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

Effectiveness evaluation of STOL transport operations

A short-takeoff and landing (STOL) systems simulation model has been developed and implemented in a computer code (known as STOL OPS) which permits evaluation of the operation of a STOL aircraft and its avionics in a commercial airline operating environment. STOL OPS concentrated on the avionics functions of navigation, guidance, control, communication, hazard aviodance, and systems management. External world factors influencing the operation of the STOL aircraft include each airport and its geometry, air traffic at each airport, air traffic control equipment and procedures, weather (including winds and visibility), and the flight path between each airport served by the route. The development of the STOL OPS program provides NASA a set of computer programs which can be used for detailed analysis of a STOL aircraft and its avionics and permit establishment of system requirements as a function of airline mission performance goals

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

A randomized, phase II study of afatinib versus cetuximab in metastatic or recurrent squamous cell carcinoma of the head and neck.

BackgroundAfatinib is an oral, irreversible ErbB family blocker that has shown activity in epidermal growth factor receptor (EGFR)-mutated lung cancer. We hypothesized that the agent would have greater antitumor activity compared with cetuximab in recurrent or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) patients, whose disease has progressed after platinum-containing therapy.Patients and methodsAn open-label, randomized, phase II trial was conducted in 43 centers; 124 patients were randomized (1 : 1) to either afatinib (50 mg/day) or cetuximab (250 mg/m(2)/week) until disease progression or intolerable adverse events (AEs) (stage I), with optional crossover (stage II). The primary end point was tumor shrinkage before crossover assessed by investigator (IR) and independent central review (ICR).ResultsA total of 121 patients were treated (61 afatinib, 60 cetuximab) and 68 crossed over to stage II (32 and 36 respectively). In stage I, mean tumor shrinkage by IR/ICR was 10.4%/16.6% with afatinib and 5.4%/10.1% with cetuximab (P = 0.46/0.30). Objective response rate was 16.1%/8.1% with afatinib and 6.5%/9.7% with cetuximab (IR/ICR). Comparable disease control rates were observed with afatinib (50%) and cetuximab (56.5%) by IR; similar results were seen by ICR. Most common grade ≥3 drug-related AEs (DRAEs) were rash/acne (18% versus 8.3%), diarrhea (14.8% versus 0%), and stomatitis/mucositis (11.5% versus 0%) with afatinib and cetuximab, respectively. Patients with DRAEs leading to treatment discontinuation were 23% with afatinib and 5% with cetuximab. In stage II, disease control rate (IR/ICR) was 38.9%/33.3% with afatinib and 18.8%/18.8% with cetuximab.ConclusionAfatinib showed antitumor activity comparable to cetuximab in R/M HNSCC in this exploratory phase II trial, although more patients on afatinib discontinued treatment due to AEs. Sequential EGFR/ErbB treatment with afatinib and cetuximab provided sustained clinical benefit in patients after crossover, suggesting a lack of cross-resistance

Spectroscopy of 13B via the 13C(t,3He) reaction at 115 AMeV

Gamow-Teller and dipole transitions to final states in 13B were studied via the 13C(t,3He) reaction at Et = 115 AMeV. Besides the strong Gamow-Teller transition to the 13B ground state, a weaker Gamow-Teller transition to a state at 3.6 MeV was found. This state was assigned a spin-parity of 3/2- by comparison with shell-model calculations using the WBP and WBT interactions which were modified to allow for mixing between nhw and (n+2)hw configurations. This assignment agrees with a recent result from a lifetime measurement of excited states in 13B. The shell-model calculations also explained the relatively large spectroscopic strength measured for a low-lying 1/2+ state at 4.83 MeV in 13B. The cross sections for dipole transitions up to Ex(13B)= 20 MeV excited via the 13C(t,3He) reaction were also compared with the shell-model calculations. The theoretical cross sections exceeded the data by a factor of about 1.8, which might indicate that the dipole excitations are "quenched". Uncertainties in the reaction calculations complicate that interpretation.Comment: 11 pages, 6 figure

IT Implementation Contract Design: Analytical and Experimental

T his article analytically and experimentally investigates how firms can best capture the business value of information technology (IT) investments through IT contract design. Using a small sample of outsourcing contracts for enterprise information technology (EIT) projects in several industries-coupled with reviews of contracts used by a major enterprise software maker-the authors determine the common provisions and structural characteristics of EIT contracts. The authors use these characteristics to develop an analytical model of optimal contract design with principal-agent techniques. The model captures a set of key characteristics of EIT contracts, including a staged, multiperiod project structure; learning; probabilistic binary outcomes; variable fee structures; possibly risk-averse agents; and implementation risks. The model characterizes conditions under which multistage contracts enable clients to create and capture greater project value than single-stage projects, and how project staging enables firms to reduce project risks, capture learning benefits, and increase development effort. Finally, the authors use controlled laboratory experiments to complement their analytical approaches and demonstrate robustness of their key findings

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

The 150^{150}Nd(3^3He,tt) and 150^{150}Sm(tt,3^3He) reactions with applications to ββ\beta\beta decay of 150^{150}Nd

The $^{150}$Nd($^3$He,$t$) reaction at 140 MeV/u and $^{150}$Sm($t$,$^3$He) reaction at 115 MeV/u were measured, populating excited states in $^{150}$Pm. The transitions studied populate intermediate states of importance for the (neutrinoless) $\beta\beta$ decay of $^{150}$Nd to $^{150}$Sm. Monopole and dipole contributions to the measured excitation-energy spectra were extracted by using multipole decomposition analyses. The experimental results were compared with theoretical calculations obtained within the framework of Quasiparticle Random-Phase Approximation (QRPA), which is one of the main methods employed for estimating the half-life of the neutrinoless $\beta\beta$ decay ($0\nu\beta\beta$) of $^{150}$Nd. The present results thus provide useful information on the neutrino responses for evaluating the $0\nu\beta\beta$ and $2\nu\beta\beta$ matrix elements. The $2\nu\beta\beta$ matrix element calculated from the Gamow-Teller transitions through the lowest $1^{+}$ state in the intermediate nucleus is maximally about half of that deduced from the half-life measured in $2\nu\beta\beta$ direct counting experiments and at least several transitions through $1^{+}$ intermediate states in $^{150}$Pm are required to explain the $2\nu\beta\beta$ half-life. Because Gamow-Teller transitions in the $^{150}$Sm($t$,$^3$He) experiment are strongly Pauli-blocked, the extraction of Gamow-Teller strengths was complicated by the excitation of the $2\hbar\omega$, $\Delta L=0$, $\Delta S=1$ isovector spin-flip giant monopole resonance (IVSGMR). However, the near absence of Gamow-Teller transition strength made it possible to cleanly identify this resonance, and the strength observed is consistent with the full exhaustion of the non-energy-weighted sum rule for the IVSGMR.Comment: 18 pages, 13 figures, 2 table

Modeling oscillatory Microtubule--Polymerization

Polymerization of microtubules is ubiquitous in biological cells and under certain conditions it becomes oscillatory in time. Here simple reaction models are analyzed that capture such oscillations as well as the length distribution of microtubules. We assume reaction conditions that are stationary over many oscillation periods, and it is a Hopf bifurcation that leads to a persistent oscillatory microtubule polymerization in these models. Analytical expressions are derived for the threshold of the bifurcation and the oscillation frequency in terms of reaction rates as well as typical trends of their parameter dependence are presented. Both, a catastrophe rate that depends on the density of {\it guanosine triphosphate} (GTP) liganded tubulin dimers and a delay reaction, such as the depolymerization of shrinking microtubules or the decay of oligomers, support oscillations. For a tubulin dimer concentration below the threshold oscillatory microtubule polymerization occurs transiently on the route to a stationary state, as shown by numerical solutions of the model equations. Close to threshold a so--called amplitude equation is derived and it is shown that the bifurcation to microtubule oscillations is supercritical.Comment: 21 pages and 12 figure