The soil water retention curve (SWRC) is an essential hydraulic function for the understanding and modelling of soil hydraulic processes. Its direct determination is time consuming and sometimes ...expensive because it requires extensive sampling, especially when spatial and temporal variation of soil hydraulic properties are an issue. The use of pedotransfer functions (PTFs) is a viable alternative to predict the parameters of SWRC from more easily determined soil attributes. Splintex is a physically based engineering model containing two PTFs to estimate SWRC parameters and saturated hydraulic conductivity, but its performance and functionality have not yet been fully evaluated and disseminated for soil science. We examined the functionality of the PTFs available in Splintex to estimate parameters of the Van Genuchten–Mualem (VGM) SWRC equation with a laboratory‐measured dataset containing information on particle size, bulk and particle density, saturated water content and parameters of the SWRCs. In addition, we tested the performance of both PTFs for deriving some soil physical–structural variables calculated from estimated SWRC parameters. Compared with VGM parameters fitted to the laboratory dataset, the model performed well. Its predictive performance for soil air capacity, relative field capacity and soil physical–structural quality indices was also evaluated. The performance of Splintex for estimating the VGM parameters depended on the combined effect of all input variables rather than on isolated correlations between an input variable and a model parameter.
Highlights
Splintex provides two PTFs to estimate the Van Genuchten–Mualem parameters of the SWRC.
In addition to PTF1 input, PTF2 needs an additional soil water content–retention observation.
Performance of Splintex‐PTF1 against measured data and ‐PTF2 prediction is presented.
PTF2 provided better results than PTF1 for estimating SPQ indices.
B-cell chronic lymphocytic leukaemia (B-CLL) is a slowly progressing malignancy of CD5(+) B cells, for which at present no curative treatment is available. In our current study, we apply a novel ...bridging reagent to redirect cytomegalovirus (CMV)-specific cytotoxic T lymphocytes (CTL) to target B-CLL. A streptavidin-fused anti-CD20 single-chain variable fragment (scFv) is used in combination with biotinylated MHC class I molecules containing CMV pp65 peptide (HLA/CMV). We demonstrate that B-CLL cells coated with this CD20-HLA/CMV complex can be lysed by autologous CMV-specific CTL with similar efficiency as B-CLL cells directly loaded with CMV peptide. Killing is HLA restricted and occurs at scFv CD20 concentrations of >/=100 ng ml(-1) and HLA/CMV concentrations of >/=20 ng ml(-1). Furthermore, complex-coated B-CLL cells induce both proliferation and cytokine production (interferon gamma, tumour necrosis factor alpha and macrophage inflammatory protein-1 beta) in CMV-specific CD8(+) T cells. Hereby, a necessary step towards possible application of CD20-HLA/CMV complexes for immunotherapy of B-cell malignancies is constituted.
Abstract Chronic systemic ‘latent’ viral infections such as Cytomegalovirus infection (CMV) are known to leave a fingerprint in the total T-cell population. We investigated whether chronic infections ...with a ‘persistent’ viremia, such as chronic hepatitis B and C (CHB, CHC), characterized by local organ-specific inflammation, also impact the total peripheral T-cell population or other virus specific T-cells that do not target hepatitis viruses. No phenotypic or functional differences were found between CD8+ T-cells or CMV- or Epstein–Barr virus specific T-cells in viral hepatitis and healthy controls (HC). However, expression of chemokine-receptor CXCR3 was significantly higher on total peripheral CD8+ T-cells of CHB or CHC patients compared to HC ( p < 0.005) which may reflect the pervasive influence of a persistent viral infection, even when restricted to the liver. In CHB higher CXCR3 expression was associated with positive HBeAg-status and correlated with the percentage of HBsAg expressing hepatocytes found in liver biopsies, both pointing to a relation between CXCR3 expression and disease activity. In fact chemokine-receptors such as CXCR3 are important for T-cell recruitment to the liver and chemokine-ligands specific for CXCR3 are upregulated in chronic hepatitis. Modulating chemokine(receptor) expression could be a potential target for future therapy to optimize the anti-viral immunologic environment in the liver.
Mutations in the common gamma chain (γc, CD132, encoded by the IL2RG gene) can lead to B(+)T(-)NK(-) X-linked severe combined immunodeficiency, as a consequence of unresponsiveness to γc-cytokines ...such as interleukins-2, -7 and -15. Hypomorphic mutations in CD132 may cause combined immunodeficiencies with a variety of clinical presentations. We analyzed peripheral blood mononuclear cells of a 6-year-old boy with normal lymphocyte counts, who suffered from recurrent pneumonia and disseminated mollusca contagiosa. Since proliferative responses of T cells and NK cells to γc -cytokines were severely impaired, we performed IL2RG gene analysis, showing a heterozygous mutation in the presence of a single X-chromosome. Interestingly, an IL2RG reversion to normal predominated in both naïve and antigen-primed CD8(+) T cells and increased over time. Only the revertant CD8(+) T cells showed normal expression of CD132 and the various CD8(+) T cell populations had a different T-cell receptor repertoire. Finally, a fraction of γδ(+) T cells and differentiated CD4(+)CD27(-) effector-memory T cells carried the reversion, whereas NK or B cells were repeatedly negative. In conclusion, in a patient with a novel IL2RG mutation, gene-reverted CD8(+) T cells accumulated over time. Our data indicate that selective outgrowth of particular T-cell subsets may occur following reversion at the level of committed T progenitor cells.
In response to viral infection, unprimed naive CD8+, major histocompatibility complex class I—restricted, virus-specific T cells clonally expand and differentiate into memory- and effector-type ...cells. Changes in CD8+ subset distribution were studied in 17 subjects with acute human immunodeficiency virus type 1 infection and in 14 subjects with acute Epstein-Barr virus (EBV) infection, with combined CD45RO, CD27, and CD28 monoclonal antibodies. A vast expansion of memory-type CD45RO+CD27+CD8+ T cells, with high expression of the cell-cycle marker Ki-67, was observed in both infections. Strikingly, CD45RO+CD27+CD28− cells increased >10-fold in acute viral infection and had high Ki-67 expression. In acute EBV infection, a substantial portion of the expanded T cells were EBV-peptide specific. These cells resided mainly in the CD45RO+CD27+ subpopulation, with most in the CD27+CD28− subpopulation. Content of perforin expression, as a measure of cytotoxic capacity, was relatively low in the CD27+CD28+ T cells and highest in the CD27−CD28− subpopulation.
•Interobserver variability in delineation of the oesophageal GTV can be considerable.•Delineation variation is mainly located at the cranial and caudal border.•PET significantly influences the ...delineated GTV in oesophageal cancer.•The impact of PET to CT on observer variation of the GTV is limited.•Accurate GTV delineation is essential for results of radiation boost-strategies.
Accurate delineation of the primary tumour is vital to the success of radiotherapy and even more important for successful boost strategies, aiming for improved local control in oesophageal cancer patients. Therefore, the aim was to assess delineation variability of the gross tumour volume (GTV) between CT and combined PET-CT in oesophageal cancer patients in a multi-institutional study.
Twenty observers from 14 institutes delineated the primary tumour of 6 cases on CT and PET-CT fusion. The delineated volumes, generalized conformity index (CIgen) and standard deviation (SD) in position of the most cranial/caudal slice over the observers were evaluated. For the central delineated region, perpendicular distance between median surface GTV and each individual GTV was evaluated as in-slice SD.
After addition of PET, mean GTVs were significantly smaller in 3 cases and larger in 1 case. No difference in CIgen was observed (average 0.67 on CT, 0.69 on PET-CT). On CT cranial-caudal delineation variation ranged between 0.2 and 1.5 cm SD versus 0.2 and 1.3 cm SD on PET-CT. After addition of PET, the cranial and caudal variation was significantly reduced in 1 and 2 cases, respectively. The in-slice SD was on average 0.16 cm in both phases.
In some cases considerable GTV delineation variability was observed at the cranial-caudal border. PET significantly influenced the delineated volume in four out of six cases, however its impact on observer variation was limited.
We estimated SARS-CoV-2 vaccine effectiveness against onward transmission by comparing secondary attack rates among household members for vaccinated and unvaccinated index cases, based on source and ...contact tracing data collected when the Delta variant was dominant. Effectiveness of full vaccination of the index case against transmission to unvaccinated and fully vaccinated household contacts, respectively, was 63% (95% confidence interval (CI): 46–75) and 40% (95% CI: 20–54), in addition to the direct protection of vaccination of contacts against infection.
To evaluate prostate intrafraction motion using MRI during the full course of online adaptive MR-Linac radiotherapy (RT) fractions, in preparation of MR-guided extremely hypofractionated RT.
Five low ...and intermediate risk prostate cancer patients were treated with 20 × 3.1 Gy fractions on a 1.5T MR-Linac. Each fraction, initial MRI (Pre) scans were obtained at the start of every treatment session. Pre-treatment planning MRI contours were propagated and adapted to this Pre scan after which plan re-optimization was started in the treatment planning system followed by dose delivery. 3D Cine-MR imaging was started simultaneously with beam-on and acquired over the full beam-on period. Prostate intrafraction motion in this cine-MR was determined with a previously validated soft-tissue contrast based tracking algorithm. In addition, absolute accuracy of the method was determined using a 4D phantom.
Prostate motion was completely automatically determined over the full on-couch period (approx. 45 min) with no identified mis-registrations. The translation 95% confidence intervals are within clinically applied margins of 5 mm, and plan adaption for intrafraction motion was required in only 4 out of 100 fractions.
This is the first study to investigate prostate intrafraction motions during entire MR-guided RT sessions on an MR-Linac. We have shown that high quality 3D cine-MR imaging and prostate tracking during RT is feasible with beam-on. The clinically applied margins of 5 mm have proven to be sufficient for these treatments and may potentially be further reduced using intrafraction plan adaptation guided by cine-MR imaging.