SUMMARY
Microseismic observations during unconventional reservoir stimulation are typically seen as a proxy for clusters of hydraulic fractures and the extent of the stimulated reservoir. Such ...straightforward interpretation is often misleading and fails to provide a physically reasonable image of the fracturing process. This paper demonstrates the application of a physics-based machine learning algorithm which enables a rapid and accurate fracture mapping from the microseismic data. Our training and validation data set relies on a history-matched geomechanical modelling workflow implemented in GEOS software for the Hydraulic Fracturing Test Site 1 (HFTS-1) project. For this study we augmented the simulated fracture growth through geostatistical modelling of induced seismicity, so that the synthetic microseismic catalogue matches the main statistical properties of the field observations. We formulated the problem of mapping the actual fracture in the clutter of events to parallel common video segmentation workflows: several past video frames (microseismic density snapshots) are passed through a deep convolutional network to classify whether a given voxel is associated with a fracture or intact rock. We found that for accurate fracture mapping, the network’s input and architecture must be augmented to incorporate the fluid injection parameters (pressure, rate, concentration of proppant, and location of the perforation within the cluster). The error rate for the network reached as little as 10 per cent of the fracture area, while a conventional microseismic interpretation approach yielded ∼300 per cent. Our approach also yields must faster predictions than conventional methods (minutes instead of weeks), and could enable engineers to make rapid decisions regarding engineering parameters (pumping rate, viscosity) in real time during stimulation.
Many aspects of photoperception by plants and microorganisms are initiated by the phytochrome (Phy) family of photoreceptors that detect light through interconversion between red light- (Pr) and ...far-red light-absorbing (Pfr) states. Plants synthesize a small family of Phy isoforms (PhyA to PhyE) that collectively regulate photomorphogenesis and temperature perception through redundant and unique actions. While the selective roles of these isoforms have been partially attributed to their differing abundances, expression patterns, affinities for downstream partners, and turnover rates, we show here from analysis of recombinant
chromoproteins that the Phy isoforms also display distinct biophysical properties. Included are a hypsochromic shift in the Pr absorption for PhyC and varying rates of Pfr to Pr thermal reversion, part of which can be attributed to the core photosensory module in each. Most strikingly, PhyB combines strong temperature dependence of thermal reversion with an order-of-magnitude faster rate to likely serve as the main physiological thermosensor, whereby thermal reversion competes with photoconversion. In addition, comparisons of Pfr occupancies for PhyA and PhyB under a range of red- and white-light fluence rates imply that low-light environments are effectively sensed by PhyA, while high-light environments, such as full sun, are effectively sensed by PhyB. Parallel analyses of the Phy isoforms from potato and maize showed that the unique features within the
family are conserved, thus indicating that the distinct biophysical properties among plant Phy isoforms emerged early in Phy evolution, likely to enable full interrogation of their light and temperature environments.
Twin fetuses grow slower during the third trimester compared with singletons. However, the extent to which the relative smallness of twins is the result of placenta-mediated factors similar to those ...associated with fetal growth restriction in singletons remains unclear. Our aim was to address this question by comparing placental findings between small for gestational age (SGA) twins and SGA singletons.
Retrospective cohort study of all SGA non-anomalous newborns from singleton and dichorionic twin pregnancies in a single tertiary referral center between 2002 and 2015. SGA was defined as birth weight <10th percentile for gestational age according to sex-specific national reference charts. Placental findings were compared between SGA twins and SGA singletons and were classified into lesions associated with maternal vascular malperfusion, fetal vascular malperfusion, placental hemorrhage and chronic villitis.
A total of 532 SGA twins and 954 SGA singletons met the inclusion criteria. SGA twins had a higher mean placental weight (371 ± 103 g vs. 319 ± 107, p < 0.001) and a lower fetal-placental ratio (6.0 ± 2.5 vs. 6.7 ± 3.2, p < 0.001) compared with SGA singletons. Compared with SGA singletons, SGA twins were less likely to have any placental pathology (aOR 0.37, 95%-CI 0.29–0.46), hypercoiled cord (aOR 0.45, 95%-CI 0.33–0.61), placental weight<10th% (aOR 0.13, 95%-CI 0.08–0.20), maternal vascular malperfusion pathology (aOR 0.24, 95%-CI 0.18–0.30) and fetal vascular malperfusion pathology (aOR 0.62, 95%-CI 0.48–0.82). By contrast, SGA twins had higher odds of a marginal or velamentous cord insertion compared with SGA singletons (aOR 13.82, 95%-CI 10.44–18.30). Similar significant associations were observed in subgroups of SGA fetuses with a birth weight below the 5th and 3rd percentile for gestational age.
Our findings illustrate that the mechanisms underlying reduced fetal growth in dichorionic twins differ from those involved in singletons, and may provide support to the hypothesis that smallness in dichorionic twins may be more benign than in singletons.
•Placentas of SGA twins are less likely to show signs of placental insufficiency compared with SGA singletons.•SGA twins are more likely to have marginal or velamentous cord insertion.•These findings support the hypothesis that the relative smallness of twins may be more benign than in singletons.
Production simulation from fractured shale reservoirs is often performed by simplifying the hydraulic fractures as rectangular planes with homogeneous aperture. This study investigates the effects of ...heterogeneous fracture aperture and proppant distribution in realistic, non-rectangular fractures on the multi-phase production from shales. The heterogeneous hydraulic fractures are generated with the GEOS multiphysics simulator under realistic 3D stress field. These fractures are embedded into the TOUGH+ multi-phase flow simulator for production simulation. The results emphasize the importance of flow barriers within the hydraulic fractures, due both to low-aperture regions caused by the stress-shadow effect and the settling of proppant. The production rate is particularly sensitive to aperture heterogeneity if the flow barriers are close to the wellbore such that a great portion of fracture volume is isolated from the well. A stage-to-stage comparison reveals that production from different stages could vary significantly because the local stress field leads to different fracture area and aperture. The use of proppant prevents fracture closure, but if the propped regions are far from the well, they do not enhance production because flow barriers between these regions and the well act as bottlenecks. The present study highlights the importance of incorporating aperture heterogeneity into production simulation, provides insights on the relationship between flow barriers, proppant concentration, and well production, and proposes a practical method to mitigate numerical difficulties when modeling heterogeneous fractures.
MicroRNAs (miRNAs) are small noncoding RNA molecules that post-transcriptionally regulate gene expression. Dysregulation of miRNAs is frequently associated with disease and, in particular, is ...involved in prostate cancer progression. Next generation miRNA sequencing identified a panel of five miRNAs associated with prostate cancer recurrence and metastasis. High expression of one of these five miRNAs, miR-652, correlated significantly with an increased rate of prostate cancer biochemical recurrence. Overexpression of miR-652 in prostate cancer cells, PC3 and LNCaP, resulted in increased growth, migration and invasion. Prostate cancer cell xenografts overexpressing miR-652 showed increased tumorigenicity and metastases. We found that miR-652 directly targets the B" regulatory subunit, PPP2R3A, of the tumor suppressor PP2A, inducing epithelial-mesenchymal transition (EMT) in PC3 cells and neuroendocrine-like differentiation (NED) in LNCaP cells. The mesenchymal marker N-cadherin increased and epithelial marker E-cadherin decreased in PC3 cells overexpressing miR-652. In LNCaP cells and xenografted tumors, overexpression of miR-652 increased markers of NED, including chromogranin A, neuron specific enolase, and synaptophysin. MiR-652 may contribute to prostate tumor progression by promoting NED through decreased PP2A function. MiR-652 expression could serve as a biomarker for aggressive prostate cancer, as well as provide an opportunity for novel therapy in prostate cancer.
ObjectivesOur objective was to compare prostate cancer detection rates between patients undergoing serum prostate-specific antigen (PSA) vs magnetic resonance imaging (MRI) for prostate cancer ...screening.DesignPhase III open-label randomised controlled trial.SettingSingle tertiary cancer centre in Toronto, Canada.ParticipantsMen 50 years of age and older with no history of PSA screening for ≥3 years, a negative digital rectal exam and no prior prostate biopsy.InterventionsPatients were recommended to undergo a prostate biopsy if their PSA was ≥2.6 ng/mL (PSA arm) or if they had a PIRADS score of 4 or 5 (MRI arm). Patients underwent an end-of-study PSA in the MRI arm.Primary and secondary outcome measuresAdenocarcinoma on prostate biopsy. Prostate biopsy rates and the presence of clinically significant prostate cancer were also compared.ResultsA total of 525 patients were randomised, with 266 in the PSA arm and 248 in the MRI arm. Due to challenges with accrual and study execution during the COVID-19 pandemic, the study was terminated early. In the PSA arm, 48 patients had an abnormal PSA and 28 (58%) agreed to undergo a prostate biopsy. In the MRI arm, 25 patients had a PIRADS score of 4 or 5 and 24 (96%) agreed to undergo a biopsy. The relative risk for MRI to recommend a prostate biopsy was 0.52 (95% CI 0.33 to 0.82, p=0.005), compared with PSA. The cancer detection rate for patients in the PSA arm was 29% (8 of 28) vs 63% (15 of 24, p=0.019) in the MRI arm, with a higher proportion of clinically significant cancer detected in the MRI arm (73% vs 50%). The relative risk for detecting cancer and clinically significant with MRI compared with PSA was 1.89 (95% CI 0.82 to 4.38, p=0.14) and 2.77 (95% CI 0.89 to 8.59, p=0.07), respectively.ConclusionsProstate MRI as a stand-alone screening test reduced the rate of prostate biopsy. The number of clinically significant cancers detected was higher in the MRI arm, but this did not reach statistical significance. Due to early termination, the study was underpowered. More patients were willing to follow recommendations for prostate biopsy based on MRI results.Trial registration numberNCT02799303.
Transcriptional profiling of muscle-invasive bladder cancer (MIBC) using RNA sequencing (RNA-seq) technology has demonstrated the existence of intrinsic basal and luminal molecular subtypes that vary ...in their prognosis and response to therapy. However, routine use of RNA-seq in a clinical setting is restricted by cost and technical difficulties. Herein, we provide a single-sample NanoString-based seven-gene (KRT5, KRT6C, SERPINB13, UPK1A, UPK2, UPK3A and KRT20) MIBC molecular classifier that assigns a luminal and basal molecular subtype. The classifier was developed in a series of 138 chemotherapy naïve MIBCs split into training (70%) and testing (30%) datasets. Further, we validated the previously published CK5/6 and GATA3 immunohistochemical classifier which showed high concordance of 96.9% with the NanoString-based gene expression classifier. Immunohistochemistry-based molecular subtypes significantly correlated with recurrence-free survival (RFS) and disease-specific survival (DSS) in univariable (p = 0.006 and p = 0.011, respectively) and multivariate cox regression analysis for DSS (p = 0.032). Used sequentially, the immunohistochemical- and NanoString-based classifiers provide faster turnaround time, lower cost per sample and simpler data analysis for ease of clinical implementation in routine diagnostics.
PDF
