Group Chase and Escape

We describe here a new concept of one group chasing another, called "group chase and escape", by presenting a simple model. We will show that even a simple model can demonstrate rather rich and complex behavior. In particular, there are cases in which an optimal number of chasers exists for a given number of escapees (or targets) to minimize the cost of catching all targets. We have also found an indication of self-organized spatial structures formed by both groups.Comment: 13 pages, 12 figures, accepted and to appear in New Journal of Physic

Methotrexate: Underused and Ignored?

For greater than a decade, methotrexate has been known to be an effective therapeutic agent in the treatment of steroid dependent active Crohn's disease. However, international data on medication utilization suggest that this drug is rarely used in clinical practice for an indication of Crohn's disease. This review investigates the potential reasons for the underuse of methotrexate in patients with inflammatory bowel diseases

Use of Biologics in Pouchitis: A Systematic Review

Data about the effectiveness of biologics, including anti-TNF therapy and anti-integrin strategies, in antibiotic refractory pouchitis or Crohn’s disease-associated pouch complications are sparse. We performed a systematic review of the literature in Medline and Web of Science. All English language publications and meeting abstracts describing patients with pouchitis treated with anti-TNF or anti-integrin therapies were included. We identified a total of 17 papers and 2 abstracts, most of these retrospective case series, including a total of 192 patients treated either with infliximab (IFX; n=140) or adalimumab (ADA; n=52). No reports were found for anti-integrin therapies or other anti-TNF agents such as certolizumab pegol or golimumab. Due to the heterogeneity of the studies, small numbers of patients, differing co-treatments and subjective outcome definitions, the exact efficacy of these biologic therapies cannot be assessed in a combined fashion. Overall IFX appears to have good clinical effectiveness in selected patients achieving up to 80% short and around 50% long-term response, whereas the few data available for ADA are not sufficient to draw valid conclusions. Larger prospectively collected multi-center data with clearly defined inclusion criteria and outcomes are necessary to better define the clinical value of anti-TNF therapy in patients with antibiotic refractory pouchitis or Crohn’s-like complications of the pouch

Efficacy of methotrexate in ulcerative colitis: Failure or promise

Low-dose methotrexate is a widely used and efficacious therapy in chronic inflammatory disorders such as psoriasis and rheumatoid arthritis. Prospective randomized controlled trials have demonstrated the efficacy of parenteral methotrexate in Crohn’s disease (CD). We performed a systematic review of the efficacy of methotrexate in ulcerative colitis (UC) and discuss the results in the context of the known pharmacokinetics and adverse events of methotrexate therapy in inflammatory bowel diseases and other inflammatory conditions

A Randomized, Placebo-Controlled, Phase II Study of Tetomilast in Active Ulcerative Colitis

BACKGROUND & AIMS: Tetomilast (OPC-6535), a novel thiazole compound, inhibits phosphodiesterase-4 and proinflammatory functions of leukocytes including superoxide production and cytokine release. METHODS: One hundred eighty-six patients with mildly to moderately active ulcerative colitis (Disease Activity Index [DAI] 4-11 points) from 35 centers were randomized to receive an oral, once-daily dose of placebo or tetomilast 25 mg or 50 mg for 8 weeks. RESULTS: Percentages of patients reaching the primary end point (improvement as defined by reduction in DAI > or =3 at week 8) were not significantly different between placebo (35%) and either the 25 mg tetomilast (52%) or the 50 mg tetomilast (39%) groups (intent-to-treat population). Remission rates (DAI 0-1) were 7%, 16%, and 21%, respectively (not significant). Mean reduction in DAI at week 8 was greater in the 25-mg group than under placebo (2.8 +/- 0.4 vs 1.7 +/- 0.36, respectively, P = .041) and approached statistical significance in the 50-mg group (2.8 +/- 0.46, P = .056). A post hoc analysis focusing on patients with high activity scores (baseline DAI 7-11) suggested differences between tetomilast and placebo that will require further investigation. No significant safety concerns were raised. Main adverse effects included gastrointestinal problems (nausea, vomiting) and were preferentially seen in the 50-mg tetomilast group. CONCLUSIONS: This phase II trial of tetomilast in ulcerative colitis did not achieve statistical significance for the primary end point. Secondary end points indicate a potential clinical activity of tetomilast. The post hoc analysis suggests that further clinical development should focus on patients with objective parameters of inflammation

Direct measurement of antiferromagnetic domain fluctuations

Measurements of magnetic noise emanating from ferromagnets due to domain motion were first carried out nearly 100 years ago and have underpinned much science and technology. Antiferromagnets, which carry no net external magnetic dipole moment, yet have a periodic arrangement of the electron spins extending over macroscopic distances, should also display magnetic noise, but this must be sampled at spatial wavelengths of order several interatomic spacings, rather than the macroscopic scales characteristic of ferromagnets. Here we present the first direct measurement of the fluctuations in the nanometre-scale spin- (charge-) density wave superstructure associated with antiferromagnetism in elemental Chromium. The technique used is X-ray Photon Correlation Spectroscopy, where coherent x-ray diffraction produces a speckle pattern that serves as a "fingerprint" of a particular magnetic domain configuration. The temporal evolution of the patterns corresponds to domain walls advancing and retreating over micron distances. While the domain wall motion is thermally activated at temperatures above 100K, it is not so at lower temperatures, and indeed has a rate which saturates at a finite value - consistent with quantum fluctuations - on cooling below 40K. Our work is important because it provides an important new measurement tool for antiferromagnetic domain engineering as well as revealing a fundamental new fact about spin dynamics in the simplest antiferromagnet.Comment: 19 pages, 4 figure

A randomized, controlled, double-blind trial of air vs carbon dioxide insufflation during ERCP

Visualization during gastrointestinal endoscopy requires distention of the bowel lumen. Carbon dioxide (CO2) insufflation decreases post-procedure abdominal discomfort and distension after colonoscopy, but there have been few published studies on its use in endoscopic retrograde cholangiopancreatography (ERCP)

DIAPH3 Governs the Cellular Transition to the Amoeboid Tumour Phenotype

Therapies for most malignancies are generally ineffective once metastasis occurs. While tumour cells migrate through tissues using diverse strategies, the signalling networks controlling such behaviours in human tumours are poorly understood. Here we define a role for the Diaphanous-related formin-3 (DIAPH3) as a non-canonical regulator of metastasis that restrains conversion to amoeboid cell behaviour in multiple cancer types. The DIAPH3 locus is close to RB1, within a narrow consensus region of deletion on chromosome 13q in prostate, breast and hepatocellular carcinomas. DIAPH3 silencing in human carcinoma cells destabilized microtubules and induced defective endocytic trafficking, endosomal accumulation of EGFR, and hyperactivation of EGFR/MEK/ERK signalling. Silencing also evoked amoeboid properties, increased invasion and promoted metastasis in mice. In human tumours, DIAPH3 down-regulation was associated with aggressive or metastatic disease. DIAPH3-silenced cells were sensitive to MEK inhibition, but showed reduced sensitivity to EGFR inhibition. These findings have implications for understanding mechanisms of metastasis, and suggest that identifying patients with chromosomal deletions at DIAPH3 may have prognostic value

Solid stress facilitates spheroid formation: potential involvement of hyaluronan

When neoplastic cells grow in confined spaces in vivo, they exert a finite force on the surrounding tissue resulting in the generation of solid stress. By growing multicellular spheroids in agarose gels of defined mechanical properties, we have recently shown that solid stress inhibits the growth of spheroids and that this growth-inhibiting stress ranges from 45 to 120 mmHg. Here we show that solid stress facilitates the formation of spheroids in the highly metastatic Dunning R3327 rat prostate carcinoma AT3.1 cells, which predominantly do not grow as spheroids in free suspension. The maximum size and the growth rate of the resulting spheroids decreased with increasing stress. Relieving solid stress by enzymatic digestion of gels resulted in gradual loss of spheroidal morphology in 8 days. In contrast, the low metastatic variant AT2.1 cells, which grow as spheroids in free suspension as well as in the gels, maintained their spheroidal morphology even after stress removal. Histological examination revealed that most cells in AT2.1 spheroids are in close apposition whereas a regular matrix separates the cells in the AT3.1 gel spheroids. Staining with the hyaluronan binding protein revealed that the matrix between AT3.1 cells in agarose contained hyaluronan, while AT3.1 cells had negligible or no hyaluronan when grown in free suspension. Hyaluronan was found to be present in both free suspensions and agarose gel spheroids of AT2.1. We suggest that cell–cell adhesion may be adequate for spheroid formation, whereas solid stress may be required to form spheroids when cell–matrix adhesion is predominant. These findings have significant implications for tumour growth, invasion and metastasis