Spatial distribution of early red lesions is a risk factor for development of vision-threatening diabetic retinopathy

Aims/hypothesis Diabetic retinopathy is characterised by morphological lesions related to disturbances in retinal blood flow. It has previously been shown that the early development of retinal lesions temporal to the fovea may predict the development of treatment-requiring diabetic maculopathy. The aim of this study was to map accurately the area where lesions could predict progression to vision-threatening retinopathy. Methods The predictive value of the location of the earliest red lesions representing haemorrhages and/or microaneurysms was studied by comparing their occurrence in a group of individuals later developing vision-threatening diabetic retinopathy with that in a group matched with respect to diabetes type, age, sex and age of onset of diabetes mellitus who did not develop vision-threatening diabetic retinopathy during a similar observation period. Results The probability of progression to vision-threatening diabetic retinopathy was higher in a circular area temporal to the fovea, and the occurrence of the first lesions in this area was predictive of the development of vision-threatening diabetic retinopathy. The calculated peak value showed that the risk of progression was 39.5% higher than the average. There was no significant difference in the early distribution of lesions in participants later developing diabetic maculopathy or proliferative diabetic retinopathy. Conclusions/interpretation The location of early red lesions in diabetic retinopathy is predictive of whether or not individuals will later develop vision-threatening diabetic retinopathy. This evidence should be incorporated into risk models used to recommend control intervals in screening programmes for diabetic retinopathy

Effective Dark Matter Model: Relic density, CDMS II, Fermi LAT and LHC

The Cryogenic Dark Matter Search recently announced the observation of two signal events with a 77% confidence level. Although statistically inconclusive, it is nevertheless suggestive. In this work we present a model-independent analysis on the implication of a positive signal in dark matter scattering off nuclei. Assuming the interaction between (scalar, fermion or vector) dark matter and the standard model induced by unknown new physics at the scale $\Lambda$, we examine various dimension-6 tree-level induced operators and constrain them using the current experimental data, e.g. the WMAP data of the relic abundance, CDMS II direct detection of the spin-independent scattering, and indirect detection data (Fermi LAT cosmic gamma-ray), etc. Finally, the LHC reach is also explored

Analogue peptides for the immunotherapy of human acute myeloid leukemia

Accepted manuscript. The final publication is available at: http://link.springer.com/article/10.1007%2Fs00262-015-1762-9The use of peptide vaccines, enhanced by adjuvants, has shown some efficacy in clinical trials. However, responses are often short-lived and rarely induce notable memory responses. The reason is that self-antigens have already been presented to the immune system as the tumor develops, leading to tolerance or some degree of host tumor cell destruction. To try to break tolerance against self-antigens, one of the methods employed has been to modify peptides at the anchor residues to enhance their ability to bind major histocompatibility complex molecules, extending their exposure to the T-cell receptor. These modified or analogue peptides have been investigated as stimulators of the immune system in patients with different cancers with variable but sometimes notable success. In this review we describe the background and recent developments in the use of analogue peptides for the immunotherapy of acute myeloid leukemia describing knowledge useful for the application of analogue peptide treatments for other malignancies

f(R) theories

Over the past decade, f(R) theories have been extensively studied as one of the simplest modifications to General Relativity. In this article we review various applications of f(R) theories to cosmology and gravity - such as inflation, dark energy, local gravity constraints, cosmological perturbations, and spherically symmetric solutions in weak and strong gravitational backgrounds. We present a number of ways to distinguish those theories from General Relativity observationally and experimentally. We also discuss the extension to other modified gravity theories such as Brans-Dicke theory and Gauss-Bonnet gravity, and address models that can satisfy both cosmological and local gravity constraints.Comment: 156 pages, 14 figures, Invited review article in Living Reviews in Relativity, Published version, Comments are welcom

Detecting functional magnetic resonance imaging activation in white matter: Interhemispheric transfer across the corpus callosum

<p>Abstract</p> <p>Background</p> <p>It is generally believed that activation in functional magnetic resonance imaging (fMRI) is restricted to gray matter. Despite this, a number of studies have reported white matter activation, particularly when the corpus callosum is targeted using interhemispheric transfer tasks. These findings suggest that fMRI signals may not be neatly confined to gray matter tissue. In the current experiment, 4 T fMRI was employed to evaluate whether it is possible to detect white matter activation. We used an interhemispheric transfer task modelled after neurological studies of callosal disconnection. It was hypothesized that white matter activation could be detected using fMRI.</p> <p>Results</p> <p>Both group and individual data were considered. At liberal statistical thresholds (p < 0.005, uncorrected), group level activation was detected in the isthmus of the corpus callosum. This region connects the superior parietal cortices, which have been implicated previously in interhemispheric transfer. At the individual level, five of the 24 subjects (21%) had activation clusters that were located primarily within the corpus callosum. Consistent with the group results, the clusters of all five subjects were located in posterior callosal regions. The signal time courses for these clusters were comparable to those observed for task related gray matter activation.</p> <p>Conclusion</p> <p>The findings support the idea that, despite the inherent challenges, fMRI activation can be detected in the corpus callosum at the individual level. Future work is needed to determine whether the detection of this activation can be improved by utilizing higher spatial resolution, optimizing acquisition parameters, and analyzing the data with tissue specific models of the hemodynamic response. The ability to detect white matter fMRI activation expands the scope of basic and clinical brain mapping research, and provides a new approach for understanding brain connectivity.</p

Dilaton dominance relaxes LHC and cosmological constraints in supersymmetric models

It has been pointed out recently that the presence of dilaton field in the early Universe can dilute the neutralino dark matter (DM) abundance, if Universe is not radiation dominated at DM decoupling, due to its dissipative-like coupling to DM. In this scenario two basic mechanisms compete, the modified Hubble expansion rate tending to increase the relic density and a dissipative force that tends to decrease it. The net effect can lead to an overall dramatic decrease of the predicted relic abundance, sometimes by amounts of the order of O(10^2) or so. This feature is rather generic, independent of any particular assumption on the underlying string dynamics, provided dilaton dominates at early eras after the end of inflation but before Big Bang Nucleosynthesis (BBN). The latter ensures that BBN is not upset by the presence of the dilaton. In this paper, within the context of such a scenario, we study the phenomenology of the constrained minimal supersymmetric model (CMSSM) by taking into account all recent experimental constraints, including those from the LHC searches. We find that the allowed parameter space is greatly enlarged and includes regions that are beyond the reach of LHC. The allowed regions are compatible with Direct Dark Matter searches since the small neutralino annihilation rates, that are now in accord with the cosmological data on the relic density, imply small neutralino-nucleon cross sections below the sensitivities of the Direct Dark Matter experiments. It is also important that the new cosmologically accepted regions are compatible with Higgs boson masses larger than 120 GeV, as it is indicated from the LHC experimental data. The smaller annihilation cross sections needed to explain WMAP data require that the detector performances of current and planned indirect DM search experiments through gamma rays should be greatly improved in order to probe the CMSSM regions.Comment: 20 pages, 10 eps figures. Revised and extended version to appear in JHEP; a section on gamma rays adde

The influence of learning styles on knowledge acquisition in public sector management

This research note outlines a project designed to investigate the role of training institutions in providing effective training and development programmes for managers. The investigation is being carried out in the light of recent criticisms levelled against the nature of formal learning environments prevalent in most institutional settings. The traditional role of trainers and developers as the providers of knowledge and skills for the development of competent managers runs contrary to recent findings, which suggest that managers learn more effectively in informal settings, rather than the formal settings evident in many development programmes. The idea that explicitly extracted competencies are the target every manager should aim for to improve their effectiveness is also challenged because competencies alone are no longer regarded as a sufficient criterion for success. Recent research has attached greater importance to the need for helping managers to see knowledge as a social phenomenon, and one factor that might distinguish successful managers from others is tacit knowledge (Wagner & Sternberg, 1987; Argyris, 1999). A major focus of this study is to explore the possibility that the level and content of tacit knowledge acquired by managers may be influenced by their individual learning styles, and the degree to which their dominant styles are matched with the context of their work environment

R1507, an Anti-Insulin-Like Growth Factor-1 Receptor (IGF-1R) Antibody, and EWS/FLI-1 siRNA in Ewing's Sarcoma: Convergence at the IGF/IGFR/Akt Axis

A subset of patients with Ewing's sarcoma responds to anti-insulin-like growth factor-1 receptor (IGF-1R) antibodies. Mechanisms of sensitivity and resistance are unknown. We investigated whether an anti-IGF-1R antibody acts via a pathway that could also be suppressed by small interfering (si) RNA against the EWS/FLI-1 fusion protein, the hallmark of Ewing's sarcoma. The growth of two Ewing's sarcoma cell lines (TC-32 and TC-71) was inhibited by the fully human anti-IGF-1R antibody, R1507 (clonogenic and MTT assays). TC-32 and TC-71 cells express high levels of IGF-2, while RD-ES and A4573 Ewing's cell lines, which were less responsive to R1507 in our assays, express low or undetectable IGF-2, respectively. TC-71 cells also expressed high levels of IGF-1R, and R1507 decreased steady-state levels of this receptor by internalization/degradation, an effect which was associated with a decrease in p-IGF-1R, p-IRS-1, and p-Akt. EWS/FLI-1 siRNA also decreased p-Akt, due to its ability to increase IGF-BP3 levels and subsequently decrease IGF-1 and IGF-2 levels, thus inhibiting signaling through p-IGF-1R. This inhibition correlated with growth suppression and apoptosis. The attenuation of Akt activation was confirmed in TC-71 and HEK-293 (human embryonic kidney) cells by transfecting them with IGF-1R siRNA. We conclude that antibodies and siRNA to IGF-1R, as well as siRNA to EWS/FLI-1, act via intersecting IGF/IGF-1R signals that suppress a common point in this pathway, namely the phosphorylation of Akt

Factors confounding the assessment of reflection: a critical review

BACKGROUND: Reflection on experience is an increasingly critical part of professional development and lifelong learning. There is, however, continuing uncertainty about how best to put principle into practice, particularly as regards assessment. This article explores those uncertainties in order to find practical ways of assessing reflection. DISCUSSION: We critically review four problems: 1. Inconsistent definitions of reflection; 2. Lack of standards to determine (in)adequate reflection; 3. Factors that complicate assessment; 4. Internal and external contextual factors affecting the assessment of reflection. SUMMARY: To address the problem of inconsistency, we identified processes that were common to a number of widely quoted theories and synthesised a model, which yielded six indicators that could be used in assessment instruments. We arrived at the conclusion that, until further progress has been made in defining standards, assessment must depend on developing and communicating local consensus between stakeholders (students, practitioners, teachers, supervisors, curriculum developers) about what is expected in exercises and formal tests. Major factors that complicate assessment are the subjective nature of reflection's content and the dependency on descriptions by persons being assessed about their reflection process, without any objective means of verification. To counter these validity threats, we suggest that assessment should focus on generic process skills rather than the subjective content of reflection and where possible to consider objective information about the triggering situation to verify described reflections. Finally, internal and external contextual factors such as motivation, instruction, character of assessment (formative or summative) and the ability of individual learning environments to stimulate reflection should be considered