Diagnostic tools for early detection of cardiac dysfunction in childhood cancer survivors: Methodological aspects of the Dutch late effects after childhood cancer (LATER) cardiology study

Background: Cancer therapy-related cardiac dysfunction and heart failure are major problems in long-term childhood cancer survivors (CCS). We hypothesize that assessment of more sensitive echo- and electrocardiographic measurements, and/or biomarkers will allow for improved recognition of patients with cardiac dysfunction before heart failure develops, and may also identify patients at lower risk for heart failure. Objective: To describe the methodology of the Dutch LATER cardiology study (LATER CARD). Methods: The LATER CARD study is a cross-sectional study in long-term CCS treated with (potentially) cardiotoxic cancer therapies and sibling controls. We will evaluate 1) the prevalence and associated (treatment related) risk factors of subclinical cardiac dysfunction in CCS compared to sibling controls and 2) the diagnostic value of echocardiography including myocardial strain and diastolic function parameters, blood biomarkers for cardiomyocyte apoptosis, oxidative stress, cardiac remodeling and inflammation and ECG or combinations of them in the surveillance for cancer therapy-related cardiac dysfunction. From 2017 to 2020 we expect to include 1900 CCS and 500 siblings. Conclusions: The LATER CARD study will provide knowledge on different surveillance modalities for detection of cardiac dysfunction in long-term CCS at risk for heart

Diagnostic tools for early detection of cardiac dysfunction in childhood cancer survivors: Methodological aspects of the Dutch late effects after childhood cancer (LATER) cardiology study

Background: Cancer therapy-related cardiac dysfunction and heart failure are major problems in long-term childhood cancer survivors (CCS). We hypothesize that assessment of more sensitive echo- and electrocardiographic measurements, and/or biomarkers will allow for improved recognition of patients with cardiac dysfunction before heart failure develops, and may also identify patients at lower risk for heart failure. Objective: To describe the methodology of the Dutch LATER cardiology study (LATER CARD). Methods: The LATER CARD study is a cross-sectional study in long-term CCS treated with (potentially) cardiotoxic cancer therapies and sibling controls. We will evaluate 1) the prevalence and associated (treatment related) risk factors of subclinical cardiac dysfunction in CCS compared to sibling controls and 2) the diagnostic value of echocardiography including myocardial strain and diastolic function parameters, blood biomarkers for cardiomyocyte apoptosis, oxidative stress, cardiac remodeling and inflammation and ECG or combinations of them in the surveillance for cancer therapy-related cardiac dysfunction. From 2017 to 2020 we expect to include 1900 CCS and 500 siblings. Conclusions: The LATER CARD study will provide knowledge on different surveillance modalities for detection of cardiac dysfunction in long-term CCS at risk for heart failure. The results of the study will enable us to improve long-term follow-up surveillance guidelines for CCS at risk for heart failure

Interactive vs. automatic ultrasound image segmentation methods for staging hepatic lipidosis.

Item does not contain fulltextThe aim of this study was to test the hypothesis that automatic segmentation of vessels in ultrasound (US) images can produce similar or better results in grading fatty livers than interactive segmentation. A study was performed in postpartum dairy cows (N=151), as an animal model of human fatty liver disease, to test this hypothesis. Five transcutaneous and five intraoperative US liver images were acquired in each animal and a liverbiopsy was taken. In liver tissue samples, triacylglycerol (TAG) was measured by biochemical analysis and hepatic diseases other than hepatic lipidosis were excluded by histopathologic examination. Ultrasonic tissue characterization (UTC) parameters--Mean echo level, standard deviation (SD) of echo level, signal-to-noise ratio (SNR), residual attenuation coefficient (ResAtt) and axial and lateral speckle size--were derived using a computer-aided US (CAUS) protocol and software package. First, the liver tissue was interactively segmented by two observers. With increasing fat content, fewer hepatic vessels were visible in the ultrasound images and, therefore, a smaller proportion of the liver needed to be excluded from these images. Automatic-segmentation algorithms were implemented and it was investigated whether better results could be achieved than with the subjective and time-consuming interactive-segmentation procedure. The automatic-segmentation algorithms were based on both fixed and adaptive thresholding techniques in combination with a 'speckle'-shaped moving-window exclusion technique. All data were analyzed with and without postprocessing as contained in CAUS and with different automated-segmentation techniques. This enabled us to study the effect of the applied postprocessing steps on single and multiple linear regressions ofthe various UTC parameters with TAG. Improved correlations for all US parameters were found by using automatic-segmentation techniques. Stepwise multiple linear-regression formulas where derived and used to predict TAG level in the liver. Receiver-operating-characteristics (ROC) analysis was applied to assess the performance and area under the curve (AUC) of predicting TAG and to compare the sensitivity and specificity of the methods. Best speckle-size estimates and overall performance (R2 = 0.71, AUC = 0.94) were achieved by using an SNR-based adaptive automatic-segmentation method (used TAG threshold: 50 mg/g liver wet weight). Automatic segmentation is thus feasible and profitable.1 juli 201

Multiple water isotope proxy reconstruction of extremely low last glacial temperatures in Eastern Beringia (Western Arctic)

Precipitation isotopes are commonly used for paleothermometry in high latitude regions. Here we present multiple water isotope proxies from the same sedimentary context - perennially frozen loess deposits in the Klondike Goldfields in central Yukon, Canada, representing parts of Marine Isotope Stages (MIS) 4, 3 and 2 - allowing us to uniquely corroborate fractionations and temperature conversions during these Late Pleistocene cold stages. We include new and existing proxy data from: relict wedge ice, a direct archive for snowmelt; relict pore ice, an archive for bulk soil water integrating year-round precipitation; and hydrated volcanic glass shards and fossil plant waxes, which are also thought to integrate year-round precipitation but are subject to large fractionations. In some cases, our temperature estimates based on existing proxy data are much cooler than previously estimated due to our use of source water corrections for the glacial ocean, new transfer functions calibrated specifically for northern North America (δDprecip = 3.1‰·°C-1 × T - 155‰; and δ18Oprecip = 0.41‰·°C-1 × T - 20.2‰), and novel insights on the apparent net fractionation correction for Eastern Beringian steppe-tundra plant waxes (εwax/precip = -59 ± 10‰). The snowmelt origin of wedge ice ensures a relatively constrained winter-spring seasonality of contributing precipitation, as supported by the consistency between water isotope measurements from Late Holocene wedge ice and modern winter-spring precipitation. Wedge ice dating to the transitional MIS 3/2 is isotopically depleted relative to modern spring-winter precipitation by an amount that indicates a temperature depression of ~14 ± 5 °C below modern. The soil water origin of pore ice, and other proxies integrating year-round precipitation from soil water, allows for a more variable precipitation seasonality. The isotopic composition of modern pore ice is consistent with mean annual precipitation. However, the isotopic composition of pore ice during MIS 3/2 converges on wedge ice values, signalling an increase in the ratio of cold-to-warm-season precipitation integrated by pore ice during glacial times, possibly due to drier summers as supported by the fossil record and climate model simulations. In the study region, water isotope proxies integrating year-round precipitation may overestimate annual temperature differences between today and recent cold stages due to transient precipitation seasonality, as detected here, and thus are best interpreted as upper bound estimates. Based on these proxies, we estimate that annual temperatures during MIS 4, 3/2 and 2 were depressed below the modern climate to a maximum of ~18 °C, 16 °C and 21 °C ± 4-°C, respectively. Our study highlights the value of multiple water isotope proxies towards understanding changes in precipitation seasonality and developing robust reconstructions of past climate, and may be particularly important for studies of the major climate transformations over glacial-interglacial timescales

Quantitative Evaluation of an Automated Cone-based Breast Ultrasound Scanner for MRI - 3D US Image Fusion

Breast cancer is one of the most diagnosed types of cancer worldwide. Volumetric ultrasound breast imaging, combined with MRI can improve lesion detection rate, reduce examination time, and improve lesion diagnosis. However, to our knowledge, there are no 3D US breast imaging systems available that facilitate 3D US - MRI image fusion. In this paper, a novel Automated Cone-based Breast Ultrasound System (ACBUS) is introduced. The system facilitates volumetric ultrasound acquisition of the breast in a prone position without deforming it by the US transducer. Quality of ACBUS images for reconstructions at different voxel sizes (0.25 and 0.50 mm isotropic) was compared to quality of the Automated Breast Volumetric Scanner (ABVS) (Siemens Ultrasound, Issaquah, WA, USA) in terms of signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and resolution using a custom made phantom. The ACBUS image data were registered to MRI image data utilizing surface matching and the registration accuracy was quantified using an internal marker. The technology was also evaluated in vivo. The phantom-based quantitative analysis demonstrated that ACBUS can deliver volumetric breast images with an image quality similar to the images delivered by a currently commercially available Siemens ABVS. We demonstrate on the phantom and in vivo that ACBUS enables adequate MRI-3D US fusion. To our conclusion, ACBUS might be a suitable candidate for a second-look breast US exam, patient follow-up, and US guided biopsy planning

The 2000HIV study: Design, multi-omics methods and participant characteristics

Background: Even during long-term combination antiretroviral therapy (cART), people living with HIV (PLHIV) have a dysregulated immune system, characterized by persistent immune activation, accelerated immune ageing and increased risk of non-AIDS comorbidities. A multi-omics approach is applied to a large cohort of PLHIV to understand pathways underlying these dysregulations in order to identify new biomarkers and novel genetically validated therapeutic drugs targets. Methods: The 2000HIV study is a prospective longitudinal cohort study of PLHIV on cART. In addition, untreated HIV spontaneous controllers were recruited. In-depth multi-omics characterization will be performed, including genomics, epigenomics, transcriptomics, proteomics, metabolomics and metagenomics, functional immunological assays and extensive immunophenotyping. Furthermore, the latent viral reservoir will be assessed through cell associated HIV-1 RNA and DNA, and full-length individual proviral sequencing on a subset. Clinical measurements include an ECG, carotid intima-media thickness and plaque measurement, hepatic steatosis and fibrosis measurement as well as psychological symptoms and recreational drug questionnaires. Additionally, considering the developing pandemic, COVID-19 history and vaccination was recorded. Participants return for a two-year follow-up visit. The 2000HIV study consists of a discovery and validation cohort collected at separate sites to immediately validate any finding in an independent cohort. Results: Overall, 1895 PLHIV from four sites were included for analysis, 1559 in the discovery and 336 in the validation cohort. The study population was representative of a Western European HIV population, including 288 (15.2%) cis-women, 463 (24.4%) non-whites, and 1360 (71.8%) MSM (Men who have Sex with Men). Extreme phenotypes included 114 spontaneous controllers, 81 rapid progressors and 162 immunological non-responders. According to the Framingham score 321 (16.9%) had a cardiovascular risk of >20% in the next 10 years. COVID-19 infection was documented in 234 (12.3%) participants and 474 (25.0%) individuals had received a COVID-19 vaccine. Conclusion: The 2000HIV study established a cohort of 1895 PLHIV that employs multi-omics to discover new biological pathways and biomarkers to unravel non-AIDS comorbidities, extreme phenotypes and the latent viral reservoir that impact the health of PLHIV. The ultimate goal is to contribute to a more personalized approach to the best standard of care and a potential cure for PLHIV

The 2000HIV study:Design, multi-omics methods and participant characteristics

Background: Even during long-term combination antiretroviral therapy (cART), people living with HIV (PLHIV) have a dysregulated immune system, characterized by persistent immune activation, accelerated immune ageing and increased risk of non-AIDS comorbidities. A multi-omics approach is applied to a large cohort of PLHIV to understand pathways underlying these dysregulations in order to identify new biomarkers and novel genetically validated therapeutic drugs targets. Methods: The 2000HIV study is a prospective longitudinal cohort study of PLHIV on cART. In addition, untreated HIV spontaneous controllers were recruited. In-depth multi-omics characterization will be performed, including genomics, epigenomics, transcriptomics, proteomics, metabolomics and metagenomics, functional immunological assays and extensive immunophenotyping. Furthermore, the latent viral reservoir will be assessed through cell associated HIV-1 RNA and DNA, and full-length individual proviral sequencing on a subset. Clinical measurements include an ECG, carotid intima-media thickness and plaque measurement, hepatic steatosis and fibrosis measurement as well as psychological symptoms and recreational drug questionnaires. Additionally, considering the developing pandemic, COVID-19 history and vaccination was recorded. Participants return for a two-year follow-up visit. The 2000HIV study consists of a discovery and validation cohort collected at separate sites to immediately validate any finding in an independent cohort. Results: Overall, 1895 PLHIV from four sites were included for analysis, 1559 in the discovery and 336 in the validation cohort. The study population was representative of a Western European HIV population, including 288 (15.2%) cis-women, 463 (24.4%) non-whites, and 1360 (71.8%) MSM (Men who have Sex with Men). Extreme phenotypes included 114 spontaneous controllers, 81 rapid progressors and 162 immunological non-responders. According to the Framingham score 321 (16.9%) had a cardiovascular risk of >20% in the next 10 years. COVID-19 infection was documented in 234 (12.3%) participants and 474 (25.0%) individuals had received a COVID-19 vaccine. Conclusion: The 2000HIV study established a cohort of 1895 PLHIV that employs multi-omics to discover new biological pathways and biomarkers to unravel non-AIDS comorbidities, extreme phenotypes and the latent viral reservoir that impact the health of PLHIV. The ultimate goal is to contribute to a more personalized approach to the best standard of care and a potential cure for PLHIV