Breakdown of Conformal Invariance at Strongly Random Critical Points

We consider the breakdown of conformal and scale invariance in random systems with strongly random critical points. Extending previous results on one-dimensional systems, we provide an example of a three-dimensional system which has a strongly random critical point. The average correlation functions of this system demonstrate a breakdown of conformal invariance, while the typical correlation functions demonstrate a breakdown of scale invariance. The breakdown of conformal invariance is due to the vanishing of the correlation functions at the infinite disorder fixed point, causing the critical correlation functions to be controlled by a dangerously irrelevant operator describing the approach to the fixed point. We relate the computation of average correlation functions to a problem of persistence in the RG flow.Comment: 9 page

Comprehensive evaluation of the Copernicus Atmosphere Monitoring Service (CAMS) reanalysis against independent observations: Reactive gases

The Copernicus Atmosphere Monitoring Service (CAMS) is operationally providing forecast and reanalysis products of air quality and atmospheric composition. In this article, we present an extended evaluation of the CAMS global reanalysis data set of four reactive gases, namely, ozone (O-3), carbon monoxide (CO), nitrogen dioxide (NO2), and formaldehyde (HCHO), using multiple independent observations. Our results show that the CAMS model system mostly provides a stable and accurate representation of the global distribution of reactive gases over time. Our findings highlight the crucial impact of satellite data assimilation and emissions, investigated through comparison with a model run without assimilated data. Stratospheric and tropospheric O-3 are mostly well constrained by the data assimilation, except over Antarctica after 2012/2013 due to changes in the assimilated data. Challenges remain for O-3 in the Tropics and high-latitude regions during winter and spring. At the surface and for short-lived species (NO2), data assimilation is less effective. Total column CO in the CAMS reanalysis is well constrained by the assimilated satellite data. The control run, however, shows large overestimations of total column CO in the Southern Hemisphere and larger year-to-year variability in all regions. Concerning the long-term stability of the CAMS model, we note drifts in the time series of biases for surface O-3 and CO in the Northern midlatitudes and Tropics and for NO2 over East Asia, which point to biased emissions. Compared to the previous Monitoring Atmospheric Composition and Climate reanalysis, changes in the CAMS chemistry module and assimilation system helped to reduce biases and enhance the long-term temporal consistency of model results for the CAMS reanalysis

Dendritic cell-mediated vaccination relies on interleukin-4 receptor signaling to avoid tissue damage after Leishmania major infection of BALB/c mice

Prevention of tissue damages at the site of Leishmania major inoculation can be achieved if the BALB/c mice are systemically given L. major antigen (LmAg)-loaded bone marrow-derived dendritic cells (DC) that had been exposed to CpG-containing oligodeoxynucleotides (CpG ODN). As previous studies allowed establishing that interleukin-4 (IL-4) is involved in the redirection of the immune response towards a type 1 profile, we were interested in further exploring the role of IL-4. Thus, wild-type (wt) BALB/c mice or DC-specific IL-4 receptor alpha (IL-4Rα)-deficient (CD11ccreIL-4Rα−/lox) BALB/c mice were given either wt or IL-4Rα-deficient LmAg-loaded bone marrow-derived DC exposed or not to CpG ODN prior to inoculation of 2×105 stationary-phase L. major promastigotes into the BALB/c footpad. The results provide evidence that IL4/IL-4Rα-mediated signaling in the vaccinating DC is required to prevent tissue damage at the site of L. major inoculation, as properly conditioned wt DC but not IL-4Rα-deficient DC were able to confer resistance. Furthermore, uncontrolled L. major population size expansion was observed in the footpad and the footpad draining lymph nodes of CD11ccreIL-4Rα−/lox mice immunized with CpG ODN-exposed LmAg-loaded IL-4Rα-deficient DC, indicating the influence of IL-4Rα-mediated signaling in host DC to control parasite replication. In addition, no footpad damage occurred in BALB/c mice that were systemically immunized with LmAg-loaded wt DC doubly exposed to CpG ODN and recombinant IL-4. We discuss these findings and suggest that the IL4/IL4Rα signaling pathway could be a key pathway to trigger when designing vaccines aimed to prevent damaging processes in tissues hosting intracellular microorganisms

Primary small cell carcinoma of the esophagus: clinicopathological and immunohistochemical features of 21 cases

BACKGROUND: Primary small cell carcinoma (SCC) of the esophagus is a rare and aggressive tumor with poor prognosis. In this study, we report the clinicopathological characteristics of 21 cases of small cell carcinoma of the esophagus treated at the Cancer Center of Sun Yat-Sen University, with particular focus on the histologic and immunohistochemical findings. METHODS: Twenty-one patient records were reviewed including presenting symptoms, demographics, disease stage, treatment, and follow-up. Histologic features were observed and immunohistochemical detection of cytokeratin (CK), epithelial membrane antigen (EMA), neuron specific enolase (NSE), synaptophysin (Syn), chromogranin A (CgA), neuronal cell adhesion molecules (CD56), thyroid transcriptional factor-1 (TTF-1) and S100 protein (S100) was performed. RESULTS: The median age of patients in the study was 56 years, with a male-to-female ratio of 3.2:1. Histologically, there were 19 "homogenous" SCC esophageal samples and 2 samples comprised of SCC and well-differentiated squamous cell carcinoma. The percentages of SCC samples with positive immunoreactivity were Syn 95.2%, CD56 76.2%, TTF-1 71.4%, NSE 61.9%, CgA 61.9%, CK 57.1%, EMA 61.9%, and S100 19.0%, respectively. The median patient survival time was 18.3 months after diagnosis. The 2-year survival rate was 28.6%. CONCLUSION: Our study suggests that esophageal SCC has similar histology to SCC that arises in the lung compartment, and Chinese patients have a poor prognosis. Higher proportion of positive labeling of Syn, CD56, CgA, NSE, and TTF-1 in esophageal SCC implicate that they are valuably applied in differential diagnosis of the malignancy

Neutrophils: the forgotten cell in JIA disease pathogenesis

Juvenile idiopathic arthritis (JIA) has long been assumed to be an autoimmune disease, triggered by aberrant recognition of "self" antigens by T-cells. However, systems biology approaches to this family of diseases have suggested complex interactions between innate and adaptive immunity that underlie JIA. In particular, new data suggest an important role for neutrophils in JIA pathogenesis. In this short review, we will discuss the new data that support a role for neutrophils in JIA, discuss regulatory functions that link neutrophils to adaptive immune responses, and discuss future areas of investigation. Above all else, we invite the reader to re-consider the use of the term "autoimmunity" as applied to the family of illnesses we collectively call JIA

‘A phase II study of oral uracil/ftorafur (UFT®) plus leucovorin combined with oxaliplatin (TEGAFOX) as first-line treatment in patients with metastatic colorectal cancer'

This phase II trial was performed to evaluate the efficacy and tolerability of a new combination of Uracil/Ftorafur (UFT®)/leucovorin (LV) and oxaliplatin in patients (pts) with metastatic colorectal cancer (MCRC) who had not received prior chemotherapy for metastatic disease. Between February 2002 and October 2002, 64 patients received UFT® 300 mg m−2 day−1 and LV 90 mg day−1 from day 1 to day 14 combined with oxaliplatin 130 mg m−2 on day 1, every 3 weeks. All patients were evaluable for safety analysis and 58 of 64 patients were eligible for efficacy. Responses were reviewed by an independent review committee. Of the 58 per-protocol defined assessable patients, 1 complete response and 20 partial responses were observed yielding a response rate of 34% (95% CI: 22–47). The median response duration was 8.74 months (range 1.6–14). The median time to progression and the median survival were 5.88 months (95% CI: 4.34–8.21) and 18.2 months (95% CI: 10–20.7), respectively. Diarrhoea and peripheral neuropathy were the most frequent and predictable toxicities. These events were reversible, noncumulative and manageable. Grade 3 diarrhoea occurred in only 11% of the patients. No grade 4 gastrointestinal toxicity was reported in the study. The incidence of grade 3/4 (National Cancer Institute Common Toxicity Criteria 2: NCI-CTC 2) peripheral neuropathy was 15%. Haematological toxicity was of mild to moderate intensity with 10% of the patients with Grade 3/4 neutropenia without any episode of complication. The TEGAFOX regimen, a new combination using UFT®/LV and oxaliplatin every 3 weeks is feasible on an outpatient basis. The combination is safe and active and may offer a promising alternative to the intravenous route. Nevertheless this efficacy results should be confirmed by randomized phase III trials

Alternating irinotecan with oxaliplatin combined with UFT plus leucovorin (SCOUT) in metastatic colorectal cancer

Tegafur–uracil (UFT) plus leucovorin® (LV, folinic acid) with alternating irinotecan and oxaliplatin were effective and well tolerated in patients with metastatic colorectal cancer (mCRC) in a phase I study. This study expanded the maximum tolerated dose group. Patients aged ⩾18 years had histologically confirmed, inoperable, previously untreated, measurable mCRC. Patients received irinotecan 180 mg m−2 on day 1, oxaliplatin 100 mg m−2 on day 15 and UFT 250 mg m−2 plus LV 90 mg on days 1–21 every 28 days. The phase I/II study comprised 45 patients, 29 at the maximum tolerated dose (MTD). The response rate in 38 evaluable patients was 63% (95% confidence interval (CI): 49–80). Median time to progression and overall survival were 8.7 months (95% CI: 7.9–10.4) and 16.8 months (95% CI: 9.6–25.3), respectively. In the MTD group, one patient had grade 3 leucopaenia; one had grade 3 neutropaenia; three had grade 3 diarrhoea; and one had grade 3 neurotoxicity. No hand–foot syndrome grade >1 was seen. In total, 67% of eligible patients received second-line therapy. UFT plus LV with alternating irinotecan and oxaliplatin is an efficacious first-line treatment for mCRC, with minimal neurotoxicity and hand–foot syndrome

Leukocyte Attraction by CCL20 and Its Receptor CCR6 in Humans and Mice with Pneumococcal Meningitis

We previously identified CCL20 as an early chemokine in the cerebrospinal fluid (CSF) of patients with pneumococcal meningitis but its functional relevance was unknown. Here we studied the role of CCL20 and its receptor CCR6 in pneumococcal meningitis. In a prospective nationwide study, CCL20 levels were significantly elevated in the CSF of patients with pneumococcal meningitis and correlated with CSF leukocyte counts. CCR6 deficient mice with pneumococcal meningitis and WT mice with pneumococcal meningitis treated with anti-CCL20 antibodies both had reduced CSF white blood cell counts. The reduction in CSF pleocytosis was also accompanied by an increase in brain bacterial titers. Additional in vitro experiments showed direct chemoattractant activity of CCL20 for granulocytes. In summary, our results identify the CCL20-CCR6 axis as an essential component of the innate immune defense against pneumococcal meningitis, controlling granulocyte recruitment