Real-Time Profiling of Respiratory Motion: Baseline Drift, Frequency Variation and Fundamental Pattern Change

To precisely ablate tumor in radiation therapy, it is important to locate the tumor position in real time during treatment. However, respiration-induced tumor motions are difficult to track. They are semi-periodic and exhibit variations in baseline, frequency and fundamental pattern (oscillatory amplitude and shape). In this study, we try to decompose the above-mentioned components from discrete observations in real time. Baseline drift, frequency (equivalently phase) variation and fundamental pattern change characterize different aspects of respiratory motion and have distinctive clinical indications. Furthermore, smoothness is a valid assumption for each one of these components in their own spaces, and facilitates effective extrapolation for the purpose of estimation and prediction. We call this process 'profiling' to reflect the integration of information extraction, decomposition, processing and recovery. The proposed method has three major ingredients: (1) real-time baseline and phase estimation based on elliptical shape tracking in augmented state space and Poincaré sectioning principle; (2) estimation of the fundamental pattern by unwarping the observation with phase estimate from the previous step; (3) filtering of individual components and assembly in the original temporal-displacement signal space. We tested the proposed method with both simulated and clinical data. For the purpose of prediction, the results are comparable to what one would expect from a human operator. The proposed approach is fully unsupervised and data driven, making it ideal for applications requiring economy, efficiency and flexibility.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/85908/1/Fessler14.pd

A multiscale hybrid model for pro-angiogenic calcium signals in a vascular endothelial cell

Cytosolic calcium machinery is one of the principal signaling mechanisms by which endothelial cells (ECs) respond to external stimuli during several biological processes, including vascular progression in both physiological and pathological conditions. Low concentrations of angiogenic factors (such as VEGF) activate in fact complex pathways involving, among others, second messengers arachidonic acid (AA) and nitric oxide (NO), which in turn control the activity of plasma membrane calcium channels. The subsequent increase in the intracellular level of the ion regulates fundamental biophysical properties of ECs (such as elasticity, intrinsic motility, and chemical strength), enhancing their migratory capacity. Previously, a number of continuous models have represented cytosolic calcium dynamics, while EC migration in angiogenesis has been separately approached with discrete, lattice-based techniques. These two components are here integrated and interfaced to provide a multiscale and hybrid Cellular Potts Model (CPM), where the phenomenology of a motile EC is realistically mediated by its calcium-dependent subcellular events. The model, based on a realistic 3-D cell morphology with a nuclear and a cytosolic region, is set with known biochemical and electrophysiological data. In particular, the resulting simulations are able to reproduce and describe the polarization process, typical of stimulated vascular cells, in various experimental conditions.Moreover, by analyzing the mutual interactions between multilevel biochemical and biomechanical aspects, our study investigates ways to inhibit cell migration: such strategies have in fact the potential to result in pharmacological interventions useful to disrupt malignant vascular progressio

Biological impact of geometric uncertainties: what margin is needed for intra-hepatic tumors?

<p>Abstract</p> <p>Background</p> <p>To evaluate and compare the biological impact on different proposed margin recipes for the same geometric uncertainties for intra-hepatic tumors with different tumor cell types or clinical stages.</p> <p>Method</p> <p>Three different margin recipes based on tumor motion were applied to sixteen IMRT plans with a total of twenty two intra-hepatic tumors. One recipe used the full amplitude of motion measured from patients to generate margins. A second used 70% of the full amplitude of motion, while the third had no margin for motion. The biological effects of geometric uncertainty in these three situations were evaluated with Equivalent Uniform Doses (EUD) for various survival fractions at 2 Gy (SF₂).</p> <p>Results</p> <p>There was no significant difference in the biological impact between the full motion margin and the 70% motion margin. Also, there was no significant difference between different tumor cell types. When the margin for motion was eliminated, the difference of the biological impact was significant among different cell types due to geometric uncertainties. Elimination of the motion margin requires dose escalation to compensate for the biological dose reduction due to the geometric misses during treatment.</p> <p>Conclusions</p> <p>Both patient-based margins of full motion and of 70% motion are sufficient to prevent serious dosimetric error. Clinical implementation of margin reduction should consider the tumor sensitivity to radiation.</p

Feasibility, reliability, and validity of adolescent health status measurement by the Child Health Questionnaire Child Form (CHQ-CF): internet administration compared with the standard paper version

AIMS: In this study we evaluated indicators of the feasibility, reliability, and validity of the Child Health Questionnaire-Child Form (CHQ-CF). We compared the results in a subgroup of adolescents who completed the standard paper version of the CHQ-CF with the results in another subgroup of adolescents who completed an internet version, i.e., an online, web-based CHQ-CF questionnaire. METHODS: Under supervision at school, 1,071 adolescents were randomized to complete the CHQ-CF and items on chronic conditions by a paper questionnaire or by an internet administered questionnaire. RESULTS: The participation rate was 87%; age range 13–7 years. The internet administration resulted in fewer missing answers. All but one multi-item scale showed internal consistency reliability (Cronbach’s α > 0.70). All scales clearly discriminated between adolescents with no, a few, or many self-reported chronic conditions. The paper administration resulted in statistically significant, higher scores on 4 of 10 CHQ-CF scales compared with the internet administration (P < 0.05), but Cohen’s effect sizes d were ≤0.21. Mode of administration interacted significantly with age (P < 0.05) on four CHQ-CF scales, but Cohen’s effect sizes for these differences were also ≤0.21. CONCLUSION: This study supports the feasibility, internal consistency reliability of the scales, and construct validity of the CHQ-CF administered by either a paper questionnaire or online questionnaire. Given Cohen’s suggested guidelines for the interpretation of effect sizes, i.e., 0.20–.50 indicates a small effect, differences in CHQ-CF scale scores between paper and internet administration can be considered as negligible or small

Profiling of dynamics in protein–lipid–water systems: a time-resolved fluorescence study of a model membrane protein with the label BADAN at specific membrane depths

Profiles of lipid-water bilayer dynamics were determined from picosecond time-resolved fluorescence spectra of membrane-embedded BADAN-labeled M13 coat protein. For this purpose, the protein was labeled at seven key positions. This places the label at well-defined locations from the water phase to the center of the hydrophobic acyl chain region of a phospholipid model membrane, providing us with a nanoscale ruler to map membranes. Analysis of the time-resolved fluorescence spectroscopic data provides the characteristic time constant for the twisting motion of the BADAN label, which is sensitive to the local flexibility of the protein–lipid environment. In addition, we obtain information about the mobility of water molecules at the membrane–water interface. The results provide an unprecedented nanoscale profiling of the dynamics and distribution of water in membrane systems. This information gives clear evidence that the actual barrier of membranes for ions and aqueous solvents is located at the region of carbonyl groups of the acyl chains

A Cellular Potts Model simulating cell migration on and in matrix environments

Cell migration on and through extracellular matrix plays a critical role in a wide variety of physiological and pathological phenomena, and in scaffold-based tissue engineering. Migration is regulated by a number of extracellular matrix- or cell-derived biophysical parameters, such as matrix fiber orientation, gap size, and elasticity, or cell deformation, proteolysis, and adhesion. We here present an extended Cellular Potts Model (CPM) able to qualitatively and quantitatively describe cell migratory phenotype on both two-dimensional substrates and within three-dimensional environments, in a close comparison with experimental evidence. As distinct features of our approach, the cells are represented by compartmentalized discrete objects, differentiated in the nucleus and in the cytosolic region, while the extracellular matrix is composed of a fibrous mesh and of a homogeneous fluid. Our model provides a strong correlation of the directionality of migration with the topological ECM distribution and, further, a biphasic dependence of migration on the matrix density, and in part adhesion, in both two-dimensional and three-dimensional settings. Moreover, we demonstrate that the directional component of cell movement is strongly correlated with the topological distribution of the ECM fibrous network. In the three-dimensional networks, we also investigate the effects of the matrix mechanical microstructure, observing that, at a given distribution of fibers, cell motility has a subtle bimodal relation with the elasticity of the scaffold. Finally, cell locomotion requires deformation of the cell's nucleus and/or cell-derived proteolysis of steric fibrillar obstacles within rather rigid matrices characterized by small pores, not, however, for sufficiently large pores. In conclusion, we here propose a mathematical modeling approach that serves to characterize cell migration as a biological phenomen in health, disease and tissue engineering applications. The research that led to the present paper was partially supported by a grant of the group GNFM of INdA

From Things to Thinking: Cognitive Archaeology

Cognitive archaeologists infer from material remains to the cognitive features of past societies. We characterize cognitive archaeology in terms of trace-based reasoning, which in the case of cognitive archaeology involves inferences drawing upon background theory linking objects from the archaeological record to cognitive (including psychological, symbolic, and ideological) features. We analyse such practices, examining work on cognitive evolution, language, and musicality. We argue that the central epistemic challenge for cognitive archaeology is often not a paucity of material remains, but insufficient constraint from cognitive theories. However, we also argue that the success of cognitive archaeology does not necessarily require well-developed cognitive theories: Success might instead lead to them

A Unique Human-Fox Burial from a Pre-Natufian Cemetery in the Levant (Jordan)

New human burials from northern Jordan provide important insights into the appearance of cemeteries and the nature of human-animal relationships within mortuary contexts during the Epipalaeolithic period (c. 23,000–11,600 cal BP) in the Levant, reinforcing a socio-ideological relationship that goes beyond predator-prey. Previous work suggests that archaeological features indicative of social complexity occur suddenly during the latest Epipalaeolithic phase, the Natufian (c. 14,500–11,600 cal BP). These features include sedentism, cemeteries, architecture, food production, including animal domestication, and burials with elaborate mortuary treatments. Our findings from the pre-Natufian (Middle Epipalaeolithic) cemetery of ‘Uyun al-Hammam demonstrate that joint human-animal mortuary practices appear earlier in the Epipalaeolithic. We describe the earliest human-fox burial in the Near East, where the remains of dogs have been found associated with human burials at a number of Natufian sites. This is the first time that a fox has been documented in association with human interments pre-dating the Natufian and with a particular suite of grave goods. Analysis of the human and animal bones and their associated artefacts provides critical data on the nature and timing of these newly-developing relationships between people and animals prior to the appearance of domesticated dogs in the Natufian