De gebiedsontwikkelaar:onderzoeksrapport

Onderzoek in opdracht van het Kenniscentrum NoorderRuimte. Het praktijkdoel is het opzetten van een kennisnetwerk en het onderzoeken naar het huidige onderwijsaanbod op het gebied van gebiedsontwikkeling en te onderzoeken in hoeverre dit aansluit op het vak van gebiedsontwikkelaar. Met dit onderzoek wordt het fundament gelegd om met vervolgonderzoek verder aan het praktijkdoel te kunnen werken. De centrale vraag van dit onderzoek luidt: Wat zijn de kenmerken van de sociale en de fysieke taken van de gebiedsontwikkelaar

Cumulative effects assessment: proof of concept marine mammals

This development of the framework and approach for a Cumulative Effects Assessment (CEA) is based on a literature review. The literature identified some key challenges that need to be addressed for CEA to evolve into a consistent, appropriate tool to assist decision-making. These challenges included • A clear distinction of the receptor-led CEA from the dominating stressor-led Environmental Impact Assessment (EIA) approaches and • Enabling CEA to provide ecosystem-relevant information at an appropriate regional scale. Therefore this CEA is explicitly developed to be a receptor-led and fully integrated framework, i.e. involving multiple occurrences of multiple pressures (from single and/or different sources) on multiple receptors, as opposed to other existing approaches dealing with only a subset of those pressures or receptors, hence our use of the phrase iCEA for integrated CEA. As a proof of concept for this iCEA we selected one receptor, the ecosystem component marine mammals. The main conclusions of this exercise (see Chapter 6) are that the iCEA framework and approach presented in this study appear suitable to fulfil its main purpose and ultimately inform the policy process as described in the conception phase. However it should be acknowledged this is only the very first step in a process where through many iterations new information can be introduced and assessed (relative to existing information) based on the criteria provided resulting in an improved iCEA with increasing confidence levels. As more information becomes available the relative importance of impact chains and its corresponding information modules may change giving direction to new areas for research. For further development of this iCEA towards its intended applications we can distinguish between the first purpose, i.e. identification of the main impact chains contributing to the risk that a specific ecosystem component is impacted, which can be achieved with the approach presented here focussing on one specific ecosystem component and the second purpose, i.e. an evaluation of the performance of possible management strategies, which would require all ecosystem components to be included as would be required for ecosystem-based management. Thus to further the development and application of this iCEA towards its (two) purpose(s) the recommendation is to: • Include the available information presented in this report into the iCEA and develop the Bayesian Belief Network such that it can process this information and its associated confidence into an assessment that identifies the main impact chains for the marine mammals. • Extend the framework and approach to (all) the other ecosystem components so that a truly integrated CEA is possible. Note that this is likely to affect the identification of what should be considered the main pressures to guide management. • Improve the information modules that emerged from the evaluation as the most promising to increase the confidence in the outcome of the iCEA. Note that the previous two steps may result in a different prioritisation of the information modules as the importance of pressures and hence impact chains changes

Relation of arterial geometry to luminal narrowing and histologic markers for plaque vulnerability: the remodeling paradox

AbstractObjective. To relate local arterial geometry with markers that are thought to be related to plaque rupture.Background. Plaque rupture often occurs at sites with minor luminal stenosis and has retrospectively been characterized by colocalization of inflammatory cells. Recent studies have demonstrated that luminal narrowing is related with the mode of atherosclerotic arterial remodeling.Methods. We obtained 1,521 cross section slices at regular intervals from 50 atherosclerotic femoral arteries. Per artery, the slices with the largest and smallest lumen area, vessel area and plaque area were selected for staining on the presence of macrophages (CD68), T-lymphocytes (CD45RO), smooth muscle cells (alpha-actin) and collagen.Results. Inflammation of the cap or shoulder of the plaque was observed in 33% of all cross sections. Significantly more CD68 and CD45RO positive cells, more atheroma, less collagen and less alpha-actin positive staining was observed in cross sections with the largest plaque area and largest vessel area vs. cross sections with the smallest plaque area and smallest vessel area, respectively. No difference in the number of inflammatory cells was observed between cross sections with the largest and smallest lumen area.Conclusion. Intraindividually, pathohistologic markers previously reported to be related to plaque vulnerability were associated with a larger plaque area and vessel area. In addition, inflammation of the cap and shoulder of the plaque was a common finding in the atherosclerotic femoral artery

Effects of Eprosartan on Diastolic Function and Neurohormones in Patients with Hypertension and Diastolic Dysfunction

To compare the effects of an angiotensin receptor blocker(ARB)-based regimen versus a non-ARB based regimen on diastolic function and neurohormones in patients with hypertension and diastolic dysfunction. 97 patients with a systolic blood pressure (SBP) a parts per thousand yen140 mmHg, a left ventricular ejection fraction > 0.50, and echocardiographic evidence of diastolic dysfunction were randomly assignment to open-label treatment with eprosartan (with other anti-hypertensives; n = 47) or other anti-hypertensives alone (n = 50). Echocardiography, including tissue Doppler imaging (TDI), and neurohormones were done at baseline and after 6 months. Mean age was 65 (+/- 10) years and 64% was female. During 6 months of treatment, SBP decreased from 157 +/- 16 to 145 +/- 18 mmHg in the eprosartan group and from 158 +/- 17 to 141 +/- 18 mmHg in the control group (both p <0.001; p = ns between groups). Diastolic function was unaffected in both groups and there was no correlation between changes in SBP and changes in mean TDI (r = -0.06; p = 0.58). Aldosterone levels decreased in the eprosartan group, but other neurohormones remained largely unchanged. Change in SBP was however related to the change in NT-proBNP (r = 0.26; p = 0.019). Lowering blood pressure, either with eprosartan or other anti-hypertensives in hypertensive patients with diastolic dysfunction did not change diastolic function after 6 months of treatment, but was associated with a decrease of NT-proBNP

Human monoclonal antibodies against Staphylococcus aureus surface antigens recognize in vitro and in vivo biofilm

Implant-associated Staphylococcus aureus infections are difficult to treat because of biofilm formation. Bacteria in a biofilm are often insensitive to antibiotics and host immunity. Monoclonal antibodies (mAbs) could provide an alternative approach to improve the diagnosis and potential treatment of biofilm-related infections. Here, we show that mAbs targeting common surface components of S. aureus can recognize clinically relevant biofilm types. The mAbs were also shown to bind a collection of clinical isolates derived from different biofilm-associated infections (endocarditis, prosthetic joint, catheter). We identify two groups of antibodies: one group that uniquely binds S. aureus in biofilm state and one that recognizes S. aureus in both biofilm and planktonic state. Furthermore, we show that a mAb recognizing wall teichoic acid (clone 4497) specifically localizes to a subcutaneously implanted pre-colonized catheter in mice. In conclusion, we demonstrate the capacity of several human mAbs to detect S. aureus biofilms in vitro and in vivo

Evaluating the Targeting of a Staphylococcus-aureus-Infected Implant with a Radiolabeled Antibody In Vivo

Implant infections caused by Staphylococcus aureus are difficult to treat due to biofilm formation, which complicates surgical and antibiotic treatment. We introduce an alternative approach using monoclonal antibodies (mAbs) targeting S. aureus and provide evidence of the specificity and biodistribution of S.-aureus-targeting antibodies in a mouse implant infection model. The monoclonal antibody 4497-IgG1 targeting wall teichoic acid in S. aureus was labeled with indium-111 using CHX-A”-DTPA as a chelator. Single Photon Emission Computed Tomography/computed tomographyscans were performed at 24, 72 and 120 h after administration of the 111In-4497 mAb in Balb/cAnNCrl mice with a subcutaneous implant that was pre-colonized with S. aureus biofilm. The biodistribution of this labelled antibody over various organs was visualized and quantified using SPECT/CT imaging, and was compared to the uptake at the target tissue with the implanted infection. Uptake of the 111In-4497 mAbs at the infected implant gradually increased from 8.34 %ID/cm3 at 24 h to 9.22 %ID/cm3 at 120 h. Uptake at the heart/blood pool decreased over time from 11.60 to 7.58 %ID/cm3, whereas the uptake in the other organs decreased from 7.26 to less than 4.66 %ID/cm3 at 120 h. The effective half-life of 111In-4497 mAbs was determined to be 59 h. In conclusion, 111In-4497 mAbs were found to specifically detect S. aureus and its biofilm with excellent and prolonged accumulation at the site of the colonized implant. Therefore, it has the potential to serve as a drug delivery system for the diagnostic and bactericidal treatment of biofilm

Prognostic Value of Histopathological Thrombus Age in Large Vessel Occlusion-Related Stroke

Introduction: Acute mechanical thrombectomy (MT) is the preferred treatment for large vessel occlusion-related stroke. Histopathological research on the obtained occlusive embolic thrombus may provide information regarding the aetiology and pathology of the lesion to predict prognosis and propose possible future acute ischaemic stroke therapy. Methods: A total of 75 consecutive patients who presented to the Amphia Hospital with acute large vessel occlusion-related stroke and underwent MT were included in the study. The obtained thrombus materials were subjected to standard histopathological examination. Based on histological criteria, they were considered fresh (1 day old). Patients were followed for 2 years for documentation of all-cause mortality. Results: Thrombi were classified as fresh in 40 patients (53%) and as older in 35 patients (47%). Univariate Cox regression analysis showed that thrombus age, National Institutes of Health Stroke Scale at hospital admission, and patient age were associated with long-term mortality (p < 0.1). Multivariable Cox hazards and Kaplan-Meier analysis demonstrated that after extensive adjustment for clinical and procedural variables, thrombus age persisted in being independently associated with higher long-term mortality (hazard ratio: 3.34; p = 0.038, log-rank p = 0.013). Conclusion: In this study, older thromboemboli are responsible for almost half of acute large ischaemic strokes. Moreover, the presence of an old thrombus is an independent predictor of mortality in acute large vessel occlusion-related stroke. More research is warranted regarding future therapies based on thrombus composition

Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction, GALACTIC‐HF: baseline characteristics and comparison with contemporary clinical trials

Aims: The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC‐HF) trial. Here we describe the baseline characteristics of participants in GALACTIC‐HF and how these compare with other contemporary trials. Methods and Results: Adults with established HFrEF, New York Heart Association functional class (NYHA) ≥ II, EF ≤35%, elevated natriuretic peptides and either current hospitalization for HF or history of hospitalization/ emergency department visit for HF within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic‐guided dosing: 25, 37.5 or 50 mg bid). 8256 patients [male (79%), non‐white (22%), mean age 65 years] were enrolled with a mean EF 27%, ischemic etiology in 54%, NYHA II 53% and III/IV 47%, and median NT‐proBNP 1971 pg/mL. HF therapies at baseline were among the most effectively employed in contemporary HF trials. GALACTIC‐HF randomized patients representative of recent HF registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressure &lt; 100 mmHg (n = 1127), estimated glomerular filtration rate &lt; 30 mL/min/1.73 m2 (n = 528), and treated with sacubitril‐valsartan at baseline (n = 1594). Conclusions: GALACTIC‐HF enrolled a well‐treated, high‐risk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation

Revealing Attentional Biases in Conspiracy Theory Believers

Valuable insights have been gained from studies on the subjective experience of belief in conspiracy theories. However, the focus on explicit processes might overlook relevant underlying cognitive processes. In this paper we take a different approach and explore the existence of an attentional bias among conspiracy theory believers. As an implicit measure of this attentional bias, we employ a colour-naming task containing topic- and conspiracy-related words. We hypothesized that 1) believers exhibit an attentional bias towards conspiracy-related words, 2) this bias is larger compared to non-believers, and 3) it is associated with self-reported conspiracy beliefs. In two experiments (total n = 418) conspiracy believers and non-believers completed the colour-naming task and we found support for believers’ conspiracy-related attentional bias. These findings contribute to understanding the self-sustaining nature of conspiracy beliefs, suggesting that believers may perceive or attend to information differently than non-believers. The results also indicate the promise of an implicit measure of conspiracy theory belief