Prognostic Significance of Growth Kinetics in Newly Diagnosed Glioblastomas Revealed by Combining Serial Imaging with a Novel Biomathematical Model

Glioblastomas (GBMs) are the most aggressive primary brain tumors characterized by their rapid proliferation and diffuse infiltration of the brain tissue. Survival patterns in patients with GBM have been associated with a number of clinico-pathologic factors, including age and neurological status, yet a significant quantitative link to in vivo growth kinetics of each glioma has remained elusive. Exploiting a recently developed tool for quantifying glioma net proliferation and invasion rates in individual patients using routinely available magnetic resonance images (MRIs), we propose to link these patient-specific kinetic rates of biological aggressiveness to prognostic significance. Using our biologically-based mathematical model for glioma growth and invasion, examination of serial pre-treatment MRIs of 32 GBM patients allowed quantification of these rates for each patient’s tumor. Survival analyses revealed that even when controlling for standard clinical parameters (e.g., age, KPS) these model-defined parameters quantifying biologically aggressiveness (net proliferation and invasion rates) were significantly associated with prognosis. One hypothesis generated was that the ratio of the actual survival time after whatever therapies were employed to the duration of survival predicted (by the model) without any therapy would provide a “Therapeutic Response Index” (TRI) of the overall effectiveness of the therapies. The TRI may provided important information, not otherwise available, as to the effectiveness of the treatments in individual patients. To our knowledge, this is the first report indicating that dynamic insight from routinely obtained pre-treatment imaging may be quantitatively useful in characterizing survival of individual patients with GBM. Such a hybrid tool bridging mathematical modeling and clinical imaging may allow for statifying patients for clinical studies relative to their pretreatment biological aggressiveness

Targeting inflammation to reduce cardiovascular disease risk: a realistic clinical prospect?

Data from basic science experiments is overwhelmingly supportive of the causal role of immune-inflammatory response(s) at the core of atherosclerosis, and therefore the theoretical potential to manipulate the inflammatory response to prevent cardiovascular events. However, extrapolation to humans requires care and we still lack definitive evidence to show that interfering in immune-inflammatory processes may safely lessen clinical atherosclerosis. In this review, we discuss key therapeutic targets in the treatment of vascular inflammation, placing basic research in to a wider clinical perspective, as well as identifying outstanding questions

Entrepreneurial Orientation and the Family Firm: Mapping the Field and Tracing a Path for Future Research

ABSTRACT: Despite several calls for the further study of entrepreneurial orientation in family firms, we still have a fragmented understanding of this topic, whose full potential has yet to be reached. To shed new light on this issue, this article first maps the family business field by carrying out a systematic review and content analysis of the 78 articles identified at the confluence of entrepreneurial orientation and family firms. Our study describes and critically assesses previous research as well as the conclusions reached. Second, this article identifies the main research gaps and provides a path for future investigations

Sediment Micromorphology and Site Formation Processes During the Middle to Later Stone Ages at the Haua Fteah Cave, Cyrenaica, Libya

Understanding the timing, conditions, and characteristics of the Middle to Later Stone Age (MSA/LSA) transition in North Africa is critical for debates regarding the evolution and past population dynamics of Homo sapiens, especially their dispersals within, out of, and back into, Africa. As with many cultural transitions during the Palaeolithic, our understanding is based predominantly on archaeological and paleoenvironmental records preserved within a small number of deep cave sediment sequences. To use such sequences as chronological cornerstones we must develop a robust understanding of the formation processes that created them. This paper utilizes geoarchaeological analyses (field observations, sediment micromorphology, bulk sedimentology) to examine site formation processes and stratigraphic integrity during the MSA/LSA at the Haua Fteah cave, Libya, one of North Africa's longest cultural sequences. The depositional processes identified vary in mode and energy, from eolian deposition/reworking to mass colluvial mudflows. These changing processes impact greatly on the interpretation of the paleoenvironmental and archaeological records, not least in identifying potential colluvial sediment deposition and reworking in layers identified as containing the MSA/LSA transition. This study highlights the importance of developing geoarchaeological analyses of cultural sequences to fully unravel the limitations and potential of their contained archaeological and paleoenvironmental records.ERC, NER

Case-control study on uveal melanoma (RIFA): rational and design

BACKGROUND: Although a rare disease, uveal melanoma is the most common primary intraocular malignancy in adults, with an incidence rate of up to 1.0 per 100,000 persons per year in Europe. Only a few consistent risk factors have been identified for this disease. We present the study design of an ongoing incident case-control study on uveal melanoma (acronym: RIFA study) that focuses on radiofrequency radiation as transmitted by radio sets and wireless telephones, occupational risk factors, phenotypical characteristics, and UV radiation. METHODS/DESIGN: We conduct a case-control study to identify the role of different exposures in the development of uveal melanoma. The cases of uveal melanoma were identified at the Division of Ophthalmology, University of Essen, a referral centre for tumours of the eye. We recruit three control groups: population controls, controls sampled from those ophthalmologists who referred cases to the Division of Ophthalmology, University of Duisburg-Essen, and sibling controls. For each case the controls are matched on sex and age (five year groups), except for sibling controls. The data are collected from the study participants by short self-administered questionnaire and by telephone interview. During and at the end of the field phase, the data are quality-checked. To estimate the effect of exposures on uveal melanoma risk, we will use conditional logistic regression that accounts for the matching factors and allows to control for potential confounding

A Spitzer Study of Asymptotic Giant Branch Stars. III. Dust Production and Gas Return in Local Group Dwarf Irregular Galaxies

We present the third and final part of a census of Asymptotic Giant Branch (AGB) stars in Local Group dwarf irregular galaxies. Papers I and II presented the results for WLM and IC 1613. Included here are Phoenix, LGS 3, DDO 210, Leo A, Pegasus dIrr, and Sextans A. Spitzer photometry at 3.6, 4.5, 5.8, and 8 are presented, along with a more thorough treatment of background galaxy contamination than was presented in papers I and II. We find that at least a small population of completely optically obscured AGB stars exists in each galaxy, regardless of the galaxy's metallicity, but that higher-metallicity galaxies tend to harbor more stars with slight IR excesses. The optical incompleteness increases for the redder AGB stars, in line with the expectation that some AGB stars are not detected in the optical due to large amounts of extinction associated with in situ dust production. Overall, there is an underrepresentation of 30% - 40% in the optical AGB within the 1 sigma errors for all of the galaxies in our sample. This undetected population is large enough to affect star formation histories derived from optical color-magnitude diagrams. As measured from the [3.6] - [4.5] color excesses, we find average stellar mass-loss rates ranging from 3.1E-7 - 6.6E-6 solar masses per year, and integrated galaxy mass-loss rates ranging from 4.4E-5 - 1.4E-3 solar masses per year. The integrated mass-loss rate is sufficient to sustain the current star formation rate in only LGS 3 and DDO 210, requiring either significant non-dusty mass loss or gas accretion in Phoenix, Leo A, Pegasus dIrr, Sextans A, WLM, and IC 1613 if they are to maintain their status as gas-rich galaxies.Comment: 25 pages, 17 figures, 9 tables, Accepted for publication in ApJ; updated affiliation for Boye

The twilight of the Liberal Social Contract? On the Reception of Rawlsian Political Liberalism

This chapter discusses the Rawlsian project of public reason, or public justification-based 'political' liberalism, and its reception. After a brief philosophical rather than philological reconstruction of the project, the chapter revolves around a distinction between idealist and realist responses to it. Focusing on political liberalism’s critical reception illuminates an overarching question: was Rawls’s revival of a contractualist approach to liberal legitimacy a fruitful move for liberalism and/or the social contract tradition? The last section contains a largely negative answer to that question. Nonetheless the chapter's conclusion shows that the research programme of political liberalism provided and continues to provide illuminating insights into the limitations of liberal contractualism, especially under conditions of persistent and radical diversity. The programme is, however, less receptive to challenges to do with the relative decline of the power of modern states