BACKGROUND: Metabolomics technology has the potential to revolutionize how we screen, diagnose, and treat cancer, as well as improve upon existing cancer molecular tests that may not sufficiently capture the complexity of most malignancies. In this study, we explore the clinical potential of metabolomics analysis in the diagnosis and risk-stratification of brain tumors. METHODS: To test the hypothesis that brain tumor type and survival could be predicted with metabolomics, we analyzed the pre-operative serum and urine samples of patients with glioblastoma (GBM), oligoastrocytoma (OA2), meningioma (M1) and compared them to healthy controls. (HC). Sera from immune-deficient NOD-SCID mice xenografted with human GBM brain tumor initiating cells were also studied. RESULTS: Metabolomics analysis of patient samples was able to accurately differentiate GBM, OA2, M1 and HC (p = 2.3 x 10-26). Subsequently, a prediction model developed and validated internally was able to diagnose GBM with a sensitivity of 86.7% and specificity of 93.8%, and distinguish whether a GBM patient possess O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation (p = 7.4 x 10-10). Within the MGMT methylated group, the model was able to predict longevity (p = 3.25 x 10-4). The model was also able to predict survival irrespective of MGMT methylation status (p = 2.9 x 10-6). CONCLUSIONS: In this study, we demonstrate that metabolomic analysis of patient biofluids can identify brain tumors, distinguish brain tumor subtypes, and independently predict MGMT status as well as longevity among GBM patients. Metabolomics analysis may facilitate non-invasive diagnosis of aggressive brain tumours.

Background: In RRMS patients with inadequate response to prior therapy, 2 alemtuzumab courses (12 mg/day; baseline: 5 days; 12 months later: 3 days) significantly improved outcomes versus SC IFNB-1a over 2 years (CARE-MS II [NCT00548405]). Efficacy remained durable in a 4-year extension (NCT00930553); patients could receive as-needed alemtuzumab retreatment (≥12 months apart) for disease activity, or another disease-modifying therapy (DMT). Through Year 6, 88% remained on study; 50% received neither alemtuzumab retreatment nor another DMT; 16% received ≥4 courses; 3% received ≥5 courses. We evaluated Course 4 (C4) efficacy in patients receiving ≥4 courses. Methods: Annualized relapse rate (ARR); improved/stable Expanded Disability Status Scale (EDSS) score (versus baseline); 6-month confirmed disability improvement (CDI). 11% of patients met inclusion criteria: ≥4 courses within 60 months of baseline; no DMT. Those receiving C5 were censored at that time. Results: ARR decreased after C4 (12 months pre-C4 [-12M]: 0.75; 12 months post-C4 [+12M]: 0.19; P<0.0001), remaining low (0.23) at Year 3 post-C4. More patients had stable/improved EDSS scores +12M (67.5%) versus at C4 administration (53.5%). Percentage with CDI increased post-C4 (-12M: 10.0%; +12M: 26.7%). Conclusions: C4 reduced relapses and stabilized/improved disability in patients with disease activity after initial treatment (C1, C2) plus one additional course (C3).

A total of 12902 neonatal samples collected on absorbent paper for routine metabolic screening were tested anonymously for antibodies to toxoplasma. Seroprevalence varied from 19.5% in inner London, to 11.6% in suburban London, and 7.6% in non-metropolitan districts. Much of this variation appeared to be associated with the proportions of livebirths in each district to women born outside the UK. However, additional geographical variation remained and seroprevalence in UK-born women was estimated to be 12.7% in inner London, 7.5% in suburban London, and 5.5% in non-metropolitan areas. These estimates are considerably lower than any previously reported in antenatal sera in the UK. The wide geographical variation highlights a need for further research to determine the relative importance of different routes of transmission.

BOOMERanG has recently resolved structures on the last scattering surface at redshift ˜ 1100 with high signal to noise ratio. We review the technical advances which made this possible, and we focus on the current results for maps and power spectra, with special attention to the determination of the total mass-energy density in the Universe and of other cosmological parameters.

In the 1998-99 flight, BOOMERanG has produced maps of ∼4% of the sky at high Galactic latitudes, at frequencies of 90, 150, 240 and 410 GHz, with resolution ≳ 10'. The faint structure of the Cosmic Microwave Background at horizon and sub-horizon scales is evident in these maps. These maps compare well to the maps recently obtained at lower frequencies by the WMAP experiment. Here we compare the amplitude and morphology of the structures observed in the two sets of maps. We also outline the polarization sensitive version of BOOMERanG, which was flown early this year to measure the linear polarization of the microwave sky at 150, 240 and 350 GHz.

In the current cosmological scenario, part of the linearly polarizedemission of the CMB is expected to be rotational (B-modes). Thiscomponent is due to tensor perturbations of the metric produced byprimordial gravitational waves, which are generated a split-second after theBig Bang. The signal expected is of the order of ≲ 0.1 μK, well below the non-rotational component of the polarizationsignal (E-modes), and beyond the sensitivity of present generationinstruments. New, more sensitive instruments are developed inseveral labs, with the goal to measure the B-modes. Control ofsystematics and foregrounds will be the key to make the results ofthese experiments believable. In this paper we shortly outlineBRAIN, a bolometric interferometer devoted to B-modes research,and its pathfinder experiment, devoted to test the Dome-C site.


CASPER (Concordia Atmospheric SPectroscopy of Emitted Radiation)is a spectrometer proposed for installation at Dome C, devoted tomeasurements of atmospheric emission in the spectral regionbetween 180 μm and 3 mm (3–55 cm-1). Thisinstrument will be able to perform continuous spectral sampling atdifferent altitudes at angular scales of ~1°. From therecorded data it is possible to extract atmospheric transmittancewithin 1% in the whole wide operating band, together with watervapour content and O2 and O3 concentrations. CASPER willallow us to characterize the site for future FIR/mm telescopes.Atmospheric data recorded by CASPER will allow for correction ofastrophysical and cosmological observations without the need fortelescope-specific procedures and further loss of observation timewith more precision in the observations themselves. Calibration ofground-based telescopes on known sky sources is strongly affectedby atmospheric absorption. CASPER has this as its primary goal.The spectrometer is based on a Martin-Puplett interferometer. Twodata sampling solutions will be performed: phase modulation &fast scan strategy. Sky radiation is collected towards theinterferometer by an optical setup that allows the field of view,to explore the full 0° ÷ 90° range of elevation angles. Witha low spurious polarization instrument, monitoring of polarizedatmospheric contribution will be possible.

The Arcminute Cosmology Bolometer Array Receiver (Acbar) is a multifrequency millimeter-wave receiver optimized for observations of the Cosmic Microwave Background (CMB) and the Sunyaev-Zel'dovich (SZ) effect in clusters of galaxies. Acbar was installed on the 2.1 m Viper telescope at the South Pole in January 2001 and the results presented here incorporate data through July 2002. The power spectrum of the CMB at 150 GHz over the range ℓ = 150 — 3000 measured by Acbar is presented along with estimates for the values of the cosmological parameters within the context of ΛCDM models. The inclusion of ΩΛ greatly improves the fit to the power spectrum. Three-frequency images of the SZ decrement/increment are also presented for the galaxy cluster 1E0657–67.

We show how estimates of parameters characterizing inflation-based theories of structure formation localized over the past year when large scale structure (LSS) information from galaxy and cluster surveys was combined with the rapidly developing cosmic microwave background (CMB) data, especially from the recent Boomerang and Maxima balloon experiments. All current CMB data plus a relatively weak prior probability on the Hubble constant, age and LSS points to little mean curvature (Ωtot = 1.08±0.06) and nearly scale invariant initial fluctuations (ns = 1.03±0.08), both predictions of (non-baroque) inflation theory. We emphasize the role that degeneracy among parameters in the Lpk = 212 ± 7 position of the (first acoustic) peak plays in defining the Ωtot range upon marginalization over other variables. Though the CDM density is in the expected range (Ωcdmh2 = 0.17 ± 0.02), the baryon density Ωbh2 = 0.030 ± 0.005 is somewhat above the independent 0.019 ± 0.002 nucleosynthesis estimates. CMB+LSS gives independent evidence for dark energy (ΩΛ = 0.66 ± 0.06) at the same level as from supernova (SN1) observations, with a phenomenological quintessence equation of state limited by SN1+CMB+LSS to wQ < −0.7 cf. the wQ=−1 cosmological constant case.

The intimate blending of two incompatible polymeric materials constitutes one of the most important fields of study in polymer science. A vast arsenal of techniques, ranging from copolymerization to melt-blending, has been assembled to mix intrinsically immiscible polymers and optimize the physical properties of the resultant system. For some systems, however, even established techniques cannot produce useable blends. To overcome this limitation, non-equilibrium mechanical alloying (high-energy ball milling of two or more dissimilar powders) has been employed to produce blends of poly(ethylene terephthalate) (PET) and Vectra (73/27 oxybenzoate/oxynaphthoate). Characterization of these blends by TEM is confounded by the absence of a preferential staining agent, in which case Scanning Transmission X-ray Microscopy (STXM) provides a valuable alternative in examining the morphology and chemistry of these blends.

The x-ray microscope utilizes a diffraction element called a zone plate to focus soft x-rays into a microprobe. A thin section of sample is placed in this microprobe, and the transmitted photon intensity measured.

Rubber toughening was first developed about seventy years ago as a method of increasing the impact resistance of brittle glassy polymers. Since that time, a wide variety of techniques have been developed to produce discrete dispersions of rubber within a glassy polymer matrix. We are exploring a new route to rubber-toughen polymer through the non-equilibrium process of mechanical alloying (high-energy ball milling). Here we have blended poly(methyl methacrylate) (PMMA) with polyisoprene (PI) (see the insets in Fig. 1 for chemical structures) and have characterized the resultant blends with Scanning Transmission X-ray Microscopy (STXM) in order to obtain chemical, as well as morphological, information about the blends.

The STXM technique utilizes tuneable soft x-rays that are focused with a diffraction zoneplate to a microprobe of 45 nm full width at half maximum. Thin sections of the sample are placed at the microprobe and the transmitted photon intensity is measured.

We have utilized the scanning transmission x-ray microscope at Brookhaven National Laboratory to acquire high energy resolution spectra of various polymers and to investigate the bulk characteristics of multiphasic polymeric materials with chemical sensitivity at a spatial resolution of about 50 nm. We present studies ranging from phase separated liquid crystalline polyesters and polyurethanes to various polymer blends. Improvements in the NEXAFS imaging and spectral acquisition protocol in the recent past provide much improved spectral fidelity and include in situ energy calibration with CO2.