Post-remission treatment (PRT) in patients with cytogenetically normal (CN) acute myeloid leukemia (AML) in first complete remission (CR1) is debated. We studied 521 patients with CN-AML in CR1, for ...whom mutational status of NPM1 and FLT3-ITD was available, including the FLT3-ITD allelic ratio. PRT consisted of reduced intensity conditioning (RIC) allogeneic hematopoietic stem cell transplantation (alloHSCT) (n=68), myeloablative conditioning (MAC) alloHSCT (n=137), autologous hematopoietic stem cell transplantation (autoHSCT) (n=168) or chemotherapy (n=148). Favorable overall survival (OS) was found for patients with mutated NPM1 without FLT3-ITD (71±4%). Outcome in patients with a high FLT3-ITD allelic ratio appeared to be very poor with OS and relapse-free survival (RFS) of 23±8% and 12±6%, respectively. Patients with wild-type NPM1 without FLT3-ITD or with a low allelic burden of FLT3-ITD were considered as intermediate-risk group because of similar OS and RFS at 5 years, in which PRT by RIC alloHSCT resulted in better OS and RFS as compared with chemotherapy (hazard ratio (HR) 0.56, P=0.022 and HR 0.50, P=0.004, respectively) or autoHSCT (HR 0.60, P=0.046 and HR 0.60, P=0.043, respectively). The lowest cumulative incidence of relapse (23±4%) was observed following MAC alloHSCT. These results suggest that alloHSCT may be preferred in patients with molecularly intermediate-risk CN-AML, while the choice of conditioning type may be personalized according to risk for non-relapse mortality.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
ABSTRACT
BACKGROUND AND PURPOSE
Aneurysm hemodynamics play an important role in aneurysm growth and subsequent rupture. Within the available hemodynamic characteristics, particle residence time (PRT) ...is relatively unexplored. However, some studies have shown that PRT is related to thrombus formation and inflammation. The goal of this study is to evaluate the association between PRT and aneurysm rupture and morphology.
METHODS
We determined the PRT for 113 aneurysms (61 unruptured, 53 ruptured) based on computational fluid dynamic models. Virtual particles were injected into the parent vessel and followed during multiple cardiac cycles. PRT was defined as the time needed for 99% of the particles that entered an aneurysm to leave the aneurysm. Subsequently, we evaluated the association between PRT, rupture, and morphology (aneurysm type, presence of blebs, or multiple lobulations).
RESULTS
PRT showed no significant difference between unruptured (1.1 seconds interquartile range IQR .39‐2.0 seconds) and ruptured aneurysms (1.2 seconds IQR .47‐2.3 seconds). PRT was influenced by aneurysm morphology. Longer PRTs were seen in bifurcation aneurysms (1.3 seconds IQR .54‐2.4 seconds, P = .01) and aneurysms with blebs or multiple lobulations (1.92 seconds IQR .94‐2.8 seconds, P < .001). Four of five partially thrombosed aneurysms had a long residence time (>1.9 seconds).
CONCLUSIONS
Our study shows an influence of aneurysm morphology on PRT. Nevertheless, it suggests that PRT cannot be used to differentiate unruptured and ruptured aneurysms.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Marginal water, like treated effluent or other types of wastewater, induces contaminant accumulation in different environmental compartments such as soil and groundwater. With a root zone model and ...daily rainfall data as input, accumulation in the case of two different degradation concepts was modeled: (I) the solute degrades only in the solution phase, and (II) the solute degrades in both the solution and the adsorption phase. For linear adsorption, both degradation concepts not only yield similar results, but adsorption does not affect the long‐term concentration. This can be readily explained with the governing equations. For nonlinear adsorption, the degradation concept does affect the concentration and fluxes. When the first concept is valid, the long‐term concentration is not affected by adsorption, whereas the short‐term and fluctuations are. For the second degradation concept, the long‐term average concentration and fluxes are also affected by adsorption. A correction factor was derived to correct the analytical solution of the time‐dependent concentration of nonlinearly adsorbing solutes. For all scenarios, reasonable estimates of the long‐term concentration could be obtained with analytical models for most parameter combinations, which can be used to identify contaminant species that should be prioritized for further research.
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The use of marginal water, such as reclaimed wastewater or effluent, for irrigation can reduce the pressure on existing freshwater resources. However, this can cause contaminants to accumulate in ...compartments such as the soil, crop, air, surface- and groundwater, which may harm the public health and the environment. Environmental quality standards for these compartments are generally considered separately. However, the compartments are related to each other by the fluxes between them, and the concept of sustainability should hold for all compartments simultaneously. An integrated approach is therefore required for the sustainability assessment of irrigation with marginal water. Since such an approach has not been provided yet, we develop an integrated framework in this study. We provide sustainability indicators by comparing the long-term contaminant concentration and fluxes with quality standards for each environmental compartment. These indicators give comprehensible information on which contaminants will cause problems, which environmental compartments are threatened, and on what timescale this will occur. This allows for the prioritization of mitigation and preventive measures for better sustainability management. We illustrate the use of the framework by means of a case study.
Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) are involved in tumour progression and metastasis. In this study, we investigated the in vitro and in vivo expression patterns of ...MMP-1, MMP-2, MMP-3, MMP-9, TIMP-1 and TIMP-2 mRNA and protein in a previously described human melanoma xenograft model. This model consists of eight human melanoma cell lines with different metastatic behaviour after subcutaneous (s.c.) injection into nude mice. MMP-1 mRNA was detectable in all cell lines by reverse transcription polymerase chain reaction (RT-PCR), but the expression was too low to be detected by Northern blot analysis. No MMP-1 protein could be found using Western blotting. MMP-2 mRNA and protein were present in all cell lines, with the highest expression of both latent and active MMP-2 in the highest metastatic cell lines MV3 and BLM. MMP-3 mRNA was expressed in MV3 and BLM, and in the non-metastatic cell line 530, whereas MMP-3 protein was detectable only in MV3 and BLM. None of the melanoma cell lines expressed MMP-9. TIMP-1 and TIMP-2 mRNA and protein, finally, were present in all cell lines. A correlation between TIMP expression level and metastatic capacity of cell lines, however, was lacking. MMP and TIMP mRNA and protein expression levels were also studied in s.c. xenograft lesions derived from a selection of these cell lines. RT-PCR analysis revealed that MMP-1 mRNA was present in MV3 and BLM xenografts, and to a lesser extent in 530. Positive staining for MMP-1 protein was found in xenograft lesions derived from both low and high metastatic cell lines, indicating an in vivo up-regulation of MMP-1. MMP-2 mRNA was detectable only in xenografts derived from the highly metastatic cell lines 1F6m, MV3 and BLM. In agreement with the in vitro results, the highest levels of both latent and activated MMP-2 protein were observed in MV3 and BLM xenografts. With the exception of MMP-9 mRNA expression in 530 xenografts, MMP-3, MMP-9, and TIMP-1 mRNA and protein were not detectable in any xenograft, indicating a down-regulated expression of MMP-3 and TIMP-1 in vivo. TIMP-2 mRNA and protein were present in all xenografts; interestingly, the strongest immunoreactivity of tumour cells was found at the border of necrotic areas. Our study demonstrates that of all tested components of the matrix metalloproteinase system, only expression of activated MMP-2 correlates with increased malignancy in our melanoma xenograft model, corroborating an important role of MMP-2 in human melanoma invasion and metastasis.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, SIK, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Soil sodicity originating from marginal groundwater de Craats, Daniël; der Zee, Sjoerd E.A.T.M.; Sui, Chunming ...
Vadose zone journal,
2020, 2020-01-00, 20200101, 2020-01-01, Volume:
19, Issue:
1
Journal Article
Peer reviewed
Open access
Soil salinity and sodicity are among the oldest soil and groundwater pollution problems and are widespread across the globe. Where salinity affects crop water uptake and yield, sodicity may ...additionally cause poorly reversible soil structure degradation and a severely reduced hydraulic conductivity. We use the model HYDRUS‐1D to simulate sodicity development in soils with shallow, Na‐rich groundwater under a normal weather regime with distinct dry seasons. Attention is given to the impact of a sudden fresh water input on the formation of a sodic layer. The complex interplay between soil chemistry, soil physics, soil mechanics (as far as swell–shrink behavior is concerned), and fluctuating atmospheric conditions results in a remarkably regular relation between depth, location, and severity of a sodic layer that forms within the soil as a function of rainfall intensity. A threshold behavior is observed: sodic layer formation is absent at rainfall intensities below this threshold, whereas sodic layer thickness and hydraulic conductivity reduction increase rapidly with intensities exceeding this threshold. This is the case even for different soil types and groundwater depths. Field observations agree with our simulations: the properties of the layer with sodicity‐induced structure degradation are more strongly developed, as this layer is situated at a shallower depth. The implementation of hydraulic conductivity reduction as a function of exchangeable Na percentage and ionic strength in HYDRUS‐1D can be improved towards a smooth reduction function, changing soil physical parameters due to swelling and dispersion of clay and reconsideration of the reversibility of sodicity development.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
We developed a polymerase chain reaction DNA amplification system using two distinct consensus oligonucleotide primer sets for the improved detection and typing of a broad spectrum of human genital ...papillomavirus (HPV) sequences, including those of novel viruses. The system incorporates one primer set designed to amplify a highly conserved L1 domain and a second primer set designed to amplify a domain within the E6 gene. We used this system to analyze 48 fixed, paraffin-embedded tissue sections (41 specimens from 33 cervical carcinomas, four normal cervical tissues, and several control tissues) for the presence of HPV DNA. HPV sequences were detected in all carcinoma samples and none of the control samples. Hybridization analyses showed that the results obtained with the two amplification schemes concurred completely. This approach allowed rapid confirmation of typing results and may improve the likelihood of detecting a wide variety of HPV sequences, including those of novel HPVs.
Cardiorespiratory fitness (CRF) is an independent predictor of mortality, and females typically achieve smaller improvements in CRF than males after exercise-based cardiac rehabilitation. ...High-intensity interval training (HIIT) has been shown to produce superior improvements in CRF than traditional cardiac rehabilitation, but the sex differences are unknown. The purpose of this systematic review and meta-analysis was to evaluate sex differences for changes in CRF and cardiometabolic health indicators after HIIT in adults with coronary artery disease (CAD).
A systemic search of five electronic databases for studies examining the effect of HIIT on measured CRF and cardiometabolic health indicators in adults with CAD was performed. Data (published and unpublished) from 14 studies were included in the meta-analyses with approximately eightfold greater male than female participation (n = 836 vs n = 103). Males with CAD achieved a near-significant absolute improvement in CRF (mean difference MD = 1.07, 95% confidence interval CI = -0.08 to 2.23 mL·kg-1⋅min-1, P = 0.07) after HIIT when compared with control; there were insufficient data to conduct such an analysis in females. Significantly smaller improvements in CRF were experienced by females than males (MD = -1.10, 95% CI = -2.08 to -0.12 mL·kg-1⋅min-1, P = 0.03); there was no sex difference for the relative (percentage) change in CRF after HIIT. Females achieved significantly smaller reductions in body mass index (MD = -0.25, 95% CI = -0.03 to -0.47 kg·m-2, P = 0.02) and fasting blood glucose (MD = -0.38, 95% CI = -0.05 to -0.72, P = 0.03); no sex differences were observed for other cardiometabolic health indicators.
There are no sex differences for relative improvements in CRF after HIIT; however, females are greatly underrepresented in trials. Future studies should increase female participation and perform sex-based analyses to determine sex-specific outcomes following HIIT.
Registered Replication Report Bouwmeester, S.; Verkoeijen, P. P. J. L.; Aczel, B. ...
Perspectives on psychological science,
05/2017, Volume:
12, Issue:
3
Journal Article
Peer reviewed
Open access
In an anonymous 4-person economic game, participants contributed more money to a common project (i.e., cooperated) when required to decide quickly than when forced to delay their decision (Rand, ...Greene & Nowak, 2012), a pattern consistent with the social heuristics hypothesis proposed by Rand and colleagues. The results of studies using time pressure have been mixed, with some replication attempts observing similar patterns (e.g., Rand et al., 2014) and others observing null effects (e.g., Tinghög et al., 2013; Verkoeijen & Bouwmeester, 2014). This Registered Replication Report (RRR) assessed the size and variability of the effect of time pressure on cooperative decisions by combining 21 separate, preregistered replications of the critical conditions from Study 7 of the original article (Rand et al., 2012). The primary planned analysis used data from all participants who were randomly assigned to conditions and who met the protocol inclusion criteria (an intent-to-treat approach that included the 65.9% of participants in the time-pressure condition and 7.5% in the forced-delay condition who did not adhere to the time constraints), and we observed a difference in contributions of -0.37 percentage points compared with an 8.6 percentage point difference calculated from the original data. Analyzing the data as the original article did, including data only for participants who complied with the time constraints, the RRR observed a 10.37 percentage point difference in contributions compared with a 15.31 percentage point difference in the original study. In combination, the results of the intent-to-treat analysis and the compliant-only analysis are consistent with the presence of selection biases and the absence of a causal effect of time pressure on cooperation.
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BFBNIB, NMLJ, NUK, OILJ, PNG, SAZU, UKNU, UL, UM, UPUK
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