Rescattering and chiral dynamics in B\to \rho\pi decay

We examine the role of B^0(\bar B^0) \to \sigma \pi^0 \to \pi^+\pi^- \pi^0 decay in the Dalitz plot analysis of B^0 (\bar B^0) \to \rho\pi \to \pi^+\pi^-\pi^0 decays, employed to extract the CKM parameter \alpha. The \sigma \pi channel is significant because it can break the relationship between the penguin contributions in B\to\rho^0\pi^0, B\to\rho^+\pi^-, and B\to\rho^-\pi^+ decays consequent to an assumption of isospin symmetry. Its presence thus mimics the effect of isospin violation. The \sigma\pi^0 state is of definite CP, however; we demonstrate that the B\to\rho\pi analysis can be generalized to include this channel without difficulty. The \sigma or f_0(400-1200) ``meson'' is a broad I=J=0 enhancement driven by strong \pi\pi rescattering; a suitable scalar form factor is constrained by the chiral dynamics of low-energy hadron-hadron interactions - it is rather different from the relativistic Breit-Wigner form adopted in earlier B\to\sigma\pi and D\to\sigma\pi analyses. We show that the use of this scalar form factor leads to an improved theoretical understanding of the measured ratio Br(\bar B^0 \to \rho^\mp \pi^\pm) / Br(B^-\to \rho^0 \pi^-).Comment: 26 pages, 8 figs, published version. typos fixed, minor change

Mucosal Expression of Type 2 and Type 17 Immune Response Genes Distinguishes Ulcerative Colitis From Colon-Only Crohn's Disease in Treatment-Naive Pediatric Patients

Background & Aims There is controversy regarding the role of the type 2 immune response in the pathogenesis of ulcerative colitis (UC)?few data are available from treatment-naive patients. We investigated whether genes associated with a type 2 immune response in the intestinal mucosa are up-regulated in treatment-naive pediatric patients with UC compared with patients with Crohn's disease (CD)-associated colitis or without inflammatory bowel disease (IBD), and whether expression levels are associated with clinical outcomes. Methods We used a real-time reverse-transcription quantitative polymerase chain reaction array to analyze messenger RNA (mRNA) expression patterns in rectal mucosal samples from 138 treatment-naive pediatric patients with IBD and macroscopic rectal disease, as well as those from 49 children without IBD (controls), enrolled in a multicenter prospective observational study from 2008 to 2012. Results were validated in real-time reverse-transcription quantitative polymerase chain reaction analyses of rectal RNA from an independent cohort of 34 pediatric patients with IBD and macroscopic rectal disease and 17 controls from Cincinnati Children's Hospital Medical Center. Results We measured significant increases in mRNAs associated with a type 2 immune response (interleukin [IL]5 gene, IL13, and IL13RA2) and a type 17 immune response (IL17A and IL23) in mucosal samples from patients with UC compared with patients with colon-only CD. In a regression model, increased expression of IL5 and IL17A mRNAs distinguished patients with UC from patients with colon-only CD (P =.001; area under the receiver operating characteristic curve, 0.72). We identified a gene expression pattern in rectal tissues of patients with UC, characterized by detection of IL13 mRNA, that predicted clinical response to therapy after 6 months (odds ratio [OR], 6.469; 95% confidence interval [CI], 1.553?26.94), clinical response after 12 months (OR, 6.125; 95% CI, 1.330?28.22), and remission after 12 months (OR, 5.333; 95% CI, 1.132?25.12). Conclusions In an analysis of rectal tissues from treatment-naive pediatric patients with IBD, we observed activation of a type 2 immune response during the early course of UC. We were able to distinguish patients with UC from those with colon-only CD based on increased mucosal expression of genes that mediate type 2 and type 17 immune responses. Increased expression at diagnosis of genes that mediate a type 2 immune response is associated with response to therapy and remission in pediatric patients with UC

Variation in care in the management of children with Crohn's disease: Data from a multicenter inception cohort study

Background: Variation in care is common in medical practice. Reducing variation in care is shown to improve quality and increase favorable outcomes in chronic diseases. We sought to identify factors associated with variation in care in children with newly diagnosed Crohn's disease (CD). Methods: Prospectively collected data from a 28-site multicenter inception CD cohort were analyzed for variations in diagnostic modalities, treatment, and follow-up monitoring practices, along with complicated disease outcomes over 3 years in 1046 children. Generalized linear mixed effects models were used to investigate the intercenter variations in each outcome variable. Results: The mean age at diagnosis was 12 years, and 25.9% were nonwhite. The number of participants ranged from 5 to 112 per site. No variation existed in the initial diagnostic approach. When medication exposure was analyzed, steroid exposure varied from 28.6% to 96.9% (P 0.99). Use of immunomodulators (IMs) varied among centers both within 90 days (P < 0.01) and during 3 years of follow-up (P < 0.01). A significant variation was seen at the geographic level with follow-up small bowel imaging and colonoscopy surveillance after initial therapy. Conclusions: Intercenter variation in care was seen with the initial use of steroids and anti-TNF, but there was no difference in total 3-year exposure to these drugs. Variation in the initiation and long-term use of IMs was significant among sites, but further research with objective measures is needed to explain this variation of care. Small bowel imaging or repeat colonoscopy in CD patients was not uniformly performed across sites. As our data show the widespread existence of variation in care and disease monitoring at geographic levels among pediatric CD patients, future implementation of various practice strategies may help reduce the variation in care

A Connectionist Simulation of the Empirical Acquisition of Grammatical Relations

Abstract. This paper proposes an account of the acquisition of grammatical relations using the basic concepts of connectionism and a construction-based theory of grammar. Many previous accounts of first-language acquisition assume that grammatical relations (e.g., the grammatical subject and object of a sentence) and linking rules are universal and innate; this is necessary to provide a first set of assumptions in the target language to allow deductive processes to test hypotheses and/or set parameters. In contrast to this approach, we propose that grammatical relations emerge rather late in the language-learning process. Our theoretical proposal is based on two observations. First, early production of childhood speech is formulaic and becomes systematic in a progressive fashion. Second, grammatical relations themselves are family-resemblance categories that cannot be described by a single parameter. This leads to the notion that grammatical relations are learned in a bottom up fashion. Combining this theoretical position with the notion that the main purpose of language is communication, we demonstrate the emergence of the notion of “subject ” in a simple recurrent network that learns to map from sentences to semantic roles. We analyze the hidden layer representations of the emergent subject, and demonstrate that these representations correspond to a radially–structured category. We also claim that the pattern of generalization and undergeneralization demonstrated by the network conforms to what we expect from the data on children’s generalizations.