The effect of small-scale heterogeneity on the propagation of waves : with applications to forward modeling and inversion in global surface wave tomography

Small-scale heterogeneity alters the arrival time of waves in a way that cannot be explained by ray theory. It is because ray theory is a high-frequency approximation that does not take the finite-frequency of wavefields into account. A theory based on the first Rytov approximation is developed wherein the effect of finite-frequency waves is included. It is found that the developed scattering theory predicts well the arrival time of waves propagating in media with small-scale inhomogeneity that has a characteristic length smaller in size than the width of Fresnel zones. In the regime for which scattering theory is relevant, it is found that caustics are easily generated in wavefields, but this does not influence the good prediction of finite-frequency arrival times of waves by scattering theory. The regime of scattering theory is relevant when the characteristic length of inhomogeneity is smaller than the width of Fresnel zones. By using ray perturbation theory, a condition for the development of triplications is defined for plane wave sources and for point sources in 2-D and 3-D media. This theory is applied to two cases of slowness media: 1-D slowness perturbation models and 2-D Gaussian random media. The focus position in 1-D slowness models is proportional to the inverse of the square root of the relative slowness fluctuations. For Gaussian random media, the distance at which caustics generate is dependent on the relative slowness perturbation to the power of minus two thirds. The developed scattering theory is tested in a 2-D numerical finite-differences experiment using models with small-scale heterogeneity and in a 3-D physical laboratory experiment where ultrasonic waves propagate through samples of granite with small grain-sizes of the minerals. For both kind of modelling experiments, the length-scale of inhomogeneity of the slowness models is smaller than the width of the Fresnel zones. The results of the 2-D and 3- D modelling experiment confirm that the developed scattering theory is better than ray theory in predicting the arrival time of waves propagating in complex media for which the conditions for ray theory are not valid. In general, ray theory overestimates the observed timeshifts of waves or even worse the ray theoretical timeshifts are anti-correlated with the observed ones for waves propagating in media where the effect of scattering is significant. By comparing the characteristic value of the Fresnel zone with the characteristic length of heterogeneity in different experiments from exploration seismics and seismology, it is shown that the resolution in present-day seismological tomography is that the limits of the validity of ray theory. With an emphasis on surface wave tomography, I show that it is important to implement the effect of finite-frequency waves in tomographic imaging techniques in order to retrieve small-scale structured Earth models with the correct theory. The theory for the scattering of waves is applied in global surface wave tomography for Love waves at 40 s and 150s. The estimated tomographic surface wave models derived from ray theory and scattering theory are similar, because a restrictive regularisation condition is incorperated in the inversion so that structures with length-scales smaller than the Fresnel zones are mostly suppressed. I treat a special case of inverse problem theory, namely the spectral leakage problem. The term spectral leakage indicates that observed data affected by structures with a length-scale that is not account for in a given inverse can leak into the long-wavelength structures that are part of the estimated model. In the case of global surface wave tomography, surface wave scattering theory is used in an inversion including the spectral leakage correction of phase velocity measurements for Love waves at periods of 40 s and 150 s. The global phase velocity models from the spectral leakage inversion are obtained without applying any damping, but they show, however, a good correlation with tectonic features such as plate boundaries, ridges and trenches

Surgical management of skull base tumors

AimTo present a review of the contemporary surgical management of skull base tumors.BackgroundOver the last two decades, the treatment of skull base tumors has evolved from observation, to partial resection combined with other therapy modalities, to gross total resection and no adjuvant treatment with good surgical results and excellent clinical outcomes.Materials and methodsThe literature review of current surgical strategies and management of skull base tumors was performed and complemented with the experience of Barrow Neurological Institute.ResultsSkull base tumors include meningiomas, pituitary tumors, sellar/parasellar tumors, vestibular and trigeminal schwannomas, esthesioneuroblastomas, chordomas, chondrosarcomas, and metastases. Surgical approaches include the modified orbitozygomatic, pterional, middle fossa, retrosigmoid, far lateral craniotomy, midline suboccipital craniotomy, and a combination of these approaches. The selection of an appropriate surgical approach depends on the characteristics of the patient and the tumor, as well as the experience of the neurosurgeon.ConclusionModern microsurgical techniques, diagnostic imaging, intraoperative neuronavigation, and endoscopic technology have remarkably changed the concept of skull base surgery. These refinements have extended the boundaries of tumor resection with minimal morbidity

Impact of molecular profiling on overall survival of patients with advanced ovarian cancer

OBJECTIVE: Patients with recurrent epithelial ovarian cancer (EOC) have limited treatment options. Studies have reported that biomarker profiling may help predict patient response to available treatments. This study sought to determine the value of biomarker profiling in recurrent EOC. RESULTS: Patients in the Matched cohort had a median OS of 36 months compared to 27 months for patients in the Unmatched cohort (HR 0.62, 95% CI 0.41-0.96; p < 0.03). Individual biomarkers were analyzed, with TUBB3, and PGP prognostic for survival. Biomarker analysis also identified a molecular subtype (positive for at least two of the following markers: ERCC1, RRM1, TUBB3, PGP) with particularly poor overall survival. METHODS: 224 patients from a commercial registry (NCT02678754) with stage IIIC/IV EOC at diagnosis, or restaged to IIIC/IV EOC at the time of molecular profiling, were retrospectively divided into two cohorts based on whether or not the drugs they received matched their profile recommendations. The Matched cohort received no drugs predicted to be lack-of-benefit while the Unmatched cohort received at least one drug predicted to be lack-of-benefit. Profile biomarker/drug associations were based on multiple test platforms including immunohistochemistry, fluorescent in situ hybridization and DNA sequencing. CONCLUSIONS: This report demonstrates the ability of multi-platform molecular profiling to identify EOC patients at risk of inferior survival. It also suggests a potential beneficial role of avoidance of lack-of-benefit therapies which, when administered, resulted in decreased survival relative to patients who received only therapies predicted to be of benefit

A database of ground-motion recordings, site profiles, and amplification factors from the Groningen gas field in the Netherlands

A comprehensive database that has been used to develop ground motion models for induced earthquakes in the Groningen gas field is provided in a freely accessible online repository. The database includes more than 8500 processed ground motion recordings from 87 earthquakes of local magnitude ML between 1.8 and 3.6, obtained from a large network of surface accelerographs and borehole geophones placed at 50 m depth intervals to a depth of 200 m. The 5%-damped pseudo-acceleration spectra and Fourier amplitude spectra of the records are also provided. Measured shear-wave velocity (VS) profiles, obtained primarily from seismic Cone Penetration Tests (CPTs), are provided for 80 of the ∼100 recording stations. A model representing the regional dynamic soil properties is presented for the entire gas field plus a 5 km onshore buffer zone, specifying lithology, VS, and damping for all layers above the reference baserock horizon located at about 800 m depth. Transfer functions and frequency-dependent amplification factors from the reference rock horizon to the surface for the locations of the recording stations are also included. The database provides a valuable resource for further refinement of induced seismic hazard and risk modeling in Groningen as well as for generic research in site response of thick, soft soil deposits and the characteristics of ground motions from small-magnitude, shallow-focus induced earthquakes

Extracellular microRNAs in blood differentiate between ischaemic and haemorrhagic stroke subtypes.

Rapid identification of patients suffering from cerebral ischaemia, while excluding intracerebral haemorrhage, can assist with patient triage and expand patient access to chemical and mechanical revascularization. We sought to identify blood-based, extracellular microRNAs 15 (ex-miRNAs) derived from extracellular vesicles associated with major stroke subtypes using clinical samples from subjects with spontaneous intraparenchymal haemorrhage (IPH), aneurysmal subarachnoid haemorrhage (SAH) and ischaemic stroke due to cerebral vessel occlusion. We collected blood from patients presenting with IPH (n = 19), SAH (n = 17) and ischaemic stroke (n = 21). We isolated extracellular vesicles from plasma, extracted RNA cargo, 20 sequenced the small RNAs and performed bioinformatic analyses to identify ex-miRNA biomarkers predictive of the stroke subtypes. Sixty-seven miRNAs were significantly variant across the stroke subtypes. A subset of exmiRNAs differed between haemorrhagic and ischaemic strokes, and LASSO analysis could distinguish SAH from the other subtypes with an accuracy of 0.972 ± 0.002. Further analyses predicted 25 miRNA classifiers that stratify IPH from ischaemic stroke with an accuracy of 0.811 ± 0.004 and distinguish haemorrhagic from ischaemic stroke with an accuracy of 0.813 ± 0.003. Blood-based, ex-miRNAs have predictive value, and could be capable of distinguishing between major stroke subtypes with refinement and validation. Such a biomarker could one day aid in the triage of patients to expand the pool eligible for effective treatment

Extracellular microRNAs in blood differentiate between ischaemic and haemorrhagic stroke subtypes

Rapid identification of patients suffering from cerebral ischaemia, while excluding intracerebral haemorrhage, can assist with patient triage and expand patient access to chemical and mechanical revascularization. We sought to identify blood-based, extracellular microRNAs 15 (ex-miRNAs) derived from extracellular vesicles associated with major stroke subtypes using clinical samples from subjects with spontaneous intraparenchymal haemorrhage (IPH), aneurysmal subarachnoid haemorrhage (SAH) and ischaemic stroke due to cerebral vessel occlusion. We collected blood from patients presenting with IPH (n = 19), SAH (n = 17) and ischaemic stroke (n = 21). We isolated extracellular vesicles from plasma, extracted RNA cargo, 20 sequenced the small RNAs and performed bioinformatic analyses to identify ex-miRNA biomarkers predictive of the stroke subtypes. Sixty-seven miRNAs were significantly variant across the stroke subtypes. A subset of exmiRNAs differed between haemorrhagic and ischaemic strokes, and LASSO analysis could distinguish SAH from the other subtypes with an accuracy of 0.972 +/- 0.002. Further analyses predicted 25 miRNA classifiers that stratify IPH from ischaemic stroke with an accuracy of 0.811 +/- 0.004 and distinguish haemorrhagic from ischaemic stroke with an accuracy of 0.813 +/- 0.003. Blood-based, ex-miRNAs have predictive value, and could be capable of distinguishing between major stroke subtypes with refinement and validation. Such a biomarker could one day aid in the triage of patients to expand the pool eligible for effective treatment.Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

ADAPT Identifies an ESCRT Complex Composition That Discriminates VCaP From LNCaP Prostate Cancer Cell Exosomes

Libraries of single-stranded oligodeoxynucleotides (ssODNs) can be enriched for sequences that specifically bind molecules on naïve complex biological samples like cells or tissues. Depending on the enrichment strategy, the ssODNs can identify molecules specifically associated with a defined biological condition, for example a pathological phenotype, and thus are potentially useful for biomarker discovery. We performed ADAPT, a variant of SELEX, on exosomes secreted by VCaP prostate cancer cells. A library of ∼1011 ssODNs was enriched for those that bind to VCaP exosomes and discriminate them from exosomes derived from LNCaP prostate cancer cells. Next-generation sequencing (NGS) identified the best discriminating ssODNs, nine of which were resynthesized and their discriminatory ability confirmed by qPCR. Affinity purification with one of the sequences (Sequence 7) combined with LC-MS/MS identified its molecular target complex, whereof most proteins are part of or associated with the multiprotein ESCRT complex participating in exosome biogenesis. Within this complex, YBX1 was identified as the directly-bound target protein. ADAPT thus is able to differentiate exosomes from cancer cell subtypes from the same lineage. The composition of ESCRT complexes in exosomes from VCaP versus LNCaP cells might constitute a discriminatory element between these prostate cancer subtypes

Reevaluating the imaging definition of tumor progression: perfusion MRI quantifies recurrent glioblastoma tumor fraction, pseudoprogression, and radiation necrosis to predict survival

INTRODUCTION: Contrast-enhanced MRI (CE-MRI) represents the current mainstay for monitoring treatment response in glioblastoma multiforme (GBM), based on the premise that enlarging lesions reflect increasing tumor burden, treatment failure, and poor prognosis. Unfortunately, irradiating such tumors can induce changes in CE-MRI that mimic tumor recurrence, so called post treatment radiation effect (PTRE), and in fact, both PTRE and tumor re-growth can occur together. Because PTRE represents treatment success, the relative histologic fraction of tumor growth versus PTRE affects survival. Studies suggest that Perfusion MRI (pMRI)–based measures of relative cerebral blood volume (rCBV) can noninvasively estimate histologic tumor fraction to predict clinical outcome. There are several proposed pMRI-based analytic methods, although none have been correlated with overall survival (OS). This study compares how well histologic tumor fraction and OS correlate with several pMRI-based metrics. METHODS: We recruited previously treated patients with GBM undergoing surgical re-resection for suspected tumor recurrence and calculated preoperative pMRI-based metrics within CE-MRI enhancing lesions: rCBV mean, mode, maximum, width, and a new thresholding metric called pMRI–fractional tumor burden (pMRI-FTB). We correlated all pMRI-based metrics with histologic tumor fraction and OS. RESULTS: Among 25 recurrent patients with GBM, histologic tumor fraction correlated most strongly with pMRI-FTB (r = 0.82; P < .0001), which was the only imaging metric that correlated with OS (P<.02). CONCLUSION: The pMRI-FTB metric reliably estimates histologic tumor fraction (i.e., tumor burden) and correlates with OS in the context of recurrent GBM. This technique may offer a promising biomarker of tumor progression and clinical outcome for future clinical trials

Spinal arteriovenous shunts presenting as intracranial subarachnoid haemorrhage

Item does not contain fulltextBACKGROUND: In approximately 5% of patients with intracranial subarachnoid haemorrhage (SAH), the cause is another than a ruptured aneurysm or perimesencephalic haemorrhage. One of these causes is a spinal arteriovenous shunt (SAVS). The aim of this study was to investigate the characteristics of patients with SAVS who present with intracranial SAH without symptoms and signs suggesting a spinal cause. METHODS: We systematically reviewed the literature and searched the SAH database of the University Medical Center Utrecht, The Netherlands, for patients with SAVS presenting with intracranial SAH and studied the characteristics of patients with SAVS whose clinical presentation mimicked intracranial SAH caused by rupture of a saccular aneurysm. RESULTS: Thirty-five patients were identified after a review of the literature. In our SAH database, comprising 2142 patients included in the period 1985-2004, we found one patient (0.05%, 95 % CI 0.006- 0.3%). SAH due to SAVS occurred at any age (4-72 years). The SAVS was located at the craniocervical junction in 14 patients, at the cervical level in 11, and at the thoracolumbar level in the remaining 11 patients. The majority of patients (n = 26, 72%) had no disabling deficits at discharge or follow-up. CONCLUSION: Rupture of a SAVS presenting as intracranial SAH is rare and can occur at any age. The SAVS can be located not only at the craniocervical junction or cervical level but also in the thoracolumbar region. Most patients with SAVS presenting as intracranial SAH have a good recovery