Monitoring stroomgebieden : een tussenrapport : meerjaren monitoringsprogramma naar de uit- en afspoeling van nutriënten vanuit landbouwgronden in stroomgebieden en polders

In vier onderzoeksgebieden is alle bestaande kennis van het oppervlaktewatersysteem en de waterkwaliteit verzameld. Het betreft: de Drentse Aa, een zandgebied met lage nutriëntenbelasting; de Schuitenbeek, een zandgebied met hoge nutriëntenbelasting; de Krimpenerwaard, een veenpolder; Quarles van Ufford, een bemalen rivierkleigebied. Vervolgens zijn waar nodig extra veldmetingen gedaan. Deze aanvullende metingen hebben kennishiaten binnen de gebieden opgevuld en zijn ingezet voor de bouw van een model dat de relaties tussen alle onderdelen in het oppervlaktewatersysteem betrouwbaar en gedetailleerd weergeeft. Dat model is gebouwd als afgeleide van een bestaand, landelijk model (STONE), dat in fases is verfijnd en uitgebreid op basis van steeds gedetailleerdere systeemkennis en gebiedsdata. Aanpassingen in het model zijn steeds getoetst aan meetgegevens uit het gebied, waarmee direct duidelijk werd of de aanpassing resulteerde in een beter werkend model

Association of quantifiable prostate MRI parameters with any and large cribriform pattern in prostate cancer patients undergoing radical prostatectomy

Purpose: Cribriform pattern has recently been recognized as an important independent risk factor for prostate cancer (PCa) outcome. This study aimed to identify the association of quantifiable prostate magnetic resonance imaging (MRI) parameters with any and large cribriform pattern at radical prostatectomy (RP) specimens. Methods: Preoperative prostate MRI's from 188 men undergoing RP between 2010 and 2018 were retrospectively acquired. RP specimens of the patients were revised for Gleason score (GS), and presence of any and large cribriform pattern. MRI parameters such as MRI visibility, PI-RADS score, lowest apparent diffusion coefficient (ADC) value, lesion size, and radiologic extra-prostatic extension (EPE) were reviewed. The association of prostate MRI parameters for presence of any and large cribriform pattern at RP was analysed using logistic regression. Results: 116/188 (61.7%) PCa patients had any cribriform and 36/188 (19.1%) large cribriform pattern at RP. 171/188 (91.0%) men had MRI-visible lesions; 111/116 (95.7%) tumours with any and 36/36 (100%) with large cribriform pattern were visible at MRI. PCa with any and large cribriform pattern both had lower ADC values than those without (p &lt; 0.001). In adjusted analysis, lowest ADC value was as an independent predictor for any cribriform (Odds Ratio (OR) 0.2, 95% Confidence Interval (CI) 0.1–0.8; p = 0.01) and large cribriform pattern (OR 0.2, 95% CI 0.1–0.7; p = 0.01), while other parameters were not. Conclusions: The majority of PCa with cribriform pattern at RP were visible at MRI, and lowest ADC value was an independent predictor for both any and large cribriform pattern.</p

Human phosphodiesterase 4D7 (PDE4D7) expression is increased in TMPRSS2-ERG positive primary prostate cancer and independently adds to a reduced risk of post-surgical disease progression

background: There is an acute need to uncover biomarkers that reflect the molecular pathologies, underpinning prostate cancer progression and poor patient outcome. We have previously demonstrated that in prostate cancer cell lines PDE4D7 is downregulated in advanced cases of the disease. To investigate further the prognostic power of PDE4D7 expression during prostate cancer progression and assess how downregulation of this PDE isoform may affect disease outcome, we have examined PDE4D7 expression in physiologically relevant primary human samples. methods: About 1405 patient samples across 8 publically available qPCR, Affymetrix Exon 1.0 ST arrays and RNA sequencing data sets were screened for PDE4D7 expression. The TMPRSS2-ERG gene rearrangement status of patient samples was determined by transformation of the exon array and RNA seq expression data to robust z-scores followed by the application of a threshold &gt;3 to define a positive TMPRSS2-ERG gene fusion event in a tumour sample. results: We demonstrate that PDE4D7 expression positively correlates with primary tumour development. We also show a positive association with the highly prostate cancer-specific gene rearrangement between TMPRSS2 and the ETS transcription factor family member ERG. In addition, we find that in primary TMPRSS2-ERG-positive tumours PDE4D7 expression is significantly positively correlated with low-grade disease and a reduced likelihood of progression after primary treatment. Conversely, PDE4D7 transcript levels become significantly decreased in castration resistant prostate cancer (CRPC). conclusions: We further characterise and add physiological relevance to PDE4D7 as a novel marker that is associated with the development and progression of prostate tumours. We propose that the assessment of PDE4D7 levels may provide a novel, independent predictor of post-surgical disease progression

The Role of Pathology in Small Renal Mass Laparoscopic Cryoablation

Objective. We evaluated histological outcome of intraoperative biopsies at laparoscopic renal mass cryoablation (LCA), prevalence of peritumoral fat tissue invasion, and risk of tract seeding. Methods. Patients were biopsied 3–5 times (16-gauge). Histology was analyzed by general pathologists and reviewed. Peritumoral fat was histologically examined. The trocar used for biopsy-guidance was examined by cytology. Records were studied for reporting tract metastasis. Results. 77 biopsied renal masses with mean ± SD diameter 30 ± 7.4 mm were histologically classified by primary and review pathology revealing 64 and 62 malignancies, 13 and 15 benign lesions, respectively. In 30/34, the fat covered a carcinoma but revealed no malignancy. Cytology showed no malignant cells but was inconclusive in 1 case. No tract metastasis occurred. Conclusions. The use of an intraoperative biopsy protocol provides histological diagnosis of all renal masses. No existence of peritumoral fat tissue invasion or tract seeding was found

Exploring the impact of social network change:Experiences of older adults ageing in place

Social networks are sources of support and contribute to the well-being of older adults who are ageing in place. As social networks change, especially when accompanied by health decline, older adults' sources of support change and their well-being is challenged. Previous studies predominantly used quantitative measures to examine how older adults' social networks change. Alternatively, this study explores the impact of changing social networks on older adults' lives by examining their personal experiences. We held four focus groups, two with a total of 14 older adults who are ageing in place and receiving home care and two with a total of 20 home-care nurses from different regions and organisations in the Netherlands. Subsequently, an expert team of home-care professionals and managers discussed and verified the results. Procedures for grounded theory building were used for analysis. We revealed four themes of high-impact experiences: (a) struggling with illness/death of the spouse; (b) working out a changing relationship with (grand)children; (c) regretting the loss of people they have known for so long and (d) feeling dependent and stressed when helpers enter the network. Also, network dynamics were found to follow three consecutive stages: (a) awareness of social network change; (b) surprise when social network change actually occurs and (c) acceptance and adjusting to new circumstances. Together, the four themes of experiences and three stages of network change form an integrative model of the role of social network dynamics for older adults' lives when ageing in place

Characterisation of tumour vasculature in mouse brain by USPIO contrast-enhanced MRI

To enhance the success rate of antiangiogenic therapies in the clinic, it is crucial to identify parameters for tumour angiogenesis that can predict response to these therapies. In brain tumours, one such parameter is vascular leakage, which is a response to tumour-derived vascular endothelial growth factor-A and can be measured by Gadolinium-DTPA (Gd-DTPA)-enhanced magnetic resonance imaging (MRI). However, as vascular permeability and angiogenesis are not strictly coupled, tumour blood volume may be another potentially important parameter. In this study, contrast-enhanced MR imaging was performed in three orthotopic mouse models for human brain tumours (angiogenic melanoma metastases and E34 and U87 human glioma xenografts) using both Gd-DTPA to detect vascular leakage and ultrasmall iron oxide particles (USPIO) to measure blood volume. Pixel-by-pixel maps of the enhancement in the transverse relaxation rates (ΔR2 and ΔR2*) after injection of USPIO provided an index proportional to the blood volume of the microvasculature and macrovasculature, respectively, for each tumour. The melanoma metastases were characterised by a blood volume and vessel leakage higher than both glioma xenografts. The U87 glioblastoma xenografts displayed higher permeability and blood volume in the rim than in the core. The E34 glioma xenografts were characterised by a relatively high blood volume, accompanied by only a moderate blood–brain barrier disruption. Delineation of the tumour was best assessed on post-USPIO gradient-echo images. These findings suggest that contrast-enhanced MR imaging using USPIOs and, in particular, ΔR2 and ΔR2* quantitation, provides important additional information about tumour vasculature

A novel doxorubicin-glucuronide prodrug DOX-GA3 for tumour-selective chemotherapy: distribution and efficacy in experimental human ovarian cancer

The doxorubicin (DOX) prodrug N -[4-doxorubicin- N -carbonyl (oxymethyl) phenyl] O -β-glucuronyl carbamate (DOX-GA3) was synthesised for specific activation by human β-glucuronidase, which is released in necrotic areas of tumour lesions. This novel prodrug was completely activated to the parent drug by human β-glucuronidase with V max= 25.0 μmol min–1mg–1and K m= 1100 μM. The pharmacokinetics and distribution of DOX-GA3 in nude mice bearing human ovarian cancer xenografts (OVCAR-3) were determined and compared with DOX. Administration of DOX at 8 mg kg–1i.v. (maximum tolerated dose, MTD) to OVCAR-3-bearing mice resulted in a peak plasma concentration of the drug of 16.4 μM (t = 1 min). A 7.6-times lower peak plasma concentration of DOX was measured after injection of DOX-GA3 at 250 mg kg–1i.v. (50% of MTD). In normal tissues the prodrug showed peak DOX concentrations that were up to 5-fold (heart) lower than those found after DOX administration. DOX-GA3 activation by β-glucuronidase in the tumour yielded an almost 5-fold higher DOX peak concentration of 9.57 nmol g–1(P< 0.05) than the peak concentration of only 2.14 nmol g–1observed after DOX. As a consequence, the area under the curve of DOX calculated in tumour tissue after DOX-GA3 (13.1 μmol min–1g–1) was 10-fold higher than after DOX (1.31 μmol min–1g–1). The anti-tumour effects of DOX-GA3 and DOX were compared at equitoxic doses in OVCAR-3 xenografts at a mean tumour size of 125 mm3. The prodrug given i.v. at 500 mg kg–1weekly × 2 resulted in a maximum tumour growth inhibition of 87%, while the standard treatment with DOX at a dose of 8 mg kg–1i.v. weekly × 2 resulted in a maximum tumour growth inhibition of only 56%. Treatment with DOX-GA3 was also given to mice with larger tumours containing more necrosis. For tumours with a mean size of 400 mm3the specific growth delay by DOX-GA3 increased from 2.7 to 3.9. Our data indicate that DOX-GA3 is more effective than DOX and suggest that the prodrug will be specifically advantageous for treatment of advanced disease. © 2001 Cancer Research Campaign http://www.bjcancer.co

Plasma from septic shock patients induces loss of muscle protein

Contains fulltext : 97225.pdf (publisher's version ) (Open Access

Combined optical coherence tomography and intravascular ultrasound radio frequency data analysis for plaque characterization. Classification accuracy of human coronary plaques in vitro

This study was performed to characterize coronary plaque types by optical coherence tomography (OCT) and intravascular ultrasound (IVUS) radiofrequency (RF) data analysis, and to investigate the possibility of error reduction by combining these techniques. Intracoronary imaging methods have greatly enhanced the diagnostic capabilities for the detection of high-risk atherosclerotic plaques. IVUS RF data analysis and OCT are two techniques focusing on plaque morphology and composition. Regions of interest were selected and imaged with OCT and IVUS in 50 sections, from 14 human coronary arteries, sectioned post-mortem from 14 hearts of patients dying of non-cardiovascular causes. Plaques were classified based on IVUS RF data analysis (VH-IVUSTM), OCT and the combination of those. Histology was the benchmark. Imaging with both modalities and coregistered histology was successful in 36 sections. OCT correctly classified 24; VH-IVUS 25, and VH-IVUS/OCT combined, 27 out of 36 cross-sections. Systematic misclassifications in OCT were intimal thickening classified as fibroatheroma in 8 cross-sections. Misclassifications in VH-IVUS were mainly fibroatheroma as intimal thickening in 5 cross-sections. Typical image artifacts were found to affect the interpretation of OCT data, misclassifying intimal thickening as fibroatheroma or thin-cap fibroatheroma. Adding VH-IVUS to OCT reduced the error rate in this study