Comparing choice models of river health improvement for the Goulburn River

The extent of the benefits of improved river health remain uncertain. Quantifying these benefits is useful in prioritising policy investments. This study uses the Choice Modelling technique to estimate the value that households attach to attributes of improved river health. Data from a choice modelling survey supported by DSE Victoria are employed to elicit household preferences in a case study of the Goulburn River. Results from conditional and nested logit model specifications indicate that respondents hold positive values for higher levels of fish and bird populations and for increasing riverside vegetation. The standard Hausman test for Independence-from-Irrelevant-Alternatives (IIA) assumptions violations is found to give inconsistent results. The value estimates of the conditional and nested logit models are shown to be statistically similar indicating that testing for IIA violation may be more complicated than currently assumed thus raising questions about the efficacy of the more complex nested logit model.Cheap talk, choice modelling, Mekong River Delta, wetland values, willingness to pay, Resource /Energy Economics and Policy, Q25,

Nanobody-Based Probes for Subcellular Protein Identification and Visualization

Understanding how building blocks of life contribute to physiology is greatly aided by protein identification and cellular localization. The two main labeling approaches developed over the past decades are labeling with antibodies such as immunoglobulin G (IgGs) or use of genetically encoded tags such as fluorescent proteins. However, IgGs are large proteins (150 kDa), which limits penetration depth and uncertainty of target position caused by up to ∼25 nm distance of the label created by the chosen targeting approach. Additionally, IgGs cannot be easily recombinantly modulated and engineered as part of fusion proteins because they consist of multiple independent translated chains. In the last decade single domain antigen binding proteins are being explored in bioscience as a tool in revealing molecular identity and localization to overcome limitations by IgGs. These nanobodies have several potential benefits over routine applications. Because of their small size (15 kDa), nanobodies better penetrate during labeling procedures and improve resolution. Moreover, nanobodies cDNA can easily be fused with other cDNA. Multidomain proteins can thus be easily engineered consisting of domains for targeting (nanobodies) and visualization by fluorescence microscopy (fluorescent proteins) or electron microscopy (based on certain enzymes). Additional modules for e.g., purification are also easily added. These nanobody-based probes can be applied in cells for live-cell endogenous protein detection or may be purified prior to use on molecules, cells or tissues. Here, we present the current state of nanobody-based probes and their implementation in microscopy, including pitfalls and potential future opportunities

Developmental Course and Risk Factors of Physical Aggression in Late Adolescence

This study examined risk factors of physical aggression during transition from early to late adolescence using a two-wave longitudinal study. Specifically, we examined if risk factors in early adolescence predict physically aggressive behavior starting in late adolescence and why some adolescents desist physical aggressive behavior while others do not. The study sample consisted of 2289 Norwegian adolescents (1235 girls) who participated in the Young-HUNT1 study (mean age 14.5) and the follow-up study 4 years later, Young-HUNT2 study (mean age 18.4). One in six young adolescents reported engaging in physical fights. Moreover, physical aggression in early adolescence was significantly associated with male gender, attention problems, academic problems, being bullied, drinking alcohol, and smoking. Male gender and heavy drinking during early adolescence increased the risk for newly emerging aggressive behavior in late adolescence, whereas heavy drinking during early adolescence was a predictor for persistent versus desisting aggressive behavior in late adolescence.publishedVersionPaid Open Acces

Cholesterol efflux pathways, inflammation, and atherosclerosis

Plasma levels of high-density lipoprotein (HDL) inversely correlate with the incidence of cardiovascular diseases (CVD). The causal relationship between plasma HDL-cholesterol levels and CVD has been called into question by Mendelian randomization studies and the majority of clinical trials not showing any benefit of plasma HDL-cholesterol raising drugs on CVD. Nonetheless, recent Mendelian randomization studies including an increased number of CVD cases compared to earlier studies have confirmed that HDL-cholesterol levels and CVD are causally linked. Moreover, several studies in large population cohorts have shown that the cholesterol efflux capacity of HDL inversely correlates with CVD. Cholesterol efflux pathways exert anti-inflammatory and antiatherogenic effects by suppressing proliferation of hematopoietic stem and progenitor cells, and inflammation and inflammasome activation in macrophages. Cholesterol efflux pathways also suppress the accumulation of cholesteryl esters in macrophages, i.e. macrophage foam cell formation. Recent single-cell RNASeq studies on atherosclerotic plaques have suggested that macrophage foam cells have lower expression of inflammatory genes than non-foam cells, probably reflecting liver X receptor activation, upregulation of ATP Binding Cassette A1 and G1 cholesterol transporters and suppression of inflammation. However, when these pathways are defective lesional foam cells may become pro-inflammatory

Serum phosphate and social deprivation independently predict all-cause mortality in chronic kidney disease

Background: Hyperphosphataemia is linked to cardiovascular disease and mortality in chronic kidney disease (CKD). Outcome in CKD is also affected by socioeconomic status. The objective of this study was to assess the associations between serum phosphate, multiple deprivation and outcome in CKD patients. Methods: All adult patients currently not on renal replacement therapy (RRT), with first time attendance to the renal outpatient clinics in the Glasgow area between July 2010 and June 2014, were included in this prospective study. Area socioeconomic status was assessed as quintiles of the Scottish Index of Multiple Deprivation (SIMD). Outcomes were all-cause and cardiovascular mortality and commencement of RRT. Results: The cohort included 2950 patients with a median (interquartile range) age 67.6 (53.6–76.9) years. Median (interquartile range) eGFR was 38.1 (26.3–63.5) ml/min/1.73 m 2 , mean (±standard deviation) phosphate was 1.13 (±0.24) mmol/L and 31.6 % belonged to the most deprived quintile (SIMD quintile I). During follow-up 375 patients died and 98 commenced RRT. Phosphate ≥1.50 mmol/L was associated with all-cause (hazard ratio (HR) 2.51; 95 % confidence interval (CI) 1.63-3.89) and cardiovascular (HR 5.05; 95 % CI 1.90–13.46) mortality when compared to phosphate 0.90–1.09 mmol/L in multivariable analyses. SIMD quintile I was independently associated with all-cause mortality. Phosphate did not weaken the association between deprivation index and mortality, and there was no interaction between phosphate and SIMD quintiles. Neither phosphate nor SIMD predicted commencement of RRT. Conclusions Multiple deprivation and serum phosphate were strong, independent predictors of all-cause mortality in CKD and showed no interaction. Phosphate also predicted cardiovascular mortality. The results suggest that phosphate lowering should be pursued regardless of socioeconomic status

Risk factors of ischemic stroke and subsequent outcome in hemodialysis patients

Background and purpose: End stage renal disease (ESRD) requiring hemodialysis (HD) carries up to a 10-fold greater risk of stroke than normal renal function. Knowledge concerning risk factors and management strategies derived from the general population may not be applicable to those with ESRD. We studied a large ESRD population to identify risk factors and outcomes for stroke. Methods: All adult patients receiving HD for ESRD from 01/01/2007 to 31/12/2012 were extracted from the electronic patient record. Variables associated with stroke were identified by survival analysis; demographic, clinical, imaging and dialysis related variables were assessed and case-fatality determined. Follow-up was until 31/12/2013. Results: 1382 patients were identified (mean age 60.5 years, 58.5% male). The prevalence of AF was 21.2% and 59.4% were incident HD patients. 160 (11.6%) experienced a stroke during 3471 patient-years of follow-up (95% ischemic). Stroke incidence was 41.5/1000 patient-years in prevalent and 50.1/1000 patient-years in incident HD patients. Factors associated with stroke on regression analysis were prior stroke, diabetes and age at starting renal replacement therapy. AF was not significantly associated with stroke and warfarin did not affect stroke risk in warfarin treated patients. Fatality was 18.8% at 7, 26.9% at 28 and 56.3% 365 days after stroke.<p></p> Conclusions: Incidence of stroke is high in patients with ESRD on HD with high case-fatality. Incident HD patients had the highest stroke incidence. Many, but not all, important risk factors commonly associated with stroke in the general population were not associated with stroke in patients receiving HD

Client predictors of therapy dropout in a primary care setting: a prospective cohort study

Background Therapy dropout poses a major challenge. Considerable research has been conducted on predictors of dropout, however none in the context of primary mental health services in Norway. The purpose of this study was to investigate which client characteristics can predict dropout from the service Prompt Mental Health Care (PMHC). Methods We performed a secondary analysis of a Randomized Controlled Trial (RCT). Our sample consisted of 526 adult participants receiving PMHC-treatment in the municipalities of Sandnes and Kristiansand, between November 2015 to August 2017. Using logistic regression, we investigated the association between nine client characteristics and dropout. Results The dropout rate was 25.3%. The adjusted analysis indicated that older clients had a lower odds ratio (OR) of dropping out compared to younger clients (OR = 0.43, [95% CI = 0.26, 0.71]). Moreover, clients with higher education had a lower odds ratio of dropping out compared to clients with lower levels of education (OR = 00.55, 95% CI [0.34, 0.88]), while clients who were unemployed were more likely to drop-out as compared the regularly employed (OR = 2.30, [95% CI = 1.18, 4.48]). Finally, clients experiencing poor social support had a higher odds ratio of dropping out compared to clients who reported good social support (OR = 1.81, [95% CI = 1.14, 2.87]). Sex, immigrant background, daily functioning, symptom severity and duration of problems did not predict dropout. Conclusion The predictors found in this prospective study might help PMHC-therapists identify clients at risk of dropout. Strategies for preventing dropout are discussed.publishedVersio

Endocytosis of Extracellular Vesicles and Release of Their Cargo from Endosomes

Extracellular vesicles (EVs), such as exosomes, can mediate long-distance communication between cells by delivering biomolecular cargo. It is speculated that EVs undergo back-fusion at multivesicular bodies (MVBs) in recipient cells to release their functional cargo. However, direct evidence is lacking. Tracing the cellular uptake of EVs with high resolution as well as acquiring direct evidence for the release of EV cargo is challenging mainly because of technical limitations. Here, we developed an analytical methodology, combining state-of-theart molecular tools and correlative light and electron microscopy, to identify the intracellular site for EV cargo release. GFP was loaded inside EVs through the expression of GFP-CD63, a fusion of GFP to the cytosolic tail of CD63, in EV producer cells. In addition, we genetically engineered a cell line which expresses anti-GFP fluobody that specifically recognizes the EV cargo (GFP). Incubation of anti-GFP fluobody- expressing cells with GFP-CD63 EVs resulted in the formation of fluobody punctae, designating cytosolic exposure of GFP. Endosomal damage was not observed in EV acceptor cells. Ultrastructural analysis of the underlying structures at GFP/ fluobody double-positive punctae demonstrated that EV cargo release occurs from endosomes/lysosomes. Finally, we show that neutralization of endosomal pH and cholesterol accumulation in endosomes leads to blockage of EV cargo exposure. In conclusion, we report that a fraction of internalized EVs fuse with the limiting membrane of endosomes/lysosomes in an acidification-dependent manner, which results in EV cargo exposure to the cell cytosol

Comparing problem-based learning students to students in a lecture-based curriculum: learning strategies and the relation with self-study time

In educational theory, deep processing (i.e., connecting different study topics together) and self-regulation (i.e., taking control over one’s own learning process) are considered effective learning strategies. These learning strategies can be influenced by the learning environment. Problem-based learning (PBL), a student-centered educational method, is believed to stimulate the use of these effective learning strategies. Several aspects of PBL such as discussions of real-life problems, selecting literature by the students themselves, and formulating answers to learning issues encourage students’ use of deep processing and self-regulation. In the present study, third-year PBL law students were compared to third-year law students of a lecture-based program with respect to their learning strategies, which were measured with the Inventory Learning Styles (ILS; Vermunt in British Journal of Educational Psychology, 68, 149–171, 1998). In addition, the relation between time invested in self-study and learning strategies, when taking the instructional method into account, was explored. Results showed that PBL students reported to apply deep processing, self-regulation, and external regulation more frequently than their non-PBL counterparts. PBL seems to contribute to the use of effective learning strategies, but PBL students also relied more often on external sources for their regulation, such as teachers, course material, and assessment