Design and implementation of an automatic measurement system for the characterization of power MOSFETs

Peer Reviewe

Intersegmental Coordination in the Kinematics of Prehension Movements of Macaques

The most popular model to explain how prehensile movements are organized assumes that they comprise two "components", the reaching component encoding information regarding the object's spatial location and the grasping component encoding information on the object's intrinsic properties such as size and shape. Comparative kinematic studies on grasping behavior in the humans and in macaques have been carried out to investigate the similarities and differences existing across the two species. Although these studies seem to favor the hypothesis that macaques and humans share a number of kinematic features it remains unclear how the reaching and grasping components are coordinated during prehension movements in free-ranging macaque monkeys. Twelve hours of video footage was filmed of the monkeys as they snatched food items from one another (i.e., snatching) or collect them in the absence of competitors (i.e., unconstrained). The video samples were analyzed frame-by-frame using digitization techniques developed to perform two-dimensional post-hoc kinematic analyses of the two types of actions. The results indicate that only for the snatching condition when the reaching variability increased there was an increase in the amplitude of maximum grip aperture. Besides, the start of a break-point along the deceleration phase of the velocity profile correlated with the time at which maximum grip aperture occurred. These findings suggest that macaques can spatially and temporally couple the reaching and the grasping components when there is pressure to act quickly. They offer a substantial contribution to the debate about the nature of how prehensile actions are programmed

The Dusty Starburst Nucleus of M33

We have thoroughly characterized the ultraviolet to near-infrared (0.15 - 2.2 micron) spectral energy distribution (SED) of the central parsec of the M33 nucleus through new infrared photometry and optical/near-infrared spectroscopy, combined with ultraviolet/optical observations from the literature and the HST archive. The SED shows evidence for a significant level of attenuation, which we model through a Monte Carlo radiative transfer code as a shell of clumpy Milky Way-type dust (tau_V ~ 2 +/- 1). The discovery of Milky Way-type dust (with a strong 2175 A bump) internal to the M33 nucleus is different from previous work which has found SMC-like dust (no bump) near starburst regions. The amount by which dust can be processed may be related to the mass and age of the starburst as well as the extent to which the dust can shield itself. Our starburst models include the effects of this dust and can fit the SED if the nucleus was the site of a moderate (~10^8 L_sun at 10 Myrs) episode of coeval star formation about 70 Myrs ago. This result is quite different from previous studies which resorted to multiple stellar populations (between 2 and 7) attenuated by either no or very little internal dust. The M33 nuclear starburst is remarkably similar to an older version (70 Myr versus 10 Myr) of the ultra-compact starburst in the center of the Milky Way.Comment: 29 pages, 9 embedded figures, ApJ, in pres

Torsion pendulum facility for direct force measurements of LISA GRS related disturbances

A four mass torsion pendulum facility for testing of the LISA GRS is under development in Trento. With a LISA-like test mass suspended off-axis with respect to the pendulum fiber, the facility allows for a direct measurement of surface force disturbances arising in the GRS. We present here results with a prototype pendulum integrated with very large-gap sensors, which allows an estimate of the intrinsic pendulum noise floor in the absence of sensor related force noise. The apparatus has shown a torque noise near to its mechanical thermal noise limit, and would allow to place upper limits on GRS related disturbances with a best sensitivity of 300 fN/Hz^(1/2) at 1mHz, a factor 50 from the LISA goal. Also, we discuss the characterization of the gravity gradient noise, one environmental noise source that could limit the apparatus performances, and report on the status of development of the facility.Comment: Submitted to Proceedings of the 6th International LISA Symposium, AIP Conference Proceedings 200

Small optic suspensions for Advanced LIGO input optics and other precision optical experiments

We report on the design and performance of small optic suspensions developed to suppress seismic motion of out-of-cavity optics in the Input Optics subsystem of the Advanced LIGO interferometric gravitational wave detector. These compact single stage suspensions provide isolation in all six degrees of freedom of the optic, local sensing and actuation in three of them, and passive damping for the other three

Use of surrogate endpoints in healthcare policy : proposal for consistent adoption of a validation framework

We propose a three step framework for the evaluation of surrogate endpoints for health policy decisions on health technologies

Time to review the role of surrogate endpoints in health policy: state of the art and the way forward

The efficacy of medicines, medical devices, and other health technologies should be proved in trials that assess final patient-relevant outcomes such as survival or morbidity. However, market access and coverage decisions are often based on surrogate endpoints, biomarkers, or intermediate endpoints, which aim to substitute and predict patient-relevant outcomes that are unavailable due to methodological, financial, or practical constraints. We provide a summary of the current use of surrogate endpoints in healthcare policy, discussing the case for and against their adoption and reviewing validation methods. We introduce a three-step framework for policy makers to handle surrogates, which involves establishing the level of evidence, assessing the strength of the association, and quantifying relations between surrogates and final outcomes. Although use of surrogates can be problematic, they can, when selected and validated appropriately, offer important opportunities for more efficient clinical trials and faster access to new health technologies that benefit patients and healthcare systems

Digital detection of exosomes by interferometric imaging

Exosomes, which are membranous nanovesicles, are actively released by cells and have been attributed to roles in cell-cell communication, cancer metastasis, and early disease diagnostics. The small size (30–100 nm) along with low refractive index contrast of exosomes makes direct characterization and phenotypical classification very difficult. In this work we present a method based on Single Particle Interferometric Reflectance Imaging Sensor (SP-IRIS) that allows multiplexed phenotyping and digital counting of various populations of individual exosomes (>50 nm) captured on a microarray-based solid phase chip. We demonstrate these characterization concepts using purified exosomes from a HEK 293 cell culture. As a demonstration of clinical utility, we characterize exosomes directly from human cerebrospinal fluid (hCSF). Our interferometric imaging method could capture, from a very small hCSF volume (20 uL), nanoparticles that have a size compatible with exosomes, using antibodies directed against tetraspanins. With this unprecedented capability, we foresee revolutionary implications in the clinical field with improvements in diagnosis and stratification of patients affected by different disorders.This work was supported by Regione Lombardia and Fondazione Cariplo through POR-FESR, project MINER (ID 46875467); Italian Ministry of Health, Ricerca Corrente. This work was partially supported by The Scientific and Technological Research Council of Turkey (grant #113E643). (Regione Lombardia; 46875467 - Fondazione Cariplo through POR-FESR, project MINER; Italian Ministry of Health, Ricerca Corrente; 113E643 - Scientific and Technological Research Council of Turkey)Published versio

Emergence of a non trivial fluctuating phase in the XY model on regular networks

We study an XY-rotor model on regular one dimensional lattices by varying the number of neighbours. The parameter $2\ge\gamma\ge1$ is defined. $\gamma=2$ corresponds to mean field and $\gamma=1$ to nearest neighbours coupling. We find that for $\gamma<1.5$ the system does not exhibit a phase transition, while for $\gamma > 1.5$ the mean field second order transition is recovered. For the critical value $\gamma=\gamma_c=1.5$, the systems can be in a non trivial fluctuating phase for whichthe magnetisation shows important fluctuations in a given temperature range, implying an infinite susceptibility. For all values of $\gamma$ the magnetisation is computed analytically in the low temperatures range and the magnetised versus non-magnetised state which depends on the value of $\gamma$ is recovered, confirming the critical value $\gamma_{c}=1.5$

Meta-analyses of randomized controlled trials show suboptimal validity of surrogate outcomes for overall survival in advanced colorectal cancer

Comparative StudyMeta-AnalysisReviewValidation StudiesThis is the final version of the article. Available from Elsevier via the DOI in this record.OBJECTIVES: To quantify and compare the treatment effects on three surrogate end points, progression-free survival (PFS), time to progression (TTP), and tumor response rate (TR) vs. overall survival (OS) based on a meta-analysis of randomized controlled trials (RCTs) of drug interventions in advanced colorectal cancer (aCRC). STUDY DESIGN AND SETTING: We systematically searched for RCTs of pharmacologic therapies in aCRC between 2003 and 2013. Trial characteristics, risk of bias, and outcomes were recorded based on a predefined form. Univariate and multivariate random-effects meta-analyses were used to estimate pooled summary treatment effects. The ratio of hazard ratios (HRs)/odds ratios (ORs) and difference in medians were used to quantify the degree of difference in treatment effects on the surrogate end points and OS. Spearman ρ, surrogate threshold effect (STE), and R(2) were also estimated across predefined trial-level covariates. RESULTS: We included 101 RCTs. In univariate and multivariate meta-analyses, we found larger treatment effects for the surrogates than for OS. Compared with OS, treatment effects were on average 13% higher when HRs were measured and 3% to 45% higher when ORs were considered; differences in median PFS/TTP were higher than on OS by an average of 0.5 month. Spearman ρ ranged from 0.39 to 0.80, mean R(2) from 0.06 to 0.65, and STE was 0.8 for HRPFS, 0.64 for HRTTP, or 0.28 for ORTR. The stratified analyses revealed high variability across all strata. CONCLUSION: None of the end points in this study were found to achieve the level of evidence (ie, mean R(2)trial > 0.60) that has been set to select high or excellent correlation levels by common surrogate evaluation tools. Previous surrogacy relationships observed between PFS and TTP vs. OS in selected settings may not apply across other classes or lines of therapy