Imaging oligometastatic cancer before local treatment

The term oligometastases is in common clinical use, but remains poorly defined. As novel treatment strategies widen the therapeutic window for patients defined as having oligometastatic cancer, improved biomarkers to reliably define patients who benefit from these treatments are needed. Multimodal imaging should be optimized to comprehensively assess the metastatic sites, disease burden and response to neoadjuvant treatment in each disease setting. These features will likely remain important prognostic biomarkers, and are critical in planning multidisciplinary treatment. There are opportunities to extract additional phenotypic information from conventional imaging, while novel imaging techniques can also image specific aspects of tumour biology. Imaging can both characterise and localise the phenotypic heterogeneity of multiple tumour sites. Novel approaches to existing imaging datasets, and correlation with tumour biology, will be important in realizing the potential of imaging to guide treatment in the oligometastatic setting. This article discusses the current status and future directions of imaging in patients with extracranial oligometastases

Explicit Renormalization Group for D=2 random bond Ising model with long-range correlated disorder

We investigate the explicit renormalization group for fermionic field theoretic representation of two-dimensional random bond Ising model with long-range correlated disorder. We show that a new fixed point appears by introducing a long-range correlated disorder. Such as the one has been observed in previous works for the bosonic ($\phi^4$) description. We have calculated the correlation length exponent and the anomalous scaling dimension of fermionic fields at this fixed point. Our results are in agreement with the extended Harris criterion derived by Weinrib and Halperin.Comment: 5 page

Explicit asymptotic modelling of transient Love waves propagated along a thin coating

The official published version can be obtained from the link below.An explicit asymptotic model for transient Love waves is derived from the exact equations of anti-plane elasticity. The perturbation procedure relies upon the slow decay of low-frequency Love waves to approximate the displacement field in the substrate by a power series in the depth coordinate. When appropriate decay conditions are imposed on the series, one obtains a model equation governing the displacement at the interface between the coating and the substrate. Unusually, the model equation contains a term with a pseudo-differential operator. This result is confirmed and interpreted by analysing the exact solution obtained by integral transforms. The performance of the derived model is illustrated by numerical examples.This work is sponsored by the grant from Higher Education of Pakistan and by the Brunel University’s “BRIEF” research award

Psychological characteristics of children with visual impairments: learning, memory and imagery

The performance of children (and sometimes adults) with visual impairments (VI) on a range of tasks that reflect learning, memory and mental imagery is considered in this article. Sometimes the evidence suggests that there are impairments in performance in comparison with typically developing children with vision and sometimes some advantages emerge. The author’s aim is to describe some of her own and others’ findings and explore what they tell us about the cognitive characteristics of such children, so that progress with practical interventions can be advanced through understanding. The article starts by focusing on social-cognitive development and in particular considers the potential benefits of language in that development. This is followed by a review of some studies of learning and memory performance which provide a coherent picture of development without vision and finally ends with a consideration of spatial mental imagery

Effect of food on the pharmacokinetics of oral MMI270B (CGS 27023A), a novel matrix metalloproteinase inhibitor

MMI270B is a matrix metalloproteinase inhibitor (MMPI) with in vitro and in vivo activity. To exert optimal target inhibition, MMPI must be given chronically, and therefore, oral bioavailability is important. We analyzed the effect of food intake on AUC0-8 h, Cmax, and Tmax. Seventeen patients were entered into the study. Doses of MMI270B were 150, 400, and 600 mg. The first day, patients ingested the drug in a fasted state and were not allowed to eat for 2 h. The second day, patients ingested the drug 30 min after a light breakfast. Mean AUC0-8 h was not significantly influenced by food intake. Plasma concentrations were well above the IC50 of several MMPs at all doses tested. Mean Cmax was significantly decreased after food intake. Mean Tmax was significantly delayed after food intake. Food intake did not result in a significant change in exposure to MMI270B (AUC0-8 h) but did result in a significant, although not clinically relevant, decrease in peak plasma levels and time to reach peak plasma levels. No specific guidelines concerning the ingestion of MMI270B in either a fed or a fasted state are recommended

Hypoxia regulates FGFR3 expression via HIF-1α and miR-100 and contributes to cell survival in non-muscle invasive bladder cancer

Background: Non-muscle invasive (NMI) bladder cancer is characterised by increased expression and activating mutations of FGFR3. We have previously investigated the role of microRNAs in bladder cancer and have shown that FGFR3 is a target of miR-100. In this study, we investigated the effects of hypoxia on miR-100 and FGFR3 expression, and the link between miR-100 and FGFR3 in hypoxia. Methods: Bladder cancer cell lines were exposed to normoxic or hypoxic conditions and examined for the expression of FGFR3 by quantitative PCR (qPCR) and western blotting, and miR-100 by qPCR. The effect of FGFR3 and miR-100 on cell viability in twodimensional (2-D) and three-dimensional (3-D) was examined by transfecting siRNA or mimic-100, respectively. Results: In NMI bladder cancer cell lines, FGFR3 expression was induced by hypoxia in a transcriptional and HIF-1a-dependent manner. Increased FGFR3 was also in part dependent on miR-100 levels, which decreased in hypoxia. Knockdown of FGFR3 led to a decrease in phosphorylation of the downstream kinases mitogen-activated protein kinase (MAPK) and protein kinase B (PKB), which was more pronounced under hypoxic conditions. Furthermore, transfection of mimic-100 also decreased phosphorylation of MAPK and PKB. Finally, knocking down FGFR3 profoundly decreased 2-D and 3-D cell growth, whereas introduction of mimic-100 decreased 3-D growth of cells. Conclusion: Hypoxia, in part via suppression of miR-100, induces FGFR3 expression in bladder cancer, both of which have an important role in maintaining cell viability under conditions of stress

Providing the Context for Intentional Learning

This article is written in response to Sharon Derry's article “Remediating Academic Difficulties Through Strategy Training: The Acquisition of Useful Knowledge.” The features of effective strategy instruction, to which Derry refers, are illustrated by examining the nature of the decisions the teacher confronts; specifically, determining the purposes of instruction, the context in which instruction occurs, and the roles of the teacher and students in instruction.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/69150/2/10.1177_074193259001100608.pd

A first-in-human phase I study to determine the maximum tolerated dose of the oral Src/ABL inhibitor AZD0424

BACKGROUND: Src is involved in cancer invasion and metastasis. AZD0424, an oral inhibitor of Src and ABL1, has shown evidence of anti-tumour activity in pre-clinical studies. METHODS: A phase Ia, dose escalation study was performed to assess the safety of continuous oral dosing with AZD0424 in advanced solid tumours. Secondary objectives included investigation of AZD0424 pharmacokinetics, effect on Src activity using markers of bone turnover, and anti-tumour activity. RESULTS: 41 patients were treated; 34 received AZD0424 once-daily at doses ranging from 5 mg to 150 mg, and 7 received 40 mg bi-daily 41.5% of patients experienced at least one AZD0424-related adverse event that was Grade 3-5 in severity, with patients treated at doses above 60 mg per day experiencing multiple treatment-related toxicities. The most commonly observed AZD0424-related adverse events were nausea, fatigue, anorexia and alopecia. Cmaxand AUC increased linearly with dose and the mean±standard deviation t1/2was 8.4±2.8 h. Clear evidence of Src target inhibition was seen at doses ⩾20 mg per day. No responses were observed and 7 patients (17.1%) achieved stable disease lasting 6 weeks or more. CONCLUSIONS: AZD0424 displayed no evidence of efficacy as monotherapy despite a clear pharmacodynamic effect. Further evaluation of AZD0424 monotherapy in patients with solid tumours is not recommended

Comment on "Short-range magnetic interactions in the spin-ice compound Ho2Ti2O7"

In their recent communication (Phys. Rev. B 64, 060406(R) (2001)) Cornelius and Gardner have reported the results of magnetization and susceptibility studies on single crystals of the pyrochlore Ho2Ti2O7. The observed field dependence of magnetization is totally unexpected, as it seems to suggest that the magnetic moments in this compound do not obey the 'ice-rule'. We have re-measured the magnetization curves for Ho2Ti2O7 single crystal for the three principal directions of an applied magnetic field and found nearly perfect agreement with the predictions for a nearest-neighbor spin-ice model.Comment: comment on Phys. Rev. B 64, 060406(R) (2001

Bosonic Excitations in Random Media

We consider classical normal modes and non-interacting bosonic excitations in disordered systems. We emphasise generic aspects of such problems and parallels with disordered, non-interacting systems of fermions, and discuss in particular the relevance for bosonic excitations of symmetry classes known in the fermionic context. We also stress important differences between bosonic and fermionic problems. One of these follows from the fact that ground state stability of a system requires all bosonic excitation energy levels to be positive, while stability in systems of non-interacting fermions is ensured by the exclusion principle, whatever the single-particle energies. As a consequence, simple models of uncorrelated disorder are less useful for bosonic systems than for fermionic ones, and it is generally important to study the excitation spectrum in conjunction with the problem of constructing a disorder-dependent ground state: we show how a mapping to an operator with chiral symmetry provides a useful tool for doing this. A second difference involves the distinction for bosonic systems between excitations which are Goldstone modes and those which are not. In the case of Goldstone modes we review established results illustrating the fact that disorder decouples from excitations in the low frequency limit, above a critical dimension $d_c$, which in different circumstances takes the values $d_c=2$ and $d_c=0$. For bosonic excitations which are not Goldstone modes, we argue that an excitation density varying with frequency as $\rho(\omega) \propto \omega^4$ is a universal feature in systems with ground states that depend on the disorder realisation. We illustrate our conclusions with extensive analytical and some numerical calculations for a variety of models in one dimension