Enter the matrix:On how to improve thyroid nodule management using 3D ultrasound

Roughly two-thirds of the adult population has a thyroid nodule, of which 90% are benign. Of the adults that have a nodule, approximately 5% will experience symptoms that include a feeling of a marble stuck in the throat, difficulty swallowing and breathing, and cosmetic complaints. Thyroid nodule management primarily makes use of ultrasound as the imaging modality for diagnosis, image guidance during therapy (radiofrequency ablation i.e. RFA), and follow-up. Although ultrasound is relatively easy to apply, it is hard to standardize for repeated measurements and across various users. Further, RFA can benefit from 3D imaging information and a planning and navigation system to improve clinical outcome. These challenges may be overcome by using 3D ultrasound. In this thesis, two phantoms were created on which these methods can be developed. Further, it offers insight into the use of 2D and 3D ultrasound for thyroid nodule management.To assess the impact of changes to an intervention, a baseline was determined of the effectiveness of RFA in Dutch hospitalsUsing a simple phantom, we have shown that utilizing a volume-based measurement technique, that the matrix transducer offers, results in improved measurement accuracy. The more complex, anthropomorphic, phantom serves as a platform on which thermal treatments, such as RFA, can be improved. Using this phantom, we have shown that the impact of 2D and 3D ultrasound on RFA efficacy does not differ from one another; however, the matrix transducer might be more user-friendly for needle placement due to the dual-plane imaging. An additional use case for these phantoms is their capacity to compare dominant and non-dominant hand ablations, as well as serve as a training platform. Additional research is required that employs more operators to find stronger evidence supporting a difference between the ablating hands and the difference in effect of 2D and 3D ultrasound guidance.To make full use of 3D ultrasound, stitching algorithms should be integrated into the ultrasound systems to acquire larger volumes. These can then be processed by deep-learning algorithms for use in computer-aided diagnosis and intervention systems. To further improve the applicability of 3D ultrasound in the clinic, integrating analysis methods such as 3D elastography and 3D Doppler is suggested

Genome-wide methylation analysis in patients with proximal hypospadias–a pilot study and review of the literature

In patients with proximal hypospadias, often no genetic cause is identified despite extensive genetic testing. Many genes involved in sex development encode transcription factors with strict timing and dosing of the gene products. We hypothesised that there might be recurrent differences in DNA methylation in boys with hypospadias and that these might differ between patients born small versus appropriate for gestational age. Genome-wide Methylated DNA sequencing (MeD-seq) was performed on 32bp LpnPI restriction enzyme fragments after RE-digestion in leucocytes from 16 XY boys with unexplained proximal hypospadias, one with an unexplained XX testicular disorder/difference of sex development (DSD) and twelve, healthy, sex- and age-matched controls. Five of seven differentially methylated regions (DMRs) between patients and XY controls were in the Long Intergenic Non-Protein Coding RNA 665 (LINC00665; CpG24525). Three patients showed hypermethylation of MAP3K1. Finally, no DMRs in XX testicular DSD associated genes were identified in the XX boy versus XX controls. In conclusion, we observed no recognizable epigenetic signature in 16 boys with XY proximal hypospadias and no difference between children born small versus appropriate for gestational age. Comparison to previous methylation studies in individuals with hypospadias did not show consistent findings, possibly due to the use of different inclusion criteria, tissues and methods.</p

Bragg spectroscopy of a superfluid Bose-Hubbard gas

Bragg spectroscopy is used to measure excitations of a trapped, quantum-degenerate gas of 87Rb atoms in a 3-dimensional optical lattice. The measurements are carried out over a range of optical lattice depths in the superfluid phase of the Bose-Hubbard model. For fixed wavevector, the resonant frequency of the excitation is found to decrease with increasing lattice depth. A numerical calculation of the resonant frequencies based on Bogoliubov theory shows a less steep rate of decrease than the measurements.Comment: 11 pages, 4 figure

Comparison of different definitions to classify remission and sustained remission: 1 year TEMPO results

To assess methods to calculate achieving and sustaining remission in a double blind randomised trial in patients with RA who received etanercept, methotrexate, or an etanercept/methotrexate combination. Remission was defined as DAS <1.6, DAS28 <2.6, and ACR70 response. Sustaining remission was analysed in three ways: (a) analysis of sustained DAS remission, DAS28 remission, or ACR70 response continuously for 6 months; (b) analysis of sustained remission appraised through a continuity rewarded scoring system, which is the weighted sum of all intervals in the study in which patients are in DAS or DAS28 remission; or (c) longitudinal modelling of remission odds using generalised estimating equations. Significantly more patients treated with the etanercept/methotrexate combination reached DAS remission (37%) than those treated with either methotrexate (14%) or etanercept (18%) alone (p <0.01). Results for DAS28 and for the ACR70 response were similar. Agreement between DAS remission and DAS28 remission was good, but agreement between either of these and the ACR70 response was less. Patients in DAS or DAS28 remission had a lower level of disease activity (fewer active joints, lower ESR) than those achieving ACR70 response; the converse was seen using pain VAS. The three methods were comparable for sustainability of remission and showed significant advantage for combination therapy, which increased the number and durability of remission periods. DAS and DAS28 remission results were similar for assessing achieving and sustaining remission in RA, frequently differing from patients classified as ACR70 responders. The three methods of examining duration of remission produced comparable result

Measurement properties of quality of life measurement instruments for infants, children and adolescents with eczema: protocol for a systematic review

Background: Eczema is a common chronic or chronically relapsing skin disease that has a substantial impact on quality of life (QoL). By means of a consensus-based process, the Harmonising Outcome Measures in Eczema (HOME) initiative has identified QoL as one of the four core outcome domains to be assessed in all eczema trials. Few measurement instruments exist to measure QoL in infants and children with eczema, but there is a great variability in both content and quality (for example, reliability and validity) of the instruments used, and it is not always clear if the best instrument is being used. Therefore, the aim of the proposed research is a comprehensive systematic assessment of the measurement properties of the existing measurement instruments that were developed and/or validated for the measurement of patient-reported QoL in infants and children with eczema. Methods/Design: This study is a systematic review of the measurement properties of patient-reported measures of QoL developed and/or validated for infants and children with eczema. Medline via PubMed and EMBASE will be searched using a selection of relevant search terms. Eligible studies will be primary empirical studies evaluating, describing, or comparing measurement properties of QoL instruments for infants and children with eczema. Eligibility assessment and data abstraction will be performed independently by two reviewers. Evidence tables will be generated for study characteristics, instrument characteristics, measurement properties, and interpretability. The adequacy of the measurement properties will be assessed using predefined criteria. Methodological quality of studies will be assessed using the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) checklist. A best evidence synthesis will be undertaken if more than one study has investigated a particular measurement property. Discussion: The proposed systematic review will produce a comprehensive assessment of measurement properties of existing QoL instruments in infants and children with eczema. We aim to identify one best currently available instrument to measure QoL in infants and/or children with eczema

Systematic review of definitions and outcome measures for return of bowel function after gastrointestinal surgery

Background Ileus is common after gastrointestinal surgery and has been identified as a research priority. Several issues have limited previous research, including a widely accepted definition and agreed outcome measure. This review is the first stage in the development of a core outcome set for the return of bowel function after gastrointestinal surgery. It aims to characterize the extent of variation in current outcome reporting. Methods A systematic search of MEDLINE, Embase, CINAHL (Cumulative Index to Nursing and Allied Health Literature) and the Cochrane Library was performed for 1990–2017. RCTs of adults undergoing gastrointestinal surgery, including at least one reported measure relating to return of bowel function, were eligible. Trial registries were searched across the same period for ongoing and completed (but not published) RCTs. Definitions of ileus and outcome measures describing the return of bowel function were extracted. Results Of 5670 manuscripts screened, 215 (reporting 217 RCTs) were eligible. Most RCTs involved patients undergoing colorectal surgery (161 of 217, 74·2 per cent). A total of 784 outcomes were identified across all published RCTs, comprising 73 measures (clinical: 63, 86 per cent; radiological: 6, 8 per cent; physiological: 4, 5 per cent). The most commonly reported outcome measure was ‘time to first passage of flatus’ (140 of 217, 64·5 per cent). The outcomes ‘ileus’ and ‘prolonged ileus’ were defined infrequently and variably. Conclusion Outcome reporting for the return of bowel function after gastrointestinal surgery is variable and not fit for purpose. An agreed core outcome set will improve the consistency, reliability and clinical value of future studies

Deep learning-based recognition of key anatomical structures during robot-assisted minimally invasive esophagectomy

Objective: To develop a deep learning algorithm for anatomy recognition in thoracoscopic video frames from robot-assisted minimally invasive esophagectomy (RAMIE) procedures using deep learning. Background: RAMIE is a complex operation with substantial perioperative morbidity and a considerable learning curve. Automatic anatomy recognition may improve surgical orientation and recognition of anatomical structures and might contribute to reducing morbidity or learning curves. Studies regarding anatomy recognition in complex surgical procedures are currently lacking. Methods: Eighty-three videos of consecutive RAMIE procedures between 2018 and 2022 were retrospectively collected at University Medical Center Utrecht. A surgical PhD candidate and an expert surgeon annotated the azygos vein and vena cava, aorta, and right lung on 1050 thoracoscopic frames. 850 frames were used for training of a convolutional neural network (CNN) to segment the anatomical structures. The remaining 200 frames of the dataset were used for testing the CNN. The Dice and 95% Hausdorff distance (95HD) were calculated to assess algorithm accuracy. Results: The median Dice of the algorithm was 0.79 (IQR = 0.20) for segmentation of the azygos vein and/or vena cava. A median Dice coefficient of 0.74 (IQR = 0.86) and 0.89 (IQR = 0.30) were obtained for segmentation of the aorta and lung, respectively. Inference time was 0.026 s (39 Hz). The prediction of the deep learning algorithm was compared with the expert surgeon annotations, showing an accuracy measured in median Dice of 0.70 (IQR = 0.19), 0.88 (IQR = 0.07), and 0.90 (0.10) for the vena cava and/or azygos vein, aorta, and lung, respectively. Conclusion: This study shows that deep learning-based semantic segmentation has potential for anatomy recognition in RAMIE video frames. The inference time of the algorithm facilitated real-time anatomy recognition. Clinical applicability should be assessed in prospective clinical studies.</p

Statins, but not proprotein convertase subtilisin-kexin type 9 inhibitors, lower chemerin in hypercholesterolemia via low-density lipoprotein receptor upregulation

Hypercholesterolemia is characterized by elevated low-density lipoprotein (LDL)-cholesterol levels and an increased risk of cardiovascular disease. The adipokine chemerin is an additional risk factor. Here we investigated whether cholesterol-lowering with statins or proprotein convertase subtilisin-kexin type 9 inhibitors (PCSK9i) affects chemerin. Both statins and PCKS9i lowered plasma LDL-cholesterol, triglycerides and total cholesterol in hypercholesterolemic patients, and increased high-density lipoprotein (HDL)-cholesterol. Yet, only statins additionally reduced chemerin and high-sensitivity C-reactive protein (hsCRP). Applying PCSK9i on top of statins did not further reduce chemerin. Around 20% of chemerin occurred in the HDL2/HDL3 fractions, while &gt;75% was free. Statins lowered both HDL-bound and free chemerin. Pull-down assays revealed that chemerin binds to the HDL-component Apolipoprotein A-I (ApoA-I). The statins, but not PCSK9i, diminished chemerin secretion from HepG2 cells by upregulating LDL receptor mRNA. Furthermore, chemerin inhibited HDL-mediated cholesterol efflux via its chemerin chemokine-like receptor 1 in differentiated macrophages. In conclusion, statins, but not PCSK9i, lower circulating chemerin by directly affecting its release from hepatocytes. Chemerin binds to ApoA-I and inhibits HDL-mediated cholesterol efflux. Statins prevent this by lowering HDL-bound chemerin. Combined with their anti-inflammatory effect evidenced by hsCRP suppression, this represents a novel cardiovascular protective function of statins that distinguishes them from PCSK9i.</p

Reliability of resilience estimation based on multi-instrument time series

This is the final version. Available from Copernicus Publications via the DOI in this record. Code and data availability: Data used in this study are publicly available from Moesinger et al. (2020) (https://doi.org/10.5281/zenodo.2575599, Moesinger et al., 2019), https://doi.org/10.3390/rs6086929 (Pinzon and Tucker, 2014), https://doi.org/10.5067/MODIS/MCD12Q1.061 (Friedl and Sulla-Menashe, 2015), and https://doi.org/10.5067/MODIS/MOD13C1.006 (Didan, 2015). Code to reproduce the synthetic data used in this study can be found on Zenodo: https://doi.org/10.5281/zenodo.7009414 (Smith and Boers, 2022)Many widely used observational data sets are comprised of several overlapping instrument records. While data inter-calibration techniques often yield continuous and reliable data for trend analysis, less attention is generally paid to maintaining higher-order statistics such as variance and autocorrelation. A growing body of work uses these metrics to quantify the stability or resilience of a system under study and potentially to anticipate an approaching critical transition in the system. Exploring the degree to which changes in resilience indicators such as the variance or autocorrelation can be attributed to non-stationary characteristics of the measurement process - rather than actual changes in the dynamical properties of the system - is important in this context. In this work we use both synthetic and empirical data to explore how changes in the noise structure of a data set are propagated into the commonly used resilience metrics lag-one autocorrelation and variance. We focus on examples from remotely sensed vegetation indicators such as vegetation optical depth and the normalized difference vegetation index from different satellite sources. We find that time series resulting from mixing signals from sensors with varied uncertainties and covering overlapping time spans can lead to biases in inferred resilience changes. These biases are typically more pronounced when resilience metrics are aggregated (for example, by land-cover type or region), whereas estimates for individual time series remain reliable at reasonable sensor signal-to-noise ratios. Our work provides guidelines for the treatment and aggregation of multi-instrument data in studies of critical transitions and resilience.Horizon 2020Marie Skłodowska-Curie ActionsBundesministerium für Bildung und ForschungBrandenburger Staatsministerium für Wissenschaft, Forschung und Kultur (NEXUS