Report on short-term side effects of treatments with 177Lu- octreotate in combination with capecitabine in seven patients with gastroenteropancreatic neuroendocrine tumours

Purpose: Treatment with the radiolabelled somatostatin analogue177Lu-octreotate results in tumour remission in 47% of patients with gastroenteropancreatic neuroendocrine tumours. Adding capecitabine to177Lu-octreotate, as a radio-sensitiser, may enhance these anti-tumour effects. We now present the short-term toxicity profile of this novel combination. Methods: Seven patients were treated with 7.4 GBq177Lu-octreotate and capecitabine (1650 mg/m2per day) for 2 weeks with an intended number of four cycles. Toxicity, and especially haematological and renal parameters, were monitored on a weekly basis for the first two cycles and 4 and 6 weeks after subsequent cycles. Results: None of the patients had hand-foot syndrome. One patient had grade 1 stomatitis occurring after one of four cycles. Grade 3 or 4 leukopenia or neutropenia did not occur. One patient had grade 3 anaemia, but none had grade 4 anaemia. One patient had grade 2 thrombocytopenia after the fourth cycle, and one had grade 3 thrombocytopenia. Grade 4 thrombocytopenia did not occur. No significant changes in serum creatinine levels were observed. None of the patients had symptoms of cardiac ischaemia. Conclusions: Treatment with the combination of177Lu-octreotate and capecitabine was feasible and safe considering acute and subacute side effects. We therefore started a randomised, controlled clinical trial to compare this combination with177Lu-octreotate as single agent with regard to anti-tumour effects and side effects

Stability of Spatial Optical Solitons

We present a brief overview of the basic concepts of the soliton stability theory and discuss some characteristic examples of the instability-induced soliton dynamics, in application to spatial optical solitons described by the NLS-type nonlinear models and their generalizations. In particular, we demonstrate that the soliton internal modes are responsible for the appearance of the soliton instability, and outline an analytical approach based on a multi-scale asymptotic technique that allows to analyze the soliton dynamics near the marginal stability point. We also discuss some results of the rigorous linear stability analysis of fundamental solitary waves and nonlinear impurity modes. Finally, we demonstrate that multi-hump vector solitary waves may become stable in some nonlinear models, and discuss the examples of stable (1+1)-dimensional composite solitons and (2+1)-dimensional dipole-mode solitons in a model of two incoherently interacting optical beams.Comment: 34 pages, 9 figures; to be published in: "Spatial Optical Solitons", Eds. W. Torruellas and S. Trillo (Springer, New York

Conscious monitoring and control (reinvestment) in surgical performance under pressure.

Research on intraoperative stressors has focused on external factors without considering individual differences in the ability to cope with stress. One individual difference that is implicated in adverse effects of stress on performance is "reinvestment," the propensity for conscious monitoring and control of movements. The aim of this study was to examine the impact of reinvestment on laparoscopic performance under time pressure

Magnetorheology in an aging, yield stress matrix fluid

Field-induced static and dynamic yield stresses are explored for magnetorheological (MR) suspensions in an aging, yield stress matrix fluid composed of an aqueous dispersion of Laponite® clay. Using a custom-built magnetorheometry fixture, the MR response is studied for magnetic field strengths up to 1 T and magnetic particle concentrations up to 30 v%. The yield stress of the matrix fluid, which serves to inhibit sedimentation of dispersed carbonyl iron magnetic microparticles, is found to have a negligible effect on the field-induced static yield stress for sufficient applied fields, and good agreement is observed between field-induced static and dynamic yield stresses for all but the lowest field strengths and particle concentrations. These results, which generally imply a dominance of inter-particle dipolar interactions over the matrix fluid yield stress, are analyzed by considering a dimensionless magnetic yield parameter that quantifies the balance of stresses on particles. By characterizing the applied magnetic field in terms of the average particle magnetization, a rheological master curve is generated for the field-induced static yield stress that indicates a concentration–magnetization superposition. The results presented herein will provide guidance to formulators of MR fluids and designers of MR devices who require a field-induced static yield stress and a dispersion that is essentially indefinitely stable to sedimentation.Petroleum Research Fund (ACS-PRF Grant No. 49956-ND9)American Chemical Society (ACS-PRF Grant No. 49956-ND9

Molecular crowding defines a common origin for the Warburg effect in proliferating cells and the lactate threshold in muscle physiology

Aerobic glycolysis is a seemingly wasteful mode of ATP production that is seen both in rapidly proliferating mammalian cells and highly active contracting muscles, but whether there is a common origin for its presence in these widely different systems is unknown. To study this issue, here we develop a model of human central metabolism that incorporates a solvent capacity constraint of metabolic enzymes and mitochondria, accounting for their occupied volume densities, while assuming glucose and/or fatty acid utilization. The model demonstrates that activation of aerobic glycolysis is favored above a threshold metabolic rate in both rapidly proliferating cells and heavily contracting muscles, because it provides higher ATP yield per volume density than mitochondrial oxidative phosphorylation. In the case of muscle physiology, the model also predicts that before the lactate switch, fatty acid oxidation increases, reaches a maximum, and then decreases to zero with concomitant increase in glucose utilization, in agreement with the empirical evidence. These results are further corroborated by a larger scale model, including biosynthesis of major cell biomass components. The larger scale model also predicts that in proliferating cells the lactate switch is accompanied by activation of glutaminolysis, another distinctive feature of the Warburg effect. In conclusion, intracellular molecular crowding is a fundamental constraint for cell metabolism in both rapidly proliferating- and non-proliferating cells with high metabolic demand. Addition of this constraint to metabolic flux balance models can explain several observations of mammalian cell metabolism under steady state conditions

A formative study exploring perceptions of physical activity and physical activity monitoring among children and young people with cystic fibrosis and health care professionals

Background: Physical activity (PA) is associated with reduced hospitalisations and maintenance of lung function in patients with Cystic Fibrosis (CF). PA is therefore recommended as part of standard care. Despite this, there is no consensus for monitoring of PA and little is known about perceptions of PA monitoring among children and young people with CF. Therefore, the research aimed to explore patients’ perceptions of PA and the acceptability of using PA monitoring devices with children and young people with CF. Methods: An action research approach was utilised, whereby findings from earlier research phases informed subsequent phases. Four phases were utilised, including patient interviews, PA monitoring, follow-up patient interviews and health care professional (HCP) interviews. Subsequently, an expert panel discussed the study to develop recommendations for practice and future research. Results: Findings suggest that experiences of PA in children and young people with CF are largely comparable to their non-CF peers, with individuals engaging in a variety of activities. CF was not perceived as a barrier per se, although participants acknowledged that they could be limited by their symptoms. Maintenance of health emerged as a key facilitator, in some cases PA offered patients the opportunity to ‘normalise’ their condition. Participants reported enjoying wearing the monitoring devices and had good compliance. Wrist-worn devices and devices providing feedback were preferred. HCPs recognised the potential benefits of the devices in clinical practice. Recommendations based on these findings are that interventions to promote PA in children and young people with CF should be individualised and involve families to promote PA as part of an active lifestyle. Patients should receive support alongside the PA data obtained from monitoring devices. Conclusions: PA monitoring devices appear to be an acceptable method for objective assessment of PA among children and young people with CF and their clinicians. Wrist-worn devices, which are unobtrusive and can display feedback, were perceived as most acceptable. By understanding the factors impacting PA, CF health professionals will be better placed to support patients and improve health outcomes

Observation of Coherent Elastic Neutrino-Nucleus Scattering

The coherent elastic scattering of neutrinos off nuclei has eluded detection for four decades, even though its predicted cross-section is the largest by far of all low-energy neutrino couplings. This mode of interaction provides new opportunities to study neutrino properties, and leads to a miniaturization of detector size, with potential technological applications. We observe this process at a 6.7-sigma confidence level, using a low-background, 14.6-kg CsI[Na] scintillator exposed to the neutrino emissions from the Spallation Neutron Source (SNS) at Oak Ridge National Laboratory. Characteristic signatures in energy and time, predicted by the Standard Model for this process, are observed in high signal-to-background conditions. Improved constraints on non-standard neutrino interactions with quarks are derived from this initial dataset

Observation of the Baryonic Flavor-Changing Neutral Current Decay Lambda_b -> Lambda mu+ mu-

We report the first observation of the baryonic flavor-changing neutral current decay Lambda_b -> Lambda mu+ mu- with 24 signal events and a statistical significance of 5.8 Gaussian standard deviations. This measurement uses ppbar collisions data sample corresponding to 6.8fb-1 at sqrt{s}=1.96TeV collected by the CDF II detector at the Tevatron collider. The total and differential branching ratios for Lambda_b -> Lambda mu+ mu- are measured. We find B(Lambda_b -> Lambda mu+ mu-) = [1.73+-0.42(stat)+-0.55(syst)] x 10^{-6}. We also report the first measurement of the differential branching ratio of B_s -> phi mu+ mu- using 49 signal events. In addition, we report branching ratios for B+ -> K+ mu+ mu-, B0 -> K0 mu+ mu-, and B -> K*(892) mu+ mu- decays.Comment: 8 pages, 2 figures, 4 tables. Submitted to Phys. Rev. Let

Shipping as a Knowledge Industry: Research and Strategic Planning at Ocean Group

This chapter approaches the question of how transformations in the world of shipping relate to wider trends in business and general history through the lens of knowledge. It will investigate how technological and managerial knowledge was created, developed and exploited as a corporate resource from the 1950s onwards in Ocean Transport and Trading, one of the UK’s leading liner shipping firms. The chapter will, first, briefly discuss the resource-based view of the firm and the importance of knowledge as a corporate resource. It will then examine Ocean’s use of technological and operational knowledge in the post-war era. The following section examines the introduction of modern management concepts at Ocean from the late 1960s and their impact on corporate strategy. In conclusion, the chapter will argue that the introduction of managerial concepts of knowledge contributed to Ocean’s gradual withdrawal from shipping and transformation into a provider of global logistics services and that analyzing shipping as a knowledge industry helps make sense of the transformation of the industry

Geography of non-melanoma skin cancer and ecological associations with environmental risk factors in England.

This is the author's peer reviewed version of the article. Please cite the published, final version which is available via the DOI link in this record.This study investigates the geography of non-melanoma skin cancer (NMSC) in England, and ecological associations with three widespread environmental hazards: radon, arsenic and ultraviolet radiation from the sun.European Regional Development FundEuropean Social Fund Convergence Programme for Cornwall and the Isles of Scill