The Birmingham Boron Neutron Capture Therapy (BNCT) project : developments towards selective internal particle therapy

This paper will review progress on two aspects of the Birmingham BNCT project. Firstly on evaluation of the effects of high and low LET radiations when delivered simultaneously, and secondly on attempts to optimise delivery of the boron carrier compound BPA through pharmacokinetic studies. Simultaneous or non-simultaneous irradiations of V79 cells with alpha-particle and X-ray irradiations were performed. Alpha doses of 2 and 2.5 Gy were chosen and the impact on survival when delivered separately or simultaneously with variable doses of X-rays was evaluated. The pharmacokinetics of the delivery of a new formulation of BPA (BPA-mannitol) are being investigated in brain tumour patients through a study with 2 × 2 design featuring intravenous and intracarotid artery infusion of BPA, with or without a mannitol bolus. On the combined effect of low and high LET radiations, a synergistic effect was observed when alpha and X-ray doses are delivered simultaneously. The effect is only present at the 2.5 Gy alpha dose and is a very substantial effect on both the shape of the survival curve and the level of cell killing. This indicates that the alpha component may have the effect of inhibiting the repair of damage from the low LET radiation dose delivered simultaneously. On the pharmacokinetics of BPA, data on the first three cohorts indicate that bioavailability of BPA in brain ECF is increased substantially through the addition of a mannitol bolus, as well as by the use of intracarotid artery route of infusion. In both cases, for some patients the levels after infusion approach those seen in blood, whereas the ECF levels for intravenous infusion without mannitol are typically less than 10% of the blood values

Mapping the Galactic Halo I. The `Spaghetti' Survey

We describe a major survey of the Milky Way halo designed to test for kinematic substructure caused by destruction of accreted satellites. We use the Washington photometric system to identify halo stars efficiently for spectroscopic followup. Tracers include halo giants (detectable out to more than 100 kpc), blue horizontal branch stars, halo stars near the main sequence turnoff, and the ``blue metal-poor stars'' of Preston et al (1994). We demonstrate the success of our survey by showing spectra of stars we have identified in all these categories, including giants as distant as 75 kpc. We discuss the problem of identifying the most distant halo giants. In particular, extremely metal-poor halo K dwarfs are present in approximately equal numbers to the distant giants for V fainter than 18, and we show that our method will distinguish reliably between these two groups of metal-poor stars. We plan to survey 100 square degrees at high galactic latitude, and expect to increase the numbers of known halo giants, BHB stars and turnoff stars by more than an order of magnitude. In addition to the strong test that this large sample will provide for the question `was the Milky Way halo accreted from satellite galaxies?', we will improve the accuracy of mass measurements of the Milky Way beyond 50 kpc via the kinematics of the many distant giants and BHB stars we will find. We show that one of our first datasets constrains the halo density law over galactocentric radii of 5-20 kpc and z heights of 2-15 kpc. The data support a flattened power-law halo with b/a of 0.6 and exponent -3.0. More complex models with a varying axial ratio may be needed with a larger dataset.Comment: 55 pages, 22 figures, to appear in the Astronomical Journa

Astrometric Methods and Instrumentation to Identify and Characterize Extrasolar Planets: A Review

I present a review of astrometric techniques and instrumentation utilized to search for, detect, and characterize extra-solar planets. First, I briefly summarize the properties of the present-day sample of extrasolar planets, in connection with predictions from theoretical models of planet formation and evolution. Next, the generic approach to planet detection with astrometry is described, with significant discussion of a variety of technical, statistical, and astrophysical issues to be faced by future ground-based as well as space-borne efforts in order to achieve the required degree of measurement precision. After a brief summary of past and present efforts to detect planets via milli-arcsecond astrometry, I then discuss the planet-finding capabilities of future astrometric observatories aiming at micro-arcsecond precision. Lastly, I outline a number experiments that can be conducted by means of high-precision astrometry during the next decade, to illustrate its potential for important contributions to planetary science, in comparison with other indirect and direct methods for the detection and characterization of planetary systems.Comment: 61 pages, 8 figures, PASP, accepted (October 2005 issue

The brain tumor experience from the relatives' perspective

Article describes the clinical optimization of uptake parameters of Boronophenylalanin

The photometric evolution of FU Orionis objects: disc instability and wind-envelope interaction

We present the results of a photometric monitoring campaign of three well studied FU Orionis systems (FU Orionis, V1057 Cygni and V1515 Cygni) undertaken at Maidanak Observatory between 1981 and 2003. When combined with photometric data in the literature, this database provides a valuable resource for searching for short timescale variability - both periodic and aperiodic - as well as for studying the secular evolution of these systems. In the case of V1057 Cyg (which is the system exhibiting the largest changes in brightness since it went into outburst) we compare the photometric data with time dependent models. We show that prior to the end of the `plateau' stage in 1996, the evolution of V1057 Cyg in the $V-(B-V)$ colour-magnitude diagram is well represented by disc instability models in which the outburst is triggered by some agent - such as an orbiting planet - in the inner disc. Following the end of the plateau phase in 1996, the dimming and irregular variations are consistent with occultation of the source by a variable dust screen, which has previously been interpreted in terms of dust condensation events in the observed disc wind. Here we instead suggest that this effect results from the interaction between the wind and an infalling dusty envelope, the existence of this envelope having been previously invoked in order to explain the mid infrared emissio of FU Orionis systems. We discuss how this model may explain some of the photometric and spectroscopic characteristics of FU Orionis systems in general.Comment: 14 pages, 12 figures, MNRAS, accepted. Data files with detailed photometry can be found at http://www.ast.cam.ac.uk/~giuseppe/Publications

Differential Effects of Antibiotic Therapy on the Structure and Function of Human Gut Microbiota

The human intestinal microbiota performs many essential functions for the host. Antimicrobial agents, such as antibiotics (AB), are also known to disturb microbial community equilibrium, thereby having an impact on human physiology. While an increasing number of studies investigate the effects of AB usage on changes in human gut microbiota biodiversity, its functional effects are still poorly understood. We performed a follow-up study to explore the effect of ABs with different modes of action on human gut microbiota composition and function. Four individuals were treated with different antibiotics and samples were taken before, during and after the AB course for all of them. Changes in the total and in the active (growing) microbiota as well as the functional changes were addressed by 16S rRNA gene and metagenomic 454-based pyrosequencing approaches. We have found that the class of antibiotic, particularly its antimicrobial effect and mode of action, played an important role in modulating the gut microbiota composition and function. Furthermore, analysis of the resistome suggested that oscillatory dynamics are not only due to antibiotic-target resistance, but also to fluctuations in the surviving bacterial community. Our results indicated that the effect of AB on the human gut microbiota relates to the interaction of several factors, principally the properties of the antimicrobial agent, and the structure, functions and resistance genes of the microbial community

Changes in Human Fecal Microbiota Due to Chemotherapy Analyzed by TaqMan-PCR, 454 Sequencing and PCR-DGGE Fingerprinting

BACKGROUND: We investigated whether chemotherapy with the presence or absence of antibiotics against different kinds of cancer changed the gastrointestinal microbiota. METHODOLOGY/PRINCIPAL FINDINGS: Feces of 17 ambulant patients receiving chemotherapy with or without concomitant antibiotics were analyzed before and after the chemotherapy cycle at four time points in comparison to 17 gender-, age- and lifestyle-matched healthy controls. We targeted 16S rRNA genes of all bacteria, Bacteroides, bifidobacteria, Clostridium cluster IV and XIVa as well as C. difficile with TaqMan qPCR, denaturing gradient gel electrophoresis (DGGE) fingerprinting and high-throughput sequencing. After a significant drop in the abundance of microbiota (p = 0.037) following a single treatment the microbiota recovered within a few days. The chemotherapeutical treatment marginally affected the Bacteroides while the Clostridium cluster IV and XIVa were significantly more sensitive to chemotherapy and antibiotic treatment. DGGE fingerprinting showed decreased diversity of Clostridium cluster IV and XIVa in response to chemotherapy with cluster IV diversity being particularly affected by antibiotics. The occurrence of C. difficile in three out of seventeen subjects was accompanied by a decrease in the genera Bifidobacterium, Lactobacillus, Veillonella and Faecalibacterium prausnitzii. Enterococcus faecium increased following chemotherapy. CONCLUSIONS/SIGNIFICANCE: Despite high individual variations, these results suggest that the observed changes in the human gut microbiota may favor colonization with C. difficile and Enterococcus faecium. Perturbed microbiota may be a target for specific mitigation with safe pre- and probiotics

Detection and Characterization of Planetary Systems with μ\muas Astrometry

Astrometry as a technique has so far proved of limited utility when employed as either a follow-up tool or to independently search for planetary mass companions orbiting nearby stars. However, this is bound to change during the next decade. In this review, I start by summarizing past and present efforts to detect planets via milli-arcsecond astrometry. Next, I provide an overview of the variety of technical, statistical, and astrophysical challenges that must be met by future ground-based and space-borne efforts in order to achieve the required degree of astrometric measurement precision. Then, I discuss the planet-finding capabilities of future astrometric observatories aiming at micro-arcsecond precision, with a particular focus on their ability to fully describe multiple-component systems. I conclude by putting astrometry in context, illustrating its potential for important contributions to planetary science, as a complement to other indirect and direct methods for the detection and characterization of planetary systems.Comment: 22 pages, 4 figures. Invited contribution at the conference Extrasolar Planets in Multi-Body Systems: Theory and Observations (Torun, Poland, August 25-29, 2008). To appear in the European Astronomical Society Publication Serie