Conformal Radiotherapy Facilitates the Delivery of Concurrent Chemotherapy and Radiotherapy: A Case of Primitive Neuroectodermal Tumour of the Chest Wall

We illustrate the principle of conformal radiotherapy by discussing the case of a patient with a primitive neuroectodermal tumour of the chest wall. Recent advances in radiotherapy planning enable precise localization of the planning target volume (PTV) and normal organs at risk of irradiation. Customized blocks are subsequently designed to produce a treatment field that ‘conforms’ to the PTV. The use of conformal radiotherapy (CRT) in this case facilitated the delivery of concurrent chemotherapy and radiotherapy by significantly reducing the volume of red marrow irradiated.The lack of acute and late toxicities was attributed to optimal exclusion of normal tissues from the treatment field, made possible by CRT

Asymmetric detection of changes in volatility: Implications for risk perception.

Variance of the outcomes associated with an option often provides a measure of the riskiness of that option. Hence, it is important that organisms are able to detect any sudden changes in outcome variance. In Experiment 1, we presented people with graphs of share price time series or water level time series. In half the graphs, variance (financial or flooding risk) changed at some point. People were better at detecting increases than decreases in risk - maybe because it is more important to detect increases in danger than decreases in it. However, in Experiment 2, people were still better at detecting increases than decreases in variance even when those changes did not reflect altered levels of risk. Our findings may reflect the fact that the actual change in variance exceeds the change needed to identify a regime change in variance by a larger amount for upward than for downward changes

Precision neuromodulation: Promises and challenges of spinal stimulation for multi-modal rehabilitation

Spinal cord injury results in multiple, simultaneous sensorimotor deficits. These include, but are not limited to, full or partial paralysis of muscles below the lesion, muscle spasms, spasticity, and neuropathic pain. Bowel, bladder, and sexual dysfunction are also prevalent. Yet, the majority of emerging spinal stimulation-based therapies focus on a single issue: locomotor rehabilitation. Despite the enormous potential of these translational advances to transform the lives of people living with spinal cord injury, meaningful recovery in other domains deemed critical priorities remains lacking. Here, we highlight the importance of considering the diverse patterns of neural transmission that underlie clinically similar presentations when developing spinal stimulation-based therapies. We also motivate advancement of multi-modal rehabilitation paradigms, which leverage the dense interconnectivity of sensorimotor spinal networks and the unique ability of electrical stimulation to modulate these networks to facilitate and guide simultaneous rehabilitation across domains

The Cleo Rich Detector

We describe the design, construction and performance of a Ring Imaging Cherenkov Detector (RICH) constructed to identify charged particles in the CLEO experiment. Cherenkov radiation occurs in LiF crystals, both planar and ones with a novel ``sawtooth''-shaped exit surface. Photons in the wavelength interval 135--165 nm are detected using multi-wire chambers filled with a mixture of methane gas and triethylamine vapor. Excellent pion/kaon separation is demonstrated.Comment: 75 pages, 57 figures, (updated July 26, 2005 to reflect reviewers comments), to be published in NIM

The novel choline kinase inhibitor ICL-CCIC-0019 reprograms cellular metabolism and inhibits cancer cell growth.

The glycerophospholipid phosphatidylcholine is the most abundant phospholipid species of eukaryotic membranes and essential for structural integrity and signaling function of cell membranes required for cancer cell growth. Inhibition of choline kinase alpha (CHKA), the first committed step to phosphatidylcholine synthesis, by the selective small-molecule ICL-CCIC-0019, potently suppressed growth of a panel of 60 cancer cell lines with median GI50 of 1.12 μM and inhibited tumor xenograft growth in mice. ICL-CCIC-0019 decreased phosphocholine levels and the fraction of labeled choline in lipids, and induced G1 arrest, endoplasmic reticulum stress and apoptosis. Changes in phosphocholine cellular levels following treatment could be detected non-invasively in tumor xenografts by [18F]-fluoromethyl-[1,2–2H4]-choline positron emission tomography. Herein, we reveal a previously unappreciated effect of choline metabolism on mitochondria function. Comparative metabolomics demonstrated that phosphatidylcholine pathway inhibition leads to a metabolically stressed phenotype analogous to mitochondria toxin treatment but without reactive oxygen species activation. Drug treatment decreased mitochondria function with associated reduction of citrate synthase expression and AMPK activation. Glucose and acetate uptake were increased in an attempt to overcome the metabolic stress. This study indicates that choline pathway pharmacological inhibition critically affects the metabolic function of the cell beyond reduced synthesis of phospholipids

Magnetic properties of some carbonatites from Tanzania, East Africa

The magnetization of fresh natrocarbonatite lavas from Oldoinyo Lengai in Tanzania is dominated by small amounts of single- or pseudo-single-domain grains of a spinel in the solid solution series jacobsite (MnFe 2 O 4 )-magnetite (Fe 3 O 4 ). Although this phase may acquire TRM before carbonatite lava crust has ceased being mobile, the Oldoinyo Lengai samples are good palaeomagnetic recorders of the field they cooled in. In comparison, samples from older carbonatites in Tanzania have very different magnetic mineralogies and unstable behaviour of remanent magnetization. There are two possible explanations for the contrast in magnetic properties. Recrystallization of fresh carbonatites during weathering may destroy the original remanence and lead to the production of various authigenic magnetic minerals. Alternatively, the different magnetic mineralogies may derive from distinct types of carbonatite magmas. Some older calcitic carbonatites may have associated magnetic anomalies that could be useful in prospecting for economically valuable minerals often associated with carbonatites.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73225/1/j.1365-246X.1990.tb01756.x.pd

Hyperpolarised 13C MRI: a new horizon for non-invasive diagnosis of aggressive breast cancer

Hyperpolarised 13C MRI (HP-MRI) is a novel imaging technique that allows real-time analysis of metabolic pathways in vivo. 1 The technology to conduct HP-MRI in humans has recently become available and is starting to be clinically applied. As knowledge of molecular biology advances, it is increasingly apparent that cancer cell metabolism is related to disease outcomes, with lactate attracting specific attention. 2 Recent reviews of breast cancer screening programs have raised concerns and increased public awareness of over treatment. The scientific community needs to shift focus from improving cancer detection alone to pursuing novel methods of distinguishing aggressive breast cancers from those which will remain indolent. HP-MRI offers the opportunity to identify aggressive tumour phenotypes and help monitor/predict therapeutic response. Here we report one of the first cases of breast cancer imaged using HP-MRI alongside correlative conventional imaging, including breast MRI