Broadband Records of Earthquakes in Deep Gold Mines and a Comparison with Results from SAFOD, California

For one week during September 2007, we deployed a temporary network of field recorders and accelerometers at four sites within two deep, seismically active mines. The ground-motion data, recorded at 200 samples/sec, are well suited to determining source and ground-motion parameters for the mining-induced earthquakes within and adjacent to our network. Four earthquakes with magnitudes close to 2 were recorded with high signal/noise at all four sites. Analysis of seismic moments and peak velocities, in conjunction with the results of laboratory stick-slip friction experiments, were used to estimate source processes that are key to understanding source physics and to assessing underground seismic hazard. The maximum displacements on the rupture surfaces can be estimated from the parameter Rv, where v is the peak ground velocity at a given recording site, and R is the hypocentral distance. For each earthquake, the maximum slip and seismic moment can be combined with results from laboratory friction experiments to estimate the maximum slip rate within the rupture zone. Analysis of the four M 2 earthquakes recorded during our deployment and one of special interest recorded by the in-mine seismic network in 2004 revealed maximum slips ranging from 4 to 27 mm and maximum slip rates from 1.1 to 6:3 m=sec. Applying the same analyses to an M 2.1 earthquake within a cluster of repeating earthquakes near the San Andreas Fault Observatory at Depth site, California, yielded similar results for maximum slip and slip rate, 14 mm and 4:0 m=sec

Positron emission tomography PET/CT harmonisation study of different clinical PET/CT scanners using commercially available software

Objectives: Harmonisation is the process whereby standardised uptake values from different scanners can be made comparable. This PET/CT pilot study aimed to evaluate the effectiveness of harmonisation of a modern scanner with image reconstruction incorporating resolution recovery (RR) with another vendor older scanner operated in two-dimensional (2D) mode, and for both against a European standard (EARL). The vendor-proprietary software EQ•PET was used, which achieves harmonisation with a Gaussian smoothing. A substudy investigated effect of RR on harmonisation. Methods: Phantom studies on each scanner were performed to optimise the smoothing parameters required to achieve successful harmonisation. 80 patients were retrospectively selected; half were imaged on each scanner. As proof of principle, a cohort of 10 patients was selected from the modern scanner subjects to study the effects of RR on harmonisation. Results: Before harmonisation, the modern scanner without RR adhered to EARL specification. Using the phantom data, filters were derived for optimal harmonisation between scanners and with and without RR as applicable, to the EARL standard. The 80-patient cohort did not reveal any statistically significant differences. In the 10-patient cohort SUVmax for RR > no RR irrespective of harmonisation but differences lacked statistical significance (one-way ANOVA F(3.36) = 0.37, p = 0.78). Bland-Altman analysis showed that harmonisation reduced the SUVmax ratio between RR and no RR to 1.07 (95% CI 0.96–1.18) with no outliers. Conclusions: EQ•PET successfully enabled harmonisation between modern and older scanners and against the EARL standard. Harmonisation reduces SUVmax and dependence on the use of RR in the modern scanner. Advances in knowledge: EQ•PET is feasible to harmonise different PET/CT scanners and reduces the effect of RR on SUVmax

The neural correlates of intimate partner violence in women

Objective: To examine hippocampal volume and white matter tracts in women with and without intimate partner violence (IPV). Method: Nineteen women with IPV exposure in the last year, and 21 women without IPV exposure in the last year underwent structural magnetic resonance imaging (MRI) including diffusion tensor imaging (DTI) sequences. Additional data on alcohol use and presence of psychiatric disorder was collected. Differences in fractional anisotropy (FA) between the two groups were examined, using a statistical model that included demographic measures, alcohol use and psychiatric disorder. Results: IPV subjects did not demonstrate significantly different hippocampal volumes compared to subjects without recent IPV. FA was, however, significantly reduced in the body of the corpus callosum of IPV subjects. Adjusting for age, alcohol use, smoking and psychiatric diagnosis did not change the significance of the result. Conclusion: Data on hippocampal volume in IPV are inconsistent, perhaps reflecting the fact that multiple factors influence this measure. Reduced FA in the body of the corpus callosum in IPV suggests altered integrity of this white matter tract; additional work is needed to address the underlying mechanisms and clinical correlates of this finding

The neural correlates of intimate partner violence in women

Objective: To examine hippocampal volume and white matter tracts in women with and without intimate partner violence (IPV). Method: Nineteen women with IPV exposure in the last year, and 21 women without IPV exposure in the last year underwent structural magnetic resonance imaging (MRI) including diffusion tensor imaging (DTI) sequences. Additional data on alcohol use and presence of psychiatric disorder was collected. Differences in fractional anisotropy (FA) between the two groups were examined, using a statistical model that included demographic measures, alcohol use and psychiatric disorder. Results: IPV subjects did not demonstrate significantly different hippocampal volumes compared to subjects without recent IPV. FA was, however, significantly reduced in the body of the corpus callosum of IPV subjects. Adjusting for age, alcohol use, smoking and psychiatric diagnosis did not change the significance of the result. Conclusion: Data on hippocampal volume in IPV are inconsistent, perhaps reflecting the fact that multiple factors influence this measure. Reduced FA in the body of the corpus callosum in IPV suggests altered integrity of this white matter tract; additional work is needed to address the underlying mechanisms and clinical correlates of this finding.Key Words: Corpus callosum; Hippocampal volume; Intimate partner violence; Neuroimagin

Comprehensive Cardiovascular magnetic resonance of myocardial mechanics in mice using three-dimensional cine DENSE

<p>Abstract</p> <p>Background</p> <p>Quantitative noninvasive imaging of myocardial mechanics in mice enables studies of the roles of individual genes in cardiac function. We sought to develop comprehensive three-dimensional methods for imaging myocardial mechanics in mice.</p> <p>Methods</p> <p>A 3D cine DENSE pulse sequence was implemented on a 7T small-bore scanner. The sequence used three-point phase cycling for artifact suppression and a stack-of-spirals <it>k</it>-space trajectory for efficient data acquisition. A semi-automatic 2D method was adapted for 3D image segmentation, and automated 3D methods to calculate strain, twist, and torsion were employed. A scan protocol that covered the majority of the left ventricle in a scan time of less than 25 minutes was developed, and seven healthy C57Bl/6 mice were studied.</p> <p>Results</p> <p>Using these methods, multiphase normal and shear strains were measured, as were myocardial twist and torsion. Peak end-systolic values for the normal strains at the mid-ventricular level were 0.29 ± 0.17, -0.13 ± 0.03, and -0.18 ± 0.14 for <it>E_rr</it>, <it>E_cc</it>, and <it>E_ll</it>, respectively. Peak end-systolic values for the shear strains were 0.00 ± 0.08, 0.04 ± 0.12, and 0.03 ± 0.07 for <it>E_rc</it>, <it>E_rl</it>, and <it>E_cl</it>, respectively. The peak end-systolic normalized torsion was 5.6 ± 0.9°.</p> <p>Conclusions</p> <p>Using a 3D cine DENSE sequence tailored for cardiac imaging in mice at 7 T, a comprehensive assessment of 3D myocardial mechanics can be achieved with a scan time of less than 25 minutes and an image analysis time of approximately 1 hour.</p

Profiling the Essential Nature of Lipid Metabolism in Asexual Blood and Gametocyte Stages of Plasmodium falciparum

SummaryDuring its life cycle, Plasmodium falciparum undergoes rapid proliferation fueled by de novo synthesis and acquisition of host cell lipids. Consistent with this essential role, Plasmodium lipid synthesis enzymes are emerging as potential drug targets. To explore their broader potential for therapeutic interventions, we assayed the global lipid landscape during P. falciparum sexual and asexual blood stage (ABS) development. Using liquid chromatography-mass spectrometry, we analyzed 304 lipids constituting 24 classes in ABS parasites, infected red blood cell (RBC)-derived microvesicles, gametocytes, and uninfected RBCs. Ten lipid classes were previously uncharacterized in P. falciparum, and 70%–75% of the lipid classes exhibited changes in abundance during ABS and gametocyte development. Utilizing compounds that target lipid metabolism, we affirmed the essentiality of major classes, including triacylglycerols. These studies highlight the interplay between host and parasite lipid metabolism and provide a comprehensive analysis of P. falciparum lipids with candidate pathways for drug discovery efforts

Virtual reality exposure therapy as treatment for pain catastrophizing in fibromyalgia patients: proof-of-concept study (Study Protocol)

<p>Abstract</p> <p>Background</p> <p>Albeit exercise is currently advocated as one of the most effective management strategies for fibromyalgia syndrome (FMS); the implementation of exercise as a FMS treatment in reality is significantly hampered by patients' poor compliance. The inference that pain catastrophizing is a key predictor of poor compliance in FMS patients, justifies considering the alteration of pain catastrophizing in improving compliance towards exercises in FMS patients. The aim of this study is to provide proof-of-concept for the development and testing of a novel virtual reality exposure therapy (VRET) program as treatment for exercise-related pain catastrophizing in FMS patients.</p> <p>Methods</p> <p>Two interlinked experimental studies will be conducted. Study 1 aims to objectively ascertain if neurophysiological changes occur in the functional brain areas associated with pain catastrophizing, when catastrophizing FMS subjects are exposed to visuals of exercise activities. Study 2 aims to ascertain the preliminary efficacy and feasibility of exposure to visuals of exercise activities as a treatment for exercise-related pain catastrophizing in FMS subjects. Twenty subjects will be selected from a group of FMS patients attending the Tygerberg Hospital in Cape Town, South Africa and randomly allocated to either the <b>VRET </b>(intervention) group or <b>waiting list </b>(control) group. Baseline neurophysiological activity for subjects will be collected in study 1 using functional magnetic resonance imaging (fMRI). In study 2, clinical improvement in pain catastrophizing will be measured using fMRI (objective) and the pain catastrophizing scale (subjective).</p> <p>Discussion</p> <p>The premise is if exposing FMS patients to visuals of various exercise activities trigger the functional brain areas associated with pain catastrophizing; then as a treatment, repeated exposure to visuals of the exercise activities using a VRET program could possibly decrease exercise-related pain catastrophizing in FMS patients. Proof-of-concept will either be established or negated. The results of this project are envisaged to revolutionize FMS and pain catastrophizing research and in the future, assist health professionals and FMS patients in reducing despondency regarding FMS management.</p> <p>Trial registration</p> <p>PACTR201011000264179</p

Inhibition of resistance-refractory P. falciparum kinase PKG delivers prophylactic, blood stage, and transmission-blocking antiplasmodial activity

The search for antimalarial chemotypes with modes of action unrelated to existing drugs has intensified with the recent failure of first-line therapies across Southeast Asia. Here, we show that the trisubstituted imidazole MMV030084 potently inhibits hepatocyte invasion by Plasmodium sporozoites, merozoite egress from asexual blood stage schizonts, and male gamete exflagellation. Metabolomic, phosphoproteomic, and chemoproteomic studies, validated with conditional knockdown parasites, molecular docking, and recombinant kinase assays, identified cGMP-dependent protein kinase (PKG) as the primary target of MMV030084. PKG is known to play essential roles in Plasmodium invasion of and egress from host cells, matching MMV030084's activity profile. Resistance selections and gene editing identified tyrosine kinase-like protein 3 as a low-level resistance mediator for PKG inhibitors, while PKG itself never mutated under pressure. These studies highlight PKG as a resistance-refractory antimalarial target throughout the Plasmodium life cycle and promote MMV030084 as a promising Plasmodium PKG-targeting chemotype