F-061 * A COMPARATIVE STUDY AMONG MINIATURIZED ULTRASOUND PROBES FOR PULMONARY NODULES DETECTION IN AN EX VIVO LUNG PERFUSION MODEL

n/

Tolerability and safety of novel half milliliter formulation of glatiramer acetate for subcutaneous injection: an open-label, multicenter, randomized comparative study

Daily glatiramer acetate (GA) 20 mg/1.0 mL is a first-line treatment for relapsing-remitting multiple sclerosis (RRMS). To reduce the occurrence of injection pain and local injection site reactions (LISRs), a reduced volume formulation of GA was developed. This study compared pain and LISRs after injecting the marketed and the novel formulations. RRMS patients currently injecting GA participated in this multicenter, randomized, crossover comparative study. All patients administered once-daily subcutaneous injections of GA 20 mg/1.0 mL (marketed formulation) or GA 20 mg/0.5 mL (reduced volume formulation) for 14 days. Patients were crossed-over to the alternate treatment for an additional 14 days. Using a Visual Analog Scale (VAS), patients recorded in daily diaries the severity of injection pain immediately and 5 min post-injection, and the presence and severity of LISRs (swelling, redness, itching, lump) within 5 min and 24 h post-injection. VAS pain scores were ranked significantly lower immediately and 5 min after GA 20 mg/0.5 mL injections (p < 0.0001). Although LISRs were rare for both preparations, the severity of reactions ranked significantly lower and fewer symptoms occurred within 5 min and 24 h of using the reduced volume formulation (p < 0.0001). GA injected subcutaneously in a reduced volume formulation is a more tolerable option

Atmospheric neutrino induced muons in the MACRO detector

A measurement of the flux of neutrino-induced muons using the MACRO detector is presented. Different event topologies, corresponding to different neutrino parent energies can be detected. The upward throughgoing muon sample is the larger event sample. The observed upward-throughgoing muons are 26% fewer than expected and the zenith angle distribution does not fit with the expected one. Assuming neutrino oscillations, both measurements suggest maximum mixing and Dm2 of a few times 10-3 eV2. The other samples are due to the internally produced events and to upward-going stopping muons. These data show a regular deficit of observed events in each angular bin, as expected assuming neutrino oscillations with maximum mixing, in agreement with the analysis of the upward-throughgoing muon sample.Comment: 7 pages 6 figures to appear in the proceedings of XVIII International Conference on Neutrino Physics and Astrophysics (Neutrino'98), Takayama, Japan 4-9 June, 199

Measurement of the atmospheric neutrino-induced upgoing muon flux using MACRO

We present a measurement of the flux of neutrino-induced upgoing muons (~100 GeV) using the MACRO detector. The ratio of the number of observed to expected events integrated over all zenith angles is 0.74 +/- 0.036 (stat) +/- 0.046(systematic) +/- 0.13 (theoretical). The observed zenith distribution for -1.0 < cos(theta) < -0.1 does not fit well with the no oscillation expectation, giving a maximum probability for chi^2 of 0.1%. The acceptance of the detector has been extensively studied using downgoing muons, independent analyses and Monte-Carlo simulations. The other systematic uncertainties cannot be the source of the discrepancies between the data and expectations. We have investigated whether the observed number of events and the shape of the zenith distribution can be explained by a neutrino oscillation hypothesis. Fitting either the flux or zenith distribution independently yields mixing parameters of sin^2 (2theta)=1.0 and delta m^2 of a few times 10^-3 eV^2. However, the observed zenith distribution does not fit well with any expectations giving a maximum probability for chi^2 of 5% for the best oscillation hypothesis, and the combined probability for the shape and number of events is 17%. We conclude that these data favor a neutrino oscillation hypothesis, but with unexplained structure in the zenith distribution not easily explained by either the statistics or systematics of the experiment.Comment: 7 pages (two-column) with 4 figure

Observation of the Shadowing of Cosmic Rays by the Moon using a Deep Underground Detector

Using data collected by the MACRO experiment during the years 1989-1996, we show evidence for the shadow of the moon in the underground cosmic ray flux with a significance of 3.6 sigma. This detection of the shadowing effect is the first by an underground detector. A maximum-likelihood analysis is used to determine that the angular resolution of the apparatus is 0.9+/-0.3 degrees. These results demonstrate MACRO's capabilities as a muon telescope by confirming its absolute pointing ability and quantifying its angular resolution.Comment: 14 pages, 8 figures Submitted to Phys. Rev.

Transition to secondary progression in relapsing-onset multiple sclerosis: Definitions and risk factors

Background: No uniform criteria for a sensitive identification of the transition from relapsing–remitting multiple sclerosis (MS) to secondary-progressive multiple sclerosis (SPMS) are available. Objective: To compare risk factors of SPMS using two definitions: one based on the neurologist judgment (ND) and an objective data-driven algorithm (DDA). Methods: Relapsing-onset MS patients (n = 19,318) were extracted from the Italian MS Registry. Risk factors for SPMS and for reaching irreversible Expanded Disability Status Scale (EDSS) 6.0, after SP transition, were estimated using multivariable Cox regression models. Results: SPMS identified by the DDA (n = 2343, 12.1%) were older, more disabled and with a faster progression to severe disability (p &lt; 0.0001), than those identified by the ND (n = 3868, 20.0%). In both groups, the most consistent risk factors (p &lt; 0.05) for SPMS were a multifocal onset, an age at onset &gt;40 years, higher baseline EDSS score and a higher number of relapses; the most consistent protective factor was the disease-modifying therapy (DMT) exposure. DMT exposure during SP did not impact the risk of reaching irreversible EDSS 6.0. Conclusion: A DDA definition of SPMS identifies more aggressive progressive patients. DMT exposure reduces the risk of SPMS conversion, but it does not prevent the disability accumulation after the SP transition

Limits on dark matter WIMPs using upward-going muons in the MACRO detector

We perform an indirect search for Weakly Interacting Massive Particles (WIMPs) using the MACRO detector to look for neutrino-induced upward-going muons resulting from the annihilation of WIMPs trapped in the Sun and Earth. The search is conducted in various angular cones centered on the Sun and Earth to accommodate a range of WIMP masses. No significant excess over the background from atmospheric neutrinos is seen and limits are placed on the upward-going muon fluxes from Sun and Earth. These limits are used to constrain neutralino particle parameters from supersymmetric theory, including those suggested by recent results from DAMA/NaI.Comment: 14 pages, 7 figures, submitted to Phys. Rev.

Persistence on therapy and propensity matched outcome comparison of two subcutaneous interferon beta 1a dosages for multiple sclerosis

To compare treatment persistence between two dosages of interferon &beta;-1a in a large observational multiple sclerosis registry and assess disease outcomes of first line MS treatment at these dosages using propensity scoring to adjust for baseline imbalance in disease characteristics. Treatment discontinuations were evaluated in all patients within the MSBase registry who commenced interferon &beta;-1a SC thrice weekly (n = 4678). Furthermore, we assessed 2-year clinical outcomes in 1220 patients treated with interferon &beta;-1a in either dosage (22 &micro;g or 44 &micro;g) as their first disease modifying agent, matched on propensity score calculated from pre-treatment demographic and clinical variables. A subgroup analysis was performed on 456 matched patients who also had baseline MRI variables recorded. Overall, 4054 treatment discontinuations were recorded in 3059 patients. The patients receiving the lower interferon dosage were more likely to discontinue treatment than those with the higher dosage (25% vs. 20% annual probability of discontinuation, respectively). This was seen in discontinuations with reasons recorded as &ldquo;lack of efficacy&rdquo; (3.3% vs. 1.7%), &ldquo;scheduled stop&rdquo; (2.2% vs. 1.3%) or without the reason recorded (16.7% vs. 13.3% annual discontinuation rate, 22 &micro;g vs. 44 &micro;g dosage, respectively). Propensity score was determined by treating centre and disability (score without MRI parameters) or centre, sex and number of contrast-enhancing lesions (score including MRI parameters). No differences in clinical outcomes at two years (relapse rate, time relapse-free and disability) were observed between the matched patients treated with either of the interferon dosages. Treatment discontinuations were more common in interferon &beta;-1a 22 &micro;g SC thrice weekly. However, 2-year clinical outcomes did not differ between patients receiving the different dosages, thus replicating in a registry dataset derived from &ldquo;real-world&rdquo; database the results of the pivotal randomised trial. Propensity score matching effectively minimised baseline covariate imbalance between two directly compared sub-populations from a large observational registry

SEARCH FOR SLOWLY MOVING MAGNETIC MONOPOLES WITH THE MACRO DETECTOR

A search for slowly moving magnetic monopoles in the cosmic radiation was conducted from October 1989 to November 1991 using the large liquid scintillator detector subsystem of the first supermodule of the MACRO detector at the Gran Sasso underground laboratory. The absence of candidates established an upper limit on the monopole flux of 5.6 x 10(-15) cm-2 sr-1 s-1 at 90% confidence level in the velocity range of 10(-4) less than or similar to beta < 4 x 10(-3). This result places a new constraint on the abundance of monopoles trapped in our solar system