We utilize several lines of evidence to argue that slow slip on pre-existing fractures and faults is an important deformation mechanism contributing to the effectiveness of slick-water hydraulic fracturing for stimulating production in extremely low permeability shale gas reservoirs. First, we carried out rate and state friction experiments in the laboratory using shale samples from three different formations with a large range of clay content. These experiements indicated that slip on faults in shales comprised of less than about 30% clay is expected to propagate unstably, thus generating conventional microseismic events. In contrast, in formations containing more than about 30% clay are expected to slip slowly. Second, we illustrate through modeling that slip induced by high fluid pressure on faults that are poorly oriented for slip in the current stress field is expected to be slow, principally because slip cannot occur faster than fluid pressure propagates along the fault plane. Because slow fault slip does not generate high frequency seismic waves, conventional microseismic monitoring does not routinely detect what appears to be a critical process during stimulation. Thus, microseismic events are expected to give only a generalized picture of where pressurization is occurring in a shale gas reservoir during stimulation which helps explain why microseismicity does not appear to correlate with relative productivity. We review observations of long-period-longduration seismic events that appear to be generated by slow slip on mis-oriented fault planes during stimulation of the Barnett shale. Prediction of how pre-existing faults and fractures shear in response to hydraulic stimulation can help optimize field operations and improve recovery.

Nutrients are not only organic compounds fueling bioenergetics and biosynthesis, but also key chemical signals controlling growth and metabolism. Nutrients enormously impact the production of reactive oxygen species (ROS), which play essential roles in normal physiology and diseases. How nutrient signaling is integrated with redox regulation is an interesting, but not fully understood, question. Herein, we report that superoxide dismutase 1 (SOD1) is a conserved component of the mechanistic target of rapamycin complex 1 (mTORC1) nutrient signaling. mTORC1 regulates SOD1 activity through reversible phosphorylation at S39 in yeast and T40 in humans in response to nutrients, which moderates ROS level and prevents oxidative DNA damage. We further show that SOD1 activation enhances cancer cell survival and tumor formation in the ischemic tumor microenvironment and protects against the chemotherapeutic agent cisplatin. Collectively, these findings identify a conserved mechanism by which eukaryotes dynamically regulate redox homeostasis in response to changing nutrient conditions.

PurposeReported breast cancer incidence is rising in South Africa, where some women are diagnosed late and have poor outcomes. We studied patient and provider factors associated with clinical stage at diagnosis among women diagnosed at the Chris Hani Baragwanath Academic Hospital in Soweto, Johannesburg in 2015–2016.MethodsFrom face-to-face interviewer-administered questionnaires we compared self-reported socioeconomics, demographics, comorbidities, risk factors, personal and health system barriers, and from patient clinical records, clinical staging, receptor subtype, and tumor grade among 499 consecutive women newly diagnosed with advanced stage (III/IV) breast cancer versus those diagnosed early (stage 0/I/II). Logistic regression models were used to identify factors associated with advanced stage at diagnosis.ResultsAmong the women, 243 (49%) were diagnosed at early and 256 (51%) at advanced stages. In the multiple logistic regression adjusted model, completion of high school or beyond (odds ratio (OR) 0.59, and greater breast cancer knowledge and awareness (OR 0.86) were associated with lower stage of breast cancer at presentation. Advanced stage was associated with Luminal B (OR 2.25) and triple-negative subtypes (OR 3.17) compared to luminal A, with delays >3 months from first breast symptoms to accessing the health system (OR 2.79) and with having more than 1 visit within the referral health system (OR 3.19) for 2 visits; OR 2.73 for ≥3 visits).ConclusionsLimited patient education, breast cancer knowledge and awareness, and health system inefficiencies were associated with advanced stage at diagnosis. Sustained community and healthcare worker education may down-stage disease and improve cancer outcomes.

We report here a series of long-period and long-duration (LPLD) seismic events observed during hydraulic fracturing in a shale gas reservoir. These unusual events, 10–100 s in duration, are observed most clearly in the frequency band of 10–80 Hz and are remarkably similar in appearance to tectonic tremor sequences first observed in subduction zones. These complex but coherent wave trains have finite moveouts obtained from cross-correlation. The moveout direction of the events confirms that they originate in the reservoir from the area where the fracturing is going on. Clear P- and S-wave arrivals cannot be resolved within the LPLD episodes but, in some cases, small micro-earthquakes occur in the sequences. Whether these micro-earthquakes are causal or coincidental is not known. It has also been observed that in three contiguous frac-stages, all LPLD events appear to come from two distinct places along one of two hypothetical fracture planes. Interestingly, the stages which have the largest number of LPLD events also have the highest observed pumping pressures during fracturing, the highest density of natural fractures, and the greatest number of micro-earthquakes. One possible explanation of these LPLD events is that the high pore fluid pressure during hydraulic fracturing stimulates slow slip on pre-existing fault planes. In the absence of elevated pressure, slip would not be expected on these planes as they are poorly oriented to the stress field. Slip on these fault planes may be occurring because the fluid pressure is close to the magnitude of the least principal stress. We observe a few events between pumping cycles perhaps indicating that, once triggered, these planes continue to slip due to the high transient pressure within the fault planes after pumping has stopped.

Long-period long-duration (LPLD) seismic events are relatively low-amplitude signals that have been observed during hydraulic fracturing in several shale-gas and tight-gas reservoirs. These events are similar in appearance to tectonic tremor sequences observed in subduction zones and transform fault boundaries. LPLD events are predominantly composed of S-waves, but weaker P-waves have also been identified. In some cases, microearthquakes are observed during the events. Based on the similarity with tectonic tremors and our observations of several impulsive S-wave arrivals within the LPLD events, we interpret the LPLD events as resulting from the superposition of slow shear-slip events on relatively large faults. Most large LPLD waveforms appear to start as a relatively slower, low-amplitude precursor, lacking clear impulsive arrivals. We estimate the energy carried by the larger LPLD events to be ∼1000 times greater than a ∼M W − 2 microseismic event that is typical of the events that occur during hydraulic stimulation. Over the course of the entire stimulation activity of five wells in the Barnett formation (each hydraulically fractured ten times), the LPLD events were found to cumulatively release over an order of magnitude higher energy than microearthquakes. The large size of these LPLD events, compared to microearthquakes, suggests that they represent slip on relatively large faults during stimulation of these extremely low-permeability reservoirs. Moreover, they imply that the accompanying slow slip on faults, probably mostly undetected, is a significant deformation process during multistage hydraulic fracturing.