Effectiveness of the Strengthening Families Programme 10–14 in Poland: cluster randomized controlled trial

Background: The Strengthening Families Programme for youth aged 10-14 and parents/carers (SFP10-14) is a family-based prevention intervention with positive results in trials in the United States. We assessed the effectiveness of SFP10-14 for preventing substance misuse in Poland. Methods: Cluster randomized controlled trial with 20 communities (511 families; 614 young people) were allocated to SFP10-14 or a control arms. Primary outcomes were alcohol, smoking and other drug use. Secondary outcomes included parenting practices, parent–child relations, and child problem behaviour. Interview-based questionnaires were administered at baseline and at 12- and 24-months post-baseline, with respective 70.4% and 54.4% follow-up rates. Results: In Bayesian regression models with complete case data we found no effects of SFP10-14 for any of the primary or secondary outcomes at either follow-up. For example at 24-months, posterior odds ratios and 95% credible intervals for past year alcohol use, past month binge drinking, past year smoking, and past year other drug use, were 0.83 (0.44-1.56), 0.83 (0.27-2.65), 1.94 (0.76-5.38), and 0.74 (0.15-3.58), respectively. Although moderate to high attrition rates, together with some evidence of systematic attrition bias according to parent education and family disposable income, could have biased the results, the results were supported in further analyses with propensity score matched data and 40 multiple imputed datasets. Conclusion: We found no evidence for the effectiveness of SFP10-14 on the prevention of alcohol or tobacco use, parenting behaviour, parent-child relations or 4 child problem behaviour at 12- or 24-month follow-up in a large cluster randomised controlled trial in Poland

Molecular Chemical Engines: Pseudo-Static Processes and the Mechanism of Energy Transduction

We propose a simple theoretical model for a molecular chemical engine that catalyzes a chemical reaction and converts the free energy released by the reaction into mechanical work. Binding and unbinding processes of reactant and product molecules to and from the engine are explicitly taken into account. The work delivered by the engine is calculated analytically for infinitely slow (``pseudo-static'') processes, which can be reversible (quasi-static) or irreversible, controlled by an external agent. It is shown that the work larger than the maximum value limited by the second law of thermodynamics can be obtained in a single cycle of operation by chance, although the statistical average of the work never exceeds this limit and the maximum work is delivered if the process is reversible. The mechanism of the energy transductionis also discussed.Comment: 8 pages, 3 figues, submitted to J. Phys. Soc. Jp

Multimodal Theranostic Nanoformulations Permit Magnetic Resonance Bioimaging of Antiretroviral Drug Particle Tissue-Cell Biodistribution

RATIONALE: Long-acting slow effective release antiretroviral therapy (LASER ART) was developed to improve patient regimen adherence, prevent new infections, and facilitate drug delivery to human immunodeficiency virus cell and tissue reservoirs. In an effort to facilitate LASER ART development, “multimodal imaging theranostic nanoprobes” were created. These allow combined bioimaging, drug pharmacokinetics and tissue biodistribution tests in animal models. METHODS: Europium (Eu3+)- doped cobalt ferrite (CF) dolutegravir (DTG)- loaded (EuCF-DTG) nanoparticles were synthesized then fully characterized based on their size, shape and stability. These were then used as platforms for nanoformulated drug biodistribution. RESULTS: Folic acid (FA) decoration of EuCF-DTG (FA-EuCF-DTG) nanoparticles facilitated macrophage targeting and sped drug entry across cell barriers. Macrophage uptake was higher for FA-EuCF-DTG than EuCF-DTG nanoparticles with relaxivities of r2 = 546 mM-1s-1 and r2 = 564 mM-1s-1 in saline, and r2 = 850 mM-1s-1 and r2 = 876 mM-1s-1 in cells, respectively. The values were ten or more times higher than what was observed for ultrasmall superparamagnetic iron oxide particles (r2 = 31.15 mM-1s-1 in saline) using identical iron concentrations. Drug particles were detected in macrophage Rab compartments by dual fluorescence labeling. Replicate particles elicited sustained antiretroviral responses. After parenteral injection of FA-EuCF-DTG and EuCF-DTG into rats and rhesus macaques, drug, iron and cobalt levels, measured by LC-MS/MS, magnetic resonance imaging, and ICP-MS were coordinate. CONCLUSION: We posit that these theranostic nanoprobes can assess LASER ART drug delivery and be used as part of a precision nanomedicine therapeutic strategy

Stochastic Gravity: Theory and Applications

Whereas semiclassical gravity is based on the semiclassical Einstein equation with sources given by the expectation value of the stress-energy tensor of quantum fields, stochastic semiclassical gravity is based on the Einstein-Langevin equation, which has in addition sources due to the noise kernel.In the first part, we describe the fundamentals of this new theory via two approaches: the axiomatic and the functional. In the second part, we describe three applications of stochastic gravity theory. First, we consider metric perturbations in a Minkowski spacetime: we compute the two-point correlation functions for the linearized Einstein tensor and for the metric perturbations. Second, we discuss structure formation from the stochastic gravity viewpoint. Third, we discuss the backreaction of Hawking radiation in the gravitational background of a quasi-static black hole.Comment: 75 pages, no figures, submitted to Living Reviews in Relativit

Stochastic Gravity: A Primer with Applications

Stochastic semiclassical gravity of the 90's is a theory naturally evolved from semiclassical gravity of the 70's and 80's. It improves on the semiclassical Einstein equation with source given by the expectation value of the stress-energy tensor of quantum matter fields in curved spacetimes by incorporating an additional source due to their fluctuations. In stochastic semiclassical gravity the main object of interest is the noise kernel, the vacuum expectation value of the (operator-valued) stress-energy bi-tensor, and the centerpiece is the (stochastic) Einstein-Langevin equation. We describe this new theory via two approaches: the axiomatic and the functional. The axiomatic approach is useful to see the structure of the theory from the framework of semiclassical gravity. The functional approach uses the Feynman-Vernon influence functional and the Schwinger-Keldysh close-time-path effective action methods which are convenient for computations. It also brings out the open systems concepts and the statistical and stochastic contents of the theory such as dissipation, fluctuations, noise and decoherence. We then describe the application of stochastic gravity to the backreaction problems in cosmology and black hole physics. Intended as a first introduction to this subject, this article places more emphasis on pedagogy than completeness.Comment: 46 pages Latex. Intended as a review in {\it Classical and Quantum Gravity

Stochastic Gravity: Theory and Applications

Whereas semiclassical gravity is based on the semiclassical Einstein equation with sources given by the expectation value of the stress-energy tensor of quantum fields, stochastic semiclassical gravity is based on the Einstein-Langevin equation, which has in addition sources due to the noise kernel. In the first part, we describe the fundamentals of this new theory via two approaches: the axiomatic and the functional. In the second part, we describe three applications of stochastic gravity theory. First, we consider metric perturbations in a Minkowski spacetime, compute the two-point correlation functions of these perturbations and prove that Minkowski spacetime is a stable solution of semiclassical gravity. Second, we discuss structure formation from the stochastic gravity viewpoint. Third, we discuss the backreaction of Hawking radiation in the gravitational background of a black hole and describe the metric fluctuations near the event horizon of an evaporating black holeComment: 100 pages, no figures; an update of the 2003 review in Living Reviews in Relativity gr-qc/0307032 ; it includes new sections on the Validity of Semiclassical Gravity, the Stability of Minkowski Spacetime, and the Metric Fluctuations of an Evaporating Black Hol

LSST: from Science Drivers to Reference Design and Anticipated Data Products

(Abridged) We describe here the most ambitious survey currently planned in the optical, the Large Synoptic Survey Telescope (LSST). A vast array of science will be enabled by a single wide-deep-fast sky survey, and LSST will have unique survey capability in the faint time domain. The LSST design is driven by four main science themes: probing dark energy and dark matter, taking an inventory of the Solar System, exploring the transient optical sky, and mapping the Milky Way. LSST will be a wide-field ground-based system sited at Cerro Pach\'{o}n in northern Chile. The telescope will have an 8.4 m (6.5 m effective) primary mirror, a 9.6 deg$^2$ field of view, and a 3.2 Gigapixel camera. The standard observing sequence will consist of pairs of 15-second exposures in a given field, with two such visits in each pointing in a given night. With these repeats, the LSST system is capable of imaging about 10,000 square degrees of sky in a single filter in three nights. The typical 5$\sigma$ point-source depth in a single visit in $r$ will be $\sim 24.5$ (AB). The project is in the construction phase and will begin regular survey operations by 2022. The survey area will be contained within 30,000 deg$^2$ with $\delta<+34.5^\circ$, and will be imaged multiple times in six bands, $ugrizy$, covering the wavelength range 320--1050 nm. About 90\% of the observing time will be devoted to a deep-wide-fast survey mode which will uniformly observe a 18,000 deg$^2$ region about 800 times (summed over all six bands) during the anticipated 10 years of operations, and yield a coadded map to $r\sim27.5$. The remaining 10\% of the observing time will be allocated to projects such as a Very Deep and Fast time domain survey. The goal is to make LSST data products, including a relational database of about 32 trillion observations of 40 billion objects, available to the public and scientists around the world.Comment: 57 pages, 32 color figures, version with high-resolution figures available from https://www.lsst.org/overvie

Successful recruitment to trials : findings from the SCIMITAR+ Trial

BACKGROUND: Randomised controlled trials (RCT) can struggle to recruit to target on time. This is especially the case with hard to reach populations such as those with severe mental ill health. The SCIMITAR+ trial, a trial of a bespoke smoking cessation intervention for people with severe mental ill health achieved their recruitment ahead of time and target. This article reports strategies that helped us to achieve this with the aim of aiding others recruiting from similar populations. METHODS: SCIMITAR+ is a multi-centre pragmatic two-arm parallel-group RCT, which aimed to recruit 400 participants with severe mental ill health who smoke and would like to cut down or quit. The study recruited primarily in secondary care through community mental health teams and psychiatrists with a smaller number of participants recruited through primary care. Recruitment opened in October 2015 and closed in December 2016, by which point 526 participants had been recruited. We gathered information from recruiting sites on strategies which led to the successful recruitment in SCIMITAR+ and in this article present our approach to trial management along with the strategies employed by the recruiting sites. RESULTS: Alongside having a dedicated trial manager and trial management team, we identified three main themes that led to successful recruitment. These were: clinicians with a positive attitude to research; researchers and clinicians working together; and the use of NHS targets. The overriding theme was the importance of relationships between both the researchers and the recruiting clinicians and the recruiting clinicians and the participants. CONCLUSIONS: This study makes a significant contribution to the limited evidence base of real-world cases of successful recruitment to RCTs and offers practical guidance to those planning and conducting trials. Building positive relationships between clinicians, researchers and participants is crucial to successful recruitment

Non-local heat transport, rotation reversals and up/down impurity density asymmetries in Alcator C-Mod ohmic L-mode plasmas

Several seemingly unrelated effects in Alcator C-Mod ohmic L-mode plasmas are shown to be closely connected: non-local heat transport, core toroidal rotation reversals, energy confinement saturation and up/down impurity density asymmetries. These phenomena all abruptly transform at a critical value of the collisionality. At low densities in the linear ohmic confinement regime, with collisionality ν[subscript *] ≤ 0.35 (evaluated inside of the q = 3/2 surface), heat transport exhibits non-local behaviour, core toroidal rotation is directed co-current, edge impurity density profiles are up/down symmetric and a turbulent feature in core density fluctuations with k[subscript θ] up to 15 cm[superscript −1] (k[subscript θ]ρ[subscript s] ~ 1) is present. At high density/collisionality with saturated ohmic confinement, electron thermal transport is diffusive, core rotation is in the counter-current direction, edge impurity density profiles are up/down asymmetric and the high k[subscript θ] turbulent feature is absent. The rotation reversal stagnation point (just inside of the q = 3/2 surface) coincides with the non-local electron temperature profile inversion radius. All of these observations suggest a possible unification in a model with trapped electron mode prevalence at low collisionality and ion temperature gradient mode domination at high collisionality.United States. Dept. of Energy (Contract DE-FC02-99ER54512)United States. Dept. of Energy. Office of Fusion Energy Sciences (Postdoctoral Research Program

Brownian motors: noisy transport far from equilibrium

Transport phenomena in spatially periodic systems far from thermal equilibrium are considered. The main emphasize is put on directed transport in so-called Brownian motors (ratchets), i.e. a dissipative dynamics in the presence of thermal noise and some prototypical perturbation that drives the system out of equilibrium without introducing a priori an obvious bias into one or the other direction of motion. Symmetry conditions for the appearance (or not) of directed current, its inversion upon variation of certain parameters, and quantitative theoretical predictions for specific models are reviewed as well as a wide variety of experimental realizations and biological applications, especially the modeling of molecular motors. Extensions include quantum mechanical and collective effects, Hamiltonian ratchets, the influence of spatial disorder, and diffusive transport.Comment: Revised version (Aug. 2001), accepted for publication in Physics Report