Three patients (2%) required temporary cardiopulmonary bypass support. Postoperative complications included renal failure requiring long-term dialysis in four, bleeding requiring rethoracotomy in four, respiratory complication requiring reintubation in eight and sepsis in four patients, respectively. Thirty-day mortality was 13 (8.7%) for the total cohort and 2/57 (3.5%) for patients receiving the 29-mm valve, respectively. Echocardiography at discharge showed none or trivial aortic incompetence (AI) in 71% and mild-AI in 22% of the patients. Post-implantation AI was predominantly paravalvular and ≥2+ in 7% of patients. One patient required reoperation for AI within 30 days.
CONCLUSIONS
The PREVAIL TA multicentre trial demonstrates good functionality and good outcomes for TA-AVI, using the SAPIEN XT™ prosthesis and its second-generation ASCENDRA-II™ delivery system, as well successful introduction of the 29-mm SAPIEN XT™ valve for the benefit of high-risk elderly patients.
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