A feasibility trial of skin surface motion-gated stereotactic body radiotherapy for treatment of upper abdominal or lower thoracic targets using a novel O-ring gantry

BACKGROUND AND PURPOSE: A novel O-ring gantry can deliver stereotactic body radiation therapy (SBRT) with artificial intelligence-facilitated, CT-guided online plan adaptation. It gates mobile targets by optically monitoring skin surface motion. However, this gating solution has not been clinically validated. We conducted a trial to evaluate the feasibility of optical skin surface-guided gating for patients with mobile upper abdominal or lower thoracic malignancies treated with SBRT on this platform (NCT05030454). MATERIALS AND METHODS: Ten patients who were prescribed SBRT to a thoracic or abdominal target and were capable of breath-hold for at least 17 s enrolled. They received SBRT in five fractions with breath-hold technique and optical skin surface motion monitored-gating with a ± 2 mm tolerance. Online plan adaptation was left to the discretion of the daily treating physician. The primary endpoint was defined as successful completion of \u3e 75 % of attempted fractions. Exploratory endpoints included local control and acute grade ≥ 3 toxicity rates after three months. For adapted fractions the contouring, planning, quality assurance, and treatment delivery times were recorded. RESULTS: Forty-seven of 51 SBRT fractions (92 %) were successfully gated at breath-hold by optical skin surface motion monitoring. The tumor centroid position during breath-hold varied by a mean of approximately 2 mm. Sixty-three percent of fractions were adapted online with a median total treatment time of 78.5 min. After three months no local recurrences or acute grade ≥ 3 toxicities were observed. CONCLUSIONS: SBRT treatment to mobile targets with surface-monitored gating on a novel O-ring gantry was prospectively validated

Use of a mixed tissue RNA design for performance assessments on multiple microarray formats

The comparability and reliability of data generated using microarray technology would be enhanced by use of a common set of standards that allow accuracy, reproducibility and dynamic range assessments on multiple formats. We designed and tested a complex biological reagent for performance measurements on three commercial oligonucleotide array formats that differ in probe design and signal measurement methodology. The reagent is a set of two mixtures with different proportions of RNA for each of four rat tissues (brain, liver, kidney and testes). The design provides four known ratio measurements of >200 reference probes, which were chosen for their tissue-selectivity, dynamic range coverage and alignment to the same exemplar transcript sequence across all three platforms. The data generated from testing three biological replicates of the reagent at eight laboratories on three array formats provides a benchmark set for both laboratory and data processing performance assessments. Close agreement with target ratios adjusted for sample complexity was achieved on all platforms and low variance was observed among platforms, replicates and sites. The mixed tissue design produces a reagent with known gene expression changes within a complex sample and can serve as a paradigm for performance standards for microarrays that target other species

Mutations causing medullary cystic kidney disease type 1 lie in a large VNTR in MUC1 missed by massively parallel sequencing

Although genetic lesions responsible for some mendelian disorders can be rapidly discovered through massively parallel sequencing of whole genomes or exomes, not all diseases readily yield to such efforts. We describe the illustrative case of the simple mendelian disorder medullary cystic kidney disease type 1 (MCKD1), mapped more than a decade ago to a 2-Mb region on chromosome 1. Ultimately, only by cloning, capillary sequencing and de novo assembly did we find that each of six families with MCKD1 harbors an equivalent but apparently independently arising mutation in sequence markedly under-represented in massively parallel sequencing data: the insertion of a single cytosine in one copy (but a different copy in each family) of the repeat unit comprising the extremely long (~1.5–5 kb), GC-rich (>80%) coding variable-number tandem repeat (VNTR) sequence in the MUC1 gene encoding mucin 1. These results provide a cautionary tale about the challenges in identifying the genes responsible for mendelian, let alone more complex, disorders through massively parallel sequencing.National Institutes of Health (U.S.) (Intramural Research Program)National Human Genome Research Institute (U.S.)Charles University (program UNCE 204011)Charles University (program PRVOUK-P24/LF1/3)Czech Republic. Ministry of Education, Youth, and Sports (grant NT13116-4/2012)Czech Republic. Ministry of Health (grant NT13116-4/2012)Czech Republic. Ministry of Health (grant LH12015)National Institutes of Health (U.S.) (Harvard Digestive Diseases Center, grant DK34854

25th annual computational neuroscience meeting: CNS-2016

The same neuron may play different functional roles in the neural circuits to which it belongs. For example, neurons in the Tritonia pedal ganglia may participate in variable phases of the swim motor rhythms [1]. While such neuronal functional variability is likely to play a major role the delivery of the functionality of neural systems, it is difficult to study it in most nervous systems. We work on the pyloric rhythm network of the crustacean stomatogastric ganglion (STG) [2]. Typically network models of the STG treat neurons of the same functional type as a single model neuron (e.g. PD neurons), assuming the same conductance parameters for these neurons and implying their synchronous firing [3, 4]. However, simultaneous recording of PD neurons shows differences between the timings of spikes of these neurons. This may indicate functional variability of these neurons. Here we modelled separately the two PD neurons of the STG in a multi-neuron model of the pyloric network. Our neuron models comply with known correlations between conductance parameters of ionic currents. Our results reproduce the experimental finding of increasing spike time distance between spikes originating from the two model PD neurons during their synchronised burst phase. The PD neuron with the larger calcium conductance generates its spikes before the other PD neuron. Larger potassium conductance values in the follower neuron imply longer delays between spikes, see Fig. 17.Neuromodulators change the conductance parameters of neurons and maintain the ratios of these parameters [5]. Our results show that such changes may shift the individual contribution of two PD neurons to the PD-phase of the pyloric rhythm altering their functionality within this rhythm. Our work paves the way towards an accessible experimental and computational framework for the analysis of the mechanisms and impact of functional variability of neurons within the neural circuits to which they belong

Earthquake Characteristics as Imaged by the Back-Projection Method

This dissertation explores the capability of dense seismic array data for imaging the rupture properties of earthquake sources using a method known as back-projection. Only within the past 10 or 15 years has implementation of the method become feasible through the development of large aperture seismic arrays such as the High Sensitivity Seismograph Network in Japan and the Transportable Array in the United States. Coincidentally, this buildup in data coverage has also been accompanied by a global cluster of giant earthquakes (Mw>8.0). Much of the material in this thesis is devoted to imaging the source complexity of these large events. In particular, evidence for rupture segmentation, dynamic triggering, and frequency dependent energy release is presented. These observations have substantial implications for evaluating the seismic and tsunami hazards of future large earthquakes. In many cases, the details of the large ruptures can only be imaged by the back-projection method through the addition of different data sets and incorporating additional processing steps that enhance low-amplitude signals. These improvements to resolution can also be utilized to study much smaller events. This approach is taken for studying two very different types of earthquakes. First, a global study of the enigmatic intermediate-depth (100-300 km) earthquakes is performed. The results show that these events commonly have sub-horizontal rupture planes and suggest dynamic triggering of multiple sub-events. From these observations, a hypothesis for the generation of intermediate-depth events is proposed. Second, the early aftershock sequences of the 2004 Mw 9.1 Sumatra-Andaman and 2011 Mw 9.0 Tohoku, Japan earthquakes are studied using the back-projection method. These analyses show that many events can be detected that are not in any local or global earthquake catalogues. In particular, the locations of aftershocks in the back-projection results of the 2011 Tohoku sequence fill in gaps in the aftershock distribution of the Japan Meteorological Agency catalogue. These results may change inferences of the behavior of the 2011 mainshock, as well as the nature of future seismicity in this region. In addition, the rupture areas of the largest aftershocks can be determined, and compared to the rupture area of the mainshock. For the Tohoku event, this comparison reveals that the aftershocks contribute significantly to the cumulative failure area of the subduction interface. This result implies that future megathrust events in this region can have larger magnitudes than the 2011 event.Earth and Planetary Science

Lower Mantle Seismicity Following the 2015 Mw 7.9 Bonin Islands Deep‐Focus Earthquake

Deep-focus earthquakes provide insight into how subducting slabs deform over a range of spatial and temporal scales as they descend into the mantle. This study uses a 4D source imaging approach to determine centroid locations of the 2015 Mw 7.9 Bonin Islands deep-focus earthquake and its aftershock sequence. Imaged sources of the mainshock show a complex rupture, but one that is compatible with a sub-horizontal rupture plane. Previously undetected early aftershocks are imaged down to depths of approximately 750 km and represent the first reported earthquakes that initiate in the lower mantle. These events and a previously reported group of shallower distal aftershocks occur at the lower and upper boundaries of an imaged slab segment that deforms as it penetrates into the lower mantle. We hypothesize that mainshock failure allowed gravitational settling of the slab segment to occur which produced the distal aftershock sequences. © 2021. American Geophysical Union. All Rights Reserved.National Science Foundation6 month embargo; first published: 26 June 2021This 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]

Magma reservoirs from the upper crust to the Moho inferred from high-resolution Vp and Vs models beneath Mount St. Helens, Washington State, USA

[EN]The size, frequency, and intensity of volcanic eruptions are strongly controlled by the volume and connectivity of magma within the crust. Several geophysical and geochemical studies have produced a comprehensive model of the magmatic system to depths near 7 km beneath Mount St. Helens (Washington State, USA), currently the most active volcano in the Cascade Range. Data limitations have precluded imaging below this depth to observe the entire primary shallow magma reservoir, as well as its connection to deeper zones of magma accumulation in the crust. The inversion of P and S wave traveltime data collected during the active-source component of the iMUSH (Imaging Magma Under St. Helens) project reveals a high P-wave (Vp)/S-wave (Vs) velocity anomaly beneath Mount St. Helens between depths of 4 and 13 km, which we interpret as the primary upper–middle crustal magma reservoir. Beneath and southeast of this shallow reservoir, a low Vp velocity column extends from 15 km depth to the Moho. Deep long-period events near the boundary of this column indicate that this anomaly is associated with the injection of magmatic fluids. Southeast of Mount St. Helens, an upper–middle crustal high Vp/Vs body beneath the Indian Heaven Volcanic Field may also have a magmatic origin. Both of these high Vp/Vs bodies are at the boundaries of the low Vp middle–lower crustal column and both are directly above high Vp middle–lower crustal regions that may represent cumulates associated with recent Quaternary or Paleogene–Neogene Cascade magmatism. Seismicity immediately following the 18 May 1980 eruption terminates near the top of the inferred middle–lower crustal cumulates and directly adjacent to the inferred middle–lower crustal magma reservoir. These spatial relationships suggest that the boundaries of these high-density cumulates play an important role in both vertical and lateral transport of magma through the crust

Segmentation and Radial Anisotropy of the Deep Crustal Magmatic System Beneath the Cascades Arc

Abstract Volcanic arcs consist of many distinct vents that are ultimately fueled by the common melting processes in the subduction zone mantle wedge. Seismic imaging of crustal‐scale magmatic systems can provide insight into how melt is organized in the deep crust and eventually focused beneath distinct vents as it ascends and evolves. Here, we investigate the crustal‐scale structure beneath a section of the Cascades arc spanning four major stratovolcanoes: Mt. Hood, Mt. St. Helens (MSH), Mt. Adams (MA), and Mt. Rainier, based on ambient noise data from 234 seismographs. Simultaneous inversion of Rayleigh and Love wave dispersion constrains the isotropic shear velocity (Vs) and identifies radially anisotropic structures. Isotropic Vs shows two sub‐parallel low‐Vs zones (∼3.45–3.55 km/s) at ∼15–30 km depth with one connecting Mt. Rainier to MA, and another connecting MSH to Mt. Hood, which are interpreted as deep crustal magma reservoirs containing up to ∼2.5%–6% melt, assuming near‐equilibrium melt geometry. Negative radial anisotropy, from vertical fractures like dikes, is prevalent in this part of the Cascadia, but is interrupted by positive radial anisotropy, from subhorizontal features like sills, extending vertically beneath MA and Mt. Rainier at ∼10–30 km depth and weaker and west‐dipping positive anisotropy beneath MSH. The positive anisotropy regions are adjacent to rather than co‐located with the isotropic low‐Vs anomalies. Ascending melt that stalled and mostly crystallized in sills with possible compositional differences from the country rock may explain the near‐average Vs and positive radial anisotropy adjacent to the active deep crustal magma reservoirs

Injection‐Induced Earthquakes on Complex Fault Zones of the Raton Basin Illuminated by Machine‐Learning Phase Picker and Dense Nodal Array

Seismicity in the Raton Basin over the past two decades suggests reactivation of basement faults due to waste-water injection. In the summer of 2018, 96 short period three-component nodal instruments were installed in a highly active region of the basin for a month. A machine-learning based phase picker (PhaseNet) was adopted and identified millions of picks, which were associated into events using an automated algorithm-REAL (Rapid Earthquake Association and Location). After hypocenter relocation with hypoDD, the earthquake catalog contains 9,259 M-L-2.2 to 3 earthquakes focused at depths of 4-6 km. Magnitude of completeness (Mc) varies from -1 at nighttime to -0.5 in daytime, likely reflecting noise variation modulated by wind. The clustered hypocenters with variable depths and focal mechanisms suggest a complex network of basement faults. Frequency-magnitude statistics and the spatiotemporal evolution of seismicity are comparable to tectonic systems.6 month embargo; first published: 18 June 2020This 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]

Injection-Induced Earthquakes on Complex Fault Zones of the Raton Basin Illuminated by Machine-Learning Phase Picker and Dense Nodal Array

Seismicity in the Raton Basin over the past two decades suggests reactivation of basement faults due to waste-water injection. In the summer of 2018, 96 short period three-component nodal instruments were installed in a highly active region of the basin for a month. A machine-learning based phase picker (PhaseNet) was adopted and identified millions of picks, which were associated into events using an automated algorithm-REAL (Rapid Earthquake Association and Location). After hypocenter relocation with hypoDD, the earthquake catalog contains 9,259 M-L-2.2 to 3 earthquakes focused at depths of 4-6 km. Magnitude of completeness (Mc) varies from -1 at nighttime to -0.5 in daytime, likely reflecting noise variation modulated by wind. The clustered hypocenters with variable depths and focal mechanisms suggest a complex network of basement faults. Frequency-magnitude statistics and the spatiotemporal evolution of seismicity are comparable to tectonic systems.6 month embargo; first published: 18 June 2020This 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]