Four-jointed knock-out delays renal failure in an ADPKD model with kidney injury

Autosomal Dominant Polycystic Kidney Disease is characterised by the development of fluid-filled cysts in the kidneys which lead to end-stage renal disease (ESRD). In the majority of cases, the disease is caused by a mutation in the Pkd1 gene. In a previous study, we demonstrated that renal injury can accelerate cyst formation in Pkd1 knock-out (KO) mice. In that study, we found that after injury four-jointed (Fjx1), an upstream regulator of planar cell polarity and the Hippo pathway, was aberrantly expressed in Pkd1 KO mice compared to WT. Therefore, we hypothesised a role for Fjx1 in injury/repair and cyst formation. We generated single and double deletion mice for Pkd1 and Fjx1, and we induced toxic renal injury using the nephrotoxic compound 1,2-dichlorovinyl-cysteine. We confirmed that nephrotoxic injury can accelerate cyst formation in Pkd1 mutant mice. This caused Pkd1 KO mice to reach ESRD significantly faster; unexpectedly, double KO mice survived significantly longer. Cyst formation was comparable in both models, but we found significantly less fibrosis and macrophage infiltration in double KO mice. Taken together, these data suggest that Fjx1 disruption protects the cystic kidneys against kidney failure by reducing inflammation and fibrosis. Moreover, we describe, for the first time, an interesting (yet unidentified) mechanism that partially discriminates cyst growth from fibrogenesis. © 2019 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland

Development and field testing of a vision-based displacement system using a low cost wireless action camera

This is the author accepted manuscript. The final version is available from Elsevier via the DOI in this recordThis paper describes development of a contactless, low cost vision-based system for displacement measurement of civil structures. Displacement measurements provide a valuable insight into the structural condition and service behaviour of bridges under live loading. Conventional displacement gauges or GPS based systems have limitations in terms of access to the infrastructure and accuracy. The system introduced in this paper provides a low cost durable alternative which is rapidly deployable in the field and does not require direct contact or access to the infrastructure or its vicinity. A commercial action camera was modified to facilitate the use of a telescopic lens and paired with the development of robust displacement identification algorithms based on pattern matching. Performance was evaluated first in a series of controlled laboratory tests and validated against displacement measurements obtained using a fibre optic displacement gauge. The efficiency of the system for field applications was then demonstrated by capturing the validated bridge response of two structures under live loading including the iconic peace bridge. Located in the City of Derry, Northern Ireland, the Peace Bridge is a 310 m curved self-anchored suspension pedestrian bridge structure. The vision-based results of the field experiment were confirmed against displacements calculated from measured accelerations during a dynamic assessment of the structure under crowd loading. In field applications the developed system can achieve a root mean square error (RMSE) of 0.03 mm against verified measurements

MHD models of Pulsar Wind Nebulae

Pulsar Wind Nebulae (PWNe) are bubbles or relativistic plasma that form when the pulsar wind is confined by the SNR or the ISM. Recent observations have shown a richness of emission features that has driven a renewed interest in the theoretical modeling of these objects. In recent years a MHD paradigm has been developed, capable of reproducing almost all of the observed properties of PWNe, shedding new light on many old issues. Given that PWNe are perhaps the nearest systems where processes related to relativistic dynamics can be investigated with high accuracy, a reliable model of their behavior is paramount for a correct understanding of high energy astrophysics in general. I will review the present status of MHD models: what are the key ingredients, their successes, and open questions that still need further investigation.Comment: 18 pages, 5 figures, Invited Review, Proceedings of the "ICREA Workshop on The High-Energy Emission from Pulsars and their Systems", Sant Cugat, Spain, April 12-16, 201

Cost-effectiveness of vaccination of immunocompetent older adults against herpes zoster in the Netherlands: a comparison between the adjuvanted subunit and live-attenuated vaccines.

BACKGROUND: The newly registered adjuvanted herpes zoster subunit vaccine (HZ/su) has a higher efficacy than the available live-attenuated vaccine (ZVL). National decision-makers soon need to decide whether to introduce HZ/su or to prefer HZ/su above ZVL. METHODS: Using a Markov model with a decision tree, we conducted a cost-effectiveness analysis of vaccination with HZ/su (two doses within 2 months) or zoster vaccine live (ZVL) (single dose, or single dose with a booster after 10 years) for cohorts of 50-, 60-, 70- or 80-year-olds in the Netherlands. The model was parameterized using vaccine efficacy data from randomized clinical trials and up-to-date incidence, costs and health-related quality of life data from national datasets. We used a time horizon of 15 years, and the analysis was conducted from the societal perspective. RESULTS: At a coverage of 50%, vaccination with two doses of HZ/su was estimated to prevent 4335 to 10,896 HZ cases, depending on the cohort age. In comparison, this reduction was estimated at 400-4877 for ZVL and 427-6466 for ZVL with a booster. The maximum vaccine cost per series of HZ/su to remain cost-effective to a willingness-to-pay threshold of €20,000 per quality-adjusted life year (QALY) gained ranged from €109.09 for 70-year-olds to €63.68 for 50-year-olds. The cost-effectiveness of ZVL changed considerably by age, with corresponding maximum vaccine cost per dose ranging from €51.37 for 60-year-olds to €0.73 for 80-year-olds. Adding a ZVL booster after 10 years would require a substantial reduction of the maximum cost per dose to remain cost-effective as compared to ZVL single dose. Sensitivity analyses on the vaccine cost demonstrated that there were scenarios in which vaccination with either HZ/su (two doses), ZVL single dose or ZVL + booster could be the most cost-effective strategy. CONCLUSIONS: A strategy with two doses of HZ/su was superior in reducing the burden of HZ as compared to a single dose or single dose + booster of ZVL. Both vaccines could potentially be cost-effective to a conventional Dutch willingness-to-pay threshold for preventive interventions. However, whether HZ/su or ZVL would be the most cost-effective alternative depends largely on the vaccine cost

Disturbance and Recovery of Salt Marsh Arthropod Communities following BP Deepwater Horizon Oil Spill

Oil spills represent a major environmental threat to coastal wetlands, which provide a variety of critical ecosystem services to humanity. The U.S. Gulf of Mexico is a hub of oil and gas exploration activities that historically have impacted intertidal habitats such as salt marsh. Following the BP Deepwater Horizon oil spill, we sampled the terrestrial arthropod community and marine invertebrates found in stands of Spartina alterniflora, the most abundant plant in coastal salt marshes. Sampling occurred in 2010 as oil was washing ashore and a year later in 2011. In 2010, intertidal crabs and terrestrial arthropods (insects and spiders) were suppressed by oil exposure even in seemingly unaffected stands of plants; however, Littoraria snails were unaffected. One year later, crab and arthropods had largely recovered. Our work is the first attempt that we know of assessing vulnerability of the salt marsh arthropod community to oil exposure, and it suggests that arthropods are both quite vulnerable to oil exposure and quite resilient, able to recover from exposure within a year if host plants remain healthy

Are health care professionals able to judge cancer patients' health care preferences correctly? A cross-sectional study

Background: Health care for cancer patients is primarily shaped by health care professionals. This raises the question to what extent health care professionals are aware of patients' preferences, needs and values. The aim of this study was to explore to what extent there is concordance between patients' preferences in cancer care and patients' preferences as estimated by health care professionals. We also examined whether there were gender differences between health care professionals with regard to the degree in which they can estimate patients' preferences correctly. Methods: To obtain unbiased insight into the specific preferences of cancer patients, we developed the 'Cancer patients' health care preferences' questionnaire'. With this questionnaire we assessed a large sample of cancer patients (n = 386). Next, we asked health care professionals (medical oncologists, nurses and policymakers, n = 60) to fill out this questionnaire and to indicate preferences they thought cancer patients would have. Mean scores between groups were compared using Mann-Whitney tests. Effect sizes (ESs) were calculated for statistically significant differences. Results: We found significant differences (ESs 0.31 to 0.90) between patients and professionals for eight out of twenty-one scales and two out of eight single items. Patients valued care aspects related to expertise and attitude of health care providers and accessibility of services as more important than the professionals thought they would do. Health care professionals overestimated the value that patients set on particularly organisational and environmental aspects. We found significant gender-related differences between the professionals (ESs 0.69 to 1.39) for eight out of twenty-one scales and two out of eight single items. When there were significant differences between male and female healthcare professionals in their estimation of patients health care preferences, female health care professionals invariably had higher scores. Generally, female health care professionals did not estimate patients' preferences and needs better than their male colleagues. Conclusions: Health care professionals are reasonably well able to make a correct estimation of patients preferences, but they should be aware of their own bias and use additional resources to gain a better understanding of patients' specific preferences for each patient is different and ultimately the care needs and preferences will also be unique to the person

Participation in and attitude towards the national immunization program in the Netherlands: data from population-based questionnaires

Contains fulltext : 108971.pdf (publisher's version ) (Open Access)BACKGROUND: Knowledge about the determinants of participation and attitude towards the National Immunisation Program (NIP) may be helpful in tailoring information campaigns for this program. Our aim was to determine which factors were associated with nonparticipation in the NIP and which ones were associated with parents' intention to accept remaining vaccinations. Further, we analyzed possible changes in opinion on vaccination over a 10 year period. METHODS: We used questionnaire data from two independent, population-based, cross-sectional surveys performed in 1995-96 and 2006-07. For the 2006-07 survey, logistic regression modelling was used to evaluate what factors were associated with nonparticipation and with parents' intention to accept remaining vaccinations. We used multivariate multinomial logistic regression modelling to compare the results between the two surveys. RESULTS: Ninety-five percent of parents reported that they or their child (had) participated in the NIP. Similarly, 95% reported they intended to accept remaining vaccinations. Ethnicity, religion, income, educational level and anthroposophic beliefs were important determinants of nonparticipation in the NIP. Parental concerns that played a role in whether or not they would accept remaining vaccinations included safety of vaccinations, maximum number of injections, whether vaccinations protect the health of one's child and whether vaccinating healthy children is necessary. Although about 90% reported their opinion towards vaccination had not changed, a larger proportion of participants reported to be less inclined to accept vaccination in 2006-07 than in 1995-96. CONCLUSION: Most participants had a positive attitude towards vaccination, although some had doubts. Groups with a lower income or educational level or of non-Western descent participated less in the NIP than those with a high income or educational level or indigenous Dutch and have been less well identified previously. Particular attention ought to be given to these groups as they contribute in large measure to the rate of nonparticipation in the NIP, i.e., to a greater extent than well-known vaccine refusers such as specific religious groups and anthroposophics. Our finding that the proportion of the population inclined to accept vaccinations is smaller than it was 10 years ago highlights the need to increase knowledge about attitudes and beliefs regarding the NIP

Which dressing do donor site wounds need?: study protocol for a randomized controlled trial

Donor site wounds after split-skin grafting are rather 'standard' wounds. At present, lots of dressings and topical agents for donor site wounds are commercially available. This causes large variation in the local care of these wounds, while the optimum 'standard' dressing for local wound care is unclear. This protocol describes a trial in which we investigate the effectiveness of various treatment options for these donor site wounds. A 14-center, six-armed randomized clinical trial is being carried out in the Netherlands. An a-priori power analysis and an anticipated dropout rate of 15% indicates that 50 patients per group are necessary, totaling 300 patients, to be able to detect a 25% quicker mean time to complete wound healing. Randomization has been computerized to ensure allocation concealment. Adult patients who need a split-skin grafting operation for any reason, leaving a donor site wound of at least 10 cm2 are included and receive one of the following dressings: hydrocolloid, alginate, film, hydrofiber, silicone dressing, or paraffin gauze. No combinations of products from other intervention groups in this trial are allowed. Optimum application and changes of these dressings are pursued according to the protocol as supplied by the dressing manufacturers. Primary outcomes are days to complete wound healing and pain (using a Visual Analogue Scale). Secondary outcomes are adverse effects, scarring, patient satisfaction, and costs. Outcome assessors unaware of the treatment allocation will assess whether or not an outcome has occurred. Results will be analyzed according to the intention to treat principle. The first patient was randomized October 1, 2009. This study will provide comprehensive data on the effectiveness of different treatment options for donor site wounds. The dressing(s) that will prevail in effectiveness, satisfaction and costs will be promoted among clinicians dealing with such patients. Thus, we aim to contribute a well-designed trial, relevant to all clinicians involved in the care for donor site wounds, which will help enhance uniformity and quality of care for these patients. http://www.trialregister.nl, NTR1849. Date registered: June 9, 200

Intravenous fluid restriction after major abdominal surgery: a randomized blinded clinical trial

Background: Intravenous (IV) fluid administration is an essential part of postoperative care. Some studies suggest that a restricted post-operative fluid regime reduces complications and postoperative hospital stay after surgery. We investigated the effects of postoperative fluid restriction in surgical patients undergoing major abdominal surgery. Methods: In a blinded randomized trial, 62 patients (ASA I-III) undergoing elective major abdominal surgical procedures in a university hospital were allocated either to a restricted (1.5 L/24 h) or a standard postoperative IV fluid regime (2.5 L/24 h). Primary endpoint was length of postoperative hospital stay (PHS). Secondary endpoints included postoperative complications and time to restore gastric functions. Results: After a 1-year inclusion period, an unplanned interim analysis was made because of many protocol violations due to patient deterioration. In the group with the restricted regime we found a significantly increased PHS (12.3 vs. 8.3 days; p = 0.049) and significantly more major complications: 12 in 30 (40%) vs. 5 in 32 (16%) patients (Absolute Risk Increase: 0.24 [95%CI: 0.03 to 0.46], i.e. a number needed to harm of 4 [95%CI: 2-33]). Therefore, the trial was stopped prematurely. Intention to treat analysis showed no differences in time to restore gastric functions between the groups. Conclusion: Restricted postoperative IV fluid management, as performed in this trial, in patients undergoing major abdominal surgery appears harmful as it is accompanied by an increased risk of major postoperative complications and a prolonged postoperative hospital stay

Cognitive attraction and online misinformation

© The Author(s) 2019. The spread of online misinformation has gained mainstream attention in recent years. This paper approaches this phenomenon from a cultural evolution and cognitive anthropology perspective, focusing on the idea that some cultural traits can be successful because their content taps into general cognitive preferences. This research involves 260 articles from media outlets included in two authoritative lists of websites known for publishing hoaxes and ‘fake news’, tracking the presence of negative content, threat-related information, presence of sexually related material, elements associated to disgust, minimally counterintuitive elements (and a particular category of them, i.e., violations of essentialist beliefs), and social information, intended as presence of salient social interactions (e.g., gossip, cheating, formation of alliances), and as news about celebrities. The analysis shows that these features are, to a different degree, present in most texts, and thus that general cognitive inclinations may contribute to explain the success of online misinformation. This account can elucidate questions such as whether and why misinformation online is thriving more than accurate information, or the role of ‘fake news’ as a weapon of political propaganda. Online misinformation, while being an umbrella term covering many different phenomena, can be characterised, in this perspective, not as low-quality information that spreads because of the inefficiency of online communication, but as high-quality information that spreads because of its efficiency. The difference is that ‘quality’ is not equated to truthfulness but to psychological appeal.The Netherlands Organisation for Scientific Research (NWO VIDI-grant 016.144312)