Internationale handel en doorvoer:een nieuwe statistiek

From way back, the Netherlands is a trading nation. International trade and transport are important sources of income. However, the international transport flows also lead to costs for society. Therefore, careful assessments are needed when investing in infrastructure, transport and logistics. To make such assessments, the availability of quantitative information on international trade and transport flows is essential. The information on international commodity flows is distributed among several statistical products by Statistics Netherlands (CBS): the statistics of international trade in goods and the six transport statistics. Even together these statistics cannot complete the picture of international commodity flows of the Netherlands. Transit is not visible in the statistics. Furthermore, a complete view of the value and weight of commodity flows broken down by content, origin, destination and transport mode is lacking. Now, a new statistics integrates the statistics of international trade and transport by using a Bayesian integration model. The model takes care that the trade and transport figures are mutually consistent and satisfy logical restrictions. This results in a better view of the international commodity flows to, from and through the Netherlands broken down by commodity type and continent of origin or destination. For the first time since 1997, a reliable estimate of transit is available again. Furthermore, the margins around the estimates are determined, which gives insight in the reliability of the figures

Development and validation of the DIabetes Severity SCOre (DISSCO) in 139 626 individuals with type 2 diabetes: a retrospective cohort study

OBJECTIVE: Clinically applicable diabetes severity measures are lacking, with no previous studies comparing their predictive value with glycated hemoglobin (HbA1c). We developed and validated a type 2 diabetes severity score (the DIabetes Severity SCOre, DISSCO) and evaluated its association with risks of hospitalization and mortality, assessing its additional risk information to sociodemographic factors and HbA1c. RESEARCH DESIGN AND METHODS: We used UK primary and secondary care data for 139 626 individuals with type 2 diabetes between 2007 and 2017, aged ≥35 years, and registered in general practices in England. The study cohort was randomly divided into a training cohort (n=111 748, 80%) to develop the severity tool and a validation cohort (n=27 878). We developed baseline and longitudinal severity scores using 34 diabetes-related domains. Cox regression models (adjusted for age, gender, ethnicity, deprivation, and HbA1c) were used for primary (all-cause mortality) and secondary (hospitalization due to any cause, diabetes, hypoglycemia, or cardiovascular disease or procedures) outcomes. Likelihood ratio (LR) tests were fitted to assess the significance of adding DISSCO to the sociodemographics and HbA1c models. RESULTS: A total of 139 626 patients registered in 400 general practices, aged 63±12 years were included, 45% of whom were women, 83% were White, and 18% were from deprived areas. The mean baseline severity score was 1.3±2.0. Overall, 27 362 (20%) people died and 99 951 (72%) had ≥1 hospitalization. In the training cohort, a one-unit increase in baseline DISSCO was associated with higher hazard of mortality (HR: 1.14, 95% CI 1.13 to 1.15, area under the receiver operating characteristics curve (AUROC)=0.76) and cardiovascular hospitalization (HR: 1.45, 95% CI 1.43 to 1.46, AUROC=0.73). The LR tests showed that adding DISSCO to sociodemographic variables significantly improved the predictive value of survival models, outperforming the added value of HbA1c for all outcomes. Findings were consistent in the validation cohort. CONCLUSIONS: Higher levels of DISSCO are associated with higher risks for hospital admissions and mortality. The new severity score had higher predictive value than the proxy used in clinical practice, HbA1c. This reproducible algorithm can help practitioners stratify clinical care of patients with type 2 diabetes

Mapping QTL influencing gastrointestinal nematode burden in Dutch Holstein-Friesian dairy cattle

BACKGROUND: Parasitic gastroenteritis caused by nematodes is only second to mastitis in terms of health costs to dairy farmers in developed countries. Sustainable control strategies complementing anthelmintics are desired, including selective breeding for enhanced resistance. RESULTS AND CONCLUSION: To quantify and characterize the genetic contribution to variation in resistance to gastro-intestinal parasites, we measured the heritability of faecal egg and larval counts in the Dutch Holstein-Friesian dairy cattle population. The heritability of faecal egg counts ranged from 7 to 21% and was generally higher than for larval counts. We performed a whole genome scan in 12 paternal half-daughter groups for a total of 768 cows, corresponding to the approximately 10% most and least infected daughters within each family (selective genotyping). Two genome-wide significant QTL were identified in an across-family analysis, respectively on chromosomes 9 and 19, coinciding with previous findings in orthologous chromosomal regions in sheep. We identified six more suggestive QTL by within-family analysis. An additional 73 informative SNPs were genotyped on chromosome 19 and the ensuing high density map used in a variance component approach to simultaneously exploit linkage and linkage disequilibrium in an initial inconclusive attempt to refine the QTL map position

A Framework for Local Mechanical Characterization of Atherosclerotic Plaques: Combination of Ultrasound Displacement Imaging and Inverse Finite Element Analysis

Biomechanical models have the potential to predict plaque rupture. For reliable models, correct material properties of plaque components are a prerequisite. This study presents a new technique, where high resolution ultrasound displacement imaging and inverse finite element (FE) modeling is combined, to estimate material properties of plaque components. Iliac arteries with plaques were excised from 6 atherosclerotic pigs and subjected to an inflation test with pressures ranging from 10 to 120 mmHg. The arteries were imaged with high frequ

Assessing the severity of Type 2 diabetes using clinical data-based measures:a systematic review

Aims To identify and critically appraise measures that use clinical data to grade the severity of Type 2 diabetes. Methods We searched MEDLINE, Embase and PubMed between inception and June 2018. Studies reporting on clinical data‐based diabetes‐specific severity measures in adults with Type 2 diabetes were included. We excluded studies conducted solely in participants with other types of diabetes. After independent screening, the characteristics of the eligible measures including design and severity domains, the clinical utility of developed measures, and the relationship between severity levels and health‐related outcomes were assessed. Results We identified 6798 studies, of which 17 studies reporting 18 different severity measures (32 314 participants in 17 countries) were included: a diabetes severity index (eight studies, 44%); severity categories (seven studies, 39%); complication count (two studies, 11%); and a severity checklist (one study, 6%). Nearly 89% of the measures included diabetes‐related complications and/or glycaemic control indicators. Two of the severity measures were validated in a separate study population. More severe diabetes was associated with increased healthcare costs, poorer cognitive function and significantly greater risks of hospitalization and mortality. The identified measures differed greatly in terms of the included domains. One study reported on the use of a severity measure prospectively. Conclusions Health records are suitable for assessment of diabetes severity; however, the clinical uptake of existing measures is limited. The need to advance this research area is fundamental as higher levels of diabetes severity are associated with greater risks of adverse outcomes. Diabetes severity assessment could help identify people requiring targeted and intensive therapies and provide a major benchmark for efficient healthcare services

Renal Denervation Reduces Pulmonary Vascular Remodeling and Right Ventricular Diastolic Stiffness in Experimental Pulmonary Hypertension

Neurohormonal overactivation plays an important role in pulmonary hypertension (PH). In this context, renal denervation, which aims to inhibit the neurohormonal systems, may be a promising adjunct therapy in PH. In this proof-of-concept study, we have demonstrated in 2 experimental models of PH that renal denervation delayed disease progression, reduced pulmonary vascular remodeling, lowered right ventricular afterload, and decreased right ventricular diastolic stiffness, most likely by suppression of the renin-angiotensin-aldosterone system

Exacerbated inflammatory signaling underlies aberrant response to BMP9 in pulmonary arterial hypertension lung endothelial cells

Imbalanced transforming growth factor beta (TGFβ) and bone morphogenetic protein (BMP) signaling are postulated to favor a pathological pulmonary endothelial cell (EC) phenotype in pulmonary arterial hypertension (PAH). BMP9 is shown to reinstate BMP receptor type-II (BMPR2) levels and thereby mitigate hemodynamic and vascular abnormalities in several animal models of pulmonary hypertension (PH). Yet, responses of the pulmonary endothelium of PAH patients to BMP9 are unknown. Therefore, we treated primary PAH patient-derived and healthy pulmonary ECs with BMP9 and observed that stimulation induces transient transcriptional signaling associated with the process of endothelial-to-mesenchymal transition (EndMT). However, solely PAH pulmonary ECs showed signs of a mesenchymal trans-differentiation characterized by a loss of VE-cadherin, induction of transgelin (SM22α), and reorganization of the cytoskeleton. In the PAH cells, a prolonged EndMT signaling was found accompanied by sustained elevation of pro-inflammatory, pro-hypoxic, and pro-apoptotic signaling. Herein we identified interleukin-6 (IL6)-dependent signaling to be the central mediator required for the BMP9-induced phenotypic change in PAH pulmonary ECs. Furthermore, we were able to target the BMP9-induced EndMT process by an IL6 capturing antibody that normalized autocrine IL6 levels, prevented mesenchymal transformation, and maintained a functional EC phenotype in PAH pulmonary ECs. In conclusion, our results show that the BMP9-induced aberrant EndMT in PAH pulmonary ECs is dependent on exacerbated pro-inflammatory signaling mediated through IL6

WhiskEras: A New Algorithm for Accurate Whisker Tracking

Rodents engage in active touch using their facial whiskers: they explore their environment by making rapid back-and-forth movements. The fast nature of whisker movements, during which whiskers often cross each other, makes it notoriously difficult to track individual whiskers of the intact whisker field. We present here a novel algorithm, WhiskEras, for tracking of whisker movements in high-speed videos of untrimmed mice, without requiring labeled data. WhiskEras consists of a pipeline of image-processing steps: first, the points that form the whisker centerlines are detected with sub-pixel accuracy. Then, these points are clustered in order to distinguish individual whiskers. Subsequently, the whiskers are parameterized so that a single whisker can be described by four parameters. The last step consists of tracking individual whiskers over time. We describe that WhiskEras performs better than other whisker-tracking algorithms on several metrics. On our four video segments, WhiskEras detected more whiskers per frame than the Biotact Whisker Tracking Tool. The signal-to-noise ratio of the output of WhiskEras was higher than that of Janelia Whisk. As a result, the correlation between reflexive whisker movements and cerebellar Purkinje cell activity appeared to be stronger than previously found using other tracking algorithms. We conclude that WhiskEras facilitates the study of sensorimotor integration by markedly improving the accuracy of whisker tracking in untrimmed mice

Fine mapping of the celiac disease-associated LPP locus reveals a potential functional variant

Transplantation and immunomodulatio

Innovative remote plasma source for atomic layer deposition for GaN devices

High-quality dielectric films could enable GaN normally off high-electron-mobility transistors (HEMTs). Plasma atomic layer deposition (ALD) is known to allow for controlled high-quality thin-film deposition, and in order to not exceed energy and flux levels leading to device damage, the plasma used should preferably be remote for many applications. This article outlines ion energy flux distribution functions and flux levels for a new remote plasma ALD system, Oxford Instruments Atomfab™, which includes an innovative, RF-driven, remote plasma source. The source design is optimized for ALD for GaN HEMTs for substrates up to 200 mm in diameter and allows for Al2O3 ALD cycles of less than 1 s. Modest ion energies of <50 eV and very low ion flux levels of <1013 cm−2 s−1 were found at low-damage conditions. The ion flux can be increased to the high 1014 cm−2 s−1 range if desired for other applications. Using low-damage conditions, fast ALD saturation behavior and good uniformity were demonstrated for Al2O3. For films of 20 nm thickness, a breakdown voltage value of 8.9 MV/cm was obtained and the Al2O3 films were demonstrated to be suitable for GaN HEMT devices where the combination with plasma pretreatment and postdeposition anneals resulted in the best device parameters