Evaluation of two supplementation strategies to improve long-chain omega-3 fatty acid status in healthy subjects

This work was intended to evaluate two supplementation strategies to improve long-chain omega-3 fatty acid (n-3 LCPUFA) status in healthy adults. Two randomised, double blind, placebo-controlled intervention studies with parallel design were performed. The first study investigated the effects of a docosahexaenoic acid (DHA)-rich, almost eicosapentaenoic acid (EPA)-free microalgae oil (Ulkenia sp.) on red blood cell (RBC) and plasma fatty acids, plasma lipids and several safety parameters. Normolipidaemic vegetarians (87 f, 27 m) consumed daily microalgae oil (0.94 g DHA/d) or olive oil (as placebo) for 8 wk. DHA supplementation significantly increased DHA levels in RBC total lipids (from 4.4 to 7.9 wt%, means), in RBC phosphatidylethanolamine (from 6.5 to 12.1 wt%), in RBC phosphatidylcholine (from 1.4 to 3.8 wt%), and in plasma phospholipids (from 2.8 to 7.4 wt%). EPA levels rose to a much lesser extent. Microalgae oil provided for an increase in omega-3 index (from 4.8 to 8.4 wt%); after intervention, 69% of DHA supplemented subjects, but no subject of the placebo group reached an omega-3 index with a desirable value > 8 wt%. DHA supplementation decreased plasma triacylglycerol (TG) by 23% from 1.08 to 0.83 mmol/l. Plasma total, LDL and HDL cholesterol increased significantly in the DHA group, resulting in a lower TG:HDL cholesterol ratio and unchanged LDL:HDL and total cholesterol:HDL cholesterol ratios. The intake of DHA-rich microalgae oil did not result in any physiologically relevant changes of safety and haemostatic factors. In conclusion, DHA-rich oil from microalgae Ulkenia sp. was well tolerated and can be considered a suitable vegetarian source of n-3 LCPUFA. Although DHA supplementation improved some cardiovascular risk factors (plasma TG, TG:HDL cholesterol ratio), LDL cholesterol increased. Therefore, the overall effects of this intervention on cardiovascular risk deserve further investigation. The second study investigated the effects of a fish oil / evening primrose oil (FO/EPO) blend (456 mg DHA/day and 353 mg gamma-linolenic acid (GLA)/day) compared to a placebo (mixture of habitual dietary fatty acids) on the plasma fatty acid (FA) composition in two groups of 20 non-pregnant women. FA were quantified in plasma total lipids, phospholipids, cholesterol esters, and TG at weeks 0, 4, 6 and 8. After 8 weeks of intervention, percentage changes from baseline values of plasma total lipid FA were significantly different between FO/EPO and placebo for GLA (+49.9% vs. +2.1%, means), dihomo-gamma-linolenic acid (DGLA, +13.8% vs. +0.7%) and DHA (+59.6% vs. +5.5%), while there was no significant difference for arachidonic acid (ARA, -2.2% vs. -5.9%). FA changes were largely comparable between plasma lipid fractions. As compared to placebo, FO/EPO supplementation did not result in any physiologically relevant changes of safety parameters (blood cell count, liver enzymes). In conclusion, in women of childbearing age the tested FO/EPO blend is well tolerated and appears safe. It increases plasma GLA, DGLA, and DHA levels without impairing ARA status. These data provide a basis for testing this FO/EPO blend in pregnant women for its effects on maternal and neonatal FA status and infant development

Accuracy of non-invasive prenatal testing using cell-free DNA for detection of Down, Edwards and Patau syndromes : a systematic review and meta-analysis

Objective: To measure test accuracy of non-invasive prenatal testing (NIPT) for Down, Edwards and Patau syndromes using cell-free fetal DNA and identify factors affecting accuracy. Design: Systematic review and meta-analysis of published studies. Data sources: PubMed, Ovid Medline, Ovid Embase and the Cochrane Library published from 1997 to 9 February 2015, followed by weekly autoalerts until 1 April 2015. Eligibility: Criteria for selecting studies English language journal articles describing case–control studies with ≥15 trisomy cases or cohort studies with ≥50 pregnant women who had been given NIPT and a reference standard. Results: 41, 37 and 30 studies of 2012 publications retrieved were included in the review for Down, Edwards and Patau syndromes. Quality appraisal identified high risk of bias in included studies, funnel plots showed evidence of publication bias. Pooled sensitivity was 99.3% (95% CI 98.9% to 99.6%) for Down, 97.4% (95.8% to 98.4%) for Edwards, and 97.4% (86.1% to 99.6%) for Patau syndrome. The pooled specificity was 99.9% (99.9% to 100%) for all three trisomies. In 100 000 pregnancies in the general obstetric population we would expect 417, 89 and 40 cases of Downs, Edwards and Patau syndromes to be detected by NIPT, with 94, 154 and 42 false positive results. Sensitivity was lower in twin than singleton pregnancies, reduced by 9% for Down, 28% for Edwards and 22% for Patau syndrome. Pooled sensitivity was also lower in the first trimester of pregnancy, in studies in the general obstetric population, and in cohort studies with consecutive enrolment. Conclusions: NIPT using cell-free fetal DNA has very high sensitivity and specificity for Down syndrome, with slightly lower sensitivity for Edwards and Patau syndrome. However, it is not 100% accurate and should not be used as a final diagnosis for positive cases

Translating potential improvement in the precision and accuracy of lung nodule measurements on computed tomography scans by software derived from artificial intelligence into impact on clinical practice:a simulation study

Objectives Accurate measurement of lung nodules is pivotal to lung cancer detection and management. Nodule size forms the main basis of risk categorisation in existing guidelines. However, measurements can be highly variable between manual readers. This paper explores the impact of potentially improved nodule size measurement assisted by generic artificial intelligence (AI)-derived software on clinical management compared with manual measurement. Methods The simulation study created a baseline cohort of people with lung nodules, guided by nodule size distributions reported in the literature. Precision and accuracy were simulated to emulate measurement of nodule size by radiologists with and without the assistance of AI-derived software and by the software alone. Nodule growth was modelled over a 4-year time frame, allowing evaluation of management strategies based on existing clinical guidelines. Results Measurement assisted by AI-derived software increased cancer detection compared to an unassisted radiologist for a combined solid and sub-solid nodule population (62.5% vs 61.4%). AI-assisted measurement also correctly identified more benign nodules (95.8% vs 95.4%), however it was associated with over an additional month of surveillance on average (5.12 vs 3.95 months). On average, with AI assistance people with cancer are diagnosed faster, and people without cancer are monitored longer. Conclusions In this simulation, the potential benefits of improved accuracy and precision associated with AI-based diameter measurement is associated with additional monitoring of non-cancerous nodules. AI may offer additional benefits not captured in this simulation, and it is important to generate data supporting these, and adjust guidelines as necessary. Advances in Knowledge This paper shows the effects of greater measurement accuracy associated with AI assistance compared with unassisted measurement

miRNA Expression Characterizes Histological Subtypes and Metastasis in Penile Squamous Cell Carcinoma

Although microRNAs are described as promising biomarkers in many tumor types, little is known about their role in PSCC. Thus, we attempted to identify miRNAs involved in tumor development and metastasis in distinct histological subtypes considering the impact of HPV infection. In a first step, microarray analyses were performed on RNA from formalin-fixed, paraffin-embedded tumor (22), and normal (8) tissue samples. Microarray data were validated for selected miRNAs by qRT-PCR on an enlarged cohort, including 27 tumor and 18 normal tissues. We found 876 significantly differentially expressed miRNAs (p ≤ 0.01) between HPV-positive and HPV-negative tumor samples by microarray analysis. Although no significant differences were detected between normal and tumor tissue in the whole cohort, specific expression patterns occurred in distinct histological subtypes, such as HPV-negative usual PSCC (95 differentially expressed miRNAs, p ≤ 0.05) and HPV-positive basaloid/warty subtypes (247 differentially expressed miRNAs, p ≤ 0.05). Selected miRNAs were confirmed by qRT-PCR. Furthermore, microarray data revealed 118 miRNAs (p ≤ 0.01) that were significantly differentially expressed in metastatic versus non-metastatic usual PSCC. The lower expression levels for miR-137 and miR-328-3p in metastatic usual PSCC were validated by qRT-PCR. The results of this study confirmed that specific miRNAs could serve as potential diagnostic and prognostic markers in single PSCC subtypes and are associated with HPV-dependent pathways

Turbulent interactions between stream flow and near-subsurface flow: a laboratory approach using particle image velocimetry and refractive index matching

Turbulent flow over a rough, porous gravel bed (particle diameter, D = 1.27 cm) is investigated in the laboratory using particle image velocimetry (PIV) and refractive index matching (RIM). This combination allows for detailed examination of flow fields both in the near-bed region and within the pore spaces at two flow Reynolds numbers. In additional experiments, a channel-spanning cylinder and a single spherical grain were mounted to the top of the bed to study the turbulent flow around obstacles adjacent to a highly permeable wall. Supplementary experiments involving a mobile bed (D = 1.3 mm) in a very thin flume are also presented. With no obstacle on top of the bed, the mean velocity flow structure resembles that of a classic boundary layer, but with a significant slip velocity at the bed interface. In addition, the permeability of the interface allows for large instantaneous near-bed streamwise momentum due to vertical momentum exchange by turbulence. In the pore spaces, mean velocities are subhorizontal in direction and 5-10% of the maximum free stream velocity. High Reynolds stresses near the bed, particularly around the crests of spherical roughness elements, suggest turbulence is produced by flow separation and the shedding of vortices from streambed grains, rather than via viscous friction as in a classic smooth wall boundary layer. The geometry and dimensions of turbulent flow structures—determined via multi-point correlations of velocity fluctuations and Galilean decompositions—appear similar to those of hairpin vortices, although the resemblance remains unconfirmed without time-resolved data. The structure of the turbulent flow field is strongly affected by the addition of a cylindrical obstacle. In particular, the cylinder produces strong downwelling into the bed upstream of its location and upwelling in discrete jets downstream. The velocity directions in the pore spaces reflect this upwelling and downwelling in the stream above. Mean velocities in the pore spaces beneath the cylinder are accelerated up to 30% of the maximum free stream velocity. Downstream of the cylinder, flow separation produces a shear layer with high magnitude Reynolds stresses. However, rather than reattaching downstream, the shear layer dissipates in the outer region of flow, reaching the bed outside of the field of view, at ~11.5D downstream, with reduced Reynolds stresses. Furthermore, the streamlines do not reattach; rather, they are, like the Reynolds stresses, disturbed by upwelling fluid downstream of the cylinder, and the recirculation zone only extends 0.75D downstream and is truncated by the upwelling. Overall, the location of turbulence production is shifted away from the wall and to the height of the obstacle. Mesoscale turbulent flow structures appear to be produced by the rolling over of separated flow from the cylinder, while the dimensions of macroscale structures from upstream are strongly diminished by the obstacle. The single spherical grain produces a similar flow pattern to that of the cylinder, but the mean flow is more three-dimensional. Overall, the sphere presents less of a blockage to flow than the cylinder, and because flow can accelerate around the sphere in the streamwise-spanwise plane, the magnitude of fluid forced into the bed via downwelling and expelled via upwelling decreases by 50% in comparison to the cylinder. In addition, the magnitude of Reynolds stresses in the separated flow downstream of the single grain is 20% less than those observed for the cylinder. Similar to the cylindrical obstacle, the mean velocity streamlines and shear layer do not reattach downstream and are disturbed by upwelling flow. The recirculation zone is also affected, being rendered almost nonexistent, with a length of less than 0.25D. No standing horseshoe vortex is observed wrapping around the sphere, as often observed around hemispheres and spheres mounted to smooth walls, but rather turbulent flow structures are limited to hairpin-like vortices produced by the shear layer. The results of these experiments have important implications for hyporheic exchange and sediment transport. In particular, the transfer of momentum across the streambed interface by turbulence not only increases net hyporheic exchange in highly permeable sediments but also provides an explanation for the bedform morphology of gravel bed rivers. Overall, the experiments described in this thesis make it clear that the permeability of gravel systems must be addressed for accurate descriptions of stream flow