Traumatic Brain Injury-Practice Based Evidence Study: Design and Patients, Centers, Treatments, and Outcomes

OBJECTIVES: To describe study design, patients, centers, treatments, and outcomes of a traumatic brain injury (TBI) practice-based evidence (PBE) study and to evaluate the generalizability of the findings to the U.S. TBI inpatient rehabilitation population. DESIGN: Prospective, longitudinal, observational study. SETTING: Ten inpatient rehabilitation centers. PARTICIPANTS: Patients (N=2130) enrolled between October 2008 and September 2011 and admitted for inpatient rehabilitation after an index TBI injury. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Return to acute care during rehabilitation, rehabilitation length of stay, FIM at discharge, residence at discharge, and 9 months postdischarge rehospitalization, FIM, participation, and subjective well-being. RESULTS: The level of admission FIM cognitive score was found to create relatively homogeneous subgroups for the subsequent analysis of best treatment combinations. There were significant differences in patient and injury characteristics, treatments, rehabilitation course, and outcomes by admission FIM cognitive subgroups. TBI-PBE study patients were overall similar to U.S. national TBI inpatient rehabilitation populations. CONCLUSIONS: This TBI-PBE study succeeded in capturing naturally occurring variation in patients and treatments, offering opportunities to study best treatments for specific patient impairments. Subsequent articles in this issue report differences between patients and treatments and associations with outcomes in greater detail

Quantum simplicial geometry in the group field theory formalism: reconsidering the Barrett-Crane model

A dual formulation of group field theories, obtained by a Fourier transform mapping functions on a group to functions on its Lie algebra, has been proposed recently. In the case of the Ooguri model for SO(4) BF theory, the variables of the dual field variables are thus so(4) bivectors, which have a direct interpretation as the discrete B variables. Here we study a modification of the model by means of a constraint operator implementing the simplicity of the bivectors, in such a way that projected fields describe metric tetrahedra. This involves a extension of the usual GFT framework, where boundary operators are labelled by projected spin network states. By construction, the Feynman amplitudes are simplicial path integrals for constrained BF theory. We show that the spin foam formulation of these amplitudes corresponds to a variant of the Barrett-Crane model for quantum gravity. We then re-examin the arguments against the Barrett-Crane model(s), in light of our construction.Comment: revtex, 24 page

A new look at loop quantum gravity

I describe a possible perspective on the current state of loop quantum gravity, at the light of the developments of the last years. I point out that a theory is now available, having a well-defined background-independent kinematics and a dynamics allowing transition amplitudes to be computed explicitly in different regimes. I underline the fact that the dynamics can be given in terms of a simple vertex function, largely determined by locality, diffeomorphism invariance and local Lorentz invariance. I emphasize the importance of approximations. I list open problems.Comment: 15 pages, 5 figure

Negotiating daughterhood and strangerhood: retrospective accounts of serial migration

Most considerations of daughtering and mothering take for granted that the subjectivities of mothers and daughters are negotiated in contexts of physical proximity throughout daughters’ childhoods. Yet many mothers and daughters spend periods separated from each other, sometimes across national borders. Globally, an increasing number of children experience life in transnational families. This paper examines the retrospective narratives of four women who were serial migrants as children (whose parents migrated before they did) . It focuses on their accounts of the reunion with their mothers and how these fit with the ways in which they construct their mother-daughter relationships. We take a psychosocial approach by using a psychoanalytically-informed reading of these narratives to acknowledge the complexities of the attachments produced in the context of migration and to attend to the multi-layered psychodynamics of the resulting relationships. The paper argues that serial migration positioned many of the daughters in a conflictual emotional landscape from which they had to negotiate ‘strangerhood’ in the context of sadness at leaving people to whom they were attached in order to join their mothers (or parents). As a result, many were resistant to being positioned as daughters, doing daughtering and being mothered in their new homes

3d Spinfoam Quantum Gravity: Matter as a Phase of the Group Field Theory

An effective field theory for matter coupled to three-dimensional quantum gravity was recently derived in the context of spinfoam models in hep-th/0512113. In this paper, we show how this relates to group field theories and generalized matrix models. In the first part, we realize that the effective field theory can be recasted as a matrix model where couplings between matrices of different sizes can occur. In a second part, we provide a family of classical solutions to the three-dimensional group field theory. By studying perturbations around these solutions, we generate the dynamics of the effective field theory. We identify a particular case which leads to the action of hep-th/0512113 for a massive field living in a flat non-commutative space-time. The most general solutions lead to field theories with non-linear redefinitions of the momentum which we propose to interpret as living on curved space-times. We conclude by discussing the possible extension to four-dimensional spinfoam models.Comment: 17 pages, revtex4, 1 figur

Coupling gauge theory to spinfoam 3d quantum gravity

We construct a spinfoam model for Yang-Mills theory coupled to quantum gravity in three dimensional riemannian spacetime. We define the partition function of the coupled system as a power series in g_0^2 G that can be evaluated order by order using grasping rules and the recoupling theory. With respect to previous attempts in the literature, this model assigns the dynamical variables of gravity and Yang-Mills theory to the same simplices of the spinfoam, and it thus provides transition amplitudes for the spin network states of the canonical theory. For SU(2) Yang-Mills theory we show explicitly that the partition function has a semiclassical limit given by the Regge discretization of the classical Yang-Mills action.Comment: 18 page

Area-angle variables for general relativity

We introduce a modified Regge calculus for general relativity on a triangulated four dimensional Riemannian manifold where the fundamental variables are areas and a certain class of angles. These variables satisfy constraints which are local in the triangulation. We expect the formulation to have applications to classical discrete gravity and non-perturbative approaches to quantum gravity.Comment: 7 pages, 1 figure. v2 small changes to match published versio

Single-cell deconvolution of head and neck squamous cell carcinoma

Complexities in cell-type composition have rightfully led to skepticism and caution in the interpretation of bulk transcriptomic analyses. Recent studies have shown that deconvolution algorithms can be utilized to computationally estimate cell-type proportions from the gene expression data of bulk blood samples, but their performance when applied to tumor tissues, including those from head and neck, remains poorly characterized. Here, we use single-cell data (~6000 single cells) collected from 21 head and neck squamous cell carcinoma (HNSCC) samples to generate cell-type-specific gene expression signatures. We leverage bulk RNA-seq data from \u3e500 HNSCC samples profiled by The Cancer Genome Atlas (TCGA), and using single-cell data as a reference, apply two newly developed deconvolution algorithms (CIBERSORTx and MuSiC) to the bulk transcriptome data to quantitatively estimate cell-type proportions for each tumor in TCGA. We show that these two algorithms produce similar estimates of constituent/major cell-type proportions and that a high T-cell fraction correlates with improved survival. By further characterizing T-cell subpopulations, we identify that regulatory T-cells (

Some investigations into non passive listening

Our knowledge of the function of the auditory nervous system is based upon a wealth of data obtained, for the most part, in anaesthetised animals. More recently, it has been generally acknowledged that factors such as attention profoundly modulate the activity of sensory systems and this can take place at many levels of processing. Imaging studies, in particular, have revealed the greater activation of auditory areas and areas outside of sensory processing areas when attending to a stimulus. We present here a brief review of the consequences of such non-passive listening and go on to describe some of the experiments we are conducting to investigate them. In imaging studies, using fMRI, we can demonstrate the activation of attention networks that are non-specific to the sensory modality as well as greater and different activation of the areas of the supra-temporal plane that includes primary and secondary auditory areas. The profuse descending connections of the auditory system seem likely to be part of the mechanisms subserving attention to sound. These are generally thought to be largely inactivated by anaesthesia. However, we have been able to demonstrate that even in an anaesthetised preparation, removing the descending control from the cortex leads to quite profound changes in the temporal patterns of activation by sounds in thalamus and inferior colliculus. Some of these effects seem to be specific to the ear of stimulation and affect interaural processing. To bridge these observations we are developing an awake behaving preparation involving freely moving animals in which it will be possible to investigate the effects of consciousness (by contrasting awake and anaesthetized), passive and active listening

Anti-Trypanosomal Proteasome Inhibitors Cure Hemolymphatic and Meningoencephalic Murine Infection Models of African Trypanosomiasis

Current anti-trypanosomal therapies suffer from problems of longer treatment duration, toxicity and inadequate efficacy, hence there is a need for safer, more efficacious and 'easy to use' oral drugs. Previously, we reported the discovery of the triazolopyrimidine (TP) class as selective kinetoplastid proteasome inhibitors with in vivo efficacy in mouse models of leishmaniasis, Chagas Disease and African trypanosomiasis (HAT). For the treatment of HAT, development compounds need to have excellent penetration to the brain to cure the meningoencephalic stage of the disease. Here we describe detailed biological and pharmacological characterization of triazolopyrimidine compounds in HAT specific assays. The TP class of compounds showed single digit nanomolar potency against Trypanosoma brucei rhodesiense and Trypanosoma brucei gambiense strains. These compounds are trypanocidal with concentration-time dependent kill and achieved relapse-free cure in vitro. Two compounds, GNF6702 and a new analog NITD689, showed favorable in vivo pharmacokinetics and significant brain penetration, which enabled oral dosing. They also achieved complete cure in both hemolymphatic (blood) and meningoencephalic (brain) infection of human African trypanosomiasis mouse models. Mode of action studies on this series confirmed the 20S proteasome as the target in T. brucei. These proteasome inhibitors have the potential for further development into promising new treatment for human African trypanosomiasis