Site- and Location-Adjusted Approaches to Adaptive Allocation Clinical Trial Designs

Response-Adaptive (RA) designs are used to adaptively allocate patients in clinical trials. These methods have been generalized to include Covariate-Adjusted Response-Adaptive (CARA) designs, which adjust treatment assignments for a set of covariates while maintaining features of the RA designs. Challenges may arise in multi-center trials if differential treatment responses and/or effects among sites exist. We propose Site-Adjusted Response-Adaptive (SARA) approaches to account for inter-center variability in treatment response and/or effectiveness, including either a fixed site effect or both random site and treatment-by-site interaction effects to calculate conditional probabilities. These success probabilities are used to update assignment probabilities for allocating patients between treatment groups as subjects accrue. Both frequentist and Bayesian models are considered. Treatment differences could also be attributed to differences in social determinants of health (SDH) that often manifest, especially if unmeasured, as spatial heterogeneity amongst the patient population. In these cases, patient residential location can be used as a proxy for these difficult to measure SDH. We propose the Location-Adjusted Response-Adaptive (LARA) approach to account for location-based variability in both treatment response and/or effectiveness. A Bayesian low-rank kriging model will interpolate spatially-varying joint treatment random effects to calculate the conditional probabilities of success, utilizing patient outcomes, treatment assignments and residential information. We compare the proposed methods with several existing allocation strategies that ignore site for a variety of scenarios where treatment success probabilities vary

Holocene slip rate variability along the Pernicana fault system (Mt. Etna, Italy): Evidence from offset lava flows

The eastern flank of the Mount Etna stratovolcano is affected by extension and is slowly sliding eastward into the Ionian Sea. The Pernicana fault system forms the border of the northern part of this sliding area. It consists of three E-W−oriented fault sectors that are seismically active and characterized by earthquakes up to 4.7 in magnitude (M) capable of producing ground rupture and damage located mainly along the western and central sectors, and by continuous creep on the eastern sector. A new topographic study of the central sector of the Pernicana fault system shows an overall bell-shaped profile, with maximum scarp height of 35 m in the center of the sector, and two local minima that are probably due to the complex morphological relation between fault scarp and lava flows. We determined the ages of lava flows cut by the Pernicana fault system at 12 sites using cosmogenic 3He and 40Ar/39Ar techniques in order to determine the recent slip history of the fault. From the displacement-age relations, we estimate an average throw rate of ∼2.5 mm/yr over the last 15 k.y. The slip rate appears to have accelerated during the last 3.5 k.y., with displacement rates of up to ∼15 mm/yr, whereas between 3.5 and 15 ka, the throw rate averaged ∼1 mm/yr. This increase in slip rate resulted in significant changes in seismicity rates, for instance, decreasing the mean recurrence time of M ≥ 4.7 earthquakes from ∼200 to ∼20 yr. Based on empirical relationships, we attribute the variation in seismic activity on the Pernicana fault system to factors intrinsic to the system that are likely related to changes in the volcanic system. These internal factors could be fault interdependencies (such as those across the Taupo Rift, New Zealand) or they could represent interactions among magmatic, tectonic, and gravitational processes (e.g., Kīlauea volcano, Hawaii). Given their effect on earthquake recurrence intervals, these interactions need to be fully assessed in seismic hazard evaluations

Can alexithymia be assessed through an interview in adolescents? The Toronto Structured Interview for Alexithymia: Reliability, concurrent validity, discriminant validity, and relationships with emotional-behavioral symptoms

Alexithymia is connected to adolescents' psychopathology, but the current methods of assessment present limitations. The Toronto Structured Interview for Alexithymia (TSIA) was developed to overcome the limits of the main used self-rating scale in adults, but no studies investigated its feasibility with adolescents. This study involved 95 community adolescents aged 12-19 years. Adolescents were assessed with the TSIA, the 20-item Toronto Alexithymia Scale (TAS-20), the Verbal Comprehension Index of the WISC-IV for verbal skills, and the Child Behavior Checklist and Youth Self Report for emotional-behavioral symptoms. The aims were to investigate the TSIA internal consistency, concurrent validity with the TAS-20, discriminant validity with participants' verbal skills, and relationships with emotional-behavioral symptoms. TSIA showed good internal consistency, concurrent validity with the TAS-20 (except for factor DDF), and independence by participants' verbal skills, but few relationships with emotional-behavioral symptoms. In conclusion, TSIA showed some good psychometric proprieties but little convergence with research findings obtained with the TAS-20, suggesting the need for further research to check the feasibility of using the TSIA with adolescents. Meanwhile, a precautionary multi-method assessment of alexithymia is recommended

Detection of the Vortex Dynamic Regimes in MgB2 by Third Harmonic AC Susceptibility Measurements

In a type-II superconductor the generation of higher harmonics in the magnetic response to an alternating magnetic field is a consequence of the non-linearity in the I-V relationship. The shape of the current-voltage (I-V) curve is determined by the current dependence of the thermal activation energy U(J) and is thus related to the dynamical regimes governing the vortex motion. In order to investigate the vortex dynamics in MgB2 bulk superconductors we have studied the fundamental (chi1) and third (chi3) harmonics of the ac magnetic susceptibility. Measurements have been performed as a function of the temperature and the dc magnetic field, up to 9 T, for various frequencies and amplitudes of the ac field. We show that the analysis of the behaviour in frequency of chi3(T) and chi3(B) curves can provide clear information about the non-linearity in different regions of the I-V characteristic. By comparing the experimental curves with numerical simulations of the non-linear diffusion equation for the magnetic field we are able to resolve the crossover between a dissipative regime governed by flux creep and one dominated by flux flow phenomena.Comment: to be published in "Horizons in Superconductivity Research" (Nova Science Publishers, Inc., NY, 2003

Application of pactiter V3.3 code to the ACPS assessment of ITER neutral beam injectors primary heat transfer system

Activated Corrosion Products (ACPs) will be present in the various coolant loops of ITER: in-vessel and vacuum vessel, test blanket modules, auxiliary heating or diagnostic equipments. ACPs impact occupational exposure, routine effluents to the environment, and potential releases during accidents. Hence, the ACP inventory evaluation is an important task for ITER public and occupational safety. PACTITER v3.3 code is a computational tool derived from PACTOLE series of codes, modified in some modeling and computing capabilities. ITER Organization has included it as reference computer code for the ACP assessment. In the framework of its verification and validation activity, PACTITER v3.3 was used to assess the ACP inventory of the ITER Neutral Beam Injectors (NBIs) Primary Heat Transfer System (PHTS). This paper will document the preliminary results of this assessment, focusing on the impact of operation scenarios parameters (i.e. water chemistry, materials corrosion properties, etc.) and piping architecture

EChO Payload electronics architecture and SW design

EChO is a three-modules (VNIR, SWIR, MWIR), highly integrated spectrometer, covering the wavelength range from 0.55 $\mu$m, to 11.0 $\mu$m. The baseline design includes the goal wavelength extension to 0.4 $\mu$m while an optional LWIR module extends the range to the goal wavelength of 16.0 $\mu$m. An Instrument Control Unit (ICU) is foreseen as the main electronic subsystem interfacing the spacecraft and collecting data from all the payload spectrometers modules. ICU is in charge of two main tasks: the overall payload control (Instrument Control Function) and the housekeepings and scientific data digital processing (Data Processing Function), including the lossless compression prior to store the science data to the Solid State Mass Memory of the Spacecraft. These two main tasks are accomplished thanks to the Payload On Board Software (P-OBSW) running on the ICU CPUs.Comment: Experimental Astronomy - EChO Special Issue 201

Aerosol optical properties at Lampedusa (Central Mediterranean). 1. Influence of transport and identification of different aerosol types

Aerosol optical depth and Ångström exponent were obtained from multi filter rotating shadowband radiometer (MFRSR) observations carried out at the island of Lampedusa, in the Central Mediterranean, in the period July 2001–September 2003. The average aerosol optical depth at 495.7 nm, τ, is 0.24±0.14; the average Ångström exponent, α, is 0.86±0.63. The observed values of τ range from 0.03 to 1.13, and the values of α vary from −0.32 to 2.05, indicating a large variability in aerosol content and size. In cloud-free conditions, 36% of the airmasses come from Africa, 25% from Central-Eastern Europe, and 19% from Western France, Spain and the North Atlantic. In summer, 42% of the airmasses is of African origin. In almost all cases African aerosols display high values of τ and low values of α, typical of Saharan dust (average values of τ and α are 0.36 and 0.42, respectively). Particles originating from Central-Eastern Europe show relatively large average values of τ and α (0.23 and 1.5, respectively), while particles from Western France, Spain and the North Atlantic show the lowest average values of τ (0.15), and relatively small values of α (0.92). Intermediate values of α are often connected with relatively fast changes of the airmass originating sector, suggesting the contemporary presence of different types of particles in the air column. Clean marine conditions are rare at Lampedusa, and are generally associated with subsidence of the airmasses reaching the island. Average values of τ and α for clean marine conditions are 0.11 and 0.86, respectively. The largest values of α (about 2) were observed in August 2003, when large scale forest fires in Southern Europe produced consistent amounts of fine combustion particles, that were transported to the Central Mediterranean by a persistent high pressure system over Central Europe. Smoke particles in some cases mix with desert dust, producing intermediate values of α. The seasonal distribution of the meteorological patterns over the Mediterranean, the efficiency of the aerosol production mechanisms, and the variability of the particles' residence time produce a distinct seasonal cycle of aerosol optical depths and Ångström exponent values. Particles originating from all sectors show a summer maximum in aerosol optical depth. The summer increase in optical depth for European aerosols is linked with an increment in the values of α, that indicates an enhancement in the number of fine particles. The summer maximum of τ for African particles is associated with a weak reduction in the Ångström exponent, suggesting an increase in the total number of particles and a relatively more intense transport of large particles. The observations were classified according to the aerosol optical properties, and two main classes have been identified: desert dust and biomass burning/urban-industrial aerosols. Values of τ and α averaged over the whole observing period are 0.37 and 0.15 for desert dust, and 0.27 and 1.77 for urban-industrial/biomass burning aerosols

Chromosome 5 allelic losses are early events in tumours of the papilla of Vater and occur at sites similar to those of gastric cancer.

During our studies of DNA fingerprinting of tumours of the pancreas and papilla (ampulla) of Vater, using arbitrarily primed polymerase chain reaction (AP-PCR), we noticed two bands showing a decreased intensity in six of ten ampullary tumours with respect to matched normal tissues. Those bands were both assigned to chromosome 5. Such a finding was somewhat in contrast with the reportedly low frequency of APC gene mutations in ampullary cancers, located at chromosome 5q21, and suggested that loci different from that of APC might be the target of chromosome 5 allelic losses (LOH) in these tumours. Therefore, we analysed chromosome 5 LOH in a panel of 27 ampullary tumours, including eight adenomas, four early- and 15 advanced-stage cancers, using 16 PCR-amplified CA microsatellite polymorphic markers spanning the entire chromosome. Nineteen cases (70%) showed LOH, and the interstitial deletions found in these tumours described two smallest common deleted regions, in which putative suppressor genes might reside. They were at 5q13.3-q14 and at 5q23-q31 respectively, which correspond to those found in gastric tumours. In addition, the presence of 5q LOH in six of eight adenomas and in three of four early-stage cancers suggests that such phenomena occur at early stages of neoplastic progression of the ampullary epithelium