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

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

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

Corporate governance and financial constraints on strategic turnarounds

The paper extends the Robbins and Pearce (1992) two-stage turnaround response model to include governance factors. In addition to the retrenchment and recovery, the paper proposes the addition of a realignment stage, referring specifically to the re-alignment of expectations of principal and agent groups. The realignment stage imposes a threshold that must be crossed before the retrenchment and hence recovery stage can be entered. Crossing this threshold is problematic to the extent that the interests of governance-stakeholder groups diverge in a crisis situation. The severity of the crisis impacts on the bases of strategy contingent asset valuation leading to the fragmentation of stakeholder interests. In some cases the consequence may be that management are prevented from carrying out turnarounds by governance constraints. The paper uses a case study to illustrate these dynamics, and like the Robbins and Pearce study, it focuses on the textile industry. A longitudinal approach is used to show the impact of the removal of governance constraints. The empirical evidence suggests that such financial constraints become less serious to the extent that there is a functioning market for corporate control. Building on governance research and turnaround literature, the paper also outlines the general case necessary and sufficient conditions for successful turnarounds

Beta-delayed proton emission in the 100Sn region

Beta-delayed proton emission from nuclides in the neighborhood of 100Sn was studied at the National Superconducting Cyclotron Laboratory. The nuclei were produced by fragmentation of a 120 MeV/nucleon 112Sn primary beam on a Be target. Beam purification was provided by the A1900 Fragment Separator and the Radio Frequency Fragment Separator. The fragments of interest were identified and their decay was studied with the NSCL Beta Counting System (BCS) in conjunction with the Segmented Germanium Array (SeGA). The nuclei 96Cd, 98Ing, 98Inm and 99In were identified as beta-delayed proton emitters, with branching ratios bp = 5.5(40)%, 5.5+3 -2%, 19(2)% and 0.9(4)%, respectively. The bp for 89Ru, 91,92Rh, 93Pd and 95Ag were deduced for the first time with bp = 3+1.9 -1.7%, 1.3(5)%, 1.9(1)%, 7.5(5)% and 2.5(3)%, respectively. The bp = 22(1)% for 101Sn was deduced with higher precision than previously reported. The impact of the newly measured bp values on the composition of the type-I X-ray burst ashes was studied.Comment: 15 pages, 14 Figures, 4 Table

Evaluation of EGFR gene copy number as a predictive biomarker for the efficacy of cetuximab in combination with chemotherapy in the first-line treatment of recurrent and/or metastatic squamous cell carcinoma of the head and neck: EXTREME study

Background: The phase III EXTREME study demonstrated that combining cetuximab with platinum/5-fluorouracil (5-FU) significantly improved overall survival in the first-line treatment of patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN) compared with platinum/5-FU alone. The aim of this investigation was to evaluate elevated tumor EGFR gene copy number as a predictive biomarker in EXTREME study patients