Poor Accuracy of Methods Currently Used to Determine Umbilical Catheter Insertion Length

This study compares the methods of Dunn and Shukla in determining the appropriate insertion length of umbilical catheters. In July 2007, we changed our policy for umbilical catheter insertions from the method of Dunn to the method of Shukla. We report our percentage of inaccurate placement of umbilical-vein catheters (UVCs) and umbilical-artery catheters (UACs) before and after the change of policy. In the Dunn-group, 41% (28/69) of UVCs were placed directly in the correct position against 24% (20/84) in the Shukla-group. The position of the catheter-tip of UVCs in the Dunn-group and the Shukla-group was too high in 57% (39/69) and 75% (63/84) of neonates, respectively. UACs in the Dunn-group were placed directly in the correct position in 63% (24/38) compared to the 87% (39/45) of cases in Shukla-group. The position of the catheter-tip of UACs in the Dunn-group and the Shukla-group was too high in 34% (13/38) and 13% (6/45) of neonates, respectively. In conclusion, the Dunn-method is more accurate than the Shukla-method in predicting the insertion length for UVCs, whereas the Shukla-method is more accurate for UACs

The yeast protein kinase Sch9 adjusts V-ATPase assembly/disassembly to control pH homeostasis and longevity in response to glucose availability

The evolutionary conserved TOR complex 1 controls growth in response to the quality and quantity of nutrients such as carbon and amino acids. The protein kinase Sch9 is the main TORC1 effector in yeast. However, only few of its direct targets are known. In this study, we performed a genome-wide screening looking for mutants which require Sch9 function for their survival and growth. In this way, we identified multiple components of the highly conserved vacuolar proton pump (V-ATPase) which mediates the luminal acidification of multiple biosynthetic and endocytic organelles. Besides a genetic interaction, we found Sch9 also physically interacts with the V- ATPase to regulate its assembly state in response to glucose availability and TORC1 activity. Moreover, the interaction with the V-ATPase has consequences for ageing as it allowed Sch9 to control vacuolar pH and thereby trigger either lifespan extension or lifespan shortening. Hence, our results provide insights into the signaling mechanism coupling glucose availability, TORC1 signaling, pH homeostasis and longevity. As both Sch9 and the V-ATPase are highly conserved and implicated in various pathologies, these results offer fertile ground for further research in higher eukaryotes

Melanocortin Receptor 4 Deficiency Affects Body Weight Regulation, Grooming Behavior, and Substrate Preference in the Rat

Obesity is caused by an imbalance between energy intake and expenditure and has become a major health-care problem in western society. The central melanocortin system plays a crucial role in the regulation of feeding and energy expenditure, and functional loss of melanocortin receptor 4 (MC4R) is the most common genetic cause of human obesity. In this study, we present the first functional Mc4r knockout model in the rat, resulting from an N-ethyl-N-nitrosourea mutagenesis–induced point mutation. In vitro observations revealed impaired membrane-binding and subsequent nonfunctionality of the receptor, whereas in vivo observations showed that functional loss of MC4R increased body weight, food intake, white adipose mass, and changed substrate preference. In addition, intracerebroventricular (ICV) administration of Agouti-Related Protein79–129 (AgRP79–129), an MC4R inverse agonist, or Melanotan-II (MTII), an MC4R agonist, did affect feeding behavior in wild-type rats but not in homozygous mutant rats, confirming complete loss of MC4R function in vivo. Finally, ICV administration of MTII induced excessive grooming behavior in wild-type rats, whereas this effect was absent in homozygous mutant rats, indicating that MTII-induced grooming behavior is exclusively regulated via MC4R pathways. Taken together, we expect that the MC4R rat model described here will be a valuable tool for studying monogenic obesity in humans. More specifically, the relative big size and increased cognitive capacity of rats as compared to mice will facilitate complex behavioral studies and detailed mechanistic studies regarding central function of MC4R, both of which ultimately may help to further understand the specific mechanisms that induce obesity during loss of MC4R function

Cost-effectiveness of a vocational enablement protocol for employees with hearing impairment; design of a randomized controlled trial

Background: Hearing impairment at the workplace, and the resulting psychosocial problems are a major health problem with substantial costs for employees, companies, and society. Therefore, it is important to develop interventions to support hearing impaired employees. The objective of this article is to describe the design of a randomized controlled trial evaluating the (cost-) effectiveness of a Vocational Enablement Protocol (VEP) compared with usual care. Methods/Design. Participants will be selected with the 'Hearing and Distress Screener'. The study population will consist of 160 hearing impaired employees. The VEP intervention group will be compared with usual care. The VEP integrated care programme consists of a multidisciplinary assessment of auditory function, work demands, and personal characteristics. The goal of the intervention is to facilitate participation in work. The primary outcome measure of the study is 'need for recovery after work'. Secondary outcome measures are coping with hearing impairment, distress, self-efficacy, psychosocial workload, job control, general health status, sick leave, work productivity, and health care use. Outcome measures will be assessed by questionnaires at baseline, and 3, 6, 9, and 12 months after baseline. The economic evaluation will be performed from both a societal and a company perspective. A process evaluation will also be performed. Discussion. Interventions addressing occupational difficulties of hearing impaired employees are rare but highly needed. If the VEP integrated care programme proves to be (cost-) effective, the intervention can have an impact on the well-being of hearing impaired employees, and thereby, on the costs for the company as well for the society. Trial registration. Netherlands Trial Register (NTR): NTR2782. © 2012 Gussenhoven et al; BioMed Central Ltd

Targeting Toll-like receptor 7/8 enhances uptake of apoptotic leukemic cells by monocyte-derived dendritic cells but interferes with subsequent cytokine-induced maturation

Therapeutic vaccination with dendritic cells (DC) is an emerging investigational therapy for eradication of minimal residual disease in acute myeloid leukemia. Various strategies are being explored in manufacturing DC vaccines ex vivo, e.g., monocyte-derived DC (MoDC) loaded with leukemia-associated antigens (LAA). However, the optimal source of LAA and the choice of DC-activating stimuli are still not well defined. Here, loading with leukemic cell preparations (harboring both unknown and known LAA) was explored in combination with a DC maturation-inducing cytokine cocktail (CC; IL-1β, IL-6, TNF-α, and PGE2) and Toll-like receptor ligands (TLR-L) to optimize uptake. Since heat shock induced apoptotic blasts were more efficiently taken up than lysates, we focused on uptake of apoptotic leukemic cells. Uptake of apoptotic blast was further enhanced by the TLR7/8-L R848 (20–30%); in contrast, CC-induced maturation inhibited uptake. CC, and to a lesser extent R848, enhanced the ability of MoDC to migrate and stimulate T cells. Furthermore, class II-associated invariant chain peptide expression was down-modulated after R848- or CC-induced maturation, indicating enhanced processing and presentation of antigenic peptides. To improve both uptake and maturation, leukemic cells and MoDC were co-incubated with R848 for 24 h followed by addition of CC. However, this approach interfered with CC-mediated MoDC maturation as indicated by diminished migratory and T cell stimulatory capacity, and the absence of IL-12 production. Taken together, our data demonstrate that even though R848 improved uptake of apoptotic leukemic cells, the sequential use of R848 and CC is counter-indicated due to its adverse effects on MoDC maturation

Robot Skills: Design of a Constraint-Based Methodology and Software Support (Robot vaardigheden: Ontwerp van een beperkingsgebaseerde methodologie en software ondersteuning)

The days when robots were only used to move their endpoint from point Ato B, passing through point C, safely hidden behind a fence, are over. Nowadays robots have to grasp objects, move them around, manipulate them using two arms, while keeping controlled distances from humans and fragile objects or even during physical interaction with humans. Furthermore, all these tasks have to be executed as optimally as possible. Six degrees-of-freedom industrial arms are being replaced by mobile platforms with two redundant arms, both equipped with force sensors, three-fingered grippers with touch sensors, a head with cameras, laser scanners, inertial sensors, etc. In the coming years the habitat of robotic systems will evolve from the industrial work cells to domestic, cluttered and populated environments. To cope with the increasing complexity, not only a highly modular methodology for motion specificationis needed. Also the online motion coordination becomes very important since it has to cope with the dynamically changing environment in which the robotic system works.This thesis presents a highly modular control hierarchy for the coordination of constraint-based motion specification that can be used with a high variety of sensors, robotic systems and tasks. To create a highly modular coordination system, a modular motion specification methodology needs to be used as the underlying framework. iTaSC, or instantaneous Task Specification using Constraints, is such a modular framework that allows us to specify motion by imposing those constraints on the interaction between the robot and the environment that are important for the task at hand. This thesisextends the iTaSC methodology to not only allow the specificationof constraints in feature spaces, which are built up from exactly six independent geometric coordinates, but to allow the specification of constraints in any feature space for which an interaction model can befound. Calculating the robot motion from the specified constraints can be very computationally expensive in systems that include a lot of actuated joints, such as humanoid robots. Therefore the quest for efficient algorithms is still ongoing. This thesis discusses one of the most ground-breaking algorithms for acceleration-based constrained hybrid (combination of forward and inverse) dynamics, and explains how it can be extended for tree-like kinematic robot structures and how it can be used to solve an iTaSC motion specification.Building software support for the new generation of robot applications from scratch for each new robotic system, or each new application is a very elaborate task. Therefore reusable software components and formal representations of both the robotic system and the task to be executed are mandatory. This thesis presents a component-based modular architecture for the next generation of robot controllers based on the extended iTaSC motion specification and coordination. A formal representation for robotic systems and their motion specificationis presented to facilitate the creation of interchangeable file formatsfor the specification of robot skills.status: publishe

Combining cross-shore and longshore processes in long-term probabilistic coastline modelling: Development of a probabilistic framework

Many coasts around the world experience coastal erosion as a result of climate change, lack of sediment supply or human interventions. In the coming decades, coasts will be exposed to increased natural forcing because of climate change and sea level rise, leading to increased risks of coastal flooding and erosion. As sandy coasts are highly dynamic systems, it is difficult to assess the impact of these risks. Long-term coastal evolution is evaluated on large temporal and spatial scales, which introduce uncertainty. Hence, probabilistic estimates are required rather than single, deterministic values. Complex, process-based models have been developed to simulate morphological changes in coastal zones, but these come at large computational expense. As probabilistic approaches require a large number of simulations, it is necessary to reduce computational times as much as possible.Variability in coastline position is induced by both cross-shore and longshore processes, which occur perpendicular and parallel to the coastline, respectively. Extreme storm events and sea level rise are responsible for the long-term cross-shore coastal dynamics, while gradients in longshore sediment transport act as the main driver for the longshore coastline changes. This study focuses on developing a framework to combine predictions of long-term cross-shore and longshore processes in a probabilistic way. The framework combines probabilistic predictions of cross-shore effects with deterministic estimates of longshore-induced coastline change. Two separate models are studied for the cross-shore and longshore component, namely the Probabilistic Coastline Recession (PCR) model and the ShorelineS model. Both models are computationally efficient due to the use of reduced complexity sediment transport formulations and a simplified representation of the beach profile.The developed framework is validated by a case study of the IJmuiden coastline, the Netherlands, to assess the effects of the blockage of longshore sediment transport by the breakwaters between 1967 and 2007. Consequently, projections of coastline development are determined for the period of 2023 to 2100, for a range of IPCC sea level rise scenarios. To model storm erosion with the PCR model, a synthetic time series of storm events is simulated by establishing joint probabilities of wave forcing variates. Moreover, the PCR model provides stochastic estimates of coastline recession, enabled by the large number of simulations. Regarding ShorelineS, a representative wave climate based on data of local wave conditions was used to compute the longshore sediment transport.The ShorelineS simulation over the hindcasted period clearly resulted in accretion on both sides of the breakwaters in the order of 100 to 900 meters, in accordance with field observations. This outcome indicates that limited threats of coastal erosion are currently present. However, when analysing the projections for 2023-2100, the PCR model predicted that a combination of storm impact and sea level rise can definitely lead to coastline recession, with a median retreat of 18 meters and 32 meters for the RCP2.6 and RCP8.5 sea level rise scenario, respectively. Moreover, the PCR model indicated that at some point the coastline erosion might be larger than 100 meters with a probability of 1.5% for RCP2.6 and 4% for RCP8.5. The combined projections confirm the importance of accounting for both cross-shore and longshore impacts on long-term coastline evolution and show that the developed framework is a useful method for this purpose.For further research it is recommended to study long-term coastline evolution while including interaction between cross-shore and longshore processes, to analyse its contribution to long-term coastline changes. It is also advised to further investigate how to obtain stochastic projections of coastline development induced by longshore processes, as this study only presents the cross-shore component in a probabilistic way. Furthermore, stochastic projections of sea level rise and beach recovery can be studied as well.Civil Engineerin