PD-0283: 4D dose accumulation for dose painting by numbers for lung cancer

In conventional radiotherapy of locally advanced lung cancer (LALC) doses levels are homogeneously delivered to the entire PTV, whereat dose escalation is restricted by normal tissue toxicity. Several studies have shown the geometrical correlation between high FDG uptake in a PET scan and tumour recurrence. This is the rationale for FDG-based local dose escalation, e.g. by dose prescription on the voxel values of a PET scan – dose painting by numbers (DPBN). The aim of this study is to investigate the robustness of the DPBN plans against tumour motio

Screening Breakdown on the Route toward the Metal-Insulator Transition in Modulation Doped Si/SiGe Quantum Wells

Exploiting the spin resonance of two-dimensional (2D) electrons in SiGe/Si quantum wells we determine the carrier-density-dependence of the magnetic susceptibility. Assuming weak interaction we evaluate the density of states at the Fermi level D(E_F), and the screening wave vector, q_TF. Both are constant at higher carrier densities n, as for an ideal 2D carrier gas. For n < 3e11 cm-2, they decrease and extrapolate to zero at n = 7e10 cm-2. Calculating the mobility from q_TF yields good agreement with experimental values justifying the approach. The decrease in D(E_F) is explained by potential fluctuations which lead to tail states that make screening less efficient and - in a positive feedback - cause an increase of the potential fluctuations. Even in our high mobility samples the fluctuations exceed the electron-electron interaction leading to the formation of puddles of mobile carriers with at least 1 micrometer diameter.Comment: 4 pages, 3 figure

The significance of macrophage polarization subtypes for animal models of tissue fibrosis and human fibrotic diseases.

The systemic and organ-specific human fibrotic disorders collectively represent one of the most serious health problems world-wide causing a large proportion of the total world population mortality. The molecular pathways involved in their pathogenesis are complex and despite intensive investigations have not been fully elucidated. Whereas chronic inflammatory cell infiltration is universally present in fibrotic lesions, the central role of monocytes and macrophages as regulators of inflammation and fibrosis has only recently become apparent. However, the precise mechanisms involved in the contribution of monocytes/macrophages to the initiation, establishment, or progression of the fibrotic process remain largely unknown. Several monocyte and macrophage subpopulations have been identified, with certain phenotypes promoting inflammation whereas others display profibrotic effects. Given the unmet need for effective treatments for fibroproliferative diseases and the crucial regulatory role of monocyte/macrophage subpopulations in fibrogenesis, the development of therapeutic strategies that target specific monocyte/macrophage subpopulations has become increasingly attractive. We will provide here an overview of the current understanding of the role of monocyte/macrophage phenotype subpopulations in animal models of tissue fibrosis and in various systemic and organ-specific human fibrotic diseases. Furthermore, we will discuss recent approaches to the design of effective anti-fibrotic therapeutic interventions by targeting the phenotypic differences identified between the various monocyte and macrophage subpopulations

Length of migration and eating habits of Portuguese university students living in London, United Kingdom

Several studies have pointed adverse effects of long term migration on eating habits. Research is needed to understand if this effect occurs also with a short length of migration, as is the case of international students. Our aim was to evaluate the effect of short and long term migration on eating habits of Portuguese university students. Participants were 46 English and 55 Portuguese students from universities in London, United Kingdom. The findings from this study highlight the difficulties that Portuguese students faced in maintaining a traditional Mediterranean diet after moving to a Northern European environment

Food consumption trends and drivers

A picture of food consumption (availability) trends and projections to 2050, both globally and for different regions of the world, along with the drivers largely responsible for these observed consumption trends are the subject of this review. Throughout the world, major shifts in dietary patterns are occurring, even in the consumption of basic staples towards more diversified diets. Accompanying these changes in food consumption at a global and regional level have been considerable health consequences. Populations in those countries undergoing rapid transition are experiencing nutritional transition. The diverse nature of this transition may be the result of differences in socio-demographic factors and other consumer characteristics. Among other factors including urbanization and food industry marketing, the policies of trade liberalization over the past two decades have implications for health by virtue of being a factor in facilitating the ‘nutrition transition’ that is associated with rising rates of obesity and chronic diseases such as cardiovascular disease and cancer. Future food policies must consider both agricultural and health sectors, thereby enabling the development of coherent and sustainable policies that will ultimately benefit agriculture, human health and the environment

A systems model for immune cell interactions unravels the mechanism of inflammation in human skin

Inflammation is characterized by altered cytokine levels produced by cell populations in a highly interdependent manner. To elucidate the mechanism of an inflammatory reaction, we have developed a mathematical model for immune cell interactions via the specific, dose-dependent cytokine production rates of cell populations. The model describes the criteria required for normal and pathological immune system responses and suggests that alterations in the cytokine production rates can lead to various stable levels which manifest themselves in different disease phenotypes. The model predicts that pairs of interacting immune cell populations can maintain homeostatic and elevated extracellular cytokine concentration levels, enabling them to operate as an immune system switch. The concept described here is developed in the context of psoriasis, an immune-mediated disease, but it can also offer mechanistic insights into other inflammatory pathologies as it explains how interactions between immune cell populations can lead to disease phenotypes. © 2010 Valeyev et al

Dacarbazine (DTIC) versus vaccination with autologous peptide-pulsed dendritic cells (DC) in first-line treatment of patients with metastatic melanoma: a randomized phase III trial of the DC study group of the DeCOG

Background: This randomized phase III trial was designed to demonstrate the superiority of autologous peptide-loaded dendritic cell (DC) vaccination over standard dacarbazine (DTIC) chemotherapy in stage IV melanoma patients. Patients and methods: DTIC 850 mg/m2 intravenously was applied in 4-week intervals. DC vaccines loaded with MHC class I and II-restricted peptides were applied subcutaneously at 2-week intervals for the first five vaccinations and every 4 weeks thereafter. The primary study end point was objective response (OR); secondary end points were toxicity, overall (OS) and progression-free survival (PFS). Results: At the time of the first interim analysis 55 patients had been enrolled into the DTIC and 53 into the DC-arm (ITT). OR was low (DTIC: 5.5%, DC: 3.8%), but not significantly different in the two arms. The Data Safety & Monitoring Board recommended closure of the study. Unscheduled subset analyses revealed that patients with normal serum LDH and/or stage M1a/b survived longer in both arms than those with elevated serum LDH and/or stage M1c. Only in the DC-arm did those patients with (i) an initial unimpaired general health status (Karnofsky = 100) or (ii) an HLA-A2+/HLA-B44− haplotype survive significantly longer than patients with a Karnofsky index <100 (P = 0.007 versus P = 0.057 in the DTIC-arm) or other HLA haplotypes (P = 0.04 versus P = 0.57 in DTIC-treated patients). Conclusions: DC vaccination could not be demonstrated to be more effective than DTIC chemotherapy in stage IV melanoma patients. The observed association of overall performance status and HLA haplotype with overall survival for patients treated by DC vaccination should be tested in future trials employing DC vaccine