Level of evidence used in recommendations by the National Comprehensive Cancer Network (NCCN) guidelines beyond Food and Drug Administration approvals.

BackgroundA previous analysis of 113 National Comprehensive Cancer Network® (NCCN®) recommendations reported that NCCN frequently recommends beyond Food and Drug Administration (FDA)-approved indications (44 off-label recommendations) and claimed that the evidence for these recommendations was weak.MethodsIn order to determine the strength of the evidence, we carried out an in-depth re-analysis of the 44 off-label recommendations listed in the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®).ResultsOf the 44 off-label recommendations, 14 were later approved by the FDA and/or are supported by randomized controlled trial (RCT) data. In addition, 13 recommendations were either very minor extrapolations from the FDA label (n = 8) or were actually on-label (n = 5). Of the 17 remaining extrapolations, 8 were for mechanism-based agents applied in rare cancers or subsets with few available treatment options (median response rate = 43%), 7 were based on non-RCT data showing significant efficacy (>50% response rates), and 2 were later removed from the NCCN Guidelines because newer therapies with better activity and/or safety became available.ConclusionOff-label drug use is a frequent component of care for patients with cancer in the United States. Our findings indicate that when the NCCN recommends beyond the FDA-approved indications, the strength of the evidence supporting such recommendations is robust, with a significant subset of these drugs later becoming FDA approved or supported by RCT. Recommendations without RCT data are often for mechanism-based drugs with high response rates in rare cancers or subsets without effective therapies

NLC-2 graph recognition and isomorphism

NLC-width is a variant of clique-width with many application in graph algorithmic. This paper is devoted to graphs of NLC-width two. After giving new structural properties of the class, we propose a $O(n^2 m)$-time algorithm, improving Johansson's algorithm \cite{Johansson00}. Moreover, our alogrithm is simple to understand. The above properties and algorithm allow us to propose a robust $O(n^2 m)$-time isomorphism algorithm for NLC-2 graphs. As far as we know, it is the first polynomial-time algorithm.Comment: soumis \`{a} WG 2007; 12

Parameterized Edge Hamiltonicity

We study the parameterized complexity of the classical Edge Hamiltonian Path problem and give several fixed-parameter tractability results. First, we settle an open question of Demaine et al. by showing that Edge Hamiltonian Path is FPT parameterized by vertex cover, and that it also admits a cubic kernel. We then show fixed-parameter tractability even for a generalization of the problem to arbitrary hypergraphs, parameterized by the size of a (supplied) hitting set. We also consider the problem parameterized by treewidth or clique-width. Surprisingly, we show that the problem is FPT for both of these standard parameters, in contrast to its vertex version, which is W-hard for clique-width. Our technique, which may be of independent interest, relies on a structural characterization of clique-width in terms of treewidth and complete bipartite subgraphs due to Gurski and Wanke

Remoção de fósforo de efluentes da suinocultura.

Projeto/Plano de Ação: 03.11.09.01

Tecnologias para tratamento de dejeto de suínos.

Projeto/Plano de Ação: 03.11.09.012

Hyaluronan: A simple polysaccharide with diverse biological functions

Hyaluronan (HA) is a linear polysaccharide with disaccharide repeats of d-glucuronic acid and N-acetyl-d-glucosamine. It is evolutionarily conserved and abundantly expressed in the extracellular matrix (ECM), on the cell surface and even inside cells. Being a simple polysaccharide, HA exhibits an astonishing array of biological functions. HA interacts with various proteins or proteoglycans to organize the ECM and to maintain tissue homeostasis. The unique physical and mechanical properties of HA contribute to the maintenance of tissue hydration, the mediation of solute diffusion through the extracellular space and the lubrication of certain tissues. The diverse biological functions of HA are manifested through its complex interactions with matrix components and resident cells. Binding of HA with cell surface receptors activates various signaling pathways, which regulate cell function, tissue development, inflammation, wound healing and tumor progression and metastasis. Taking advantage of the inherent biocompatibility and biodegradability of HA, as well as its susceptibility to chemical modification, researchers have developed various HA-based biomaterials and tissue constructs with promising and broad clinical potential. This paper illustrates the properties of HA from a matrix biology perspective by first introducing the principles underlying the biosynthesis and biodegradation of HA, as well as the interactions of HA with various proteins and proteoglycans. It next highlights the roles of HA in physiological and pathological states, including morphogenesis, wound healing and tumor metastasis. A deeper understanding of the mechanisms underlying the roles of HA in various physiological processes can provide new insights and tools for the engineering of complex tissues and tissue models

Onset of Convection in Two Liquid Layers with Phase Change

We perform linear stability calculations for horizontal fluid bilayers that can undergo a phase transformation, taking into account both buoyancy effects and thermocapillary effects in the presence of a vertical temperature gradient. We compare the familiar case of the stability of two immiscible fluids in a bilayer geometry with the less-studied case that the two fluids represent different phases of a single-component material, e.g., the water-steam system. The two cases differ in their interfacial boundary conditions: the condition that the interface is a material surface is replaced by the continuity of mass flux across the interface, together with an assumption of thermodynamic equilibrium that in the linearized equations represents the Clausius-Clapeyron relation relating the interfacial temperature and pressures. For the two-phase case, we find that the entropy difference between the phases plays a crucial role in determining the stability of the system. For small values of the entropy difference between the phases, the two-phase system can be linearly unstable to either heating from above or below. The instability is due to the Marangoni effect in combination with the effects of buoyancy (for heating from below). For larger values of the entropy difference the two-phase system is unstable only for heating from below, and the Marangoni effect is masked by effects of the entropy difference. To help understand the mechanisms driving the instability on heating from below we have performed both long-wavelength and short-wavelength analyses of the two-phase system. The short-wavelength analysis shows that the instability is driven by a coupling between the flow normal to the interface and the latent heat generation at the interface. The mechanism for the large wavelength instability is more complicated, and the detailed form of the expansion is found to depend on the Crispation and Bond numbers as well as the entropy difference. The two-phase system allows a conventional Rayleigh-Taylor instability if the heavier fluid overlies the lighter fluid; applying a temperature gradient allows a stabilization of the interface

A New MHD Code with Adaptive Mesh Refinement and Parallelization for Astrophysics

A new code, named MAP, is written in Fortran language for magnetohydrodynamics (MHD) calculation with the adaptive mesh refinement (AMR) and Message Passing Interface (MPI) parallelization. There are several optional numerical schemes for computing the MHD part, namely, modified Mac Cormack Scheme (MMC), Lax-Friedrichs scheme (LF) and weighted essentially non-oscillatory (WENO) scheme. All of them are second order, two-step, component-wise schemes for hyperbolic conservative equations. The total variation diminishing (TVD) limiters and approximate Riemann solvers are also equipped. A high resolution can be achieved by the hierarchical block-structured AMR mesh. We use the extended generalized Lagrange multiplier (EGLM) MHD equations to reduce the non-divergence free error produced by the scheme in the magnetic induction equation. The numerical algorithms for the non-ideal terms, e.g., the resistivity and the thermal conduction, are also equipped in the MAP code. The details of the AMR and MPI algorithms are described in the paper.Comment: 44 pages, 16 figure

Compact Labelings For Efficient First-Order Model-Checking

We consider graph properties that can be checked from labels, i.e., bit sequences, of logarithmic length attached to vertices. We prove that there exists such a labeling for checking a first-order formula with free set variables in the graphs of every class that is \emph{nicely locally cwd-decomposable}. This notion generalizes that of a \emph{nicely locally tree-decomposable} class. The graphs of such classes can be covered by graphs of bounded \emph{clique-width} with limited overlaps. We also consider such labelings for \emph{bounded} first-order formulas on graph classes of \emph{bounded expansion}. Some of these results are extended to counting queries

Indução de aderência intrabdominal por prótese de retícula de polipropileno:: estudo experimental em ratos

INTRODUCTION: The correction of groin hernias using a transperitoneal videolaparoscopic method with a polypropylene mesh is becoming increasingly common. This could lead to an increased incidence of adhesion formation.MATERIALS AND METHODS: The incidence of adhesions induced by mesh placement and by reperitonization was observed in 40 male adult Wistar rats, randomlyallocated to four groups of 10 rats (Group A = no mesh, no reperitonization; B = no mesh, reperitonization; C = mesh, no reperitonization; D = mesh and reperitonization). After opening the abdominal cavity, the iliac fossa was identified and a peritoneal opening, measuring about 2 by 2 cm, was done on the parietal wall. In the rats in which a polypropylene prosthesis was used, a piece of Marlex mesh, measuring about 1.5 by 1.5 cm was placed on the peritoneal opening. A simple suture was performed in the animals submitted to reperitonization, using a 5.0 monofilamentar polypropylene thread on a cardiovascular (atraumatic) needle. The animals were killed 15 days after the operation. Macroscopic analysis was done by an investigator blinded to intervention group. Fisher’s exact test and the c2 test were used for statistical analysis of the results. A P < 0.05 was considered as significant.RESULTS: Adhesions were significantly more common in the groups in which the prosthesis was placed (59% vs. 95%; P = 0.01), as well as in the groups in whichreperitonization was performed (58% vs. 100%; P = 0.03).CONCLUSIONS: The results suggest that polypropylene mesh placement and reperitonization are each independent factors that have a role in inducing the formationof adhesions.INTRODUÇÃO: A correção de hérnias na virilha através de um método videolaparoscópico transperitoneal está se tornando cada vez mais comum. Contudo,este método poderia levar a um aumento na incidência de formação de aderências.MATERIAIS E MÉTODOS: A incidência de aderências induzidas pela colocação de retícula e pela reperitonização foram observadas em 40 ratos Wistar adultos, machos, divididos aleatoriamente em quatro grupos com 10 ratos cada um (Grupo A = sem retícula, sem reperitonização; B = sem retícula, com reperitonização; C = com retícula, sem reperitonização; D = retícula e reperitonização). Após a abertura da cavidade abdominal, a fossa ilíaca foi identificada e fez-se uma abertura de aproximadamente 2 x 2 cm na parede parietal. Nos ratos em que uma prótese de polipropileno foi utilizada, uma retícula Marlex com 1,5 x 1,5 cm foi colocada sobre a abertura peritoneal. Nos outros animais, a reperitonização foi feita com sutura simples, utilizando-se fio de polipropileno monofilamentar 5.0 com uma agulha cardiovascular (atraumática). Os animais foram sacrificados 15 dias depois da operação. A análise macroscópica foi realizada por um investigador cego quanto ao grupo de origem dos animais. A análise estatística utilizou o teste exato de Fisher e o c2. Um P < 0,05 foi considerado significativo.RESULTADOS: As aderências foram significativamente mais comuns nos grupos nos quais a prótese foi utilizada (59% vs. 95%; P = 0,01), assim como nos gruposnos quais foi feita a reperitonização (58% vs. 100%; P = 0,03).  CONCLUSÕES: Os resultados sugerem que a retícula de polipropileno e a reperitonização são fatores independentes entre si quanto à indução de formaçãode aderências