Duration of hospital participation in a nationwide stroke registry is associated with improved quality of care

BACKGROUND: There are several proven therapies for patients with ischemic stroke or transient ischemic attack (TIA), including prophylaxis of deep venous thrombosis (DVT) and initiation of antithrombotic medications within 48 h and at discharge. Stroke registries have been promoted as a means of increasing use of such interventions, which are currently underutilized. METHODS: From 1999 through 2003, 86 U.S. hospitals participated in Ethos, a voluntary web-based acute stroke treatment registry. Detailed data were collected on all patients admitted with a diagnosis of TIA or ischemic stroke. Rates of optimal treatment (defined as either receipt or a valid contraindication) were examined within each hospital as a function of its length of time in registry. Generalized estimating equations were used to adjust for patient and hospital characteristics. RESULTS: A total of 16,301 patients were discharged with a diagnosis of stroke or TIA from 50 hospitals that participated for more than 1 year. Rates of optimal treatment during the first 3 months of participation were as follows: 92.5% for antithrombotic medication within 48 h, 84.6% for antithrombotic medications at discharge, and 77.1% for DVT prophylaxis. Rates for all treatments improved with duration of participation in the registry (p < 0.05), with the most dramatic improvements in the first year. CONCLUSION: In a large cohort of patients with stroke or TIA, three targeted quality-improvement measures improved among hospitals participating in a disease-specific registry. Although the changes could be attributed to interventions other than the registry, these findings demonstrate the potential for hospital-level interventions to improve care for patients with stroke and TIA

Implications of a Modified Higgs to Diphoton Decay Width

Motivated by recent results from Higgs searches at the Large Hadron Collider, we consider possibilities to enhance the diphoton decay width of the Higgs boson over the Standard Model expectation, without modifying either its production rate or the partial widths in the WW and ZZ channels. Studying effects of new charged scalars, fermions and vector bosons, we find that significant variations in the diphoton width may be possible if the new particles have light masses of the order of a few hundred GeV and sizeable couplings to the Higgs boson. Such couplings could arise naturally if there is large mass mixing between two charged particles that is induced by the Higgs vacuum expectation value. In addition, there is generically also a shift in the Z + Gamma partial width, which in the case of new vector bosons tends to be of similar magnitude as the shift in the diphoton partial width, but smaller in other cases. Therefore simultaneous measurements in these two channels could reveal properties of new charged particles at the electroweak scale.Comment: 29 pages, 8 figures; v2: updated references and minor improvements in presentations; v3: sign of the scalar contribution to Z+Gamma amplitudes fixed. Related figures update

Higgs Low-Energy Theorem (and its corrections) in Composite Models

The Higgs low-energy theorem gives a simple and elegant way to estimate the couplings of the Higgs boson to massless gluons and photons induced by loops of heavy particles. We extend this theorem to take into account possible nonlinear Higgs interactions resulting from a strong dynamics at the origin of the breaking of the electroweak symmetry. We show that, while it approximates with an accuracy of order a few percents single Higgs production, it receives corrections of order 50% for double Higgs production. A full one-loop computation of the gg->hh cross section is explicitly performed in MCHM5, the minimal composite Higgs model based on the SO(5)/SO(4) coset with the Standard Model fermions embedded into the fundamental representation of SO(5). In particular we take into account the contributions of all fermionic resonances, which give sizeable (negative) corrections to the result obtained considering only the Higgs nonlinearities. Constraints from electroweak precision and flavor data on the top partners are analyzed in detail, as well as direct searches at the LHC for these new fermions called to play a crucial role in the electroweak symmetry breaking dynamics.Comment: 30 pages + appendices and references, 12 figures. v2: discussion of flavor constraints improved; references added; electroweak fit updated, results unchanged. Matches published versio

Transcriptional dysregulation of Interferome in experimental and human Multiple Sclerosis

Recent evidence indicates that single multiple sclerosis (MS) susceptibility genes involved in interferon (IFN) signaling display altered transcript levels in peripheral blood of untreated MS subjects, suggesting that responsiveness to endogenous IFN is dysregulated during neuroinflammation. To prove this hypothesis we exploited the systematic collection of IFN regulated genes (IRG) provided by the Interferome database and mapped Interferome changes in experimental and human MS. Indeed, central nervous system tissue and encephalitogenic CD4 T cells during experimental autoimmune encephalomyelitis were characterized by massive changes in Interferome transcription. Further, the analysis of almost 500 human blood transcriptomes showed that (i) several IRG changed expression at distinct MS stages with a core of 21 transcripts concordantly dysregulated in all MS forms compared with healthy subjects; (ii) 100 differentially expressed IRG were validated in independent case-control cohorts; and (iii) 53 out of 100 dysregulated IRG were targeted by IFN-beta treatment in vivo. Finally, ex vivo and in vitro experiments established that IFN-beta administration modulated expression of two IRG, ARRB1 and CHP1, in immune cells. Our study confirms the impairment of Interferome in experimental and human MS, and describes IRG signatures at distinct disease stages which can represent novel therapeutic targets in MS

Lineage-specific dynamic and pre-established enhancer–promoter contacts cooperate in terminal differentiation

Chromosome conformation is an important feature of metazoan gene regulation; however, enhancer–promoter contact remodeling during cellular differentiation remains poorly understood. To address this, genome-wide promoter capture Hi-C (CHi-C) was performed during epidermal differentiation. Two classes of enhancer–promoter contacts associated with differentiation-induced genes were identified. The first class ('gained') increased in contact strength during differentiation in concert with enhancer acquisition of the H3K27ac activation mark. The second class ('stable') were pre-established in undifferentiated cells, with enhancers constitutively marked by H3K27ac. The stable class was associated with the canonical conformation regulator cohesin, whereas the gained class was not, implying distinct mechanisms of contact formation and regulation. Analysis of stable enhancers identified a new, essential role for a constitutively expressed, lineage-restricted ETS-family transcription factor, EHF, in epidermal differentiation. Furthermore, neither class of contacts was observed in pluripotent cells, suggesting that lineage-specific chromatin structure is established in tissue progenitor cells and is further remodeled in terminal differentiation