Accelerated partial irradiation for breast cancer: Systematic review and meta-analysis of 8653 women in eight randomized trials

Background and purpose: Accelerated partial breast irradiation (APBI) is the strategy that allows adjuvant treatment delivery in a shorter period of time in smaller volumes. This study was undertaken to assess the effectiveness and outcomes of APBI in breast cancer compared with whole-breast irradiation (WBI). Material and methods: Systematic review and meta-analysis of randomized controlled trials of WBI versus APBI. Two authors independently selected and assessed the studies regarding eligibility criteria. Results: Eight studies were selected. A total of 8653 patients were randomly assigned for WBI versus APBI. Six studies reported local recurrence outcomes. Two studies were matched in 5 years and only one study for different time of follow-up. Meta-analysis of two trials assessing 1407 participants showed significant difference in the WBI versus APBI group regarding the 5-year local recurrence rate (HR = 4.54, 95% CI: 1.78-11.61, p = 0.002). Significant difference in favor of WBI for different follow-up times was also found. No differences in nodal recurrence, systemic recurrence, overall survival and mortality rates were observed. Conclusions: APBI is associated with higher local recurrence compared to WBI without compromising other clinical outcomes. (C) 2014 Elsevier Ireland Ltd. All rights reserved.

External Examining: an Engineering Subject Centre guide.

This handbook was prepared for external examiners and for use in training workshops for newly appointed external examiners.

Dynamical Systems in the Sensorimotor Loop: On the Interrelation Between Internal and External Mechanisms of Evolved Robot Behavior

Huelse, M., Wischmann, S., Manoonpong, P., Twickel, A.v., Pasemann, F.: Dynamical Systems in the Sensorimotor Loop: On the Interrelation Between Internal and External Mechanisms of Evolved Robot Behavior. In: M. Lungarella, F. Iida, J. Bongard, R. Pfeifer (Eds.) 50 Years of Artificial Intelligence, LNCS 4850, Springer, 186 - 195, 2007.

Growth hormone mitigates against lethal irradiation and enhances hematologic and immune recovery in mice and nonhuman primates.

Medications that can mitigate against radiation injury are limited. In this study, we investigated the ability of recombinant human growth hormone (rhGH) to mitigate against radiation injury in mice and nonhuman primates. BALB/c mice were irradiated with 7.5 Gy and treated post-irradiation with rhGH intravenously at a once daily dose of 20 microg/dose for 35 days. rhGH protected 17 out of 28 mice (60.7%) from lethal irradiation while only 3 out of 28 mice (10.7%) survived in the saline control group. A shorter course of 5 days of rhGH post-irradiation produced similar results. Compared with the saline control group, treatment with rhGH on irradiated BALB/c mice significantly accelerated overall hematopoietic recovery. Specifically, the recovery of total white cells, CD4 and CD8 T cell subsets, B cells, NK cells and especially platelets post radiation exposure were significantly accelerated in the rhGH-treated mice. Moreover, treatment with rhGH increased the frequency of hematopoietic stem/progenitor cells as measured by flow cytometry and colony forming unit assays in bone marrow harvested at day 14 after irradiation, suggesting the effects of rhGH are at the hematopoietic stem/progenitor level. rhGH mediated the hematopoietic effects primarily through their niches. Similar data with rhGH were also observed following 2 Gy sublethal irradiation of nonhuman primates. Our data demonstrate that rhGH promotes hematopoietic engraftment and immune recovery post the exposure of ionizing radiation and mitigates against the mortality from lethal irradiation even when administered after exposure.

Development of Stimulus-Responsive Ligands for the Modulation of Copper and Iron Coordination

The ability to manipulate the coordination chemistry of metal ions has significant ramifications for the study and treatment of metal-related health concerns, including iron overload, UV skin damage, and microbial infection among many other conditions. To address this concern, chelating agents that change their metal binding characteristics in response to external stimuli have been synthesized and characterized by several spectroscopic and chromatographic analytical methods. The primary stimuli of interest for this work are light and hydrogen peroxide.

Herein we report the previously unrecognized photochemistry of aroylhydrazone metal chelator ((E)-N′-[1-(2-hydroxyphenyl)ethyliden]isonicotinoylhydrazide) (HAPI) and its relation to HAPI metal binding properties. Based on promising initial results, a series of HAPI analogues was prepared to probe the structure-function relationships of aroylhydrazone photochemistry. These efforts elucidate the tunable nature of several aroylhydrazone photoswitching properties.

Ongoing efforts in this laboratory seek to develop compounds called prochelators that exhibit a switch from low to high metal binding affinity upon activation by a stimulus of interest. In this context, we present new strategies to install multiple desired functions into a single structure. The prochelator 2-((E)-1-(2-isonicotinoylhydrazono)ethyl)phenyl (E)-3-(2,4-dihydroxyphenyl)acrylate (PC-HAPI) is masked with a photolabile trans-cinnamic acid protecting group that releases umbelliferone, a UV-absorbing, antioxidant coumarin along with a chelating agent upon UV irradiation. In addition to the antioxidant effects of the coumarin, the released chelator (HAPI) inhibits metal-catalyzed production of damaging reactive oxygen species. Finally a peroxide-sensitive prochelator quinolin-8-yl (Z)-3-(4-hydroxy-2-((4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzyl)oxy)phenyl)acrylate (BCQ) has been prepared using a novel synthetic route for functionalized cis-cinnamate esters. BCQ uses a novel masking strategy to trigger a 90-fold increase in fluorescence emission, along with the release of a desired chelator, in the presence of hydrogen peroxide.

When Working Memory and Attention Compete: Characterizing the Dynamic Interdependence between our Mental Workspace and External Environment

All of us are taxed with juggling our inner mental lives with immediate external task demands. For many years, the temporary maintenance of internal information was considered to be handled by a dedicated working memory (WM) system. It has recently become increasingly clear, however, that such short-term internal activation interacts with attention focused on external stimuli. It is unclear, however, exactly why these two interact, at what level of processing, and to what degree. Because our internal maintenance and external attention processes co-occur with one another, the manner of their interaction has vast implications for functioning in daily life. The work described here has employed original experimental paradigms combining WM and attention task elements, functional magnetic resonance imaging (fMRI) to illuminate the associated neural processes, and transcranial magnetic stimulation (TMS) to clarify the causal substrates of attentional brain function. These studies have examined a mechanism that might explain why (and when) the content of WM can involuntarily capture visual attention. They have, furthermore, tested whether fundamental attentional selection processes operate within WM, and whether they are reciprocal with attention. Finally, they have illuminated the neural consequences of competing attentional demands. The findings indicate that WM shares representations, operating principles, and cognitive resources with externally-oriented attention.

Investigation of Blast Wave Propagation: Correlating External Pressures to Brain Injury Predictors

Blast-induced Traumatic Brain Injury (bTBI) is the signature injury of the Iraq and Afghanistan wars; however, current understanding of bTBI is insufficient. In this study, novel analysis methods were developed to investigate correlations between external pressures and brain injury predictors. Experiments and simulations were performed to analyze placement of helmet-mounted pressure sensors. A 2D Finite Element model of a helmeted head cross-section was loaded with a blast wave. Pressure time-histories for nodes on the inner and outer surfaces of the helmet were cross-correlated to those inside the brain. Parallel physical experiments were carried out with a helmeted headform, pressure sensors, and pressure chamber. These analysis methods can potentially lead to better helmet designs and earlier detection and treatment of bTBI.

The effect of prenatal or early postnatal irradiation on the production of anti-arsonate antibodies and Cross-reactive idiotypes

Preliminary studies on the long-term effects of prenatal and early postnatal irradiation on the immune response to arsonate were performed using A/J mice. Pregnant mice were irradiated (0·5 Gy, X-rays) or sham-irradiated on a single occasion during gestation (between day 5 and 18 post-conception). Alternatively, newborn mice received the same treatment between day 2 and 7 after birth. Mice were immunized with keyhole limpet haemocyanin-arsonate (KLH-Ars) in adjuvant from 2 months after birth. The levels of specific antibodies to arsonate (anti-Ars) were measured by radioimmunoassay. In addition, the Ars-related cross-reactive idiotype (CRIA) was measured by the haemagglutination technique. In the primary response the titre of anti-Ars was reduced in animals that had been irradiated between day 12 and 15 of gestation. In the second response, in contrast, they had increased levels of anti-Ars. After immunization with KLH-Ars, high levels of CRIA were observed in all groups. However, in mice irradiated 18-20 days after conception the level of CRIA was often much higher than the level of anti-Ars, indicating that a large proportion of the CRIA-positive molecules were not specific for Ars. Thus, in this particular case, some specificity of the immune response was lost after irradiation. The expression of recurrent idiotypes may be a sensitive indicator of immunological perturbations after irradiation. © 1988 Informa UK Ltd All rights reserved: reproduction in whole or part not permitted.

Molybdenum hexacarbonyl and DBU reduction of nitro compounds under microwave irradiation

An ethanolic mixture of molybdenurn hexacarbonyl and DBU mediates the reduction of nitroarenes to the corresponding anilines in excellent yields in 15-30 minutes under microwave irradiation.