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Geological heterogeneity is abundant in crustal fault zones; however, its role in controlling the mechanical behaviour of faults is poorly constrained. Here, we present laboratory friction experiments on laterally heterogeneous faults, with patches of strong, rate-weakening quartz gouge and weak, rate-strengthening clay gouge. The experiments show that the heterogeneity leads to a significant reduction in strength and frictional stability in comparison to compositionally identical faults with homogeneously mixed gouges. We identify a combination of weakening effects, including smearing of the weak clay; differential compaction of the two gouges redistributing normal stress; and shear localization producing stress concentrations in the strong quartz patches. The results demonstrate that geological heterogeneity and its evolution can have pronounced effects on fault strength and stability and, by extension, on the occurrence of slow-slip transients versus earthquake ruptures and the characteristics of the resulting events, and should be further studied in lab experiments and earthquake source modelling. This paper shows that faults comprised of heterogeneously distributed materials, as is typical for tectonic faults in nature, are weaker and more unstable than equivalent faults where the materials are homogeneously mixed together.

Malignant mesothelioma is a rare tumour caused by asbestos exposure that originates mainly from the pleural lining or the peritoneum. Treatment options are limited, and the prognosis is dismal. Although immune checkpoint blockade (ICB) can improve survival outcomes, the determinants of responsiveness remain elusive. Here, we report the outcomes of a multi-centre phase II clinical trial (MiST4, NCT03654833) evaluating atezolizumab and bevacizumab (AtzBev) in patients with relapsed mesothelioma. We also use tumour tissue and gut microbiome sequencing, as well as tumour spatial immunophenotyping to identify factors associated with treatment response. MIST4 met its primary endpoint with 50% 12-week disease control, and the treatment was tolerable. Aneuploidy, notably uniparental disomy (UPD), homologous recombination deficiency (HRD), epithelial-mesenchymal transition and inflammation with CD68 + monocytes were identified as tumour-intrinsic resistance factors. The log-ratio of gut-resident microbial genera positively correlated with radiological response to AtzBev and CD8 + T cell infiltration, but was inversely correlated with UPD, HRD and tumour infiltration by CD68 + monocytes. In summary, a model is proposed in which both intrinsic and extrinsic determinants in mesothelioma cooperate to modify the tumour microenvironment and confer clinical sensitivity to AtzBev. Gut microbiota represent a potentially modifiable factor with potential to improve immunotherapy outcomes for individuals with this cancer of unmet need. Although immune checkpoint blockade is a standard treatment for patients with malignant mesothelioma, only a minority of patients exhibit radiological response. In a phase II clinical trial (MIST4) investigating the efficacy, safety and molecular correlates of response following treatment with atezolizumab and bevacizumab, the authors demonstrate that the gut microbiota may modulate responsiveness to treatment.

Metamorphic reactions influence the evolution of the Earth’s crust in a range of tectonic settings. For example hydrous mineral dehydration in a subducting slab can produce fluid overpressures which may trigger seismicity. During reaction the mechanisms of chemical transport, including water expulsion, will dictate the rate of transformation and hence the evolution of physical properties such as fluid pressure. Despite the importance of such processes, direct observation of mineral changes due to chemical transport during metamorphism has been previously impossible both in nature and in experiment. Using time-resolved (4D) synchrotron X-ray microtomography we have imaged a complete metamorphic reaction and show how chemical transport evolves during reaction. We analyse the dehydration of gypsum to form bassanite and H 2 O which, like most dehydration reactions, produces a solid volume reduction leading to the formation of pore space. This porosity surrounds new bassanite grains producing fluid-filled moats, across which transport of dissolved ions to the growing grains occurs via diffusion. As moats grow in width, diffusion and hence reaction rate slow down. Our results demonstrate how, with new insights into the chemical transport mechanisms, we can move towards a more fundamental understanding of the hydraulic and chemical evolution of natural dehydrating systems.

Single nucleotide polymorphisms (SNPs) associated with average daily gain (ADG) and dry matter intake (DMI), two major components of feed efficiency in cattle, were identified in a genome-wide association study (GWAS). Uni- and multi-SNP models were used to describe feed efficiency in a training data set and the results were confirmed in a validation data set. Results from the univariate and bivariate analyses of ADG and DMI, adjusted by the feedlot beef steer maintenance requirements, were compared. The bivariate uni-SNP analysis identified (P-value <0.0001) 11 SNPs, meanwhile the univariate analyses of ADG and DMI identified 8 and 9 SNPs, respectively. Among the six SNPs confirmed in the validation data set, five SNPs were mapped to KDELC2, PHOX2A, and TMEM40. Findings from the uni-SNP models were used to develop highly accurate predictive multi-SNP models in the training data set. Despite the substantially smaller size of the validation data set, the training multi-SNP models had slightly lower predictive ability when applied to the validation data set. Six Gene Ontology molecular functions related to ion transport activity were enriched (P-value <0.001) among the genes associated with the detected SNPs. The findings from this study demonstrate the complementary value of the uni- and multi-SNP models, and univariate and bivariate GWAS analyses. The identified SNPs can be used for genome-enabled improvement of feed efficiency in feedlot beef cattle, and can aid in the design of empirical studies to further confirm the associations.

Greywacke basement rocks in New Zealand host conventional geothermal reservoirs and may supply important hotter and deeper geothermal energy resources in the future. This work combines petrological analyses and physical property measurements of Waipapa greywacke, a basement unit hosting New Zealand geothermal reservoirs, in order to understand better how structurally controlled flow networks develop and channel geothermal fluids within it. Results show intact Waipapa greywacke has high tensile and triaxial compressive strengths, and low intrinsic permeability (~ 10–21 m2). Permeability of intact Waipapa greywacke does not increase significantly during triaxial loading to failure and is accompanied by minimal changes ultrasonic wave velocities. These data taken together suggest that microcrack development during brittle deformation is very limited. Upon failure, the permeability increases by two orders of magnitude and shows similar permeability to tests performed on synthetic, single, mode I fractures in intact Waipapa greywacke. Permeability persists in Waipapa greywacke fractures under confining pressures of at least 150 MPa. It is concluded that Waipapa greywacke rocks will not allow fluid flow through the matrix of the rock and that substantial geothermal fluid flow will only occur through macrofracture networks.

Hyaloclastites commonly form high-quality reservoir rocks in volcanic geothermal provinces. Here, we investigated the effects of confinement due to burial following prolonged accumulation of eruptive products on the physical and mechanical evolution of surficial and subsurface (depths of 70 m, 556 m, and 732 m) hyaloclastites from Krafla volcano, Iceland. Upon loading in a hydrostatic cell, the porosity and permeability of the surficial hyaloclastite decreased linearly with mean effective stress, as pores and cracks closed due to elastic (recoverable) compaction up to 22-24 MPa (equivalent to ~1.3 km depth in the reservoir). Beyond this mean effective stress, denoted as P∗, we observed accelerated porosity and permeability reduction with increasing confinement, as the rock underwent permanent inelastic compaction. In comparison, the porosity and permeability of the subsurface core samples were less sensitive to mean effective stress, decreasing linearly with increasing confinement as the samples compacted elastically within the conditions tested (to 40 MPa). Although the surficial material underwent permanent, destructive compaction, it maintained higher porosity and permeability than the subsurface hyaloclastites throughout the experiments. We constrained the evolution of yield curves of the hyaloclastites, subjected to different effective mean stresses in a triaxial press. Surficial hyaloclastites underwent a brittle-ductile transition at an effective mean stress of ~10.5 MPa, and peak strength (differential stress) reached 13 MPa. When loaded to effective mean stresses of 33 and 40 MPa, the rocks compacted, producing new yield curves with a brittle-ductile transition at ~12.5 and ~19 MPa, respectively, but showed limited strength increase. In comparison, the subsurface samples were found to be much stronger, displaying higher strengths and brittle-ductile transitions at higher effective mean stresses (i.e., 37.5 MPa for 70 m sample, >75 MPa for 556 m, and 68.5 MPa for 732 m) that correspond to their lower porosities and permeabilities. Thus, we conclude that compaction upon burial alone is insufficient to explain the physical and mechanical properties of the subsurface hyaloclastites present in the reservoir at Krafla volcano. Mineralogical alteration, quantified using SEM-EDS, is invoked to explain the further reduction of porosity and increase in strength of the hyaloclastite in the active geothermal system at Krafla.

Petroleum-rich basins at a mature stage of exploration and production offer many opportunities for large-scale Carbon Capture and Storage (CCS) since oil and gas were demonstrably contained by low-permeability top-sealing rocks, such as shales. For CCS to work, there must be effectively no leakage from the injection site, so the nature of the top-seal is an important aspect for consideration when appraising prospective CCS opportunities. The Lower Cretaceous Rodby Shale and the Palaeocene Lista Shale have acted as seals to oil and gas accumulations (e.g., the Atlantic and Balmoral fields) and may now play a critical role in sealing the Acorn and East Mey subsurface carbon storage sites. The characteristics of these important shales have been little addressed in the hydrocarbon extraction phase, with an understandable focus on reservoir properties and their influence on resource recovery rates. Here, we assess the characteristics of the Rodby and Lista Shales using wireline logs, geomechanical tests, special core analysis (mercury intrusion) and mineralogical and petrographic techniques, with the aim of highlighting key properties that identify them as suitable top-seals. The two shales, defined using the relative gamma log values (or Vshale), have similar mean pore throat radius (approximately 18 nm), splitting tensile strength (approximately 2.5 MPa) and anisotropic values of splitting tensile strength, but they display significant differences in terms of wireline log character, porosity and mineralogy. The Lower Cretaceous Rodby Shale has a mean porosity of approximately 14 %, a mean permeability of 263 nD (2.58 × 10−19 m2), and is calcite rich and has clay minerals that are relatively rich in non-radioactive phases such as kaolinite. The Palaeocene Lista Shale has a mean porosity of approximately 16% a mean permeability of 225 nD (2.21 × 10−19 m2), and is calcite free, but contains abundant quartz silt and is dominated by smectite. The 2% difference in porosity does not seem to equate to a significant difference in permeability. Elastic properties derived from wireline log data show that Young’s modulus, material stiffness, is very low (5 GPa) for the most shale (clay mineral)-rich Rodby intervals, with Young’s modulus increasing as shale content decreases and as cementation (e.g., calcite) increases. Our work has shown that Young’s modulus, which can be used to inform the likeliness of tensile failure, may be predictable based on routine gamma, density and compressive sonic logs in the majority of wells where the less common shear logs were not collected. The predictability of Young’s modulus from routine well log data could form a valuable element of CCS-site top-seal appraisals. This study has shown that the Rodby and Lista Shales represent good top-seals to the Acorn and East Mey CCS sites and they can hold CO2 column heights of approximately 380 m. The calcite-rich Rodby Shale may be susceptible to localised carbonate dissolution and increasing porosity and permeability but decreasing tendency to develop fracture permeability in the presence of injected CO2, as brittle calcite dissolves. In contrast, the calcite-free, locally quartz-rich, Lista Shale will be geochemically inert to injected CO2 but retain its innate tendency to develop fracture permeability (where quartz rich) in the presence of injected CO2.

ObjectivesMedical Regulatory Authorities (MRAs) provide licences to physicians and monitor those physicians once in practice to support their continued competence. In response to physician shortages, many Canadian MRAs developed alternative licensure routes to allow physicians who do not meet traditional licensure criteria to obtain licences to practice. Many physicians have gained licensure through alternative routes, but the performance of these physicians in practice has not been previously examined. This study compared the performance of traditionally and alternatively licenced physicians in Ontario using quality indicators of primary care. The purpose of this study was to examine the practice performance of alternatively licenced physicians and provide evaluative evidence for alternative licensure policies.DesignA cross-sectional retrospective examination of Ontario health administrative data was conducted using Poisson regression analyses to compare the performance of traditionally and alternatively licenced physicians.SettingPrimary care in Ontario, Canada.ParticipantsAll family physicians who were licenced in Ontario between 2000 and 2012 and who had complete medical billing data in 2014 were included (n=11 419).Outcome measuresPrimary care quality indicators were calculated for chronic disease management, preventive paediatric care, cancer screening and hospital readmission rates using Ontario health administrative data.ResultsAlternatively licenced physicians performed similarly to traditionally licenced physicians in many primary care performance measures. Minimal differences were seen across groups in indicators of diabetic care, congestive heart failure care, asthma care and cancer screening rates. Larger differences were found in preventive care for children less than 2 years of age, particularly for alternatively licenced physicians who entered Ontario from another Canadian province.ConclusionsOur findings demonstrate that alternatively licenced physicians perform similarly to traditionally licenced physicians across many indicators of primary care. Our study also demonstrates the utility of administrative data for examining physician performance and evaluating medical regulatory policies and programmes.

Volatile organic solvents were considered to have little influence on the synthesis of mesostructured materials through evaporation-induced self-assembly （EISA）, because upon evaporation they leave the sol and hence do not interfere with the self-assembly process. We show here that the choice of solvent is crucial in the synthesis of thin films of phenylene-bridged periodic mesoporous organosilica （benzene PMO）. Methanol is found to be a better solvent for the synthesis of thin films, whereas ethanol favors the formation of （HO）3Si-C6H4-Si（OH）3 crystals, the identity and structure of which is established by X-ray diffraction. A ternary reactant composition diagram is designed to visualize the relationship among multiple synthesis experiments and to guide the interpretation of experimental results and optimization of the quality of the periodic mesoporous organosilica film. Our study highlights the importance of solvent choice, a factor often neglected in EISA. We expect it to inspire researchers to explore the effect of solvent in designing the synthesis of mesoporous materials.