Off-fault Plasticity and Earthquake Rupture Dynamics: 1. Dry Materials or Neglect of Fluid Pressure Changes

We analyze inelastic off-fault response during earthquakes. Spontaneous crack-like rupture, with slip weakening, is modeled in 2-D plane strain using an explicit dynamic finite element procedure. A Mohr-Coulomb type elastic-plastic description describes the material bordering the fault. We identify the factors which control the extent and distribution of off-fault plasticity during dynamic rupture. Those include the angle with the fault of the maximum compressive prestress, the seismic S ratio, and the closeness of the initial stress state to Mohr-Coulomb failure. Plastic response can significantly alter the rupture propagation velocity, delaying or even preventing a transition to supershear rupture in some cases. Plastic straining also alters the residual stress field left near the fault. In part 1, we consider “dry” materials bordering the fault, or at least neglect pore pressure changes within them. Part 2 addresses the effects of fluid saturation, showing that analysis procedures of this part can describe undrained fluid-saturated response. Elastic-plastic laws of the type used are prone to shear localization, resulting in an inherent grid dependence in some numerical solutions. Nevertheless, we show that in the problems addressed, the overall sizes of plastic regions and the dynamics of rupture propagation seem little different from what are obtained when we increase the assumed plastic hardening modulus or dilatancy parameter above the theoretical threshold for localization, obtaining a locally smooth numerical solution at the grid scale. Evidence for scaling of some localization features with a real (nongrid) length scale in the model is also presented.Earth and Planetary SciencesEngineering and Applied Science

Off-Fault Plasticity and Earthquake Rupture Dynamics: 2. Effects of Fluid Saturation

We present an analysis of inelastic off-fault response in fluid-saturated material during earthquake shear rupture. The analysis is conducted for 2-D plane strain deformation using an explicit dynamic finite element formulation. Along the fault, linear slip-weakening behavior is specified, and the off-fault material is described using an elastic-plastic description of the Drucker-Prager form, which characterizes the brittle behavior of rocks under compressive stress when the primary mode of inelastic deformation is frictional sliding of fissure surfaces, microcracking and granular flow. In this part (part 1), pore pressure changes were neglected in materials bordering the fault. In part 2, we more fully address the effects of fluid saturation. During the rapid stressing by a propagating rupture, the associated undrained response of the surrounding fluid-saturated material may be either strengthened or weakened against inelastic deformation. We consider poroelastoplastic materials with and without plastic dilation. During nondilatant undrained response near a propagating rupture, large increases in pore pressure on the compressional side of the fault decrease the effective normal stress and weaken the material, and decreases in pore pressure on the extensional side strengthen the material. Positive plastic dilatancy reduces pore pressure, universally strengthening the material. Dilatantly strengthened undrained deformation has a diffusive instability on a long enough timescale when the underlying drained deformation is unstable. Neglecting this instability on the short timescale of plastic straining, we show that undrained deformation is notably more resistant to shear localization than predicted by neglect of pore pressure changes.Earth and Planetary SciencesEngineering and Applied Science

Finite Element Simulations of Dynamic Shear Rupture Experiments and Dynamic Path Selection along Kinked and Branched Faults

We analyze the nucleation and propagation of shear cracks along nonplanar, kinked, and branched fault paths corresponding to the configurations used in recent laboratory fracture studies by Rousseau and Rosakis (2003, 2009). The aim is to reproduce numerically those shear rupture experiments and from that provide an insight into processes which are active when a crack, initially propagating in mode II along a straight path, interacts with a bend in the fault or a branching junction. The experiments involved impact loading of thin Homalite-100 (a photoelastic polymer) plates, which had been cut along bent or branched paths and weakly glued back together everywhere except along a starter notch near the impact site. Strain gage recordings and high-speed photography of isochromatic lines provided characterization of the transient deformation fields associated with the impact and fracture propagation. We found that dynamic explicit 2-D plane-stress finite element analyses with a simple linear slip-weakening description of cohesive and frictional strength of the bonded interfaces can reproduce the qualitative rupture behavior past the bend and branch junctions in most cases and reproduce the principal features revealed by the photographs of dynamic isochromatic line patterns. The presence of a kink or branch can cause an abrupt change in rupture propagation velocity. Additionally, the finite element results allow comparison between total slip accumulated along the main and inclined fault segments. We found that slip along inclined faults can be substantially less than slip along the main fault, and the amount depends on the branch angle and kink or branch configuration.Earth and Planetary SciencesEngineering and Applied Science

Finite element simulations of dynamic shear rupture experiments and dynamic path selection along kinked and branched faults

We analyze the nucleation and propagation of shear cracks along nonplanar, kinked, and branched fault paths corresponding to the configurations used in recent laboratory fracture studies by Rousseau and Rosakis (2003, 2009). The aim is to reproduce numerically those shear rupture experiments and from that provide an insight into processes which are active when a crack, initially propagating in mode II along a straight path, interacts with a bend in the fault or a branching junction. The experiments involved impact loading of thin Homalite‐100 (a photoelastic polymer) plates, which had been cut along bent or branched paths and weakly glued back together everywhere except along a starter notch near the impact site. Strain gage recordings and high‐speed photography of isochromatic lines provided characterization of the transient deformation fields associated with the impact and fracture propagation. We found that dynamic explicit 2‐D plane‐stress finite element analyses with a simple linear slip‐weakening description of cohesive and frictional strength of the bonded interfaces can reproduce the qualitative rupture behavior past the bend and branch junctions in most cases and reproduce the principal features revealed by the photographs of dynamic isochromatic line patterns. The presence of a kink or branch can cause an abrupt change in rupture propagation velocity. Additionally, the finite element results allow comparison between total slip accumulated along the main and inclined fault segments. We found that slip along inclined faults can be substantially less than slip along the main fault, and the amount depends on the branch angle and kink or branch configuration

Dwarf nova-type cataclysmic variable stars are significant radio emitters

We present 8–12 GHz radio light curves of five dwarf nova (DN) type cataclysmic variable stars (CVs) in outburst (RX And, U Gem, and Z Cam), or superoutburst (SU UMa and YZ Cnc), increasing the number of radio-detected DN by a factor of 2. The observed radio emission was variable on time-scales of minutes to days, and we argue that it is likely to be synchrotron emission. This sample shows no correlation between the radio luminosity and optical luminosity, orbital period, CV class, or outburst type; however, higher cadence observations are necessary to test this, as the measured luminosity is dependent on the timing of the observations in these variable objects. The observations show that the previously detected radio emission from SS Cyg is not unique in type, luminosity (in the plateau phase of the outburst), or variability time-scales. Our results prove that DN, as a class, are radio emitters in outburst

Phase I Clinical Trial of Systemically Administered TUSC2(FUS1)-Nanoparticles Mediating Functional Gene Transfer in Humans

Background: Tumor suppressor gene TUSC2/FUS1 (TUSC2) is frequently inactivated early in lung cancer development. TUSC2 mediates apoptosis in cancer cells but not normal cells by upregulation of the intrinsic apoptotic pathway. No drug strategies currently exist targeting loss-of–function genetic abnormalities. We report the first in-human systemic gene therapy clinical trial of tumor suppressor gene TUSC2. Methods: Patients with recurrent and/or metastatic lung cancer previously treated with platinum-based chemotherapy were treated with escalating doses of intravenous N-[1-(2,3-dioleoyloxy)propyl]-N,N,N-trimethylammonium chloride (DOTAP):cholesterol nanoparticles encapsulating a TUSC2 expression plasmid (DOTAP:chol-TUSC2) every 3 weeks. Results: Thirty-one patients were treated at 6 dose levels (range 0.01 to 0.09 milligrams per kilogram). The MTD was determined to be 0.06 mg/kg. Five patients achieved stable disease (2.6–10.8 months, including 2 minor responses). One patient had a metabolic response on positron emission tomography (PET) imaging. RT-PCR analysis detected TUSC2 plasmid expression in 7 of 8 post-treatment tumor specimens but not in pretreatment specimens and peripheral blood lymphocyte controls. Proximity ligation assay, performed on paired biopsies from 3 patients, demonstrated low background TUSC2 protein staining in pretreatment tissues compared with intense (10–25 fold increase) TUSC2 protein staining in posttreatment tissues. RT-PCR gene expression profiling analysis of apoptotic pathway genes in two patients with high posttreatmen

Barriers and facilitators to recruitment of physicians and practices for primary care health services research at one centre

<p>Abstract</p> <p>Background</p> <p>While some research has been conducted examining recruitment methods to engage physicians and practices in primary care research, further research is needed on recruitment methodology as it remains a recurrent challenge and plays a crucial role in primary care research. This paper reviews recruitment strategies, common challenges, and innovative practices from five recent primary care health services research studies in Ontario, Canada.</p> <p>Methods</p> <p>We used mixed qualitative and quantitative methods to gather data from investigators and/or project staff from five research teams. Team members were interviewed and asked to fill out a brief survey on recruitment methods, results, and challenges encountered during a recent or ongoing project involving primary care practices or physicians. Data analysis included qualitative analysis of interview notes and descriptive statistics generated for each study.</p> <p>Results</p> <p>Recruitment rates varied markedly across the projects despite similar initial strategies. Common challenges and creative solutions were reported by many of the research teams, including building a sampling frame, developing front-office rapport, adapting recruitment strategies, promoting buy-in and interest in the research question, and training a staff recruiter.</p> <p>Conclusions</p> <p>Investigators must continue to find effective ways of reaching and involving diverse and representative samples of primary care providers and practices by building personal connections with, and buy-in from, potential participants. Flexible recruitment strategies and an understanding of the needs and interests of potential participants may also facilitate recruitment.</p

PCR Improves Diagnostic Yield from Lung Aspiration in Malawian Children with Radiologically Confirmed Pneumonia

Accurate data on childhood pneumonia aetiology are essential especially from regions where mortality is high, in order to inform case-management guidelines and the potential of prevention strategies such as bacterial conjugate vaccines. Yield from blood culture is low, but lung aspirate culture provides a higher diagnostic yield. We aimed to determine if diagnostic yield could be increased further by polymerase chain reaction (PCR) detection of bacteria (Streptococcus pneumoniae and Haemophilus influenzae b) and viruses in lung aspirate fluid.A total of 95 children with radiological focal, lobar or segmental consolidation had lung aspirate performed and sent for bacterial culture and for PCR for detection of bacteria, viruses and Pneumocystis jirovecii. In children with a pneumococcal aetiology, pneumococcal bacterial loads were calculated in blood and lung aspirate fluid.Blood culture identified a bacterial pathogen in only 8 patients (8%). With the addition of PCR on lung aspirate samples, causative pathogens (bacterial, viral, pneumocystis) were identified singly or as co-infections in 59 children (62%). The commonest bacterial organism was S.pneumoniae (41%), followed by H. influenzae b (6%), and the commonest virus identified was adenovirus (16%), followed by human bocavirus (HBoV) (4%), either as single or co-infection.In a select group of African children, lung aspirate PCR significantly improves diagnostic yield. Our study confirms a major role of S.pneumoniae and viruses in the aetiology of childhood pneumonia in Africa

Neolithic Mitochondrial Haplogroup H Genomes and the Genetic Origins of Europeans

Haplogroup H dominates present-day Western European mitochondrial DNA variability (\u3e40%), yet was less common (~19%) among Early Neolithic farmers (~5450 BC) and virtually absent in Mesolithic hunter-gatherers. Here we investigate this major component of the maternal population history of modern Europeans and sequence 39 complete haplogroup H mitochondrial genomes from ancient human remains. We then compare this ‘real-time’ genetic data with cultural changes taking place between the Early Neolithic (~5450 BC) and Bronze Age (~2200 BC) in Central Europe. Our results reveal that the current diversity and distribution of haplogroup H were largely established by the Mid Neolithic (~4000 BC), but with substantial genetic contributions from subsequent pan-European cultures such as the Bell Beakers expanding out of Iberia in the Late Neolithic (~2800 BC). Dated haplogroup H genomes allow us to reconstruct the recent evolutionary history of haplogroup H and reveal a mutation rate 45% higher than current estimates for human mitochondria