Distinct Changes in Placental Ceramide Metabolism Characterize Type 1 and 2 Diabetic Pregnancies with Fetal Macrosomia or Preeclampsia

Disturbances of lipid metabolism are typical in diabetes. Our objective was to characterize and compare placental sphingolipid metabolism in type 1 (T1D) and 2 (T2D) diabetic pregnancies and in non-diabetic controls. Placental samples from T1D, T2D, and control pregnancies were processed for sphingolipid analysis using tandem mass spectrometry. Western blotting, enzyme activity, and immunofluorescence analyses were used to study sphingolipid regulatory enzymes. Placental ceramide levels were lower in T1D and T2D compared to controls, which was associated with an upregulation of the ceramide degrading enzyme acid ceramidase (ASAH1). Increased placental ceramide content was found in T1D complicated by preeclampsia. Similarly, elevated ceramides were observed in T1D and T2D pregnancies with poor glycemic control. The protein levels and activity of sphingosine kinases (SPHK) that produce sphingoid-1-phosphates (S1P) were highest in T2D. Furthermore, SPHK levels were upregulated in T1D and T2D pregnancies with fetal macrosomia. In vitro experiments using trophoblastic JEG3 cells demonstrated increased SPHK expression and activity following glucose and insulin treatments. Specific changes in the placental sphingolipidome characterize T1D and T2D placentae depending on the type of diabetes and feto-maternal complications. Increased exposure to insulin and glucose is a plausible contributor to the upregulation of the SPHK-S1P-axis in diabetic placentae

Product shape change by internal stresses

The design of a product component may require complex processing steps such as metal forming followed by a thermal treatment. The thermal treatment may improve the functional performance of the material itself, but may result in rather unwanted changes in the shape of the product. Here it is shown that Finite Element modeling of the various processes can assist in the design of a robust and accurate production process. The modeling approach presented allows a coupling between various complex material models, in such a way that full cold forming and thermal treatment processes are calculated. This coupling of material models is key for the design and concerns the novelty of the proposed approach. Cold forming by deep drawing is calculated whereby planar anisotropy is implemented. The thermal hardening treatment consists of three contributions: creep, thermal expansion and phase transformation. All models are based on experimental data, acquired from tensile and dilatometer tests, and are implemented into the material model either directly or by a simple fit. It is shown that the effects of a complete forming and heat treatment of a cup could be successfully calculated. The predicted cup shape change was compared to experiments, and shows excellent agreement.This research was carried out under the project number T63.3.12480 in the framework of the research program of the Materials innovation institute M2i, Delft, the Netherlands; and has been part of Press Perfect project, RFSR-CT-2012-00021 funded by the Research Fund for Coal & Steel.Peer Reviewe

Simulation-based assessment of upper abdominal ultrasound skills

Background: Ultrasound is a safe and effective diagnostic tool used within several specialties. However, the quality of ultrasound scans relies on sufficiently skilled clinician operators. The aim of this study was to explore the validity of automated assessments of upper abdominal ultrasound skills using an ultrasound simulator. Methods: Twenty five novices and five experts were recruited, all of whom completed an assessment program for the evaluation of upper abdominal ultrasound skills on a virtual reality simulator. The program included five modules that assessed different organ systems using automated simulator metrics. We used Messick’s framework to explore the validity evidence of these simulator metrics to determine the contents of a final simulator test. We used the contrasting groups method to establish a pass/fail level for the final simulator test. Results: Thirty seven out of 60 metrics were able to discriminate between novices and experts (p &lt; 0.05). The median simulator score of the final simulator test including the metrics with validity evidence was 26.68% (range: 8.1–40.5%) for novices and 85.1% (range: 56.8–91.9%) for experts. The internal structure was assessed by Cronbach alpha (0.93) and intraclass correlation coefficient (0.89). The pass/fail level was determined to be 50.9%. This pass/fail criterion found no passing novices or failing experts. Conclusions: This study collected validity evidence for simulation-based assessment of upper abdominal ultrasound examinations, which is the first step toward competency-based training. Future studies may examine how competency-based training in the simulated setting translates into improvements in clinical performances.</p

Rasch Analysis of the International Quality of Life Basic Data Set Version 2.0

Objective: To examine the internal construct validity of the International Spinal Cord Injury Quality of Life Basic Data Set Version 2.0 (QoL-BDS V2.0) and compare this with the internal construct validity of the original version of the QoL-BDS. Design: International cross-sectional psychometric study. Setting: Spinal rehabilitation units, clinics, and community. Participants: The study involved 5 sites and 4 countries, 2 of whose primary language is not English. Each site included a consecutive sample of inpatients with spinal cord injury or disease (SCI/D) and a convenience sample of individuals with SCI/D living in the community (N=565). Main outcome measures: The QoL-BDS V2.0 consists of the 3 original items on satisfaction with life as a whole, physical health, psychological health of the QoL-BDS, and an additional item on satisfaction with social life. All 4 items are answered on a 0-10 numeric rating scale. Rasch analysis was performed on versions 1.0 and 2.0 of the QoL-BDS to examine the ordering of the items' response options, item scaling, reliability, item fit, local item independence, differential item functioning, and unidimensionality. Results: The sample included 565 participants with 57% outpatients and 43% inpatients. Mean age was 51.4 years; 71% were male; 65% had a traumatic injury, 40% had tetraplegia, and 67% were wheelchair users. Item thresholds were collapsed for ordering, and subsequent analyses showed good internal construct validity for the QoL-BDS V2.0 with a person separation reliability of 0.76 and Cronbach α of 0.81. Infit and outfit statistics ranged 0.62-0.91. No local dependencies and multidimensionality were found. Differential item functioning was observed only for country and inpatients vs outpatients but not for other participants' characteristics. Differences in internal construct validity between the 3-item and 4-item versions were minimal. Conclusions: The results of this Rasch analysis support the internal construct validity of the QoL-BDS V2.0

Numerical evaluation of the general massive 2-loop 4-denominator self-mass master integral from differential equations

The differential equation in the external invariant p^2 satisfied by the master integral of the general massive 2-loop 4-denominator self-mass diagram is exploited and the expansion of the master integral at p^2=0 is obtained analytically. The system composed by this differential equation with those of the master integrals related to the general massive 2-loop sunrise diagram is numerically solved by the Runge-Kutta method in the complex p^2 plane. A numerical method to obtain results for values of p^2 at and close to thresholds and pseudo-thresholds is discussed in details.Comment: Latex, 20 pages, 7 figure

Detecting subgroups in social participation among individuals living with spinal cord injury:a longitudinal analysis of community survey data

STUDY DESIGN: Longitudinal community survey. OBJECTIVES: To determine subgroups in social participation of individuals living with spinal cord injury (SCI). SETTING: Community. METHODS: Data were collected in 2012 and 2017 as part of the community survey of the Swiss Spinal Cord Injury cohort. Participation was assessed using the 33-item Utrecht Scale of Evaluation of Rehabilitation-Participation evaluating frequency of, restrictions in and satisfaction with productive, leisure, and social activities. Linear mixed-effects model trees were used to distinguish subgroups in participation associated with sociodemographic and lesion characteristics. RESULTS: In all, 3079 observations were used for the analysis, of which 1549 originated from Survey 2012, 1530 from Survey 2017, and 761 from both surveys. Participants were mostly male (2012: 71.5%; 2017: 71.2%), aged on average 50 years (2012: 52.3; 2017: 56.5), with an incomplete paraplegia (2012: 37.5%; 2017: 41.8%) of traumatic origin (2012: 84.7%; 2017: 79.3%). There was limited within-person variation in participation over the 5-year period. Participation varied with age, SCI severity, education, financial strain, number of self-reported health conditions (SHCs), and disability pension level. Among modifiable parameters, the number of SHCs and disability pension level emerged as the most frequent partitioning variables, while education was most informative for participation in productive, leisure, and social activities. CONCLUSIONS: Long-term rehabilitation management and clinical practice should target people most prone to decreased participation in major life domains. Our study indicates that the alleviation of SHCs, engagement in further education, or adjusting disability pension level are promising areas to improve participation of persons living with SCI

One-year outcomes after transcatheter insertion of an interatrial shunt device for the management of heart failure with preserved ejection fraction

Background—Heart failure with preserved ejection fraction has a complex pathophysiology and remains a therapeutic challenge. Elevated left atrial pressure, particularly during exercise, is a key contributor to morbidity and mortality. Preliminary analyses have demonstrated that a novel interatrial septal shunt device that allows shunting to reduce the left atrial pressure provides clinical and hemodynamic benefit at 6 months. Given the chronicity of heart failure with preserved ejection fraction, evidence of longer-term benefit is required. Methods and Results—Patients (n=64) with left ventricular ejection fraction ≥40%, New York Heart Association class II–IV, elevated pulmonary capillary wedge pressure (≥15 mm Hg at rest or ≥25 mm Hg during supine bicycle exercise) participated in the open-label study of the interatrial septal shunt device. One year after interatrial septal shunt device implantation, there were sustained improvements in New York Heart Association class (P&lt;0.001), quality of life (Minnesota Living with Heart Failure score, P&lt;0.001), and 6-minute walk distance (P&lt;0.01). Echocardiography showed a small, stable reduction in left ventricular end-diastolic volume index (P&lt;0.001), with a concomitant small stable increase in the right ventricular end-diastolic volume index (P&lt;0.001). Invasive hemodynamic studies performed in a subset of patients demonstrated a sustained reduction in the workload corrected exercise pulmonary capillary wedge pressure (P&lt;0.01). Survival at 1 year was 95%, and there was no evidence of device-related complications. Conclusions—These results provide evidence of safety and sustained clinical benefit in heart failure with preserved ejection fraction patients 1 year after interatrial septal shunt device implantation. Randomized, blinded studies are underway to confirm these observations

Left Atrial Appendage Closure for Stroke Prevention in Patients with Atrial Fibrillation and Hereditary Hemorrhagic Telangiectasia

Atrial fibrillation (AF) is the most common cardiac arrhythmia, affecting millions of individuals worldwide, and a major risk factor for disabling cerebral embolic stroke. Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant inherited disorder, characterized by vascular abnormalities with high-bleeding tendency and therefore intolerance for oral anticoagulation. We report a case of percutaneous closure of the left atrial appendage, which might be a good alternative strategy instead of chronic oral anticoagulation to protect patients with high-risk AF and HHT from cerebral embolic strokes

The transcription factor GATA6 is essential for branching morphogenesis and epithelial cell differentiation during fetal pulmonary development

Recent loss-of-function studies in mice show that the transcription factor GATA6 is important for visceral endoderm differentiation. It is also expressed in early bronchial epithelium and the observation that this tissue does not receive any contribution from Gata6 double mutant embryonic stem (ES) cells in chimeric mice suggests that GATA6 may play a crucial role in lung development. The aim of this study was to determine the role of GATA6 in fetal pulmonary development. We show that Gata6 mRNA is expressed predominantly in the developing pulmonary endoderm and epithelium, but at E15.5 also in the pulmonary mesenchyme. Blocking or depleting GATA6 function results in diminished branching morphogenesis both in vitro and in vivo. TTF1 expression is unaltered in chimeric lungs whereas SPC and CC10 expression are attenuated in abnormally branched areas of chimeric lungs. Chimeras generated in a ROSA26 background show that endodermal cells in these abnormally branched areas are derived from Gata6 mutant ES cells, implicating that the defect is intrinsic to the endoderm. Taken together, these data demonstrate that GATA6 is not essential for endoderm specification, but is required for normal branching morphogenesis and late epithelial cell differentiation

Spin-Orbit-Induced Magnetic Anisotropy for Impurities in Metallic Samples II. Finite Size Dependence in the Kondo Resistivity

The electrical resistivity including the Kondo resistivity increase at low temperature is calculated for thin films of dilute magnetic alloys. Assuming that in the non-magnetic host the spin-orbit interaction is strong like in Au and Cu, the magnetic impurities have a surface anisotropy calculated in part I. That anisotropy hinders the motion of the spin. Including that anisotropy the effective electron-impurity coupling is calculated by using the second order renormalization group equations. The amplitude of the Kondo resistivity contribution is reduced as the position of the impurity approaches the surface but the increase occurs approximately at the bulk Kondo temperature. Different proximity effects observed by Giordano are also explained qualitatively where the films of magnetic alloys are covered by pure second films with different mean free path. The theory explains the experimental results in those cases where a considerable amount of impurities is at the surface inside the ballistic region.Comment: 39 pages, RevTeX (using epsfig), 15 eps figures included, submitted to PR