Verspreiding inlaatwater in beeld met nieuwe tracer

Inlaatwater heeft in de polder Quarles van Ufford zelfs in een droge periode geen invloed op de waterkwaliteit van kleine landbouwsloten. Dat blijkt uit metingen van de concentratie gadolinium, die zijn uitgevoerd voor het project Monitoring Stroomgebieden. Hiermee komt voor dit gebied een einde aan de twijfel over de invloed van inlaatwater op de oppervlaktewaterkwaliteit en is er meer duidelijkheid over de belasting vanuit de landbouw

Tracing the spatial propagation of river inlet water into an agricultural polder area using anthropogenic gadolinium

Diverting river water into agricultural areas or nature reserves is a frequently applied management strategy to prevent fresh water shortage. However, the river water might have negative consequences for chemical and ecological water quality in the receiving water bodies. This study aimed to obtain a spatial image of the diverted river water propagation into a hydrologically complex polder area, the polder Quarles van Ufford in The Netherlands. We used anthropogenic gadolinium (Gd-anomaly) as a tracer for river water that was diverted into the polder. A clear reduction in the river water contribution was found between very dry conditions on 5 August 2010 and very wet conditions on 22 October. Despite the large river water impact on 5 August, the diverted river water did not propagate up into the small agricultural headwater ditches. Gadolinium proved to be an effective tracer for diverted river water in a polder system. We applied our results to upgrade the interpretation of water quality monitoring data and to validate an integrated nutrient transport mode

The Current Status of Immune Checkpoint Inhibitors in Neuro-Oncology:A Systematic Review

The introduction of immune checkpoint inhibitors (ICI), as a novel treatment modality, has transformed the field of oncology with unprecedented successes. However, the efficacy of ICI for patients with glioblastoma or brain metastases (BMs) from any tumor type is under debate. Therefore, we systematically reviewed current literature on the use of ICI in patients with glioblastoma and BMs. Prospective and retrospective studies evaluating the efficacy and survival outcomes of ICI in patients with glioblastoma or BMs, and published between 2006 and November 2019, were considered. A total of 88 studies were identified (n = 8 in glioblastoma and n = 80 in BMs). In glioblastoma, median progression-free (PFS) and overall survival (OS) of all studies were 2.1 and 7.3 months, respectively. In patients with BMs, intracranial responses have been reported in studies with melanoma and non-small-cell lung cancer (NSCLC). The median intracranial and total PFS in these studies were 2.7 and 3.0 months, respectively. The median OS in all studies for patients with brain BMs was 8.0 months. To date, ICI demonstrate limited efficacy in patients with glioblastoma or BMs. Future research should focus on increasing the local and systemic immunological responses in these patients

Allogeneic NK cells induce the <i>in vitro</i> activation of monocyte-derived and conventional type-2 dendritic cells and trigger an inflammatory response under cancer-associated conditions

Natural killer (NK) cells are innate lymphocytes capable to recognize and kill virus-infected and cancer cells. In the past years, the use of allogeneic NK cells as anti-cancer therapy gained interest due to their ability to induce graft-versus-cancer responses without causing graft-versus-host disease and multiple protocols have been developed to produce high numbers of activated NK cells. While the ability of these cells to mediate tumor kill has been extensively studied, less is known about their capacity to influence the activity of other immune cells that may contribute to a concerted anti-tumor response in the tumor microenvironment (TME). In this study, we analyzed how an allogeneic off-the-shelf cord blood stem cell-derived NK-cell product influenced the activation of dendritic cells (DC). Crosstalk between NK cells and healthy donor monocyte-derived DC (MoDC) resulted in the release of IFNγ and TNF, MoDC activation, and the release of the T-cell-recruiting chemokines CXCL9 and CXCL10. Moreover, in the presence of prostaglandin-E2, NK cell/MoDC crosstalk antagonized the detrimental effect of IL-10 on MoDC maturation leading to higher expression of multiple (co-)stimulatory markers. The NK cells also induced activation of conventional DC2 (cDC2) and CD8 + T cells, and the release of TNF, GM-CSF, and CXCL9/10 in peripheral blood mononuclear cells of patients with metastatic colorectal cancer. The activated phenotype of MoDC/cDC2 and the increased release of pro-inflammatory cytokines and T-cell-recruiting chemokines resulting from NK cell/DC crosstalk should contribute to a more inflamed TME and may thus enhance the efficacy of T-cell-based therapies.</p

Patients with Cluster A Personality Disorders in Psychotherapy: An Effectiveness Study

Abstract BACKGROUND: While psychopharmacological studies are common in patients with cluster A personality disorders, the effects of psychotherapy have received little attention. The aim of this study is to explore whether psychotherapeutic treatment yields health gains for these patients. METHODS: The study was conducted between March 2003 and June 2008 in 6 mental health care centres in the Netherlands, with a sample of 57 patients with a DSM-IV-TR axis II cluster A diagnosis. Patients were assigned to 3 settings of psychotherapeutic treatment (outpatient, day hospital, inpatient), and effectiveness was assessed at 18 months after baseline. An intention-to-treat analysis was conducted for psychiatric symptoms (Brief Symptom Inventory), psychosocial functioning (Outcome Questionnaire-45) and quality of life (EQ-5D), using multilevel statistical modelling. As the study was non-randomised, the propensity score method was used to control for initial differences. RESULTS: Patients in the day hospital and inpatient group improved substantially in terms of psychiatric symptoms, social and interpersonal functioning, and quality of life. Patients in the outpatient group showed less improvement. Direct comparison of the improvement of psychiatric symptoms showed significant results in favour of day hospital (p = 0.046) and inpatient (p = 0.01) treatment, as compared to outpatient treatment. However, due to substantial baseline differences, this direct comparison should be judged carefully. CONCLUSIONS: Cluster A psychopathology is not a contraindication to benefit from psychotherapy. This is especially true for more intensive forms like inpatient and day hospital treatment. Future research should focus more on psychotherapeutic treatment to gain further insight into effective treatment options for this patient grou

Photoactivation of lysosomally sequestered sunitinib after angiostatic treatment causes vascular occlusion and enhances tumor growth inhibition

The angiogenesis inhibitor sunitinib is a tyrosine kinase inhibitor that acts mainly on the VEGF and PDGF pathways. We have previously shown that sunitinib is sequestered in the lysosomes of exposed tumor and endothelial cells. This phenomenon is part of the drug-induced resistance observed in the clinic. Here, we demonstrate that when exposed to light, sequestered sunitinib causes immediate destruction of the lysosomes, resulting in the release of sunitinib and cell death. We hypothesized that this photoactivation of sunitinib could be used as a vaso-occlusive vascular-targeting approach to treating cancer. Spectral properties of sunitinib and its lysosomal accumulation were measured in vitro. The human A2780 ovarian carcinoma transplanted onto the chicken chorioallantoic membrane (CAM) and the Colo-26 colorectal carcinoma model in Balb/c mice were used to test the effects of administrating sunitinib and subsequently exposing tumor tissue to light. Tumors were subsequently resected and subject to immunohistochemical analysis. In A2780 ovarian carcinoma tumors, treatment with sunitinib+light resulted in immediate specific angio-occlusion, leading to a necrotic tumor mass 24 h after treatment. Tumor growth was inhibited by 70% as compared with the control group (**P= 4; P = 0.0002). Histology revealed that photoactivation of sunitinib resulted in a change in tumor vessel architecture. The current results suggest that the spectral properties of sunitinib can be exploited for application against certain cancer indications

Do I-Pass for FAIR?:A self-assessment tool to measure the FAIR-ness of an organization

The 15 FAIR data principles are intended to be applied to a dataset, but the acronym FAIR is also used as an adjective for other (digital) matters, such as FAIR data stewardship, FAIR data infrastructure and FAIR data services. Moreover, in the context of Open Science and scientific integrity, more and more Dutch universities and research organizations discuss a FAIR organization as an important goal, thus implementing RDM practices and support with the FAIR principles as a main driver. Triggered by this use of the acronym FAIR for organizations, an LCRDM (National Coordination Point Research Data Management) task group explored the definition, characteristics and principles of a so-called ‘FAIR enabling organization’. The task group delivered two products: (1) a definition for a FAIR enabling organization and (2) a self-assessment tool to evaluate the FAIR-ness of a research organization (research institute, university or university of applied sciences). This self-assessment tool is a simple instrument, presented in an editable PDF form. By answering the questions and evaluating the level (beginner, intermediate, or advanced) at which you assess the performance of your organization, you will be able to define the actual FAIR-ness. In addition you can define a Road Map to become a FAIR Enabling Research Organization using the information in de more advances level(s)