Triggering Processes in Rock Fracture.

We study triggering processes in triaxial compression experiments under a constant displacement rate on sandstone and granite samples using spatially located acoustic emission events and their focal mechanisms. We present strong evidence that event-event triggering plays an important role in the presence of large-scale or macrocopic imperfections, while such triggering is basically absent if no significant imperfections are present. In the former case, we recover all established empirical relations of aftershock seismicity including the Gutenberg-Richter relation, a modified version of the Omori-Utsu relation and the productivity relation-despite the fact that the activity is dominated by compaction-type events and triggering cascades have a swarmlike topology. For the Gutenberg-Richter relations, we find that the b value is smaller for triggered events compared to background events. Moreover, we show that triggered acoustic emission events have a focal mechanism much more similar to their associated trigger than expected by chance.

A new class of anthelmintics effective against drug-resistant nematodes.

Anthelmintic resistance in human and animal pathogenic helminths has been spreading in prevalence and severity to a point where multidrug resistance against the three major classes of anthelmintics--the benzimidazoles, imidazothiazoles and macrocyclic lactones--has become a global phenomenon in gastrointestinal nematodes of farm animals. Hence, there is an urgent need for an anthelmintic with a new mode of action. Here we report the discovery of the amino-acetonitrile derivatives (AADs) as a new chemical class of synthetic anthelmintics and describe the development of drug candidates that are efficacious against various species of livestock-pathogenic nematodes. These drug candidates seem to have a novel mode of action involving a unique, nematode-specific clade of acetylcholine receptor subunits. The AADs are well tolerated and of low toxicity to mammals, and overcome existing resistances to the currently available anthelmintics.

A laboratory perspective on accelerating preparatory processes before earthquakes and implications for foreshock detectability.

Dynamic failure in the laboratory is commonly preceded by many foreshocks which accompany premonitory aseismic slip. Aseismic slip is also thought to govern earthquake nucleation in nature, yet, foreshocks are rare. Here, we examine how heterogeneity due to different roughness, damage and pore pressures affects premonitory slip and acoustic emission characteristics. High fluid pressures increase stiffness and reduce heterogeneity which promotes more rapid slip acceleration and shorter precursory periods, similar to the effect of low geometric heterogeneity on smooth faults. The associated acoustic emission activity in low-heterogeneity samples becomes increasingly dominated by earthquake-like double-couple focal mechanisms. The similarity of fluid pressure increase and roughness reduction suggests that increased stress and geometric homogeneity may substantially shorten the duration of foreshock activity. Gradual fault activation and extended foreshock activity is more likely observable on immature faults at shallow depth.

Large-scale heterogeneities can alter the characteristics of compressive failure and accelerated seismic release.

Externally stressed brittle rocks fail once the stress is sufficiently high. This failure is typically preceded by a pronounced increase in the total energy of acoustic emission (AE) events, the so-called accelerated seismic release. Yet, other characteristics of approaching the failure point such as the presence or absence of variations in the AE size distribution and, similarly, whether the failure point can be interpreted as a critical point in a statistical physics sense differs across experiments. Here, we show that large-scale stress heterogeneities induced by a notch fundamentally change the characteristics of the failure point in triaxial compression experiments under a constant displacement rate on Westerly granite samples. Specifically, we observe accelerated seismic release without a critical point and no change in power-law exponent ε of the AE size distribution. This is in contrast to intact samples, which exhibit a significant decrease in ε before failure. Our findings imply that the presence or absence of large-scale heterogeneities play a significant role in our ability to predict compressive failure in rock.

Discovery of amino-acetonitrile derivatives, a new class of synthetic anthelmintic compounds.

A new series of amino-acetonitrile derivatives (AAD) have been discovered that exhibit high anthelmintic activity against parasitic nematode species such as Haemonchus contortus and Trichostrongylus colubriformis. Significantly, these compounds also demonstrate activity against nematode strains resistant to the currently available broad-spectrum anthelmintics. The discovery, synthesis, structure-activity relationship and biological results are presented.

The spatial footprint of injection wells in a global compilation of induced earthquake sequences.

Fluid injection can cause extensive earthquake activity, sometimes at unexpectedly large distances. Appropriately mitigating associated seismic hazards requires a better understanding of the zone of influence of injection. We analyze spatial seismicity decay in a global dataset of 18 induced cases with clear association between isolated wells and earthquakes. We distinguish two populations. The first is characterized by near-well seismicity density plateaus and abrupt decay, dominated by square-root space-time migration and pressure diffusion. Injection at these sites occurs within the crystalline basement. The second population exhibits larger spatial footprints and magnitudes, as well as a power law-like, steady spatial decay over more than 10 kilometers, potentially caused by poroelastic effects. Far-reaching spatial effects during injection may increase event magnitudes and seismic hazard beyond expectations based on purely pressure-driven seismicity.

Comment on "How will induced seismicity in Oklahoma respond to decreased saltwater injection rates?" by C. Langenbruch and M. D. Zoback.

The state of Oklahoma has experienced an unprecedented increase in earthquake activity since 2009, likely driven by large-scale wastewater injection operations. Statewide injection rates peaked in early 2015 and steadily decreased thereafter, approximately coinciding with collapsing oil prices and regulatory action. If seismic activity is primarily driven by fluid injection, a noticeable seismogenic response to the decrease in injection rates is expected. Langenbruch and Zoback suggest that "the probability of potentially damaging larger events, should significantly decrease by the end of 2016 and approach historic levels within a few years." We agree that the rate of small earthquakes has decreased toward the second half of 2016. However, their specific predictions about seismic hazard require reexamination. We test the influence of the model parameters of Langenbruch and Zoback based on fits to observed seismicity distributions. The results suggest that a range of realistic aftershock decay rates and b values can lead to an increase in moderate earthquake probabilities from 37 to 80% in 2017 without any further alteration to the model. In addition, the observation that all four M ≥ 5 earthquakes to date occurred when injection rates were below the triggering threshold of Langenbruch and Zoback challenges the applicability of the model for the most societally significant events.

Factors associated with contralateral liver hypertrophy after unilateral radioembolization for hepatocellular carcinoma.

INTRODUCTION: Radioembolization for the treatment of hepatocellular carcinoma (HCC) induces liver volume changes referred to as "atrophy-hypertrophy complex". The aim of this study was to investigate lobar liver volume changes after unilateral radioembolization and to search for factors associated with hypertrophy of the untreated lobe. MATERIALS AND METHODS: Seventy-five patients were retrospectively evaluated. Inclusion criteria were: (1) right-lobar radioembolization for unresectable unilateral HCC, (2) available liver computed tomography scans before, 1, 3, and at least 6 months after radioembolization. Baseline patient characteristics included clinical features, laboratory results, spleen volume, and liver computed tomography. Absolute and relative (referred to the whole liver volume) liver lobe volumes (LLV) as well as relative LLV (rLLV) change per month were evaluated and compared. RESULTS: Absolute and relative contralateral LLV continuously increased after radioembolization (p<0.001). Mean relative contralateral LLV increased from 36±11.6% before radioembolization to 50±15.3% 6 months after radioembolization. Median contralateral rLLV increase/month (within first 6 months) was 2.5%. Contralateral rLLV increase/month was significantly lower in patients with ascites (p = 0.017) or platelet count <100/nl (p = 0.009). An inverse correlation of contralateral rLVV increase/month with spleen volume (p = 0.017), patient age (p = 0.024), Child Pugh score (p = 0.001), and tumor burden (p = 0.001) was found. CONCLUSIONS: Significant contralateral hypertrophy and ipsilateral atrophy were common after unilateral radioembolization. Small spleen volume, low patient age, low Child Pugh score, absence of ascites, platelet count ≥100/nl, and low tumor burden were associated with increased contralateral hypertrophy, indicating that younger patients with compensated cirrhosis might benefit most from radioembolization in a "bridge-to-resection" setting.

Identification and functional validation of novel autoantigens in equine uveitis.

The development, progression, and recurrence of autoimmune diseases are frequently driven by a group of participatory autoantigens. We identified and characterized novel autoantigens by analyzing the autoantibody binding pattern from horses affected by spontaneous equine recurrent uveitis to the retinal proteome. Cellular retinaldehyde-binding protein (cRALBP) had not been described previously as autoantigen, but subsequent characterization in equine recurrent uveitis horses revealed B and T cell autoreactivity to this protein and established a link to epitope spreading. We further immunized healthy rats and horses with cRALBP and observed uveitis in both species with typical tissue lesions at cRALBP expression sites. The autoantibody profiling outlined here could be used in various autoimmune diseases to detect autoantigens involved in the dynamic spreading cascade or serve as predictive markers.