Supposed risk of malignant transformation of salivary gland pleomorphic adenoma (SGPA) is an important reason for aggressive retreatment in recurrent pleomorphic adenoma (RPA). However, although the ...diagnostic category ‘carcinoma ex‐pleomorphic adenoma’ suggests that malignant transformation of a pleomorphic adenoma is a regular event, this has to date not been shown to occur in sequential lesions of one patient. Here, we show the molecular events in transformation to malignancy of a pleomorphic adenoma of the parotid gland. Detailed molecular analysis revealed an LIFR/PLAG1 translocation characteristic for pleomorphic adenoma and, next to this, a PIK3R1 frameshift mutation and several allelic imbalances. In subsequent malignant recurrences, the same LIFR/PLAG1 translocation, PIK3R1 frameshift mutation, and allelic imbalances were present in addition to TP53 mutations. Thus, this case not only shows malignant transformation of SGPA, but also demonstrates that molecular analysis can be of help in recognising malignancy in the rare instance of RPA.
Abstract
The association between neonatal sepsis and labour epidural analgesia (EA) was evaluated. In a retrospective matched case-control study, 453 women delivering with EA (EA group) were matched ...on parity with 453 women with deliveries without EA (non-EA group). Significantly more neonates born in the EA-group had fever ≥ 38.0°C (11.6% vs 1.8%, p < 0.001) at birth. The overall incidence of neonatal sepsis, based on clinical symptoms and defined as proven (by a positive blood culture) or suspected (no positive blood culture), was significantly higher in the EA group (6.0% vs 2.2%; p = 0.002), but the incidence of proven neonatal sepsis alone was not (0.4% vs 0%; p = 0.250). EA turned out to be an independent risk factor for neonatal sepsis (adjusted OR 2.43, 95% CI 1.15-5.13; p = 0.020). However, in the EA group as well as the non-EA group, the incidence of neonatal sepsis was significantly higher in mothers with intrapartum fever compared with afebrile mothers (11.0% vs 2.9% in the EA group; p = 0.004; 8.2% vs 1.3% in the non-EA group; p = 0.006). Therefore we conclude, that the positive association between neonatal sepsis and labour EA is possibly mediated by maternal intrapartum fever.
Infants with intrauterine growth retardation are prone to intestinal disorders. The morphological and molecular mechanisms that lead to these complications are not completely understood and suitable ...experimental models are necessary. The aim of this study was to characterize mesenteric artery (MA) reactivity, small intestine morphometry and intestinal expression of vascular endothelial growth factor (VEGF) in a chicken model of hypoxia-induced fetal growth restriction. Chicken embryos (15 and 19 incubation days) and hatchlings (<3-h-old and 1-d-old) were incubated under hypoxic (15% O₂ from day 0 to day 19 of incubation) or normoxic conditions. Vascular reactivity was studied using wire miography. Intestinal morphometry was assessed in hematoxyline-eosine-stained sections. VEGF mRNA expression was determined by RT-PCR analysis. Hypoxia increased the responsiveness of chicken embryo MAs to the adrenergic agonist norepinephrine, the polypeptide endothelin (ET)-1, and the nitric oxide donor sodium nitroprusside and decreased the responsiveness to the endothelium-dependent relaxant agonist acetylcholine. However, the majority of these alterations, with the exception of the hyperresponsiveness to ET-1, were not present in the hypoxic hatchlings. When intestinal histology was analyzed, subtle hypoxia-induced changes were noted in the villi and the muscularis propria from the hatchlings. Hypoxic incubation also diminished the expression of VEGF mRNA in the terminal ileum of the hatchlings. In conclusion, chronic moderate hypoxia during incubation results in subtle but significant alterations in chicken MA reactivity, small intestine morphology and VEGF expression. Whether these alterations may have a direct effect on the functional status of the intestine remains to be investigated.
Up to 7% of term and late-preterm neonates in high-income countries receive antibiotics during the first 3 days of life because of suspected early-onset sepsis. The prevalence of culture-proven ...early-onset sepsis is 0·1% or less in high-income countries, suggesting substantial overtreatment. We assess whether procalcitonin-guided decision making for suspected early-onset sepsis can safely reduce the duration of antibiotic treatment.
We did this randomised controlled intervention trial in Dutch (n=11), Swiss (n=4), Canadian (n=2), and Czech (n=1) hospitals. Neonates of gestational age 34 weeks or older, with suspected early-onset sepsis requiring antibiotic treatment were stratified into four risk categories by their treating physicians and randomly assigned 1:1 using a computer-generated list stratified per centre to procalcitonin-guided decision making or standard care-based antibiotic treatment. Neonates who underwent surgery within the first week of life or had major congenital malformations that would have required hospital admission were excluded. Only principal investigators were masked for group assignment. Co-primary outcomes were non-inferiority for re-infection or death in the first month of life (margin 2·0%) and superiority for duration of antibiotic therapy. Intention-to-treat and per-protocol analyses were done. This trial was registered with ClinicalTrials.gov, number NCT00854932.
Between May 21, 2009, and Feb 14, 2015, we screened 2440 neonates with suspected early-onset sepsis. 622 infants were excluded due to lack of parental consent, 93 were ineligible for reasons unknown (68), congenital malformation (22), or surgery in the first week of life (3). 14 neonates were excluded as 100% data monitoring or retrieval was not feasible, and one neonate was excluded because their procalcitonin measurements could not be taken. 1710 neonates were enrolled and randomly assigned to either procalcitonin-guided therapy (n=866) or standard therapy (n=844). 1408 neonates underwent per-protocol analysis (745 in the procalcitonin group and 663 standard group). For the procalcitonin group, the duration of antibiotic therapy was reduced (intention to treat: 55·1 vs 65·0 h, p<0·0001; per protocol: 51·8 vs 64·0 h; p<0·0001). No sepsis-related deaths occurred, and 9 (<1%) of 1710 neonates had possible re-infection. The risk difference for non-inferiority was 0·1% (95% CI −4·6 to 4·8) in the intention-to-treat analysis (5 0·6% of 866 neonates in the procalcitonin group vs 4 0·5% of 844 neonates in the standard group) and 0·1% (−5·2 to 5·3) in the per-protocol analysis (5 0·7% of 745 neonates in the procalcitonin group vs 4 0·6% of 663 neonates in the standard group).
Procalcitonin-guided decision making was superior to standard care in reducing antibiotic therapy in neonates with suspected early-onset sepsis. Non-inferiority for re-infection or death could not be shown due to the low occurrence of re-infections and absence of study-related death.
The Thrasher Foundation, the NutsOhra Foundation, the Sophia Foundation for Scientific research.
High resolution time-dependent dielectric breakdown tests are carried out on 7.2
nm gate oxide capacitors (n-type) in the electric field range 8.3–13.2
MV/cm at high temperatures (160–240
°C). It is ...proven that even at these high temperatures log(
t
BD) is proportional to 1/
E
OX and the time-to-breakdown mechanism matches the anode hole injection (AHI) model (1/
E
OX model). In addition it is presented that the TDDB activation energy
E
a for this type of gate oxide has linear dependence on stress electric oxide field.
Abstract How are rain forest photosynthesis and turbulent fluxes influenced by clouds? To what extent are clouds affected by local processes driven by rain forest energy, water, and carbon fluxes? ...These interrelated questions were the main drivers of the intensive field experiment CloudRoots-Amazon22 which took place at the Amazon Tall Tower Observatory (ATTO)/Campina supersites in the Amazon rain forest during the dry season, in August 2022. CloudRoots-Amazon22 collected observational data to derive cause–effect relationships between processes occurring at the leaf level up to canopy scales in relation to the diurnal evolution of the clear-to-cloudy transition. First, we studied the impact of cloud and canopy radiation perturbations on the subdiurnal variability of stomatal conductance. Stoma opening is larger in the morning, modulated by the cloud optical thickness. Second, we combined 1-Hz frequency measurements of the stable isotopologues of carbon dioxide and water vapor with measurements of turbulence to determine carbon dioxide and water vapor sources and sinks within the canopy. Using scintillometer observations, we inferred 1-min sensible heat flux that responded within minutes to the cloud passages. Third, collocated profiles of state variables and greenhouse gases enabled us to determine the role of clouds in vertical transport. We then inferred, using canopy and upper-atmospheric observations and a parameterization, the cloud cover and cloud mass flux to establish causality between canopy and cloud processes. This shows the need for a comprehensive observational set to improve weather and climate model representations. Our findings contribute to advance our knowledge of the coupling between cloudy boundary layers and primary carbon productivity of the Amazon rain forest.
Current understanding of land–atmosphere exchange fluxes is limited by the fact that available observational techniques mainly quantify net fluxes, which are the sum of generally larger, ...bidirectional fluxes that partially cancel out. As a consequence, validation of gas exchange fluxes applied in models is challenging due to the lack of ecosystem-scale exchange flux measurements partitioned into soil, plant, and atmospheric components. One promising experimental method to partition measured turbulent fluxes uses the exchange-process-dependent isotopic fractionation of molecules like CO2 and H2O. When applying this method at a field scale, an isotope flux (δ flux) needs to be measured. Here, we present and discuss observations made during the LIAISE (Land surface Interactions with the Atmosphere over the Iberian Semi-arid Environment) 2021 field campaign using an eddy covariance (EC) system coupled to two laser spectrometers for high-frequency measurement of the isotopic composition of H2O and CO2. This campaign took place in the summer of 2021 in the irrigated Ebro River basin near Mollerussa, Spain, embedded in a semi-arid region.We present a systematic procedure to scrutinise and analyse measurements of the δ-flux variable, which plays a central role in flux partitioning. Our experimental data indicated a larger relative signal loss in the δ fluxes of H2O compared to the net ecosystem flux of H2O, while this was not true for CO2. Furthermore, we find that mole fractions and isotope ratios measured with the same instrument can be offset in time by more than a minute for the H2O isotopologues due to the isotopic memory effect. We discuss how such artefacts can be detected and how they impact flux partitioning. We argue that these effects are likely due to condensation of water on a cellulose filter in our inlet system. Furthermore, we show that these artefacts can be resolved using physically sound corrections for inlet delays and high-frequency loss. Only after such corrections and verifications are made can ecosystem-scale fluxes be partitioned using isotopic fluxes as constraints, which in turn allows for conceptual land–atmosphere exchange models to be validated.
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