Integrative analysis identifies candidate tumor microenvironment and intracellular signaling pathways that define tumor heterogeneity in NF1

Neurofibromatosis type 1 (NF1) is a monogenic syndrome that gives rise to numerous symptoms including cognitive impairment, skeletal abnormalities, and growth of benign nerve sheath tumors. Nearly all NF1 patients develop cutaneous neurofibromas (cNFs), which occur on the skin surface, whereas 40-60% of patients develop plexiform neurofibromas (pNFs), which are deeply embedded in the peripheral nerves. Patients with pNFs have a ~10% lifetime chance of these tumors becoming malignant peripheral nerve sheath tumors (MPNSTs). These tumors have a severe prognosis and few treatment options other than surgery. Given the lack of therapeutic options available to patients with these tumors, identification of druggable pathways or other key molecular features could aid ongoing therapeutic discovery studies. In this work, we used statistical and machine learning methods to analyze 77 NF1 tumors with genomic data to characterize key signaling pathways that distinguish these tumors and identify candidates for drug development. We identified subsets of latent gene expression variables that may be important in the identification and etiology of cNFs, pNFs, other neurofibromas, and MPNSTs. Furthermore, we characterized the association between these latent variables and genetic variants, immune deconvolution predictions, and protein activity predictions

Construction of coarse-grained order-parameters in non-equilibrium systems

We develop a renormalization group (RG) procedure that includes important system-specific features. The key ingredient is to systematize the coarse graining procedure that generates the RG flow. The coarse graining technology comes from control and operator theoretic model reduction. The resulting "generalized" RG is a consistent generalization of the Wilsonian RG. We derive the form of the projection operator from the dynamics of a nonlinear wave equation and renormalize the distribution of initial conditions. The probability density of the initial conditions is chosen to be the Boltzmann weight for a standard $\phi^4$-theory. In our calculation, we find that in contrast to conventional implementations of the RG, na\"ive power counting breaks down. The RG-equations that we derive are different from those derived from the conventional RG.Comment: 13 pages, 0 figure

Advice to clinicians on communication from adolescents and young adults with cancer and parents of children with cancer

Effective communication is integral to patient and family-centered care in pediatric and adolescent and young adult (AYA) oncology and improving healthcare delivery and outcomes. There is limited knowledge about whether AYAs and parents have similar communication preferences and needs. By eliciting and comparing communication advice from AYAs and parents, we can identify salient guidance for how clinicians can better communicate. We performed secondary analysis of semi-structured interviews from 2 qualitative communication studies. In one study, 80 parents of children with cancer during treatment, survivorship, or bereavement were interviewed. In the second study, AYAs with cancer during treatment or survivorship were interviewed. We asked AYAs and parents to provide communication advice for oncology clinicians. Using thematic analysis, we identified categories of advice related to three overarching themes: interpersonal relationships, informational preferences, and delivery of treatment, resources, and medical care. AYAs and parents provided similar advice about the need for compassion, strong connections, hopefulness, commitment, and transparent honesty However, AYAs placed additional emphasis on clinicians maintaining a calm demeanor

Parent-clinician communication intervention during end-of-life decision making for children with incurable cancer.

Background: In this single-site study, we evaluated the feasibility of a parent-clinician communication intervention designed to: identify parents\u27 rationale for the phase I, do-not-resuscitate (DNR), or terminal care decision made on behalf of their child with incurable cancer; identify their definition of being a good parent to their ill child; and provide this information to the child\u27s clinicians in time to be of use in the family\u27s care. Methods: Sixty-two parents of 58 children and 126 clinicians participated. Within 72 hours after the treatment decision, parents responded to 6 open-ended interview questions and completed a 10-item questionnaire about the end-of-life communication with their child\u27s clinicians. They completed the questionnaire again two to three weeks later and responded to three open-ended questions to assess the benefit:risk ratio of their study participation three months after the intervention. Clinicians received the interview data within hours of the parent interview and evaluated the usefulness of the information three weeks later. Results: All preestablished intervention feasibility criteria were met; 77.3% of families consented; and in 100% of interventions, information was successfully provided individually to 3 to 11 clinicians per child before the child died. No harm was reported by parents as a result of participating; satisfaction and other benefits were reported. Clinicians reported moderate to strong satisfaction with the intervention. Conclusion: The communication intervention was feasible within hours of decision making, was acceptable and beneficial without harm to participating parents, and was acceptable and useful to clinicians in their care of families

The stability of a cubic fixed point in three dimensions from the renormalization group

The global structure of the renormalization-group flows of a model with isotropic and cubic interactions is studied using the massive field theory directly in three dimensions. The four-loop expansions of the \bt-functions are calculated for arbitrary $N$. The critical dimensionality $N_c=2.89 \pm 0.02$ and the stability matrix eigenvalues estimates obtained on the basis of the generalized Pad$\acute{\rm e}$-Borel-Leroy resummation technique are shown to be in a good agreement with those found recently by exploiting the five-loop \ve-expansions.Comment: 18 pages, LaTeX, 5 PostScript figure

The Thermal Renormalization Group for Fermions, Universality, and the Chiral Phase-Transition

We formulate the thermal renormalization group, an implementation of the Wilsonian RG in the real-time (CTP) formulation of finite temperature field theory, for fermionic fields. Using a model with scalar and fermionic degrees of freedom which should describe the two-flavor chiral phase-transition, we discuss the mechanism behind fermion decoupling and universality at second order transitions. It turns out that an effective mass-like term in the fermion propagator which is due to thermal fluctuations and does not break chiral symmetry is necessary for fermion decoupling to work. This situation is in contrast to the high-temperature limit, where the dominance of scalar over fermionic degrees of freedom is due to the different behavior of the distribution functions. The mass-like contribution is the leading thermal effect in the fermionic sector and is missed if a derivative expansion of the fermionic propagator is performed. We also discuss results on the phase-transition of the model considered where we find good agreement with results from other methods.Comment: References added, minor typos correcte

Critical dynamics and effective exponents of magnets with extended impurities

We investigate the asymptotic and effective static and dynamic critical behavior of (d=3)-dimensional magnets with quenched extended defects, correlated in $\epsilon_d$ dimensions (which can be considered as the dimensionality of the defects) and randomly distributed in the remaining $d-\epsilon_d$ dimensions. The field-theoretical renormalization group perturbative expansions being evaluated naively do not allow for the reliable numerical data. We apply the Chisholm-Borel resummation technique to restore convergence of the two-loop expansions and report the numerical values of the asymptotic critical exponents for the model A dynamics. We discuss different scenarios for static and dynamic effective critical behavior and give values for corresponding non-universal exponents.Comment: 12 pages, 6 figure

Summing Divergent Perturbative Series in a Strong Coupling Limit. The Gell-Mann - Low Function of the \phi^4 Theory

An algorithm is proposed for determining asymptotics of the sum of a perturbative series in the strong coupling limit using given values of the expansion coefficients. Operation of the algorithm is illustrated by test examples, method for estimating errors is developed, and an optimization procedure is described. Application of the algorithm to the $\phi^4$ theory gives a behavior $\beta(g)\approx 7.4 g^{0.96}$ at large $g$ for its Gell-Mann -- Low function. The fact that the exponent is close to unity can be interpreted as a manifestation of the logarithmic branching of the type $\beta(g)\sim g (\ln g)^{-\gamma}$ (with $\gamma\approx 0.14$), which is confirmed by independent evidence. In any case, the $\phi^4$ theory is internally consistent. The procedure of summing perturbartive series with arbitrary values of expansion parameter is discussed.Comment: 23 pages, PD

On the Convergence of the Expansion of Renormalization Group Flow Equation

We compare and discuss the dependence of a polynomial truncation of the effective potential used to solve exact renormalization group flow equation for a model with fermionic interaction (linear sigma model) with a grid solution. The sensitivity of the results on the underlying cutoff function is discussed. We explore the validity of the expansion method for second and first-order phase transitions.Comment: 12 pages with 10 EPS figures included; revised versio