Effects of exercise intensity and nutrition advice on myocardial function in obese children and adolescents: a multicentre randomised controlled trial study protocol.

INTRODUCTION: The prevalence of paediatric obesity is increasing, and with it, lifestyle-related diseases in children and adolescents. High-intensity interval training (HIIT) has recently been explored as an alternate to traditional moderate-intensity continuous training (MICT) in adults with chronic disease and has been shown to induce a rapid reversal of subclinical disease markers in obese children and adolescents. The primary aim of this study is to compare the effects of HIIT with MICT on myocardial function in obese children and adolescents. METHODS AND ANALYSIS: Multicentre randomised controlled trial of 100 obese children and adolescents in the cities of Trondheim (Norway) and Brisbane (Australia). The trial will examine the efficacy of HIIT to improve cardiometabolic outcomes in obese children and adolescents. Participants will be randomised to (1) HIIT and nutrition advice, (2) MICT and nutrition advice or (3) nutrition advice. Participants will partake in supervised exercise training and/or nutrition sessions for 3 months. Measurements for study end points will occur at baseline, 3 months (postintervention) and 12 months (follow-up). The primary end point is myocardial function (peak systolic tissue velocity). Secondary end points include vascular function (flow-mediated dilation assessment), quantity of visceral and subcutaneous adipose tissue, myocardial structure and function, body composition, cardiorespiratory fitness, autonomic function, blood biochemistry, physical activity and nutrition. Lean, healthy children and adolescents will complete measurements for all study end points at one time point for comparative cross-sectional analyses. ETHICS AND DISSEMINATION: This randomised controlled trial will generate substantial information regarding the effects of exercise intensity on paediatric obesity, specifically the cardiometabolic health of this at-risk population. It is expected that communication of results will allow for the development of more effective evidence-based exercise prescription guidelines in this population while investigating the benefits of HIIT on subclinical markers of disease. TRIAL REGISTRATION NUMBER: NCT01991106

Long-distance migration and venting of methane from the base of the hydrate stability zone

\ua9 2023, The Author(s).Marine methane hydrate is an ice-like substance that is stable in sediment around marine continental margins where water depths are greater than ~450–700 m. The release of methane due to melting of hydrates is considered to be a mechanism for past global carbon-cycle perturbations and could exacerbate ongoing anthropogenic climate change. Increases in bottom-water temperature at the landward limit of marine hydrate around continental margins, where vulnerable hydrate exists at or below the seabed, cause methane to vent into the ocean. However, this setting represents only ~3.5% of the global hydrate reservoir. The potential for methane from hydrate in deeper water to reach the atmosphere was considered negligible. Here we use three-dimensional (3D) seismic imagery to show that, on the Mauritanian margin, methane migrated at least 40 km below the base of the hydrate stability zone and vented through 23 pockmarks at the shelf break, probably during warmer Quaternary interglacials. We demonstrate that, under suitable circumstances, some of the 96.5% of methane bound in deeper water distal hydrates can reach the seafloor and vent into the ocean beyond the landward limit of marine hydrate. This reservoir should therefore be considered for estimating climate change-induced methane release during a warming world

Regional Exploration and Characterisation of CO 2 Storage Prospects in the Utsira-Skade Aquifer, North Viking Graben, North Sea

From Frontiers via Jisc Publications RouterHistory: collection 2021, received 2021-03-12, accepted 2021-09-03, epub 2021-10-04Publication status: PublishedSubsurface CO2 storage is considered a key element of reducing anthropogenic emissions in virtually all scenarios compatible with limiting global warming to 1.5°C. The Utsira-Skade Aquifer (Utsira, Eir and Skade Formations), northern North Sea, has been identified as a suitable reservoir. Although the overall storage capacity of the full aquifer has been estimated based on regional data, it is lacking an integrated assessment of containment and internal heterogeneity, to identify optimal areas for injection and for calculation of site-specific storage capacities. A high-resolution, broadband 3D seismic reflection dataset, full waveform inverted velocity data and 102 exploration wells are utilised to provide a catalogue of CO2 storage prospects in the northern Utsira-Skade Aquifer. This is achieved through: 1) definition of the aquifer’s spatial limits; 2) calculation of porosity distribution; 3) assessment of the extent, geomorphology, thickness variability, and containment confidence (CC) of mudstones; and 4) mapping of closures through fill-to-spill simulations. CO2 storage capacity was calculated for the prospects using two approaches; using the full reservoir thickness (FRT) beneath the closures and using only the thickness from the closure top to the spill point (TSP), i.e., within structural traps. Porosity ranges from 29 to 39% across the aquifer and is higher in the Utsira and Eir Fms. relative to the underlying Skade Fm. The mudstone separating the Skade and Eir/Utsira Fm. has a thickness > 50 m, and is a potential barrier for CO2. Other intra-aquifer mudstones were mainly interpreted to act as baffles to flow. Structural traps at the top Utsira and Skade Fms. yield fifteen prospects, with criteria of > 700 m depth and FRT storage capacity of > 5 Mt CO2. They have a combined storage capacity of 330 Mt CO2 (FRT) or 196 Mt CO2 (TSP). Five prospects have a positive CC score (total capacity: 54 Mt CO2 FRT or 39 Mt CO2 TSP). Additional storage capacity could be achieved through more detailed analysis of the seal to upgrade the CC scores, or through use of a network of the mapped closures with a fill-to-spill approach, utilising more of the aquifer

Seismic volcanostratigraphy of the western Indian rifted margin: The pre-Deccan igneous province

The Indian Plate has been the focus of intensive research concerning the flood basalts of the Deccan Traps. Here we document a volcanostratigraphic analysis of the offshore segment of the western Indian volcanic large igneous province, between the shoreline and the first magnetic anomaly (An 28 ∼63 Ma). We have mapped the different crustal domains of the NW Indian Ocean from stretched continental crust through to oceanic crust, using seismic reflection and potential field data. Two volcanic structures, the Somnath Ridge and the Saurashtra High, are identified, extending ∼305 km NE-SW in length and 155 km NW-SE in width. These show the internal structures of buried shield volcanoes and hyaloclastic mounds, surrounded by mass-wasting deposits and volcanic sediments. The structures observed resemble seismic images from the North Atlantic and northwest Australia, as well as volcanic geometries described for Runion and Hawaii. The geometry and internal seismic facies within the volcanic basement suggest a tholeiitic composition and subaerial to shallow marine emplacement. At the scale of the western Indian Plate, the emplacement of this volcanic platform is constrained by structural lineations associated with rifting. By reviewing the volcanism in the Indian Ocean and plate reconstruction of the area, the timing of the volcanism can be associated with eruption of a pre-Deccan continental flood basalt (∼75-65.5 Ma). The volcanic platform in this study represents an addition of 19-26.5% to the known volume of the West Indian Volcanic Province. Copyright 2011 by the American Geophysical Union

Extensive marine-terminating ice sheets in Europe from 2.5 million years ago

Geometries of Early Pleistocene [2.58 to 0.78 million years (Ma) ago] ice sheets in northwest Europe are poorly constrained but are required to improve our understanding of past ocean-atmosphere-cryosphere coupling. Ice sheets are believed to have changed in their response to orbital forcing, becoming, from about 1.2 Ma ago, volumetrically larger and longer-lived. We present a multiproxy data set for the North Sea, extending to over a kilometer below the present-day seafloor, which demonstrates spatially extensive glaciation of the basin from the earliest Pleistocene. Ice sheets repeatedly entered the North Sea, south of 60°N, in water depths of up to ~250 m from 2.53 Ma ago and subsequently grounded in the center of the basin, in deeper water, from 1.87 Ma ago. Despite lower global ice volumes, these ice sheets were near comparable in spatial extent to those of the Middle and Late Pleistocene but possibly thinner and moving over slippery (low basal resistance) beds

MRI Reveals the in Vivo Cellular and Vascular Response to BEZ235 in Ovarian Cancer Xenografts with Different PI3-Kinase Pathway Activity

Background: The phosphoinositide-3 kinase (PI3K) pathway is an attractive therapeutic target. However, difficulty in predicting therapeutic response limits the clinical implementation of PI3K inhibitors. This study evaluates the utility of clinically relevant magnetic resonance imaging (MRI) biomarkers for noninvasively assessing the in vivo response to the dual PI3K/mTOR inhibitor BEZ235 in two ovarian cancer models with differential PI3K pathway activity. Methods: The PI3K signalling activity of TOV-21G and TOV-112D human ovarian cancer cells was investigated in vitro. Cellular and vascular response of the xenografts to BEZ235 treatment (65 mg kg−1, 3 days) was assessed in vivo using diffusion-weighted (DW) and dynamic contrast-enhanced (DCE)-MRI. Micro-computed tomography was performed to investigate changes in vascular morphology. Results: The TOV-21G cells showed higher PI3K signalling activity than TOV-112D cells in vitro and in vivo. Treated TOV-21G xenografts decreased in volume and DW-MRI revealed an increased water diffusivity that was not found in TOV-112D xenografts. Treatment-induced improvement in vascular functionality was detected with DCE-MRI in both models. Changes in vascular morphology were not found. Conclusions: Our results suggest that DW- and DCE-MRI can detect cellular and vascular response to PI3K/mTOR inhibition in vivo. However, only DW-MRI could discriminate between a strong and weak response to BEZ235.From twelve months after its original publication, this work is licensed under the Creative Commons Attribution-NonCommercial-Share Alike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0

Halokinetic modulation of sedimentary thickness and architecture: A numerical modelling approach

Subsurface salt flow can deform overlying strata and influence contemporaneous sedimentary systems. Studying salt-sediment interactions is challenging in the subsurface due to poor imaging adjacent to salt, and in the field due to the dissolution of halite. Discrete Element Modelling provides an efficient and inexpensive tool to model stratigraphy and deformation around salt structures, which is advantageous over other modelling techniques as it realistically recreates brittle processes such as faulting. Six 2D experiments were run representing 4.6 Myr to determine the effect of salt growth on syn-kinematic stratigraphy. Halokinetic deformation of stratigraphic architecture was assessed by varying sediment input rates through time. Results show the realistic formation and evolution of salt-related faults which define a zone of halokinetic influence ca. 3 times the width of the initial diapir. Outside of this, early diapiric and syn-kinematic stratigraphy are undeformed. Within this zone, syn-kinematic strata are initially isolated into primary salt withdrawal basins, onlapping and thinning towards the salt-cored high. In most models, syn-kinematic strata eventually thin across and cover the diapir roof. Thinning rates are up to six times greater within 350 m of the diapir, compared to further afield, and typically decrease upwards (with time) and laterally (with distance) from the diapir. Outputs are compared to a subsurface example from the Pierce field, UK North Sea, which highlights the importance of considering local fluctuations in diapir rise rate. These can create stratigraphic architectures that may erroneously be interpreted to represent increases/decreases in sedimentation rate. Exposed examples, such as the Bakio diapir, northern Spain, can be used to make inferences of the expected depositional facies, below model resolution. Our models aid the prediction of sedimentary unit thickness and thinning rates and can be used to test interpretations arising from incomplete or low-resolution subsurface and outcrop data when building geological models for subsurface energy

Distinct choline metabolic profiles are associated with differences in gene expression for basal-like and luminal-like breast cancer xenograft models

<p>Abstract</p> <p>Background</p> <p>Increased concentrations of choline-containing compounds are frequently observed in breast carcinomas, and may serve as biomarkers for both diagnostic and treatment monitoring purposes. However, underlying mechanisms for the abnormal choline metabolism are poorly understood.</p> <p>Methods</p> <p>The concentrations of choline-derived metabolites were determined in xenografted primary human breast carcinomas, representing basal-like and luminal-like subtypes. Quantification of metabolites in fresh frozen tissue was performed using high-resolution magic angle spinning magnetic resonance spectroscopy (HR MAS MRS).</p> <p>The expression of genes involved in phosphatidylcholine (PtdCho) metabolism was retrieved from whole genome expression microarray analyses.</p> <p>The metabolite profiles from xenografts were compared with profiles from human breast cancer, sampled from patients with estrogen/progesterone receptor positive (ER+/PgR+) or triple negative (ER-/PgR-/HER2-) breast cancer.</p> <p>Results</p> <p>In basal-like xenografts, glycerophosphocholine (GPC) concentrations were higher than phosphocholine (PCho) concentrations, whereas this pattern was reversed in luminal-like xenografts. These differences may be explained by lower choline kinase (<it>CHKA</it>, <it>CHKB</it>) expression as well as higher PtdCho degradation mediated by higher expression of phospholipase A2 group 4A (<it>PLA2G4A</it>) and phospholipase B1 (<it>PLB1</it>) in the basal-like model. The glycine concentration was higher in the basal-like model. Although glycine could be derived from energy metabolism pathways, the gene expression data suggested a metabolic shift from PtdCho synthesis to glycine formation in basal-like xenografts. In agreement with results from the xenograft models, tissue samples from triple negative breast carcinomas had higher GPC/PCho ratio than samples from ER+/PgR+ carcinomas, suggesting that the choline metabolism in the experimental models is representative for luminal-like and basal-like human breast cancer.</p> <p>Conclusions</p> <p>The differences in choline metabolite concentrations corresponded well with differences in gene expression, demonstrating distinct metabolic profiles in the xenograft models representing basal-like and luminal-like breast cancer. The same characteristics of choline metabolite profiles were also observed in patient material from ER+/PgR+ and triple-negative breast cancer, suggesting that the xenografts are relevant model systems for studies of choline metabolism in luminal-like and basal-like breast cancer.</p