Comparison of three methods for measuring psoriasis severity in clinical studies (Part 1 of 2): change during therapy in Psoriasis Area and Severity Index, Static Physician's Global Assessment and Lattice System Physician's Global Assessment

BackgroundAccurate and reliable assessment of changes in psoriasis severity is critical in clinical trials of therapies.ObjectiveTo compare Psoriasis Area and Severity Index (PASI), static Physician's Global Assessment (sPGA), and the Lattice System Physician's Global Assessment (LS‐PGA) in a trial of systemic treatments for plaque psoriasis vulgaris and to assess whether they measure change in psoriasis induced by therapy.MethodsPatients were randomized to voclosporin or cyclosporine for 24 weeks (the ‘24‐week‐treatment’ group, n = 366), or placebo for 12 weeks followed by voclosporin for 12 weeks (the ‘initial‐placebo’ group, n = 89).ResultsAll scoring systems changed in concert and were sensitive enough to detect reductions in severity during placebo therapy as well as with active therapy (P < 0.01 for each measurement). At study onset, there were poorer correlations of sPGA with PASI (r = 0.45) and LS‐PGA (r = 0.39) than between PASI and LS‐PGA (r = 0.68). After therapy, all correlations were stronger, but sPGA continued to be less well correlated (with PASI, r = 0.85; with LS‐PGA, r = 0.79) than LS‐PGA with PASI (r = 0.90). Two‐ or three‐step improvements in LS‐PGA showed very good to excellent accuracy in corresponding to PASI‐50 and PASI‐75, respectively, and were more accurate than comparable changes in sPGA.ConclusionPASI, sPGA and LS‐PGA are responsive to the varying degrees of improvement in psoriasis induced by either placebo or active therapy. While the three systems capture similar information, each has different reasons for use in a clinical trial.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/111966/1/jdv13132.pd

Optical application and measurement of torque on microparticles of isotropic nonabsorbing material

We show how it is possible to controllably rotate or align microscopic particles of isotropic nonabsorbing material in a TEM00 Gaussian beam trap, with simultaneous measurement of the applied torque using purely optical means. This is a simple and general method of rotation, requiring only that the particle is elongated along one direction. Thus, this method can be used to rotate or align a wide range of naturally occurring particles. The ability to measure the applied torque enables the use of this method as a quantitative tool--the rotational equivalent of optical tweezers based force measurement. As well as being of particular value for the rotation of biological specimens, this method is also suitable for the development of optically-driven micromachines.Comment: 8 pages, 6 figure

Time of admission to the PICU and mortality

Objectives: To evaluate for any association between time of admission to the PICU and mortality. Design: Retrospective cohort study of admissions to PICUs in the Virtual Pediatric Systems (VPS, LLC, Los Angeles, CA) database from 2009 to 2014. Setting: One hundred and twenty-nine PICUs in the United States. Patients: Patients less than 18 years old admitted to participating PICUs; excluding those post cardiac bypass. Interventions: None. Measurements and Main Results: A total of 391,779 admissions were included with an observed PICU mortality of 2.31%. Overall mortality was highest for patients admitted from 07:00 to 07:59 (3.32%) and lowest for patients admitted from 14:00 to 14:59 (1.99%). The highest mortality on weekdays occurred for admissions from 08:00 to 08:59 (3.30%) and on weekends for admissions from 09:00 to 09:59 (4.66%). In multivariable regression, admission during the morning 06:00-09:59 and midday 10:00-13:59 were independently associated with PICU death when compared with the afternoon time period 14:00-17:59 (morning odds ratio, 1.15; 95% CI, 1.04-1.26; p = 0.006 and midday odds ratio, 1.09; 95% CI; 1.01-1.18; p = 0.03). When separated into weekday versus weekend admissions, only morning admissions were associated with increased odds of death on weekdays (odds ratio, 1.13; 95% CI, 1.01-1.27; p = 0.03), whereas weekend admissions during the morning (odds ratio, 1.33; 95% CI, 1.14-1.55; p = 0.004), midday (odds ratio, 1.27; 95% CI, 1.11-1.45; p = 0.0006), and afternoon (odds ratio, 1.17; 95% CI, 1.03-1.32; p = 0.01) were associated with increased risk of death when compared with weekday afternoons. Conclusions: Admission to the PICU during the morning period from 06:00 to 09:59 on weekdays and admission throughout the day on weekends (06:00-17:59) were independently associated with PICU death as compared to admission during weekday afternoons. Potential contributing factors deserving further study include handoffs of care, rounds, delays related to resource availability, or unrecognized patient deterioration prior to transfer

A Proof System for Compositional Verification of Probabilistic Concurrent Processes

Abstract. We present a formal proof system for compositional verification of probabilistic concurrent processes. Processes are specified using an SOS-style process algebra with probabilistic operators. Properties are expressed using a probabilistic modal µ-calculus. And the proof system is formulated as a sequent calculus in which sequents are given a quantitative interpretation. A key feature is that the probabilistic scenario is handled by introducing the notion of Markov proof, according to which proof trees contain probabilistic branches and are required to satisfy a condition formulated byinterpretingthemas Markov Decision Processes. We present simple but illustrative examples demonstrating the applicability of the approach to the compositional verification of infinite state processes. Our main result is the soundness of the proof system, which is proved by applying the coupling method from probability theory to the game semantics of the probabilistic modal µ-calculus.

Fano Resonances in Electronic Transport through a Single Electron Transistor

We have observed asymmetric Fano resonances in the conductance of a single electron transistor resulting from interference between a resonant and a nonresonant path through the system. The resonant component shows all the features typical of quantum dots, but the origin of the non-resonant path is unclear. A unique feature of this experimental system, compared to others that show Fano line shapes, is that changing the voltages on various gates allows one to alter the interference between the two paths.Comment: 8 pages, 6 figures. Submitted to PR

A global database of C4 photosynthesis in grasses

C3,C4 or Crassulacean acid metabolism (CAM) photosynthetic pathways represent a fundamental axis of trait variation in plants,with importance at scales from genome to biome. Knowing the distribution of these pathways among wild species is a crucial first step in understanding the patterns and processes of photosynthetic evolution and its role in ecological processes at large scales (e.g. changes in the composition of biomes under global change). C4 photosynthesis is most prevalent in the Poaceae (grasses), which account for about half of all C4 species (Sage et al.,1999a).Research on the evolution and ecology of these plants has undergone a renaissance during the last 7 yr, catalyzed by phylogenetic analyses showing multiple parallel C4 origins (e.g. Christin et al. , 2007; Vicentini et al., 2008; GPWG II, 2012), insights into the distribution of C4 species and assembly of the C4 grassland biome (Edwards & Still, 2008; Edwards & Smith, 2010; Edwards et al., 2010), and efforts to introduce the C4 pathway into rice (Hibberd et al., 2008; von Caemmerer et al., 2012). C4 photosynthesis is an excellent model for investigating complex trait evolution, because of the broad knowledge base describing its biochemical basis, evolutionary history, and ecological interactions (Christin et al., 2010)

Palaeontology, the biogeohistory of Victoria

The broad-scale distribution of fossils within Victoria is controlled by general global patterns in the biological evolution of life on Earth, the local development and environmental evolution of habitats, and the occurrence of geological processes conducive to the preservation of fossil floras and faunas. Early Palaeozoic fossils are mostly marine in origin because of the predominance of marine sedimentary rocks in Victoria and because life on land was not significant during most of this time interval. Middle Palaeozoic sequences have both terrestrial and marine fossil records. Within Victoria, marine rocks are only very minor components of strata deposited during the late Palaeozoic, so that few marine fossils are known from this time period. A similar situation existed during most of the Mesozoic except towards the end of this era when marine conditions began to prevail in the Bass Strait region. During long intervals in the Cainozoic, large areas of Victoria were flooded by shallow-marine seas, particularly in the southern basins of Bass Strait, as well as in the northwest of the State (Murray Basin). Cainozoic sediments contain an extraordinary range of animal and plant fossils. During the Quaternary, the landscape of Victoria became, and continues to be, dominated by continental environments including, at times, extensive freshwater lake systems. Fossil floras and faunas from sediments deposited in these lake systems and from other continental sediments, as well as from Quaternary sediments deposited in marginal marine environments, collectively record a history of rapid fluctuations in climate and sea level.<br /

Coexistence of 'alpha+ 208Pb' cluster structures and single-particle excitations in 212Po

Excited states in 212Po have been populated by alpha transfer using the 208Pb(18O,14C) reaction at 85MeV beam energy and studied with the EUROBALL IV gamma multidetector array. The level scheme has been extended up to ~ 3.2 MeV excitation energy from the triple gamma coincidence data. Spin and parity values of most of the observed states have been assigned from the gamma angular distributions and gamma -gamma angular correlations. Several gamma lines with E(gamma) < 1 MeV have been found to be shifted by the Doppler effect, allowing for the measurements of the associated lifetimes by the DSAM method. The values, found in the range [0.1-0.6] ps, lead to very enhanced E1 transitions. All the emitting states, which have non-natural parity values, are discussed in terms of alpha-208Pb structure. They are in the same excitation-energy range as the states issued from shell-model configurations.Comment: 21 pages, 19 figures, corrected typos, revised arguments in Sect. III

Ionization of the Venusian atmosphere from solar and galactic cosmic rays

The atmospheres of the terrestrial planets are exposed to solar and galactic cosmic rays, the most energetic of which are capable of affecting deep atmospheric layers through extensive nuclear and electromagnetic particle cascades. In the Venusian atmosphere, cosmic rays are expected to be the dominant ionization source below ∼100 km altitude. While previous studies have considered the effect of cosmic ray ionization using approximate transport methods, we have for the first time performed full 3D Monte Carlo modelling of cosmic ray interaction with the Venusian atmosphere, including the contribution of high-Z cosmic ray ions (Z=1-28). Our predictions are similar to those of previous studies at the ionization peak near 63 km altitude, but are significantly different to these both above and below this altitude. The rate of atmospheric ionization is a fundamental atmospheric property and the results of this study have wide-reaching applications in topics including atmospheric electrical processes, cloud microphysics and atmospheric chemistry

Observing Supermassive Black Holes across cosmic time: from phenomenology to physics

In the last decade, a combination of high sensitivity, high spatial resolution observations and of coordinated multi-wavelength surveys has revolutionized our view of extra-galactic black hole (BH) astrophysics. We now know that supermassive black holes reside in the nuclei of almost every galaxy, grow over cosmological times by accreting matter, interact and merge with each other, and in the process liberate enormous amounts of energy that influence dramatically the evolution of the surrounding gas and stars, providing a powerful self-regulatory mechanism for galaxy formation. The different energetic phenomena associated to growing black holes and Active Galactic Nuclei (AGN), their cosmological evolution and the observational techniques used to unveil them, are the subject of this chapter. In particular, I will focus my attention on the connection between the theory of high-energy astrophysical processes giving rise to the observed emission in AGN, the observable imprints they leave at different wavelengths, and the methods used to uncover them in a statistically robust way. I will show how such a combined effort of theorists and observers have led us to unveil most of the SMBH growth over a large fraction of the age of the Universe, but that nagging uncertainties remain, preventing us from fully understating the exact role of black holes in the complex process of galaxy and large-scale structure formation, assembly and evolution.Comment: 46 pages, 21 figures. This review article appears as a chapter in the book: "Astrophysical Black Holes", Haardt, F., Gorini, V., Moschella, U and Treves A. (Eds), 2015, Springer International Publishing AG, Cha