4,209 research outputs found
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
The Internet of Simulation: Enabling Agile Model Based Systems Engineering for Cyber-Physical Systems
The expansion of the Internet of Things (IoT) has resulted in a complex cyber-physical system of systems that is continually evolving. With ever more complex systems being developed and changed there has been an increasing reliance on simulation as a vital part of the design process. There is also a growing need for simulation integration and co-simulation in order to analyse the complex interactions between system components. To this end we propose that the Internet of Simulation (IoS) as an extension of IoT can be used to meet these needs. The IoS allows for multiple heterogeneous simulations to be integrated together for co-simulation. It's effect on the engineer process is to facilitate agile practices without sacrificing rigour. An Industry 4.0 example case study is provided showing how IoS could be utilized
Conformal mechanics inspired by extremal black holes in d=4
A canonical transformation which relates the model of a massive relativistic
particle moving near the horizon of an extremal black hole in four dimensions
and the conventional conformal mechanics is constructed in two different ways.
The first approach makes use of the action-angle variables in the angular
sector. The second scheme relies upon integrability of the system in the sense
of Liouville.Comment: V2: presentation improved, new material and references added; the
version to appear in JHE
Continuous Hawking-Page transitions in Einstein-scalar gravity
We investigate continuous Hawking-Page transitions in Einstein's gravity
coupled to a scalar field with an arbitrary potential in the weak gravity
limit. We show that this is only possible in a singular limit where the
black-hole horizon marginally traps a curvature singularity. Depending on the
subleading terms in the potential, a rich variety of continuous phase
transitions arise. Our examples include second and higher order, including the
Berezinskii-Kosterlitz-Thouless type. In the case when the scalar is dilaton,
the condition for a continuous phase transition lead to (asymptotically)
linear-dilaton background. We obtain the scaling laws of thermodynamic
functions, as well as the viscosity coefficients near the transition. In the
limit of weak gravitational interactions, the bulk viscosity asymptotes to a
universal constant, independent of the details of the scalar potential. As a
byproduct of our analysis we obtain a one-parameter family of kink solutions in
arbitrary dimension d that interpolate between AdS near the boundary and
linear-dilaton background in the deep interior. The continuous Hawking-Page
transitions found here serve as holographic models for normal-to superfluid
transitions.Comment: 35 pages + appendice
AdS Black Hole Solutions in the Extended New Massive Gravity
We have obtained (warped) AdS black hole solutions in the three dimensional
extended new massive gravity. We investigate some properties of black holes and
obtain central charges of the two dimensional dual CFT. To obtain the central
charges, we use the relation between entropy and temperature according to the
AdS/CFT dictionary. For AdS black holes, one can also use the central charge
function formalism which leads to the same results.Comment: 24pages, some organization corrected, minor corrections, references
added, final published versio
Warped black holes in 3D general massive gravity
We study regular spacelike warped black holes in the three dimensional
general massive gravity model, which contains both the gravitational
Chern-Simons term and the linear combination of curvature squared terms
characterizing the new massive gravity besides the Einstein-Hilbert term. The
parameters of the metric are found by solving a quartic equation constrained by
an inequality that imposes the absence of closed timelike curves. Explicit
expressions for the central charges are suggested by exploiting the fact that
these black holes are discrete quotients of spacelike warped AdS(3) and a known
formula for the entropy. Previous results obtained separately in topological
massive gravity and in new massive gravity are recovered as special cases.Comment: 38 pages, 7 figures. v2: minor changes, added refs and an appendix on
self-dual and null z-warped black hole
Uterine primitive neuroectodermal tumor with adenosarcoma: a case report
<p>Abstract</p> <p>Introduction</p> <p>Primitive neuroectodermal tumor of the uterus is extremely rare. They occur as either pure primitive neuroectodermal tumors or admixed with neoplasms of mullerian origin.</p> <p>Case presentation</p> <p>A case of uterine primitive neuroectodermal tumor with adenosarcoma in a 50-year-old Asian Indian woman is presented. Histologically, the neoplasm displayed perivascular pseudorosettes and occasional Homer-Wright rosettes. A strong positivity for neuronspecific enolase and synaptophysin was noted, while chromogranin and CD99 were negative. Merging imperceptibly with the neuroectodermal components were the areas of adenosarcoma.</p> <p>Conclusion</p> <p>To the best of our knowledge, this report represents the second case of a uterine primitive neuroectodermal tumor with an admixed adenosarcoma.</p
Predicting erythropoietin resistance in hemodialysis patients with type 2 diabetes
<p>Background: Resistance to ESAs (erythropoietin stimulating agents) is highly prevalent in hemodialysis patients with diabetes and associated with an increased mortality. The aim of this study was to identify predictors for ESA resistance and to develop a prediction model for the risk stratification in these patients.</p>
<p>Methods: A post-hoc analysis was conducted of the 4D study, including 1015 patients with type 2 diabetes undergoing hemodialysis. Determinants of ESA resistance were identified by univariate logistic regression analyses. Subsequently, multivariate models were performed with stepwise inclusion of significant predictors from clinical parameters, routine laboratory and specific biomarkers.</p>
<p>Results: In the model restricted to clinical parameters, male sex, shorter dialysis vintage, lower BMI, history of CHF, use of ACE-inhibitors and a higher heart rate were identified as independent predictors of ESA resistance. In regard to routine laboratory markers, lower albumin, lower iron saturation, higher creatinine and higher potassium levels were independently associated with ESA resistance. With respect to specific biomarkers, higher ADMA and CRP levels as well as lower Osteocalcin levels were predictors of ESA resistance.</p>
<p>Conclusions: Easily obtainable clinical parameters and routine laboratory parameters can predict ESA resistance in diabetic hemodialysis patients with good discrimination. Specific biomarkers did not meaningfully further improve the risk prediction of ESA resistance. Routinely assessed data can be used in clinical practice to stratify patients according to the risk of ESA resistance, which may help to assign appropriate treatment strategies.</p>
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