Induction chemotherapy in locally advanced squamous cell carcinoma of the head and neck: role, controversy, and future directions.

BackgroundThe value of induction chemotherapy (ICT) remains under investigation despite decades of research. New advancements in the field, specifically regarding the induction regimen of choice, have reignited interest in this approach for patients with locally advanced squamous cell carcinoma of the head and neck (LA SCCHN). Sufficient evidence has accumulated regarding the benefits and superiority of TPF (docetaxel, cisplatin, and fluorouracil) over the chemotherapy doublet cisplatin and fluorouracil. We therefore sought to collate and interpret the available data and further discuss the considerations for delivering ICT safely and optimally selecting suitable post-ICT regimens.DesignWe nonsystematically reviewed published phase III clinical trials on TPF ICT in a variety of LA SCCHN patient populations conducted between 1990 and 2017.ResultsTPF may confer survival and organ preservation benefits in a subgroup of patients with functionally inoperable or poor-prognosis LA SCCHN. Additionally, patients with operable disease or good prognosis (who are not candidates for organ preservation) may benefit from TPF induction in terms of reducing local and distant failure rates and facilitating treatment deintensification in selected populations. The safe administration of TPF requires treatment by a multidisciplinary team at an experienced institution. The management of adverse events associated with TPF and post-ICT radiotherapy-based treatment is crucial. Finally, post-ICT chemotherapy alternatives to cisplatin concurrent with radiotherapy (i.e. cetuximab or carboplatin plus radiotherapy) appear promising and must be investigated further.ConclusionsTPF is an evidence-based ICT regimen of choice in LA SCCHN and confers benefits in suitable patients when it is administered safely by an experienced multidisciplinary team and paired with the optimal post-ICT regimen, for which, however, no consensus currently exists

Markov Chains and Dynamic Geometry of Polygons

In this paper we construct sequences of polygons from a given n-sided cyclic polygon by iterated procedures and study the limiting behaviors of these sequences in terms of non-negative matrices and Markov chains. (C) 2003 Elsevier Science Inc. All rights reserved

Dual Goals of Trunk Restriction and Stability are Prioritized by Individuals with Chronic Low Back Pain During a Volitional Movement

Background Individuals with chronic low back pain demonstrate impaired responses to volitional and externally-generated postural perturbations that may impact stability whilst performing activities of daily living. Understanding how balance may be impaired by strategy selection is an important consideration during rehabilitation from low back pain to prevent future injurious balance loss. Research question This cross-sectional study explored the influence of an active pain episode on volitional movement patterns and stability during a sit-to-stand task in individuals with chronic low back pain compared to those with no low back pain history. Methods Thirteen participants with low back pain who were in an active flare-up and 13 without pain sat on a height-adjusted chair and performed 5 sit-to-stand movements. Sagittal plane kinematics, kinetics, and surface electromyography were used to compute neuromuscular variables across Acceleration, Transition and Deceleration phases. Stability was assessed using times to contact of body centers of mass and pressure to base of support boundaries. Independent samples t-tests were used to examine group effects, and repeated measures analyses of variance assessed within-subjects effects across movement phases. Results Individuals with low back pain tended to restrict proximal joint motions through heightened muscle activity while increasing distal joint movement and distal muscle contributions. Individuals with low back pain used a greater driving force, indicated by a longer time to contact of the center of pressure, to achieve comparable center of mass stability. Individuals with low back pain may prioritize trunk restriction and stability through the sit-to-stand movement, possibly related to fear of pain or movement. Significance The tendency for individuals with active low back pain to restrict trunk movements may require additional effort to maintain stability. Further research should examine whether trunk restriction is related to pain-related fear of movement and whether additional cognitive resources are required to maintain movement stability

Ponticulin is the major high affinity link between the plasma membrane and the cortical actin network in Dictyostelium

Interactions between the plasma membrane and underlying actin-based cortex have been implicated in membrane organization and stability, the control of cell shape, and various motile processes. To ascertain the function of high affinity actin-membrane associations, we have disrupted by homologous recombination the gene encoding ponticulin, the major high affinity actin-membrane link in Dictyostelium discoideum amoebae. Cells lacking detectable amounts of ponticulin message and protein also are deficient in high affinity actin-membrane binding by several criteria. First, only 10-13% as much endogenous actin cosediments through sucrose and crude plasma membranes from ponticulin-minus cells, as compared with membranes from the parental strain. Second, purified plasma membranes exhibit little or no binding or nucleation of exogenous actin in vitro. Finally, only 10-30% as much endogenous actin partitions with plasma membranes from ponticulin-minus cells after these cells are mechanically unroofed with polylysine-coated coverslips. The loss of the cell\u27s major actin-binding membrane protein appears to be surprisingly benign under laboratory conditions. Ponticulin-minus cells grow normally in axenic culture and pinocytose FITC-dextran at the same rate as do parental cells. The rate of phagocytosis of particles by ponticulin-minus cells in growth media also is unaffected. By contrast, after initiation of development, cells lacking ponticulin aggregate faster than the parental cells. Subsequent morphogenesis proceeds asynchronously, but viable spores can form. These results indicate that ponticulin is not required for cellular translocation, but apparently plays a role in cell patterning during development

Problem-based Learning in Institutional and Curricular Design at the New Model Institute for Technology and Engineering (NMITE)

NMITE’s Master’s in Integrated Engineering (MEng) was created with a unique philosophy of integrating not only traditionally separate strands of engineering, but also of integrating engineering with other disciplines such as arts, humanities, and business. This broad and deep integration is made possible by adopting the principles and practices of problem-based learning (PBL) and embedding them within predetermined module challenges. In this way, each PBL challenge highlights and hones areas of engineering expertise and embeds liberal subjects whilst maintaining the integration intrinsic to the programme. Overall, this method supports the use of block learning with deep integration of employers and the community in the educational experience

Accelerate Microstructure Evolution Simulation Using Graph Neural Networks with Adaptive Spatiotemporal Resolution

Surrogate models driven by sizeable datasets and scientific machine-learning methods have emerged as an attractive microstructure simulation tool with the potential to deliver predictive microstructure evolution dynamics with huge savings in computational costs. Taking 2D and 3D grain growth simulations as an example, we present a completely overhauled computational framework based on graph neural networks with not only excellent agreement to both the ground truth phase-field methods and theoretical predictions, but enhanced accuracy and efficiency compared to previous works based on convolutional neural networks. These improvements can be attributed to the graph representation, both improved predictive power and a more flexible data structure amenable to adaptive mesh refinement. As the simulated microstructures coarsen, our method can adaptively adopt remeshed grids and larger timesteps to achieve further speedup. The data-to-model pipeline with training procedures together with the source codes are provided.Comment: 28 pages, 11 figure

Computational fluid dynamics-based modeling of liquefied soils

The residual shear strength of liquefied soil is a key parameter in evaluating liquefaction flow failures. Results from a series of dynamic centrifuge experiments where the shear strength of liquefied soil was inferred by measuring the force required to pull a thin metal plate (coupon) horizontally through the liquefied soil are assessed here using a computational fluid dynamics (CFD) based model. Viscosity is a key parameter for the Newtonian fluid constitutive model used in the simulations, and apparent viscosities of liquefied soil in the range of about 5,800 – 13,300 Pa·s were obtained when the CFD model was calibrated against coupons pulled through liquefied soil in dynamic centrifuge tests. These computational values agree reasonably with apparent viscosities of liquefied soil reported in the literature when the Reynold’s numbers exceeded 1.0. Importantly, the CFD simulations illustrated that in cases where Reynold’s numbers are \u3c 1.0, apparent viscosities of liquefied soil back-calculated using simplistic closed-form solutions commonly applied in geotechnical literature are several orders of magnitude too large; and therefore, such closed-form solutions should not be used for these cases

Pattern formation driven by nematic ordering of assembling biopolymers

The biopolymers actin and microtubules are often in an ongoing assembling/disassembling state far from thermal equilibrium. Above a critical density this leads to spatially periodic patterns, as shown by a scaling argument and in terms of a phenomenological continuum model, that meets also Onsager's statistical theory of the nematic--to--isotropic transition in the absence of reaction kinetics. This pattern forming process depends much on nonlinear effects and a common linear stability analysis of the isotropic distribution of the filaments is often misleading. The wave number of the pattern decreases with the assembling/disassembling rate and there is an uncommon discontinuous transition between the nematic and the periodic state.Comment: 4 pages, 3 figure