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Objective. Prompt-gamma imaging encompasses several approaches to the online monitoring of the beam range or deposited dose distribution in proton therapy. We test one of the imaging techniques - a coded mask approach - both experimentally and via simulations. Approach. Two imaging setups have been investigated experimentally. Each of them comprised a structured tungsten collimator in the form of a modified uniformly redundant array mask and a LYSO:Ce scintillation detector of fine granularity. The setups differed in detector dimensions and operation mode (1D or 2D imaging). A series of measurements with radioactive sources have been conducted, testing the performance of the setups for near-field gamma imaging. Additionally, Monte Carlo simulations of a larger setup of the same type were conducted, investigating its performance with a realistic gamma source distribution occurring during proton therapy. Main results. The images of point-like sources reconstructed from two small-scale prototypes' data using the maximum-likelihood expectation maximisation algorithm constitute the experimental proof of principle for the near-field coded-mask imaging modality, both in the 1D and the 2D mode. Their precision allowed us to calibrate out certain systematic offsets appearing due to the limited alignment accuracy of setup elements. The simulation of the full-scale setup yielded a mean distal falloff retrieval precision of 0.72 mm in the studies for beam energy range 89.5-107.9 MeV and with 1 × 10 8 protons (a typical number for distal spots). The implemented algorithm of image reconstruction is relatively fast-a typical procedure needs several seconds. Significance. Coded-mask imaging appears a valid option for proton therapy monitoring. The results of simulations let us conclude that the proposed full-scale setup is competitive with the knife-edge-shaped and the multi-parallel slit cameras investigated by other groups., (Creative Commons Attribution license.)

The establishment of continental-scale drainage systems on Earth is largely controlled by topography related to plate boundary deformation and buoyant mantle. Drainage patterns of the great rivers in Asia are thought to be highly dynamic during the Cenozoic collision of India and Eurasia, but the drainage pattern and landscape evolution prior to the development of high topography in eastern Tibet remain largely unknown. Here we report the results of petro-stratigraphy, heavy-mineral analysis, and detrital zircon U-Pb dating from late Cretaceous-early Palaeogene sedimentary basin strata along the present-day eastern margin of the Tibetan Plateau. Similarities in the provenance signatures among basins indicate that a continental-scale fluvial system once drained southward into the Neo-Tethyan Ocean. These results challenge existing models of drainage networks that flowed toward the East Asian marginal seas and require revisions to inference of palaeo-topography during the Late Cretaceous. The presence of a continent-scale river may have provided a stable long-term base level which, in turn, facilitated the development of an extensive low-relief landscape that is preserved atop interfluves above the deeply incised canyons of eastern Tibet., (© 2021. The Author(s).)

Purpose: The field of online monitoring of the beam range is one of the most researched topics in proton therapy over the last decade. The development of detectors that can be used for beam range verification under clinical conditions is a challenging task. One promising possible solution are modalities that record prompt-gamma radiation produced by the interactions of the proton beam with the target tissue. A good understanding of the energy spectra of the prompt gammas and the yields in certain energy regions is crucial for a successful design of a prompt-gamma detector. Monte-Carlo simulations are an important tool in development and testing of detector concepts, thus the proper modelling of the prompt-gamma emission in those simulations are of vital importance. In this paper, we confront a number of GEANT4 simulations of prompt-gamma emission, performed with different versions of the package and different physics lists, with experimental data obtained from a phantom irradiation with proton beams of four different energies in the range 70-230 MeV., Methods: The comparison is made on different levels: features of the prompt-gamma energy spectrum, gamma emission depth profiles for discrete transitions and the width of the distal fall-off in those profiles., Results: The best agreement between the measurements and the simulations is found for the GEANT4 version 10.4.2 and the reference physics list QGSP_BIC_HP., Conclusions: Modifications to prompt-gamma emission modelling in higher versions of the software increase the discrepancy between the simulation results and the experimental data., (Copyright © 2021 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.)

One of the big challenges for proton therapy is the development of tools for online monitoring of the beam range, which are suited to operate in clinical conditions and can be included in the clinical practice. A Compton camera based on stacks of heavy scintillating fibers used for prompt-gamma imaging is a promising approach for this task. It provides full, three-dimensional information on the deposited dose distribution while showing a high detection efficiency and rate capability due to its high granularity. The investigation of the rate capability and detection efficiency of such a camera under clinical conditions by means of Geant4 simulations is presented along with the event construction algorithm. The results hint towards a very low pile-up rate in the detector and a relatively high detection efficiency, so that imaging of a single proton beam spot appears to be an achievable goal., (Copyright © 2020 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.)

The shear force along convergent plate boundary faults (megathrusts) determines the height of mountain ranges that can be mechanically sustained 1-4 . However, whether the true height of mountain ranges corresponds to this tectonically supported elevation is debated 4-7 . In particular, climate-dependent erosional processes are often assumed to exert a first-order control on mountain height 5-12 , although this assumption has remained difficult to validate 12 . Here we constrain the shear force along active megathrusts using their rheological properties and then determine the tectonically supported elevation using a force balance model. We show that the height of mountain ranges around the globe matches this elevation, irrespective of climatic conditions and the rate of erosion. This finding indicates that mountain ranges are close to force equilibrium and that their height is primarily controlled by the megathrust shear force. We conclude that temporal variations in mountain height reflect long-term changes in the force balance but are not indicative of a direct climate control on mountain elevation.

Numerical models including one or more faults in a rheologically stratified lithosphere show that climate-induced variations in ice and water volumes on Earth's surface considerably affect the slip evolution of both thrust and normal faults. In general, the slip rate and hence the seismicity of a fault decreases during loading and increases during unloading. Here, we present several case studies to show that a postglacial slip rate increase occurred on faults worldwide in regions where ice caps and lakes decayed at the end of the last glaciation. Of note is that the postglacial amplification of seismicity was not restricted to the areas beneath the large Laurentide and Fennoscandian ice sheets but also occurred in regions affected by smaller ice caps or lakes, e.g. the Basin-and-Range Province. Our results do not only have important consequences for the interpretation of palaeoseismological records from faults in these regions but also for the evaluation of the future seismicity in regions currently affected by deglaciation like Greenland and Antarctica: shrinkage of the modern ice sheets owing to global warming may ultimately lead to an increase in earthquake frequency in these regions.

Objective: Although there is evidence for a pathogenic role of humoral factors in multifocal motor neuropathy (MMN), plasma exchange (PE) is assumed to be an ineffective treatment. We set out to elucidate possible reasons for this apparent contradiction., Methods: A retrospective analysis of seven patients with MMN, who underwent 4 to 18 sessions of PE. Clinical response, electrophysiological parameter and anti-ganglioside antibody titers were reviewed., Results: Two patients, who had anti-ganglioside antibodies, exhibited transient clinical responses to PE, manifested by improved neurological function. Whereas electrophysiological parameters continued to worsen in all patients, anti-ganglioside antibody titers declined during PE, but increased after PE., Conclusion: PE is of limited therapeutic value in patients with MMN, who do not respond to established treatment options. It may only be useful as an adjunctive treatment in a subset of patients. The transient decrease of anti-ganglioside-antibodies titers suggests that pathogenic humoral factors in MMN are only temporarily reduced. Further, PE treatment alone is insufficient to prevent axons from continuing degeneration, which may explain the failure of PE to substantially influence the disease course of patients with MMN.

Geologic and palaeoseismological data document a marked increase in the slip rates of the Wasatch fault and three adjacent normal faults in the Basin and Range Province during the Late Pleistocene/Early Holocene epochs. The cause of this synchronous acceleration of fault slip and the subsequent clustering of earthquakes during the Holocene has remained enigmatic, although it has been suggested that the coincidence between the acceleration of slip and the shrinkage of Lake Bonneville after the Last Glacial Maximum may indicate a causal relationship. Here we use finite-element models of a discrete normal fault within a rheologically layered lithosphere to evaluate the relative importance of two competing processes that affect fault slip: postglacial unloading (the removal of mass), which decreases the slip rate, and lithospheric rebound, which promotes faster slip. We show that lithospheric rebound caused by regression of Lake Bonneville and deglaciation of adjacent mountain ranges provides a feasible mechanism for the high Holocene rates of faulting in the Wasatch region. Our analysis implies that climate-controlled changes in loads applied to Earth's surface may exert a fundamental control on the slip history of individual normal faults.

In order to understand the dynamics of the India Asia collision zone, it is important to know the strain distribution in Central Asia, whose determination relies on the slip rates for active faults. Many previous slip-rate estimates of faults in Central Asia were based on the assumption that offset landforms are younger than the Last Glacial Maximum (approximately 20 kyr ago). In contrast, here we present surface exposure ages of 40 to 170 kyr, obtained using cosmogenic nuclide dating, for a series of terraces near a thrust at the northern margin of the Tibetan Plateau. Combined with the tectonic offset, the ages imply a long-term slip rate of only about 0.35 mm x yr(-1) for the active thrust, an order of magnitude lower than rates obtained from the assumption that the terraces formed after the Last Glacial Maximum. Our data demonstrate that the preservation potential of geomorphic features in Central Asia is higher than commonly assumed.

There is widespread agreement that chronic pain develops from, and is maintained by, a combination of neurobiological, psychological, and social factors. Nevertheless, few comprehensive models have been proposed that present specific testable predictions about how these factors interact. We propose a vulnerability-diathesis-stress model of the pathogenesis of chronic pain. This model is based on diathesis-stress models of psychopathology and on the results of recent research on psychosocial aspects of chronic pain. The goals of research on chronic pain are to understand its pathogenesis, improve its treatment, and prevent its development. To achieve these goals, prospective studies of the development and maintenance of chronic pain are needed. The vulnerability-diathesis-stress model can serve as a basis for designing and analyzing studies of the interaction among biological, psychological, and social risk factors for chronic pain.

The utility of the Peabody Picture Vocabulary Test-Revised (PPVT-R) as a surrogate for the Wechsler Adult Intelligence Test-Revised (WAIS-R) was investigated in 61 brain-injured adult participants in a postacute rehabilitation setting. Idiographic comparison revealed substantial disagreement in clinical classification between the two instruments, and it is concluded that the PPVT-R is not a good surrogate for the WAIS-R for this purpose. In contrast, the PPVT-R was judged an adequate surrogate for the WAIS-R for the purpose of group comparison, as is common in biomedical research. Finally, contrary to prior report, the PPVT-R was demonstrated to measure more than simply Vocabulary. As such, in the absence of independent validation research, perhaps the most parsimonious conclusion regarding what the PPVT-R is measuring is that like each of the various subtests of the WAIS-R, the PPVT-R shares some of the variance of the construct termed intelligence, as well as demonstrates some unique variance that is likely comprised of error and, perhaps, a unique or different facet of intelligence.

When renal amyloidosis has progressed to end-stage renal failure, most patients are severely affected by systemic amyloidosis and nephropathy. An alternative to chronic dialysis is renal transplantation. We present a patient with amyloid nephropathy who developed recurrent transplant amyloidosis. Renal transplantation was performed in 1985 with a living related donor. In 1990 the patient developed amyloidosis of the graft with membranous nephropathy and tubular acidosis due to hyporeninemic hypoaldosteronism. Secondary amyloidosis has been reported to involve glandular organs inducing hypothyroidism, hypocortisolism and hypoaldosteronism. Cyclosporine has been reported to induce hyporeninemic hypoaldosteronism and tubular acidosis, but not hypocortisolism and hypothyroidism. Progression of the amyloidosis of the graft was confirmed by a renal biopsy in 1993. Data published in the literature indicate that the survival rate of amyloidotic graft recipients is worse than those of non-amyloidotic graft recipients. This was confirmed in an analysis of the current CTS data which showed an impaired survival rate at 5-yr of 66 +/- 4% (+/- SE) for patients with amyloidosis (n = 413) as compared with 86 +/- 1% (p < 0.0001) for patients with glomerulonephritis and 84 +/- 1 (p < 0.01) for patients with polycystic kidney disease. Graft survival after 5 years was 55 +/- 4% in patients with amyloidosis as compared with 63 +/- 1% (p = 0.02) in patients with glomerulonephritis and 68 +/- 1% in patients with polycystic kidney disease. Graft survival was improved in amyloidotic patients treated with cylosporine as compared with patients on steroids and azathioprine (55 +/- 4% vs. 38 +/- 8%, p < 0.05). It is concluded that renal transplantation is the renal replacement therapy of choice for patients with AA-type amyloidosis although the overall patient survival is impaired in comparison with patients with other diseases.

Univariate and multivariate analyses were used to investigate intrinsic and contextual sources of coping variability among 90 patients with chronic pain. Pain coping strategies were assessed by the subscales of the Coping Strategies Questionnaire. Intrinsic variables included demographic characteristics and dispositional optimism. Contextual variables included pain-related variables and pain control appraisals. In univariate analyses, ethnicity was a statistically significant intrinsic source of variability for the praying and hoping coping subscale; however, comparisons between pairs of ethnic groups were not statistically significant. A multivariate perspective of the data found three independent and salient patterns of correlation between the intrinsic and contextual variables and coping subscales. These patterns of correlation accounted for 96% of the total variance and were conceptualized as optimistic active coping, educated rational coping, and optimistic restricted coping. The findings raise the prospect that there are intrinsic and contextual explanations of coping variability for patients with chronic pain.

The molecular conformation of the basic pancreatic trypsin inhibitor (BPTI) is known in considerable detail from both X-ray studies in single crystals and NMR studies in solution. The NMR experiments showed that the aromatic rings of the phenylalanyl and tyrosyl residues can undergo rapid rotational motions about the C beta--Cv bond. The present paper describes a model investigation of the mechanistic aspects of these intramolecular rotational motions. From calculations of the conformational energies for molecular species derived from the X-ray structure by rotations of individual aromatic rings, it was apparent that the rotational motions of the aromatics could only be understood in a flexible structure. Flexibility was simulated by allowing the protein to relax to an energetically favorable conformation for each of the different rotation states of the aromatic rings. It was then of particular interest to investigate how the perturbations caused by different rotation states of the aromatic rings were propagated in the protein structure. It was found that the rotation axes C beta--Cv were only slightly affected (delta X1 approximately less than 20 degrees. The most sizeable perturbations are caused by through space interactions with nearby atoms, which move away from the ring center and thus release the steric hindrance opposing the rotational motions. The values for the energy barriers obtained from the energy minimization are of the same order of magnitude as those measured by NMR.